A 42-year-old male with chest tightness and dyspnea was admitted to the hospital. Chest CT indicated diffuse interstitial lung infiltration. Despite receiving anti-infective therapy, glucocorticoid therapy, and immunosuppressive agents, the patient developed refractory hypoxaemia. Endotracheal intubation and invasive mechanical ventilation failed to improve oxygenation. Therefore the patient was diagnosed with rapidly progressive interstitial lung disease (RP-ILD) accompanied by type Ⅰ respiratory failure. Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) was initiated, and oxygenation improved in this patient. The patient subsequently underwent bilateral lung transplantation with veno-arterio-venous (VAV) ECMO support. ECMO machine was withdrawn on day 1, and extubation was achieved on day 9 after surgery. Histopathology revealed fibrotic nonspecific interstitial pneumonia (NSIP) with hyaline membrane formation. The patient developed ICU-acquired myasthenia and received early rehabilitation, with gradual recovery of muscle strength. During follow-up, graft lung function remained stable. This case demonstrates that ECMO can serve as a bridge to lung transplantation in RP-ILD patients.

ObjectiveThis study aimed to establish a monocrotaline （MCT）-induced pulmonary arterial hypertension （PAH） rat model to systematically evaluate the protective effect of Xiao Qinglongtang （XQLT） on right cardiac function in model rats and further elucidate the underlying regulatory mechanism. MethodsSixty male SD rats were randomly assigned to the normal group， model group， XQLT low-， medium-， and high-dose groups （XQLT-L/M/H）， and the beraprost sodium tablet group （BST）. Except for the normal group， rats in all other groups were given a single subcutaneous injection of MCT （60 mg·kg^-1） to induce PAH. Three weeks after injection， rats in the XQLT-L/M/H groups were administered XQLT intragastrically at 3.07， 6.14， 12.28 g·kg^-1·d^-1， respectively. Rats in the BST group received beraprost sodium at 12.6 μg·kg^-1·d^-1， and rats in the model group received an equal volume of saline. All treatments lasted for 3 weeks. Right ventricular systolic pressure （RVSP） was measured by right ventricular catheterization. Cardiac function was assessed by echocardiography. The right ventricle was weighed to calculate the right ventricular hypertrophy index （RVHI）. Hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy were used to observe myocardial morphology. Serum metabolomic changes were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）. Data-independent acquisition （DIA） proteomics was used to detect differentially expressed （DE） proteins in the right ventricle， and Western blot was used to measure the expression of uncoupling protein 3 （UCP3）， phosphatidylinositol 3-kinase catalytic subunit p110α （PIK3CA）， L1 cell adhesion molecule （L1CAM）， and quinone oxidoreductase （CRYZ）. UPLC-MS/MS was used to analyze the chemical components of XQLT. ResultsCompared with the normal group， the model group showed significantly increased RVSP and RVHI （P<0.05）， along with pathological changes in myocardial morphology. Compared with the model group， all XQLT-treated groups exhibited reductions in RVSP and RVHI as well as significant improvements in cardiac function and myocardial morphology. Among the XQLT groups， XQLT-M showed the most pronounced effects （P<0.05）， comparable to the BST group. Serum metabolomics revealed 105 differential metabolites in the XQLT groups versus the model group ［variable importance in projection （VIP） >1， P<0.05］， including 58 upregulated and 47 downregulated metabolites. KEGG enrichment analysis indicated that XQLT intervention downregulated phenylalanine metabolism （P<0.01） and upregulated unsaturated fatty acid biosynthesis （P<0.05）. Proteomics analysis showed that 982 DE proteins were identified in the MCT groups versus the normal group， including 455 upregulated and 527 downregulated proteins （|fold change （FC）| >1.3， P<0.05）. Compared with the model group， 237 DE proteins were identified in the XQLT groups， including 124 upregulated and 113 downregulated proteins （|FC| >1.3， P<0.05）， with 57 overlapping DE proteins. KEGG enrichment suggested that XQLT mainly modulated pathways related to mineral absorption， ribosomal biogenesis， peroxisomes， glycolysis/gluconeogenesis， spliceosomes， and thyroid hormone signaling. Western blot analysis showed that， compared with the model group， XQLT increased the expression of UCP3， PIK3CA， and L1CAM， while decreasing the expression of CRYZ （P<0.05）. ConclusionXQLT exerts a protective effect on right heart function in MCT-induced PAH rats， and its mechanism is associated with maintaining myocardial homeostasis and alleviating right ventricular remodeling.

Background Silicosis, caused by inhalation of silica (SiO₂) dust, remains the most prevalent occupational pneumoconiosis in China. While galectin-3 (Gal-3) is known to play pro-inflammatory and pro-fibrotic roles in various diseases, its specific mechanism in the pathogenesis of silicosis has not been fully clarified. Objective To investigate the role and underlying mechanisms of Gal-3 in silicosis using clinical samples of silicosis and a silicosis mouse model. Methods Lung nodule biopsy samples were collected from patients with stage III pneumoconiosis. Concurrently a silicosis mouse model was constructed via non-exposed tracheal intubation with instillation of a SiO₂ suspension. The expression levels of Gal-3 mRNA and protein in the lung tissues of the silicosis model mice were then detected using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) staining. Single-cell transcriptomic sequencing (scRNA-seq) was performed on both human and murine lung samples to analyze the expression of the Gal-3-encoding gene Lgals3 across different cell types. In vitro, RAW264.7 macrophages were treated with varying concentrations of SiO₂ suspension for 24 h and 48 h; the expression levels of Gal-3 mRNA and protein were measured by RT-qPCR and Western blot. The Gal-3 inhibitor TD139 was used to intervene in the SiO₂-induced in vitro macrophage model, and Western blot was used to detect the intracellular expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). Finally, mouse embryonic lung fibroblasts NIH/3T3 and Mlg2908 were treated with varying concentrations of recombinant mouse Gal-3 protein (rmGal-3) for 48 h, and Western blot was used to detect the expression of fibrosis markers [(Collagen I, Collagen III, Fibronectin, and α smooth muscle actin (α-SMA)] and proteins associated with the TGF-β1/Smads signaling pathway. Results RT-qPCR and IHC staining showed that both the gene and protein expression levels of Gal-3 were significantly elevated at all consecutive time points in the silicosis mouse model (P < 0.05). scRNA-seq revealed that Lgals3 was aberrantly highly expressed in lung tissues from pneumoconiosis patients and silicosis mouse models, with the highest expression observed in macrophages. After treatment of macrophages with different concentrations of SiO₂ for 24 h and 48 h, the mRNA and protein expression levels of Gal-3 were significantly upregulated compared with the control group (P < 0.05). Following TD139 intervention, the protein expression levels of IL-1β, TNF-α, and TGF-β1 in dust-exposed macrophages were markedly downregulated (P < 0.0001). After 48 h of stimulation with rmGal-3, the protein expression levels of Collagen I, Fibronectin, and α-SMA in mouse embryonic lung fibroblasts (NIH/3T3 and Mlg2908) were significantly increased in all treatment groups compared with the control group (P < 0.01). Moreover, Gal-3 treatment markedly upregulated TGF-β1 protein expression in Mlg2908 cells and enhanced the phosphorylation levels of Smad2 and Smad3 (P < 0.0001). Conclusion Gal-3 is abnormally expressed in silicotic lung tissues, which primarily originates from macrophages, and inhibition of Gal-3 suppresses SiO₂-induced inflammatory and pro-fibrotic responses. In addition, Gal-3 promotes fibroblast differentiation and extracellular matrix production by activating the TGF-β1/Smads signaling pathway.

Background Silicosis, caused by inhalation of silica (SiO₂) dust, remains the most prevalent occupational pneumoconiosis in China. While galectin-3 (Gal-3) is known to play pro-inflammatory and pro-fibrotic roles in various diseases, its specific mechanism in the pathogenesis of silicosis has not been fully clarified. Objective To investigate the role and underlying mechanisms of Gal-3 in silicosis using clinical samples of silicosis and a silicosis mouse model. Methods Lung nodule biopsy samples were collected from patients with stage III pneumoconiosis. Concurrently a silicosis mouse model was constructed via non-exposed tracheal intubation with instillation of a SiO₂ suspension. The expression levels of Gal-3 mRNA and protein in the lung tissues of the silicosis model mice were then detected using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) staining. Single-cell transcriptomic sequencing (scRNA-seq) was performed on both human and murine lung samples to analyze the expression of the Gal-3-encoding gene Lgals3 across different cell types. In vitro, RAW264.7 macrophages were treated with varying concentrations of SiO₂ suspension for 24 h and 48 h; the expression levels of Gal-3 mRNA and protein were measured by RT-qPCR and Western blot. The Gal-3 inhibitor TD139 was used to intervene in the SiO₂-induced in vitro macrophage model, and Western blot was used to detect the intracellular expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). Finally, mouse embryonic lung fibroblasts NIH/3T3 and Mlg2908 were treated with varying concentrations of recombinant mouse Gal-3 protein (rmGal-3) for 48 h, and Western blot was used to detect the expression of fibrosis markers [(Collagen I, Collagen III, Fibronectin, and α smooth muscle actin (α-SMA)] and proteins associated with the TGF-β1/Smads signaling pathway. Results RT-qPCR and IHC staining showed that both the gene and protein expression levels of Gal-3 were significantly elevated at all consecutive time points in the silicosis mouse model (P < 0.05). scRNA-seq revealed that Lgals3 was aberrantly highly expressed in lung tissues from pneumoconiosis patients and silicosis mouse models, with the highest expression observed in macrophages. After treatment of macrophages with different concentrations of SiO₂ for 24 h and 48 h, the mRNA and protein expression levels of Gal-3 were significantly upregulated compared with the control group (P < 0.05). Following TD139 intervention, the protein expression levels of IL-1β, TNF-α, and TGF-β1 in dust-exposed macrophages were markedly downregulated (P < 0.0001). After 48 h of stimulation with rmGal-3, the protein expression levels of Collagen I, Fibronectin, and α-SMA in mouse embryonic lung fibroblasts (NIH/3T3 and Mlg2908) were significantly increased in all treatment groups compared with the control group (P < 0.01). Moreover, Gal-3 treatment markedly upregulated TGF-β1 protein expression in Mlg2908 cells and enhanced the phosphorylation levels of Smad2 and Smad3 (P < 0.0001). Conclusion Gal-3 is abnormally expressed in silicotic lung tissues, which primarily originates from macrophages, and inhibition of Gal-3 suppresses SiO₂-induced inflammatory and pro-fibrotic responses. In addition, Gal-3 promotes fibroblast differentiation and extracellular matrix production by activating the TGF-β1/Smads signaling pathway.

Objective To analyze the spatial distribution patterns of the potential suitable habitats for Cremastrae Pseudobulbus Pleiones Pseudobulbus,including Cremastra appendiculata(D.Don)Makino,Pleione bulbocodioides(Franch.)Rolfe and Pleione yunnanensis Rolfe under current climatic conditions,and the factors influencing the spatial differentiation of their habitats.Methods Based on the maximum entropy(MaxEnt)model,a species distribution model was established using the screened species distribution data and environmental variable data.The factor detection and interaction detection of geographical detector were applied to quantify the factors influencing the spatial differentiation of the suitable areas.By overlaying the suitable areas with land cover types,the distribution characteristics of forest land and arable land in the potential suitable areas were quantified.Results Under the current climatic scenario,environmental variables such as solar radiation intensity,precipitation and temperature were closely related to the spatial distribution of Cremastrae Pseudobulbus Pleiones Pseudobulbus.The potential suitable areas for Cremastra appendiculata(D.Don)Makino,Pleione bulbocodioides(Franch.)Rolfe and Pleione yunnanensis Rolfe were 2.20×106 km2,2.75×106 km2 and 7.22×105 km2,respectively.Considering land cover types,the actual possible suitable areas for Cremastra appendiculata(D.Don)Makino,Pleione bulbocodioides(Franch.)Rolfe and Pleione yunnanensis Rolfe were 1.86×106 km2,2.20×106 km2 and 5.77×105 km2,respectively.Among these,the area of forest land was 1.17×106 km2,1.34×106 km2 and 3.67×105 km2,respectively,and the area of arable land was 6.95×105 km2,8.64×105 km2 and 2.10×105 km2,respectively.Conclusion This study can provide a basis for the protection and sustainable utilization of wild resources of the original plant materials of Cremastrae Pseudobulbus Pleiones Pseudobulbus.

Objective To investigate the spatial distribution pattern of the suitable habitats for Codonopsis pilosula(Franch.)Nannf.and the factors influencing the spatial differentiation of its habitat under current climatic conditions in China.Methods Based on maximum entropy(MaxEnt)model,a species distribution model was established with filtered species occurrence data and environmental variable data.The geographical detector was applied to quantify the factors influencing the spatial differentiation of the suitable areas,employing both factor detection and interaction detection functionalities.Additionally,an overlay analysis with land cover types was conducted to quantify the distribution characteristics of arable land and forest land within the potential suitable areas for Codonopsis pilosula(Franch.)Nannf..Results Based on the contribution rate of environmental factors and the Jackknife method,average solar radiation intensity in December,precipitation in July,and highest temperature in December were identified as key environmental factors affecting the suitability of Codonopsis pilosula(Franch.)Nannf.habitats,which were further validated by the geographical detector.The total suitable area for Codonopsis pilosula(Franch.)Nannf.in China under current climatic conditions was approximately 4.46×106 km2,with the areas of high,moderate,and low suitability being 1.08×106 km2,1.70×106 km2,and 1.68×106 km2,respectively.After overlaying with arable and forest lands,the potentially suitable total forest area for Codonopsis pilosula(Franch.)Nannf.was 1.55×106 km2,and the arable land area was 1.63×106 km2.Conclusion This study provides reference for the optimization of cultivation areas for Codonopsis pilosula(Franch.)Nannf.and the conservation of its wild resources.

In order to delve into the molecular mechanism underlying the increased pathogenicity of the recombinant Muscovy duck parvovirus(rMDPV)towards Muscovy ducklings,two sub-genom-ic fragments of the rMDPV strain ZW were cloned into the plasmid pBluescript Ⅱ(SK)to gener-ate the recombinant plasmid pZW.A single nucleotide mutation was engineered in the VP3 gene of pZW to discriminate from the parental strain ZW.pZW plasmid-lipid complex was transfected into the chorioallantoic membrane of 11-day-old embryonated Muscovy duck embryos,resulting in res-cue of infectious virus,rZW,carrying the genetic marker.The rescued virus was passaged in 12-day-old embryonated Muscovy duck embryos and exhibited the similar medium embryo lethal dose(ELD50)value and growth curve compared to the parental strain ZW.Both rZW and strain ZW led to 100％mortality in the infection tests performed with 3-day-old Muscovy duckling.Postmortem necropsy revealed a characteristic intestine embolism formed in the rZW-infected ducklings.Taken together,the generation of the infectious clone pZW lays a solid foundation for deciphering the pathogenesis of rMDPV.

Based on the target recognition ability of split aptamer and intelligent analytical capability of molecular logic gate,in this work,two split aptamers were integrated into"AND"logic gate to construct a novel ortho-nucleic acid fluorescence sensor for simultaneous detection of thrombin and myoglobin.When there was one target,the response of the signal was only a single fluorescence output signal,which was used as an evaluation standard for early low-risk judgment.When two targets coexisted,the split aptamer bound to the target to form a ternary complex and led to the head and tail ortho-nucleic acid effect respectively,and triggered the G4 chain to enhance the fluorescence signal of thioflavin T and the fluorescence signal quenching of Cyanine 3,which could be used as an evaluation criterion for early high-risk judgement.Under the optimal conditions,the linear range for detection of thrombin was 3-200 nmol/L,with a correlation coefficient of 0.9931 and a detection limit of 0.97 nmol/L,and the linear range for detection of myoglobin was 6-400 nmol/L,with a correlation coefficient of 0.9933,and a detection limit of 2.14 nmol/L.The method was applied to simultaneous determination of thrombin and myoglobin in clinical serum samples,and the recoveries were 85.4%-118.3%and 85.8%-119.9%,respectively,with relative standard deviations of less than 6.5%.Compared with the standard method,the relative error range was from-8.8%to 5.6%.In addition,the logical diagnosis results of 4 serum samples were high-risk of acute myocardial infarction in 2 cases and low-risk in 2 cases.The ″AND″ logic gate ortho-nucleic acid fluorescence sensing method showed many advantages such as high selectivity,rapidity,accuracy and simultaneous detection,which offered important reference for early diagnosis of acute myocardial infarction,and also provided a general detection design strategy and platform for simultaneous detection of biomarkers.

Objective:To evaluate the safety and effectiveness of robot-assisted coronary artery bypass(RACAB).Methods:We retrospectively analyzed the clinical outcomes from 252 consecutive patients who underwent RACAB in our center between April 2021 and August 2023. The internal mammary artery(IMA) was harvested using the skeletonized technique with the assistance of the robotic system. Then, graft-to-target vessel anastomoses were performed via a 4-6 cm left fifth intercostal thoracotomy. Coronary angiography or coronary CTA was routinely performed before discharge.Results:149 patients(59.1%) underwent multi-vessel coronary bypass. 140 patients(55.6%) underwent total arterial bypass grafting, with 131 patients(52.0%) undergoing RACAB with in situ bilateral IMA. IMA harvesting failed in 6 patients(1.6%). One patient(0.4%) was assisted by extracorporeal circulation, and 5 patients(2.0%) underwent re-thoracotomy postoperatively. The patency rate of grafts was 96.6%(449/465). The 12-month and 24-month survival rate were 97.8% and 96.5% respectively; The 12-month and 24-month MACCE-free survival rate were 95.2% and 92.6%, respectively.Conclusion:RACAB is safe and feasible. With the assistance of the robotic system, in situ bilateral IMA can be obtained and bypassed to all target vessels territory. Extended follow-up is warranted.

Objective:To analyze the safety and efficacy of multi-vessel minimally invasive cardiac surgery-coronary artery bypass graft(MICS-CABG) through perioperative angiography results and complications.Methods:Clinical data of 1 073 patients who underwent multi-vessel MICS-CABG surgery at Peking University Third Hospital from December 2015 to June 2024 were collected using an ambispective cohort study. Among them, 745 were males(69.4%), with a median age of 65 years(58, 71), and a median ejection fraction of 0.66(0.56, 0.71). Double-vessel or triple-vessel lesions accounted for 932 cases(86.9%), while left main lesions were present in 449 cases(41.8%). The primary outcome was the evaluation of graft patency based on perioperative angiography or coronary artery computed tomography angiography results, while major cardiovascular adverse events during the perioperative period, surgical complications, and other surgical information were secondary outcomes. The clinical efficacy of multi-vessel MICS-CABG was evaluated.Results:In this study, the median number of grafts was 3, and complete revascularization was performed in 1 006 cases(93.8%); total arterial revascularization was performed in 308 cases(28.6%). Perioperative mortality was 11 cases(1.0%), and the main adverse cardiovascular and cerebrovascular events(MACCE) was 50 cases(4.8%). Three cases(0.3%) had poor wound healing, and 79 patients(7.4%) required transfusion. Postoperative coronary angiography was performed in 907 patients(84.5%) and coronary CTA was performed in 52 patients(4.8%), for an overall review rate of 89.4%(959/1073). The overall patency rate of the bridge vessel was 96.9%, and the patency rate of the left internal mammary artery was 98.2%.Conclusion:Multi-vessel MICS-CABG demonstrates excellent perioperative safety and is capable of achieving complete revascularization for the 3 regions of the heart. The quality of the anastomosis and the postoperative patency rate of the grafts is satisfactory.