This study aimed to investigate the therapeutic effect of Maiwei Yangfei Decoction(MWYF) on pulmonary fibrosis and its underlying mechanisms. Seventy-two C57BL/6J mice were randomly divided into a blank group, a model group, a low-dose MWYF group, a medium-dose MWYF group, a high-dose MWYF group, and a pirfenidone group. A pulmonary fibrosis model was established by intratracheal instillation of bleomycin. The blank group and the model group were administered double-distilled water daily, while the MWYF groups received corresponding concentrations of MWYF, and the positive control group was given pirfenidone. The severity of pulmonary fibrosis was assessed through Micro-CT scans, histopathological staining of lung tissues, and the expression of collagen Ⅰ and collagen Ⅲ. Network pharmacology combined with transcriptomics analysis was used to explore the anti-fibrotic mechanism of MWYF, which was further validated through in vivo experiments. The results showed that MWYF reduced pulmonary fibrotic lesions, improved inflammation and fibrosis scores, and downregulated the protein expression of collagen Ⅰ and collagen Ⅲ. Network pharmacology and transcriptomics suggested that the anti-fibrotic effect of MWYF was associated with cellular senescence and the p53 signaling pathway. In vivo experiments demonstrated that MWYF significantly reduced senescence-associated β-galactosidase(SA-β-Gal) activity in lung tissues, downregulated the expression of key senescence-related proteins p53, p21, and p16, and decreased cellular senescence, with the high-dose group showing the most pronounced effects. Collectively, these findings demonstrated that MWYF attenuated bleomycin-induced pulmonary fibrosis in mice, likely by suppressing cellular senescence via modulation of the p53 signaling pathway.
Chronic obstructive pulmonary disease(COPD) is a systemic disease characterized by persistent airflow limitation and airway inflammation, with a consistently high incidence and a lack of effective clinical interventions to reverse disease progression. Based on the core TCM pathogenesis theory of "deficiency, phlegm, stasis, and toxin", this paper systematically explores the critical role of the "gut lung axis-neutrophil extracellular traps(NETs)" pathway in the occurrence and development of COPD, as well as its intrinsic association with TCM pathogenesis. Specifically, dysbiosis of the intestinal microecology and dysregulation of pulmonary NETs persist throughout the disease course. Among these, "deficiency of healthy Qi" serves as the initiating factor; disruption of the gut microbiota and deficiency of metabolic products lead to decreased pulmonary defensive function and immunometabolic imbalance. Furthermore, impairment of the intestinal barrier results in the translocation of lipopolysaccharide(LPS) into the bloodstream. As an "endogenous toxin", LPS activates pulmonary neutrophils, triggers oxidative stress, and promotes the formation of NETs. Moreover, the explosive release of pulmonary NETs represents the microscopic entity of the pathological products of "phlegm, stasis, and toxin". The highly viscous DNA backbone of NETs contributes to the formation of "tenacious phlegm" that obstructs the airways; NETs-induced immunothrombosis leads to "stasis obstructing lung collaterals"; and the cytotoxic proteins carried by NETs act as "virulent toxins" that directly damage the lung parenchyma. These pathological processes are the microscopic manifestations of the core pathogenesis of COPD, namely "deficiency leading to excess", "intertwining of phlegm and stasis", and "toxin damaging lung collaterals". In this context, spleen Qi deficiency drives dysregulation of the gut-lung microecology; the influx of endogenous toxins induces NETs activation; and the accumulation of phlegm, stasis, and toxin aggravates lung tissue remodeling. Accordingly, this paper proposes the application of the "consolidating the foundation and clearing the source" method to reconstruct intestinal microecology and block the origin of endogenous toxins, as well as the "removing toxins and dredging collaterals" method to target NETs regulation for resolving phlegm and removing stasis. Through dual "gut-lung" targeting to restore systemic homeostasis, this study provides a theoretical basis and new insights for the integrated TCM and western medicine prevention and treatment of COPD.
This study aimed to investigate the ameliorative effects and underlying mechanisms of the combined use of Platycodon grandiflorum and Sonchus oleraceus on pulmonary nodules in mice. C57BL/6J mice were randomly divided into blank group, model group, positive control group, P. grandiflorum extract group, S. oleraceus extract group, and combination group. The pulmonary nodule model was established by intratracheal instillation of 1×10~9 CFU Cutibacterium acnes for three consecutive days, followed by seven consecutive days of drug administration. Serum amyloid A(SAA) levels were measured, pathological changes in lung tissue were observed, and changes in interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, glutathione peroxidase(GSH-PX), superoxide dismutase(SOD), total antioxidant capacity(T-AOC), and malondialdehyde(MDA) levels in lung tissue were evaluated. Additionally, macrophage M1/M2 polarization and activation of the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB p65 subunit(NF-κB p65) signaling pathway were analyzed. The results showed that all treatment groups ameliorated lung injury in mice with pulmonary nodules. Specifically, the combination group alleviated body weight loss, reduced SAA levels, downregulated the expression of IL-6, TNF-α, and IL-1β, enhanced the activities of GSH-PX, SOD, and T-AOC, decreased MDA accumulation, restored the balance of M1/M2 macrophage phenotypes, upregulated arginase-1(ARG1) levels, suppressed the mRNA expression of inducible nitric oxide synthase(iNOS), TLR4, MyD88, and NF-κB, increased the expression of inhibitor of nuclear factor-κB alpha(IκBα), and downregulated the p-p65/p65 ratio. Meanwhile, compared with the single-herb groups, the combination group demonstrated significant advantages in suppressing inflammatory cytokines and oxidative damage. In conclusion, the combined preparation of P. grandiflorum and S. oleraceus can alleviate pulmonary inflammation and oxidative stress injury and improve pulmonary nodules by inhibiting the NF-κB signaling pathway and suppressing macrophage M1 polarization.
This study aimed to investigate the ameliorative effects of the traditional Chinese herbal compound formula, Shenge Yifei Formula, on pulmonary inflammation and function in mice with chronic obstructive pulmonary disease(COPD) and to elucidate its underlying mechanism from the perspective of inhibiting T helper 1(Th1) immune responses. A COPD model was established in C57BL/6 mice by intratracheal instillation of lipopolysaccharide(LPS) combined with passive smoking exposure. The mice were randomly divided into a blank group, a model group, a tiotropium bromide group, and low-and high-dose Shenge Yifei Formula groups. Following a 5-week intervention, pulmonary function tests and HE staining were performed to assess lung histopathological changes. Flow cytometry, multicolor immunofluorescence, and ELISA were employed to detect the proportion and distribution of CD4~+ C-X-C chemokine receptor 3(CXCR3)~+ Th1 cells in lung tissue, as well as the levels of interferon-γ(IFN-γ), interleukin-12(IL-12), and C-X-C motif chemokine ligand 10(CXCL10) in bronchoalveolar lavage fluid(BALF). Additionally, transcriptomic sequencing was conducted on lung tissue from the high-dose Shenge Yifei Formula group. The study demonstrated that, compared with the model group, Shenge Yifei Formula significantly improved pulmonary function in COPD mice and attenuated alveolar structural damage, airway remodeling, and inflammatory cell infiltration in a dose-dependent manner. Mechanistic investigations revealed that the high dose of Shenge Yifei Formula markedly reduced the proportion and density of CD4~+CXCR3~+Th1 cells in lung tissue and decreased the levels of IFN-γ, IL-12, and CXCL10 in BALF. Transcriptomic analysis further confirmed that its mechanism of action is closely associated with the modulation of immune pathways such as T cell differentiation and cytokine-cytokine receptor interaction. In conclusion, Shenge Yifei Formula effectively ameliorates pulmonary inflammation and dysfunction in COPD mice by inhibiting Th1 cell differentiation, recruitment, and the associated cytokine network. Unlike tiotropium bromide, which primarily improves ventilatory function, Shenge Yifei Formula exerts a significant inhibitory effect on the Th1 axis, suggesting a distinct advantage complementary to bronchodilator therapy at the level of immune inflammation. This study provides modern experimental evidence for the clinical application of Shenge Yifei Formula and indicates its therapeutic potential in COPD by concurrently targeting anti-inflammatory and anti-remodeling processes.
Right ventricular-pulmonary artery (RV-PA) uncoupling, expressed as the tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/PAPs) ratio, is a negative prognostic indicator in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). This study aims to investigate the association between the echocardiographically measured TAPSE/PAPs ratio and invasively determined pulmonary hypertension (PH) subtypes in this population, with the goal of identifying patients at higher risk. This study is a retrospective analysis of 667 patients who underwent TAVR for native severe symptomatic AS at our center between January 2015 and December 2022. All patients underwent a comprehensive transthoracic echocardiographic evaluation and right heart catheterization prior to the procedure. PH was classified into: no PH, isolated post-capillary PH (IpcPH), and combined pre- and post-capillary PH (CoPH). Follow-up time was defined as the time from the procedure to the last documented contact with the patient (alive) or to the time of documented death. All-cause mortality at two years was the primary endpoint. eTAPSE/PAPs showed a moderately positive correlation with pulmonary vascular resistance (Spearman's Rho = 0.52; p = 0.025) and was associated with CoPH (odds ratio 1.29, 95% confidence interval 1.10-1.30). ROC curve analysis showed that eTAPSE/PAPs discriminated presence of CoPH with an AUC of 0.740. The optimal cut-off value was 0.29 mm/mmHg (sensitivity 72%, specificity 60%). During follow-up, 157 deaths were recorded. Kaplan-Meier curves showed a significant difference in overall mortality at 2 years when patients were stratified according to eTPASE/PAPs ratio value of 0.29 (log rank = 4.94, p = 0.026). The eTAPSE/PAPs ratio identifies patients with symptomatic AS undergoing TAVR with higher risk of CoPH. These patients can benefit from an RHC to refine pre-operative risk assessment.
Acute exacerbation of chronic obstructive pulmonary disease(AECOPD) constitutes the acute deterioration phase of chronic obstructive pulmonary disease(COPD), typified by an abrupt intensification of respiratory symptomatology, encompassing exacerbated dyspnea, heightened cough severity, augmented sputum volume, and pronounced respiratory insufficiency. Systemic inflammatory cascades serve as a cardinal etiological driver of AECOPD, emanating from multifaceted host-pathogen interactions involving viral, bacterial, or polymicrobial infections, superimposed upon environmental modulators that collectively precipitate accelerated pathological progression. These contributory elements markedly escalate the inflammatory milieu within the small airways, surmounting endogenous anti-inflammatory safeguards, thereby precipitating airway epithelial barrier disruption, microvascular dilation, edema, and prolific immune cell infiltration, which in turn perpetuate an inflammatory amplification loop. Such mechanisms converge to synergistically impair pulmonary function and extend durations of inpatient care. Current therapeutic paradigms for AECOPD predominantly incorporate bronchodilators, anti-inflammatory pharmacotherapies, supplemental oxygen administration, and mechanical ventilatory support. Notwithstanding these interventions, persistent limitations include the adverse sequelae of protracted systemic glucocorticoid therapy, escalating antimicrobial resistance profiles, and ventilator-associated morbidities. Ergo, there exists an imperative to investigate novel therapeutic modalities that confer enhanced safety and efficacy. TCM proffers salient therapeutic merits via its multi-target and multi-pathway pharmacodynamics, facilitating regulation of pivotal signaling pathways, including the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB), NF-κB/NOD-like receptor pyrin domain containing 3(NLRP3), phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), Janus kinase(JAK)/signal transducer and activator of transcription(STAT), and neutrophil elastase(NE)/mucin 5AC(MUC5AC) pathways. Through such regulatory interventions, TCM efficaciously attenuates inflammatory response, ameliorates symptomatic burden, and diminishes the incidence of AECOPD. The present investigation endeavors to delineate systematically the extant advancements in TCM-mediated regulation of inflammation-related signaling pathways within the context of AECOPD, thereby furnishing a robust theoretical framework and empirical guidance for optimized clinical interventions and pharmaceutical innovations in AECOPD management.
Tenosynovial giant cell tumor (TGCT) is a rare mesenchymal neoplasm arising from the synovium, tendon sheath, or bursa. Although the localized and diffuse forms of TGCT are typically considered benign, malignant TGCT characterized by marked histologic atypia and increased mitotic activity may exhibit aggressive clinical behavior. Pulmonary metastasis from malignant TGCT is rare and, in previously reported cases, pulmonary involvement has predominantly been described as parenchymal nodules or pleural lesions. In this article, we describe a rare case of endobronchial pulmonary metastasis occurring approximately 72 months after the initial diagnosis of malignant TGCT originating from the tendon sheath of the knee.
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with an urgent need for novel therapeutic strategies. M2 macrophage-derived TGF-β1 promotes fibroblast myogenesis, contributing to IPF pathogenesis. Targeting macrophage polarization and fibroblast function thus represents an effective therapeutic approach for treating IPF. Here, we identify B-cell lymphoma 9 (BCL9) as a key upstream regulator implicated in IPF pathogenesis. We demonstrate that BCL9 drives the macrophage M2 program through the MerTK-ERK-SPP1 axis. Notably, pharmacological inhibition of BCL9 with our novel peptide, hsBCL9Z96, effectively attenuates pulmonary fibrosis by reprogramming macrophage-fibroblast crosstalk. Specifically, BCL9 inhibition promotes fibroblast lipogenesis via TGF-β1 signaling, which in turn supports alveolar type 2 (AT2) cell expansion. This macrophage-orchestrated fibroblast phenotypic switch from myogenic to lipogenic is visually corroborated by spatial transcriptomic analyses and immunofluorescence staining of human lung tissues. Functionally, the pathological role of BCL9 and efficacy of hsBCL9Z96 are validated in human cellular models, including IPF patient-derived cells, confirming its translational significance. Collectively, our findings not only elucidate a novel BCL9-driven macrophage-fibroblast-AT2 cell axis in IPF but also establish hsBCL9Z96 as a promising first-in-class therapeutic candidate, providing a strong rationale for targeting BCL9-mediated Wnt signaling in clinical IPF treatment.
Autoimmune pulmonary alveolar proteinosis (APAP) is caused by impaired surfactant clearance due to neutralizing autoantibodies against granulocyte-macrophage colony-stimulating factor. Although whole-lung lavage and inhaled granulocyte-macrophage colony-stimulating factor therapy are established treatment options, pulmonary fibrosis is increasingly recognized as a clinically relevant complication in a subset of patients with APAP. However, the clinical behavior of APAP-associated fibrosing lung disease and the role of antifibrotic therapy remain unclear. A 54-year-old man with a 15-year history of APAP was referred to our institution. High-resolution computed tomography images obtained before referral showed slow progression of reticulation and traction bronchiectasis, suggesting fibrotic progression rather than recurrence of APAP. At presentation, forced vital capacity (FVC) was 3.31 L (80.0% predicted), and diffusion capacity for carbon monoxide (DLCO) was preserved. During 6 months of observation, FVC declined to 3.03 L (73.5% predicted), accompanied by worsening dry cough and exertional dyspnea. Nintedanib was initiated for a progressive fibrosing phenotype in the context of APAP. Thereafter, FVC remained relatively stable for 2 years, whereas DLCO declined during follow-up. APAP-associated fibrosing lung disease may present with a progressive fibrosing phenotype, but its diagnosis and management remain challenging. This case highlights the importance of distinguishing fibrotic progression from recurrence of intra-alveolar proteinosis.
Population-based analyses usually classify smoking status at survey enrollment, which combines people who quit before disease recognition with those who continued smoking through diagnosis and quit afterward. This study evaluated whether smoking cessation after a self-reported cardiopulmonary disease diagnosis was associated with subsequent all-cause and cause-specific mortality among adults reconstructed as smoking at diagnosis. This secondary analysis pooled ten cross-sectional National Health and Nutrition Examination Survey (NHANES) cycles from 1999-2000 through 2017-2018 and linked survey records to mortality follow-up through 2019. Adults aged ≥40 years with self-reported cardiovascular or chronic lung disease were included when self-reported smoking initiation, diagnosis, cessation, and current-smoking information permitted classification as smoking at diagnosis. Survey-weighted Cox models compared post-diagnostic quitters with persistent smokers. Models were unadjusted, demographic-adjusted, and fully adjusted for prespecified demographic, disease-history, smoking-history, and survey-cycle covariates. Among 2319 participants, 975 were post-diagnostic quitters, and 1344 were persistent smokers. During a median follow-up of 6.33 years, 999 all-cause, 272 heart-disease, and 244 cancer deaths occurred. In the fully adjusted model, post-diagnostic quitting was associated with lower heart-disease mortality (adjusted hazard ratio, AHR=0.59; 95% CI: 0.42-0.82; p=0.001). Associations with all-cause mortality (AHR=0.90; 95% CI: 0.74-1.09; p=0.276) and cancer mortality (AHR=0.72; 95% CI: 0.49-1.06; p=0.100) were not statistically significant. Findings for heart-disease mortality were consistent across landmark, overlap-weighted, smoking-burden-adjusted, disease-restricted, quit-age reconstruction, and leave-one-covariate-out analyses. Among adults retrospectively classified as smoking when cardiopulmonary disease was diagnosed, post-diagnostic cessation was associated with lower subsequent heart-disease mortality. The findings are observational and remain susceptible to survivor selection, reverse causation, recall and social-desirability bias, exposure changes after enrollment, mortality misclassification, and residual confounding.
Patients with hepatocellular carcinoma (HCC) presenting with both portal vein tumor thrombus (PVTT) and pulmonary metastasis (PM) have a particularly poor prognosis and limited treatment options. Hepatic arterial infusion chemotherapy (HAIC)-based combination therapy has shown promising activity in advanced HCC, but evidence in this high-risk population remains limited. To evaluate the efficacy and safety of HAIC combined with lenvatinib and tislelizumab (HLP) in patients with HCC with concurrent PVTT and PM. Multicenter retrospective cohort study with propensity score matching (PSM). Treatment-naïve patients with HCC with concurrent PVTT and PM who received lenvatinib plus tislelizumab (LP), with or without HAIC, between June 2018 and June 2024 were included. PSM was performed to balance baseline characteristics between treatment groups. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). A total of 262 patients were enrolled, including 114 patients in the HLP group and 148 patients in the LP group. After 1:1 PSM, 96 matched pairs were analyzed. The HLP group achieved significantly longer median OS than the LP group (15.1 vs 7.0 months; hazard ratio (HR), 0.55; 95% confidence interval (CI), 0.40-0.76; p < 0.001) and longer median PFS (7.3 vs 3.7 months; HR, 0.77; 95% CI, 0.56-0.94; p = 0.033). The ORR (47.7% vs 19.8%; p < 0.001) and DCR (86.1% vs 49.0%; p < 0.001) were also significantly higher in the HLP group. Although both all-grade and grade 3/4 treatment-related AEs were more frequent in the HLP group, toxicities were manageable, and no grade 5 AEs were observed. In patients with HCC with concurrent PVTT and PM, HLP was associated with improved survival outcomes and tumor response compared with lenvatinib plus tislelizumab alone, with a manageable safety profile.
This study aimed to investigate the differences in the ameliorative effects and underlying mechanisms of Buyang Huanwu Decoction(BHD) and its different ethanol elution fractions on pulmonary fibrosis(PF). The content of amygdalin, formononetin, kaempferol, ferulic acid and paeoniflorin in the drug-containing sera of BHD and its different fractions were determined using ultra-high-performance liquid chromatography-tandem quadrupole mass spectrometry. A rat model of PF was established by intratracheal instillation of bleomycin(BLM). The rats were divided into seven groups: a control group, a BLM group, a prednisone acetate(PA) group, a BHD group, a 30% ethanol elution fraction(Fr30) group, a 50% ethanol elution fraction(Fr50) group, and a 90% ethanol elution fraction(Fr90) group. All treatments were administered continuously for 21 days. The degrees of lung inflammation and fibrosis were observed by HE and Masson staining. The hydroxyproline(HYP) levels in lung tissue were determined using a HYP assay kit. The levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α), and high mobility group box 1 protein(HMGB1) in lung tissue were determined using ELISA kits. The levels of total superoxide dismutase(T-SOD), malondialdehyde(MDA) and glutathione peroxidase(GSH-PX) in lung tissue were determined using corresponding commercial kits. Immunofluorescence staining and Western blot were used to detect the levels of epithelial-mesenchymal transition(EMT)-related proteins in lung tissue. RT-qPCR and Western blot were employed to determine the mRNA and protein levels of factors associated with the transforming growth factor-β1(TGF-β1)/Sma and Mad-related protein(Smad) pathway in lung tissue. The results showed that amygdalin was detected in the drug-containing sera of all groups, with the highest content in the Fr30 group and the lowest in the Fr90 group. Formononetin and kaempferol were detected in the BHD, Fr50, and Fr90 groups, with the highest content in the Fr50 group and the lowest in the Fr90 group. Ferulic acid was detected in all groups, with the highest content in the BHD group and the lowest in the Fr30 group. Paeoniflorin was only detected in the BHD and Fr30 groups, with similar content. Compared with the BLM group, the levels of HYP, TNF-α, IL-6, IL-1β, HMGB1, and MDA decreased in all treatment groups, while the levels of IL-10, T-SOD, and GSH-PX increased. However, there was no statistical significance in the changes of T-SOD level in the Fr30 group and HYP and IL-10 levels in the Fr90 group compared with the BLM group. Immunofluorescence staining showed a marked decrease in the protein expression of α-smooth muscle actin(α-SMA) in the lung tissue of the BHD, Fr30, Fr50, and Fr90 groups. Western blot analysis showed that the expression of epithelial cadherin(E-cadherin) significantly increased, while α-SMA and vimentin protein expressions significantly decreased in the lung tissue of the BHD, Fr30, Fr50, and Fr90 groups. RT-qPCR and Western blot analysis revealed that the mRNA and protein levels of TGF-β1 in the BHD and Fr30 groups significantly decreased, the phosphorylation(p)-Smad3/Smad3 ratio in all treatment groups significantly decreased, and the mRNA and protein levels of Smad7 in the BHD, Fr30 and Fr50 groups significantly increased. In conclusion, BHD and its different ethanol elution fractions may ameliorate BLM-induced PF in rats by inhibiting the TGF-β1/Smad pathway, with the Fr30 and Fr50 fractions showing better ameliorative effects.
This study aimed to investigate the mechanism by which Xinfeng Capsules(XFC), a traditional Chinese medicine preparation, ameliorates interstitial lung disease(ILD) in adjuvant arthritis(AA) model rats. It exerts the effect by regulating the adsorption of microRNA155(miR155) by metastasis-associated lung adenocarcinoma transcript 1(MALAT1), thereby ameliorating the abnormal expression of miR155 and subsequently modulating the neurogenic locus Notch homolog protein(Notch)-recombination signal binding protein for immunoglobulin kappa J region(RBP-Jκ) signaling pathway. An AA rat model was established, and after intragastric administration of XFC, pharmacodynamic evaluation was conducted on rats in each group, including arthritis index scoring, paw swelling measurement, pulmonary function test, and histopathological examinations of lung tissue and ankle joint synovium. ELISA was used to detect the levels of related inflammatory cytokines. RT-qPCR was performed to determine the expression levels of long non-coding RNA(lncRNA) MALAT1, miR155 and genes related to the Notch-RBP-Jκ signaling pathway, while Western blot was applied to examine the protein expression of ETS transcription factor-1(ETS-1) and RBP-Jκ. The results showed that, compared with the model group, XFC significantly improved pulmonary function, alleviated paw swelling, and inhibited fibrous hyperplasia and inflammatory cell infiltration in synovial and lung tissue of AA rats. It also reduced the serum levels of pro-inflammatory cytokines such as tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6), thereby alleviating the systemic inflammatory responses. In addition, XFC ameliorated the aberrant expression of lncRNA MALAT1 and miR155, inhibited the transcription of Notch homolog 1(Notch1), Jagged canonical Notch ligand 1(Jagged1), nuclear factor of activated T cells cytoplasmic 1(NFATC1) and interferon regulatory factor 8(IRF8), and further promoted the protein expression of ETS-1 while suppressing RBP-Jκ protein expression. In summary, XFC may exert its effects by enhancing the roles of lncRNA MALAT1 as a molecular sponge to adsorb miR155, thereby inhibiting the aberrant expression of miR155, which in turn modulates the overactivation and transcription of the Notch-RBP-Jκ signaling pathway, suppresses the articular inflammatory response and ameliorates ILD lesions in AA rats.
Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) can manifest with a severe vasculopathic phenotype. We report a case of anti-MDA5 DM in a woman in her early 30s complicated by refractory cutaneous ulcers and pulmonary arterial hypertension (PAH). Despite the escalation of immunosuppressive therapy with glucocorticoids, tacrolimus, intravenous immunoglobulin, and cyclophosphamide, the cutaneous ulcers remained refractory. A progressive decline in diffusing capacity of the lung for carbon monoxide raised suspicion of PAH, which was subsequently confirmed by right heart catheterization. Consequently, combination therapy with mycophenolate mofetil (MMF) and rituximab (RTX) was initiated alongside bosentan. This regimen resulted in the prompt resolution of ulcers and improvement of PAH. Bosentan was discontinued, and azathioprine was initiated to maintain remission, allowing for a successful pregnancy and delivery of a healthy infant. This case suggests a potential role for an MMF- and RTX-containing combination regimen in refractory cutaneous ulcers and PAH associated with anti-MDA5 DM.
Based on the "lung-gut axis" theory, this study explored the effects of Maxing Kugan Decoction(Mxd) on inflammation and intestinal barrier and flora in rats with bleomycin-induced idiopathic pulmonary fibrosis(IPF). A total of 24 male SD rats were randomly divided into four groups: a control group, a model group, a positive control group and an Mxd treatment group, with 6 rats in each group. After 5 days of quarantine and adaptive feeding, the IPF pathological model was induced by intratracheal instillation of bleomycin under laryngoscopic assistance in the model group, positive control group, and Mxd treatment group. Gastric gavage was initiated after successful modeling, and all SD rats were sacrificed on the 15th day post gavage. HE staining and Masson staining were used to observe histopathological changes of lung tissue, while HE staining was adopted to evaluate jejunal pathological changes. Enzyme-linked immunosorbent assay(ELISA) was performed to detect the serum levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in rats. AB-PAS staining was employed to determine the number of goblet cells in jejunal mucosal tissue. Immunofluorescence assay was used to detect the expression of zonula occludens-1(ZO-1) and occludin in rat jejunum, and 16S rDNA sequencing was conducted to analyze the intestinal microbiome of all rats. The results showed that the model group exhibited severe damage to jejunal mucosa and lung tissue accompanied by massive inflammatory cell infiltration, while the two treatment groups demonstrated partial structural defects with a small amount of inflammatory cell infiltration in the lungs and jejuna of rats. Compared with the control group, the model group showed significantly decreased body weight, number of goblet cells, and expression of ZO-1 and occludin proteins(P<0.01), while these indicators were notably increased after intervention in the two treatment groups(P<0.05 or P<0.01). According to 16S rDNA sequencing results, Mxd could regulate the richness and diversity of intestinal flora in rats. KEGG pathway analysis indicated that Mxd regulated pathways such as oxidative phosphorylation, amino sugar, and nucleotide sugar metabolism of intestinal flora in rats. In conclusion, the alteration of intestinal microbiome may be one of the potential mechanisms underlying the therapeutic effect of Mxd on IPF. Mxd can regulate the structure of intestinal microbiome, increase the abundance of beneficial bacteria, and reduce the number of harmful bacteria, as well as protect intestinal barrier and inhibit inflammatory response.
Antineutrophilic cytoplasmic antibodies glomerulonephritis (ANCA-GN) is the most common type of crescentic glomerulonephritis in the elderly. It is life-threatening, and early detection is key to facilitating complete remission with treatment. Albeit rare, more reports are implicating hydralazine use in the development of ANCA-associated vasculitis (AAV) and ANCA-GN. Classic treatment involves the use of corticosteroids with cyclophosphamide (+/- plasmapheresis) in ANCA-GN. However, a definite therapeutic approach and duration for drug-induced AAV has yet to be studied in clinical trials. In our case, we aim to provide another approach that would one day improve and structure therapy guidelines for drug-induced AAV. We present a 75-year-old female patient, with medical history of hypertension, atrial fibrillation status post ablation on anticoagulation, pulmonary hypertension, who came to the nephrology clinic with symptoms of fatigue, anorexia, nausea, weight loss, hemoptysis, and rise in serum creatinine to 2.39 mg/dL from baseline of 0.65 mg/dL, and by admission to the hospital in August 2024 was 4.6 mg/dL. Anti-MPO and anti-histone antibodies were positive; complement was normal. Renal biopsy confirmed pauci-immune necrotizing GN with crescents. Therapy included steroids, rituximab, cyclophosphamide, and plasmapheresis with clinical improvement and complete remission of extra-renal disease.
This study employed evidence mapping to systematically summarize clinical research on TCM for treating chronic obstructive pulmonary disease(COPD) in recent five years, aiming to characterize the distribution characteristics and methodological quality of the evidence, thereby providing an evidence-based reference for optimizing clinical decision-making and guiding future research directions. A computerized search was conducted in CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and the Cochrane Library for literature on TCM for COPD, with the search period spanning from January 2020 to October 2025. The focus was on both the stable phase and acute exacerbation of COPD. Evidence characteristics were presented comparatively using a combination of text and charts. A total of 962 articles were ultimately included. Publication volume in this field has shown a fluctuating downward trend in recent five years. The predominant study type was randomized controlled trial(RCT), with sample sizes in interventional studies mostly concentrated between 61 and 120 cases. The treatment regimen in experimental groups primarily involved TCM combined with western medicine. The intervention durations were mainly 3 months for stable phase of COPD and 2 weeks for acute exacerbation of COPD, involving 50 and 48 classical formulas, and 48 and 32 Chinese proprietary medicines, respectively. The primary TCM syndrome distributions were lung-kidney deficiency syndrome for stable phase of COPD and phlegm-heat obstruction in the lung for acute exacerbation of COPD. Outcome indicators covered categories such as lung function indices, clinical efficacy evaluations, serological markers, and TCM syndrome scores. Most RCTs exhibited issues such as unclear allocation concealment and insufficient application of blinding. The overall quality of systematic reviews was relatively low. TCM demonstrates unique advantages in the treatment of COPD. However, the overall quality of the existing relevant literature is variable and requires improvement. Future research needs to further standardize study designs to enhance the scientific rigor and methodological quality of clinical studies and improve the methodological standards of systematic reviews. This will provide higher-level evidence-based medical evidence for TCM in treating COPD, supporting its standardized clinical application and promotion.
Idiopathic pulmonary fibrosis(IPF) is a fatal interstitial lung disease with limited clinical therapeutic options. Traditional Chinese medicine formulas, characterized by multi-component, multi-target, and holistic regulatory properties, have shown unique potential in the prevention and treatment of IPF. Yangyin Yifei Tongluo Pills(YF) is a TCM formula with demonstrated clinical efficacy. However, its modern pharmacological mechanism against IPF remains to be systematically elucidated. In this study, ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-HRMS) was employed to identify the chemical constituents of YF. A total of 76 potential bioactive compounds were characterized, including flavonoids, phenylpropanoids and other chemicals. By integrating network pharmacology and bioinformatics analyses, drug-related targets, IPF-associated targets, differentially expressed genes, and WGCNA-derived key module genes were intersected, yielding 15 potential targets. Based on a systematic evaluation using nine machine learning algorithms, arginase 1(ARG1) and matrix metalloproteinase 14(MMP14) were identified as key core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses indicated that these targets were mainly involved in inflammatory regulation, signal transduction, and extracellular matrix(ECM) remodeling, with significant enrichment in key signaling pathways such as the TNF signaling pathway. Immune microenvironment analysis revealed that the expression levels of ARG1 and MMP14 were closely associated with immune and stromal cell infiltration characteristics. Molecular docking demonstrated favorable binding affinities between ARG1/MMP14 and several core components, including miltirone, peimine, cryptotanshinone, and sec-O-glucosylhamaudol, while molecular dynamics simulations further confirmed the conformational stability of miltirone and sec-O-glucosylhamaudol, as core potential bioactive components, with the targets under dynamic conditions. Collectively, these findings suggest that YF may exert anti-IPF effects by targeting ARG1 and MMP14 through its core potential bioactive components, synergistically modulating key processes including the immune microenvironment, fibroblast activation, and extracellular matrix remodeling. By integrating LC-MS, bioinformatics, machine learning, immune infiltration analysis, molecular docking, and molecular dynamics simulation, this study systematically elucidates the multi-component and multi-target mechanisms of YF, providing new insights and a foundation for the intervention and treatment of IPF and the mechanistic study of TCM formulas.
This study aimed to investigate the pharmacodynamic material basis and potential mechanism of Baoyuan Decoction(BYD) in treating chronic obstructive pulmonary disease(COPD) based on serum pharmacochemistry and network pharmacology. UPLC-Q-Exactive-Orbitrap-MS was employed to identify the chemical constituents of BYD and its components absorbed in rat plasma. A total of 493 chemical compounds were identified in BYD, 174 of which were reported for the first time. In the drug-containing plasma, 76 prototype components and 44 metabolites were identified, with 27 components exhibiting both prototype and metabolic properties. Through network pharmacology approaches, potential targets of the absorbed prototype components were predicted and intersected with COPD-related targets, yielding 724 common targets. Key targets such as SRC, PIK3R1, and HSP90AA1 were further screened out. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed via the DAVID database, revealing that BYD may exert its effects by regulating biological processes such as response to external stimuli and peptidyl-tyrosine phosphorylation. KEGG analysis indicated involvement of key pathways including calcium signaling pathway, neuroactive ligand-receptor interaction, and cAMP signaling pathway. A component-target-pathway network was constructed, and molecular docking results demonstrated strong binding affinity between the core components of BYD and the key targets. In summary, components such as vitexin, sanguisorbigenin, 6-gingerol, 4-hydroxycinnamic acid, 10-shogaol, liquiritin, ononin, calycosin-7-glucoside, ginsenoside Ro, and ginsenoside Rf may serve as the main pharmacodynamic material basis of BYD in treating COPD. The underlying mechanism may be associated with the regulation of targets such as SRC and PIK3R1, which influences inflammatory and oxidative stress processes. This study preliminarily clarifies the multi-component, multi-target mechanism of BYD against COPD, providing a reference for quality standard improvement and formulation development of BYD.
Mycobacterium abscessus complex is a rapidly growing non-tuberculous mycobacterium(NTM) associated with difficult-to-treat pulmonary and extrapulmonary infections. Clinical management is complicated by intrinsic antimicrobial resistance, inducible macrolide resistance, and genomic heterogeneity. This study characterised five clinical pulmonary M. abscessus isolates from India using whole-genome sequencing (WGS)-based genomic, phylogenetic, and antimicrobial resistance analysis. Five clinical isolates recovered from pulmonary specimens were sequenced using the Illumina NovaSeq platform (Illumina, Inc., San Diego, California, United States) with paired-end 151 bp chemistry. Reads were quality filtered using fastp v1.0.1. Reference-guided alignment and consensus generation were performed using Burrows-Wheeler Aligner (BWA)-Maximal Exact Match (MEM) and SAMtools-based workflows. Genome annotation was conducted using Prokka v1.14.6, functional annotation using eggNOG-mapper, variant analysis using Genome Analysis Toolkit (GATK) HaplotypeCaller and SnpEff, and antimicrobial resistance gene detection using the Comprehensive Antibiotic Resistance Database (CARD). Phenotypic antimicrobial susceptibility findings and GenoType NTM-drug resistance (DR) Line Probe Assay Version 1.0 results (Bruker Corporation, Billerica, Massachusetts, United States) were used to support the interpretation of macrolide resistance-associated findings. The isolates generated 0.92-1.24 Gb of high-quality sequencing data, with Q30 values exceeding 95%. Genome coverage at ≥30× depth exceeded 91%, and average sequencing depth ranged from 44.16× to 149.59×. Annotation identified 4,457-4,751 coding sequences, 45-48 tRNA genes, three rRNA genes, and one tmRNA gene per isolate. Reference alignment ranged from 24.86% to 64.22%, supporting isolate-level genomic heterogeneity. MAB β-lactamase (blaMab) gene was detected in all isolates, while erm(41) was detected only in LIN. WGS-enabled isolate-level characterisation of pulmonary M. abscessus isolates from India demonstrated conserved genomic features with measurable heterogeneity. blaMab supports intrinsic β-lactam resistance, while erm(41) in LIN was consistent with an inducible macrolide resistance pattern supported by available phenotypic antimicrobial susceptibility testing.