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.

ObjectiveTo explore the effect of Ganoderma leucocontextum ethanol extract (GLE) on silicosis and its potential molecular mechanism using network pharmacology, molecular docking technology and animal experiments. Methods i) The components of GLE were analyzed using ultra-performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS) method. The active components, potential molecular pathways and targets of GLE in the intervention of inflammation process of silicosis was explored using network pharmacology and molecular docking technology. ii) Specific pathogen free male C57BL6/J mice were divided into four groups with 10 mice in each group. The mice in the silicosis model group and GLE intervention group were given a dose of 80 μL silica suspension with a mass concentration of 50 g/L once by non-exposed tracheal instillation, and the mice in the blank control group and GLE control group were given an equal volume of sterile 0.9% sodium chloride solution. From the second day after modeling, GLE control group and GLE intervention group were given GLE at a dose of 200 mg/(kg•d) by gavage, while blank control group and silicosis model group were given the same volume of 0.9% sodium chloride solution by gavage, once per day for 35 days. After that, the histopathological changes of lung tissues of mice were observed, the lung mass coefficient, inflammation score and the ratio of collagen deposition area were calculated, and the levels of tumor necrosis factor (TNF) -α, interleukin (IL) -1β and IL-6 in the lung tissues of mice were detected by enzyme-linked immunosorbent assay. Results i) A total of 76 active components of GLE were detected by UPLC-QE-MS. Among them, 36 ingredients met the screening criteria of the five principles of drug-like components. A total of 67 potential targets of the 36 GLE active ingredients to improve the inflammatory response of silicosis were screened based on the network pharmacology theory. The result of Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Ontology functional analysis showed that IL signaling and cytokine signaling of immune cells played a key role in the process of anti-silicosis of GLE. The results of molecular docking showed that the top 10 targets based on the 67 intersection targets were TNF, IL6, B-cell lymphoma 2, cellular tumor antigen p53, Caspase-3 subunit p12, JUN, epidermal growth factor receptor, IL1B, 67 kDa matrix metalloproteinase-9 and prostaglandin G/H synthase 2. The result of protein-protein interaction analysis showed that glycyrrhetinic acid had the strongest affinity with the key targets TNF-α, IL-1β and IL-6, followed by ganoderma acid DM, alismatol C, ganoderma acid β and red sapogenin. ii) The results of histopathological examination showed that the inflammatory response and collagen deposition were alleviated in the lungs of mice with silicosis. The lung mass coefficient, inflammation score, ratio of collagen deposition area and IL-6 expression in lung were lower in mice of the GLE intervention group (all P<0.05), compared with the silicosis model group. However, there was no significant difference in the levels of TNF-α and IL-1β in lung tissues between the two groups (all P>0.05). Conclusion GLE may reduce silica-induced lung inflammation and fibrosis by inhibiting the IL-6 level in lung tissues of mice. Its mechanism is associated with the synergistic action of multi-components, multi-targets and multi-pathways.

Objective To explore the risk factors for developing chronic pulmonary heart disease in patients with pneumoconiosis.Methods The medical records of pneumoconiosis patients admitted to an occupational disease hospital in Sichuan Province between January 2012 and November 2021 were collected.Kaplan-Meier(K-M)method,or product-limit method,was used to plot the incidence curves of pulmonary heart disease in the pneumoconiosis patients.Cox proportional hazard regression model was used to analyze the influencing factors associated with chronic pulmonary heart disease in patients with pneumoconiosis.Results A total of 885 pneumoconiosis patients were included in this study.The follow-up time was 12 to 115 months and the median follow-up time was 43 months.A total of 138 patients developed chronic pulmonary heart disease and the incidence density of pulmonary heart disease was 38.50/1000 person-years.Multivariate Cox proportional hazard regression analysis showed that the influencing factors of pneumoconiosis inpatients developing chronic pulmonary heart disease included the following,being 50 and older(hazard ratio[HR]=1.85,95%confidence interval[CI]:1.25-2.74),stage Ⅲ pneumoconiosis(HR=2.43,95%CI:1.48-4.01),resting heart rate≥100 beats/min(HR=2.62,95%CI:1.63-4.21),the complication of chronic obstructive pulmonary disease(COPD)(HR=4.52,95%CI:2.12-9.63),underweight(HR=2.40,95%CI:1.48-3.87),overweight and obesity(HR=0.54,95%CI:0.34-0.86),and triacylglycerol(TG)(HR=0.69,95%CI:0.49-0.99).Conclusion Old age,stage Ⅲ pneumoconiosis,high resting heart rate,low BMI,and the complication of COPD are risk factors for chronic pulmonary heart disease in pneumoconiosis patients,while overweight and obesity and TG are protective factors.Early identification of the risk factors and the adoption of the corresponding prevention measures are the key to preventing chronic pulmonary heart disease in patients with pneumoconiosis.

With the development of implant dentistry and biomaterials, dental implants have become the first rehabilitative option proposed for the treatment of missing teeth. Most studies about dental implants and biomaterials currently focus on osteogenesis and the osseointegration of the implant, neglecting the importance of the immune response. In recent years, the development of osteoimmunology has been one of the greatest achievements in bone biomaterials; osteoimmunology has revealed the vital role of immune cells in regulating bone dynamics, implying the value of studies on materials with favorable osteoimmunomodulatory properties. This article reviews the integration between bone tissue and implants and summarizes the effects of the immune response during osseointegration and new bone formation to show the importance of regulating the immune response in this process. The effect of macrophages on osteogenesis and osteoclastogenesis is then reviewed due to the high plasticity and multiple roles of macrophages during this process. Accordingly, the interaction between the implants, the immune systems and the skeletal system is explained, showing the potential value of osteoimmunomodulation as a biological principle for developing bone biomaterials and new types of implants.

OBJECTIVETo study the relationship between carbon dioxide combining power(CO₂-CP) and contrast-induced acute kidney injury (CI-AKI) in patients with ST segment elevation myocardial infarction and undergoing percutaneous coronary intervention.

METHODSWe retrospectively analyzed 174 patients admitted to our hospital from March 2012 to August 2013 with ST segment elevation myocardial infarction and underwent emergency percutaneous coronary intervention. Patients were divided into three tertiles according to pre-operative CO₂-CP: T1 (CO₂-CP < 22.62 mmol/L), T2(CO₂-CP 22.62-24.30 mmol/L), T3(CO₂-CP > 24.30 mmol/L). Baseline clinical data, CI-AKI incidence, in-hospital mortality and dialysis rate were compared among groups. An increase in serum creatinine of >26.4 µmol/L and/or >50% from baseline within 48 hours after contrast exposure was defined as CI-AKI. Univariate logistic regression analysis was used to identify the risk factors of CI-AKI. The relationship between CO₂-CP and CI-AKI was assessed by multivariate logistic regression analysis. Receiver operating characteristic curve was used to identify the optimal cutoff of the CO₂-CP for predicting CI-AKI.

RESULTSCI-AKI occurred in 25 (14.4%) patients, and lower CO₂-CP was related to higher incidence of CI-AKI (27.6% (16/58) in group T1, 5.3% (3/57) in group T2, 1.7 % (1/59) in group T3, P = 0.002) and higher in-hospital mortality (10.3% (6/58) vs. 0 and 1.7% (1/59), P = 0.010). Dialysis rate was similar among 3 groups (5.2% (3/58) vs. 0 and 1.7% (1/59), P = 0.168). The incidence of CI-AKI was significantly associated with CO₂-CP < 22.00 mmol/L in univariate analyses (OR = 6.767, 95% CI 2.731-16.768, P < 0.001). After adjusting for potential confounding risk factors, CO₂-CP < 22.00 mmol/L remained significantly associated with the incidence of CI-AKI (OR = 5.835, 95%CI 1.800-18.914, P = 0.003) in multivariate logistic regression. ROC analysis revealed that the optimal cutoff of CO₂-CP to predict CI-AKI was 22.00 mmol/L (sensitivity 64.0%, specificity 79.1%, AUC = 0.714).

CONCLUSIONSPre-percutaneous coronary intervention CO₂-CP in patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention is related to CI-AKI. CO₂-CP < 22.00 mmol/L predicts higher risk of CI-AKI in this patient cohort.

Acute Kidney Injury ; etiology ; Carbon Dioxide ; analysis ; Contrast Media ; Hospital Mortality ; Humans ; Incidence ; Kidney ; Logistic Models ; Myocardial Infarction ; complications ; physiopathology ; Percutaneous Coronary Intervention ; ROC Curve ; Retrospective Studies ; Risk Factors

Objective To study the relationship between carbon dioxide combining power ( CO2-CP) and contrast-induced acute kidney injury ( CI-AKI) in patients with ST segment elevation myocardial infarction and undergoing percutaneous coronary intervention.Methods We retrospectively analyzed 174 patients admitted to our hospital from March 2012 to August 2013 with ST segment elevation myocardial infarction and underwent emergency percutaneous coronary intervention.Patients were divided into three tertiles according to pre-operative CO2-CP: T1 (CO2-CP <22.62 mmol/L),T2(CO2-CP 22.62 -24.30 mmol/L), T3(CO2-CP>24.30 mmol/L).Baseline clinical data, CI-AKI incidence, in-hospital mortality and dialysis rate were compared among groups.An increase in serum creatinine of >26.4 μmol/L and/or >50%from baseline within 48 hours after contrast exposure was defined as CI-AKI.Univariate logistic regression analysis was used to identify the risk factors of CI-AKI.The relationship between CO 2-CP and CI-AKI was assessed by multivariate logistic regression analysis.Receiver operating characteristic curve was used to identify the optimal cutoff of the CO 2-CP for predicting CI-AKI.Results CI-AKI occurred in 25(14.4%) patients, and lower CO2-CP was related to higher incidence of CI-AKI (27.6% (16/58) in group T1, 5.3%(3/57) in group T2, 1.7 % (1/59) in group T3, P=0.002) and higher in-hospital mortality (10.3%(6/58) vs.0 and 1.7%(1/59), P=0.010).Dialysis rate was similar among 3 groups (5.2%(3/58)vs.0 and 1.7%(1/59), P=0.168).The incidence of CI-AKI was significantly associated with CO2-CP<22.00 mmol/L in univariate analyses ( OR=6.767,95%CI 2.731-16.768, P<0.001).After adjusting for potential confounding risk factors , CO2-CP <22.00 mmol/L remained significantly associated with the incidence of CI-AKI (OR=5.835,95%CI 1.800-18.914, P=0.003) in multivariate logistic regression.ROC analysis revealed that the optimal cutoff of CO 2-CP to predict CI-AKI was 22.00 mmol/L (sensitivity 64.0%,specificity 79.1%, AUC=0.714).Conclusions Pre-percutaneous coronary intervention CO 2-CP in patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention is related to CI-AKI.CO2-CP<22.00 mmol/L predicts higher risk of CI-AKI in this patient cohort.

Objective To explore the safety of bedside bowel movement during the earlY phase of patients with acute myocardial infarction(AMI).Methods 55 patients were randomly divided into the experimental group(28 cases)and the control group(27 cases).The experimental group adopted bedside bowel movement while the control group used routine in-bed bowel movement.The heart rate,blood pressure and myocardial oxygen comsumption(D-P)were observed.Results The heart rate,systolic blood pressure,and diastolic blood pressure in the control group were higher than those in steady state(P＜0.05).While in the experimental group the above factors were not statistically different from those in steady state (P＞0.05).The D-P both increased in the two groups compared with that in steady state(P＜0.05).The incidence of uncomfortable complaint and complications were not different between the two groups but the rate of constipation and mean in-hospital days were lower than those in the control group(P＜0.05).Conclusion It proved safe and applicable for patients with AMI to adopt bedside bowel movement during 24 to 72hours after infarction under the electrocardiac and blood pressure monitoring if their vital signs were steady and did not have any serious complications.