OBJECTIVES: To compare the anti-inflammatory, antibacterial and analgesic effects of Yinqiao Powder (YQS) formulated granules and decoction. METHODS: We first evaluated the anti-inflammatory effects of the two dosage forms of YQS in a LPS-induced RAW 264.7 cell model using RT-qPCR and Western blotting. We further constructed zebrafish models of inflammation by copper sulfate exposure, caudal fin transection, or LPS and Poly (I:C) microinjection, and evaluated anti-inflammatory effects of YQS granules and decoction by examining neutrophil aggregation and HE staining findings. In a mouse model of acute lung injury (ALI) induced by intratracheal LPS instillation, the effects of YQS gavage at 10, 15, and 20 g/kg on lung pathologies were evaluated by calculating lung wet-dry weight ratio and using HE staining, ELISA and Western blotting. The microbroth dilution method was used to evaluate the antibacterial effect of YQS. Mouse pain models established by hot plate and intraperitoneal injection of glacial acetic acid were used to evaluate the analgesic effects of YQS at 10, 15, and 20 g/kg. RESULTS: Both YQS granules and decoction significantly reduced TNF-α, IL-6, and IL-1β expressions and p-STAT3 (Tyr 705) phosphorylation level in LPS-induced RAW 264.7 cells, and obviously inhibited neutrophil aggregation in the zebrafish models. In ALI mice, YQS granules and decoction effectively ameliorated lung injury, lowered lung wet-dry weight ratio, and reduced p-STAT3 (Tyr 705) expression and TNF-α and IL-6 levels. YQS produced obvious antibacterial effect at the doses of 15.63 and 31.25 mg/mL, and significantly reduced body torsion and increased pain threshold in the mouse pain models. CONCLUSIONS The two dosage forms of TQS have similar anti-inflammatory, antibacterial and analgesic effects with only differences in their inhibitory effect on TNF-α, IL-6 and IL-1β mRNA expressions in LPS-induced RAW 264.7 cells.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Anti-Inflammatory Agents/pharmacology* ; Analgesics/pharmacology* ; RAW 264.7 Cells ; Zebrafish ; Anti-Bacterial Agents/pharmacology* ; Powders ; Tumor Necrosis Factor-alpha/metabolism* ; Acute Lung Injury/drug therapy* ; Interleukin-6/metabolism* ; Lipopolysaccharides

OBJECTIVES: To develop an E-selectin-targeting nanomedicine delivery system that competitively inhibits E-selectin-neutrophil ligand binding to block neutrophil adhesion to vessels and suppress their recruitment to the lesion sites. METHODS: Doxorubicin hydrochloride (DOX)-loaded liposomes (IEL-Lip/DOX) conjugated with E-selectin-affinity peptide IELLQARC were developed using a post-insertion method. Two formulations [2-1P: Mol(PC): Mol(DPI)=100:1; 2-3P: 100:3] were prepared and their modification density and in vitro release characteristics were determined. Their targeting efficacy was assessed in a cell model of LPS-induced inflammation, a mouse model of acute lung injury (ALI), a rat femoral artery model of physical injury-induced inflammation, and a zebrafish model of local inflammation. RESULTS: The prepared IEL-Lip/DOX 2-1P and 2-3P had peptide modification densities of 4.76 and 7.57 pmoL/cm², respectively. Compared with unmodified liposomes, IEL-Lip/DOX exhibited significantly reduced 48-h cumulative release rates at pH 5.5. In the inflammation cell model, IEL-Lip/DOX showed increased uptake by activated inflammatory endothelial cells, and 2-1P exhibited a higher trans-endothelial ability. In ALI mice, the fluorescence intensity of IEL-Lip/Cy5.5 increased significantly in lung tissues by 53.71% [Z-(2-1P)] and 93.41% [Z-(2-3P)], and 2-1P had an increased distribution by 24.19% in the inflammatory lung tissue compared to normal mouse lung tissue. In rat femoral artery models, 2-1P had greater injured/normal vessel fluorescence intensity contrast. In the zebrafish models, both 2-1P and 2-3P showed increased aggregation at the site of inflammation. CONCLUSIONS This E-selectin-targeting nanomedicine delivery system efficiently targets activated inflammatory endothelial cells to increase drug concentration at the inflammatory site, which sheds light on new strategies for treating neutrophil-mediated inflammatory diseases and practicing the concept of "one drug for multiple diseases".
Animals ; Liposomes ; Rats ; Nanomedicine ; E-Selectin ; Drug Delivery Systems ; Inflammation/drug therapy* ; Mice ; Doxorubicin/analogs & derivatives* ; Zebrafish ; Acute Lung Injury/drug therapy*

OBJECTIVE: To analyze the clinical effectiveness of veno-venous extracorporeal membrane oxygenation (VV-ECMO) in rescuing children with severe pulmonary contusion. METHODS: A retrospective analysis was conducted on the clinical data of four children with severe pulmonary contusion who were treated with VV-ECMO in the pediatric intensive care unit of Xi'an Children's Hospital from April 2021 to December 2024. The general data, laboratory indicators within 24 hours after admission, imaging features, bronchoscopic findings, diagnostic and treatment processes, as well as therapeutic outcomes of the children were analyzed. RESULTS: All four pediatric cases were male, aged 4 years and 9 months, 6 years and 5 months, 8 years and 10 months, and 9 years and 7 months, respectively. One case resulted from a high-altitude fall and three from traffic accidents, all presenting with multiple fractures. All four cases progressed to dyspnea within 1-4 hours post-injury and received endotracheal intubation with invasive ventilator support within 2-5 hours. Three cases exhibited tachycardia upon admission and were treated with norepinephrine, all four cases presented with fine moist rales in the lungs. Imaging studies revealed diffuse exudative changes in all four cases. Bronchoscopy identified diffuse pulmonary hemorrhage, with one case additionally showing rupture of the right intermediate bronchus. Conventional mechanical ventilation failed to correct oxygenation in all cases, prompting initiation of VV-ECMO therapy within 8-22 hours post-injury. One case underwent right thoracic exploration under ECMO support. Following treatment, all four cases demonstrated gradual reduction in bloody airway secretions, resolution of pulmonary exudative changes on imaging, and absence of hemorrhage on bronchoscopy. They were successfully weaned off ECMO and ultimately discharged as cured. CONCLUSIONS Severe pulmonary contusion rapidly leads to respiratory distress, requiring ventilator-assisted ventilation within hours of injury. When conventional ventilator support is ineffective, ECMO can be life-saving, with timely intervention yielding favorable prognosis.
Humans ; Extracorporeal Membrane Oxygenation/methods* ; Male ; Retrospective Studies ; Child, Preschool ; Child ; Contusions/therapy* ; Lung Injury/therapy* ; Treatment Outcome

OBJECTIVES: To investigate the inhibitory effect of GSK484, a PAD4 inhibitor, on H3Cit expression following sepsis and its effects for improving sepsis-induced endothelial dysfunction. METHODS: Eighteen C57BL/6 mice were randomized into sham-operated group, sepsis model group and GSK484 treatment group (n=6), and in the latter two groups, models of sepsis were established by cecal ligation and puncture (CLP). The mice in GSK484 treatment group were given an intraperitoneal injection of GSK484 (4 mg/kg) on the second day following the surgery. Twenty-four hours after the injection, the mice were euthanized for measurement of serum levels of VEGF, ESM-1, IL-6 and IL-1β using ELISA. Lung tissue pathology was observed with HE staining, and pulmonary expressions of F-actin, VE-cadherin, ZO-1 and H3Cit proteins were detected using immunofluorescence staining and Western blotting. In primary cultured of mouse lung microvascular endothelial cells, the effect of stimulation with LPS (10 μg/mL) for 24 h on tube formation, proliferation, apoptosis and expressions of VEGF, ESM-1, IL-6 and IL-1β were assessed using CCK-8 assay, flow cytometry and ELISA. RESULTS: Compared to the sham-operated mice, the septic mice exhibited significant lung tissue pathologies characterized by vascular congestion, alveolar rupture, edema, and neutrophil infiltration. Serum levels of IL-6, IL-1β, VEGF, and ESM-1 were elevated, pulmonary expressions of F-actin, VE-cadherin, and ZO-1 were decreased, and H3Cit expression was increased significantly in the septic mice. GSK484 treatment effectively mitigated these changes in the septic mice. The LPS-stimulated endothelial cells showed increased productions of IL-6, IL-1β, VEGF and ESM-1, which were significantly reduced after treatment with 2.5 μmol/L GSK484. CONCLUSIONS GSK484 treatment effectively suppresses H3Cit expression in septic mice to ameliorate sepsis-induced endothelial dysfunction.
Animals ; Sepsis/drug therapy* ; Mice ; Mice, Inbred C57BL ; Lung Injury/drug therapy* ; Endothelial Cells/drug effects* ; Interleukin-6/metabolism* ; Protein-Arginine Deiminase Type 4/metabolism* ; Lung/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Interleukin-1beta/metabolism* ; Disease Models, Animal ; Cadherins/metabolism* ; Apoptosis/drug effects* ; Imidazoles ; Antigens, CD

OBJECTIVE: To systematically evaluate the impact of aspirin on the pulmonary inflammatory response in animal models of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). METHODS: Experimental research on aspirin therapy or prevention of ALI/ARDS in animal models were searched in PubMed, Web of Science, Cochrane library, Embase, China biology medicine, CNKI, Wanfang, VIP. The search time limit was from the establishment of the database to July 17, 2023. The control group established the ALI/ARDS model without any pharmacological intervention. The intervention group was given aspirin or aspirin-derived compounds or polymeric-aspirin (Poly-A) at different time points before and after the preparation of the model, of which there was no restriction on the dosage form, dosage, mode of administration, or number of doses. The primary outcome indicators included bronchoalveolar lavage fluid (BALF) or lung tissue myeloperoxidase (MPO) activity, interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and the counts of neutrophils in BALF. Two researchers screened the literature and extracted information based on inclusion and exclusion criteria. Literature quality was assessed by the bias risk assessment tool SYRCLE. RevMan 5.3 software was used for data synthesis and statistical analysis. RESULTS: A total of 17 papers were eventually included, involving a total of 449 animal models, all of which were murine. One paper was at high risk of bias and the rest 16 papers were at moderate risk of bias. Meta-analysis showed that compared with the control group, the neutrophil count in BALF [standardized mean difference (SMD) = -5.06, 95% confidence interval (95%CI) was -7.00 to -3.12, P < 0.000 01], the myeloperoxidase (MPO) activity in BALF or lung tissue (SMD = -3.45, 95%CI was -4.43 to -2.47, P < 0.000 01), the TNF-α level in BALF or lung tissue (SMD = -2.78, 95%CI was -3.58 to -1.98, P < 0.000 01), and the IL-1β level in BALF or lung tissue (SMD = -3.12, 95%CI was -4.56 to -1.69, P < 0.000 1) were significantly decreased in the ALI/ARDS model of the intervention group. CONCLUSIONS Aspirin reduces the level of lung inflammation in animal models of ALI/ARDS. However, there are problems of poor quality and significant heterogeneity of the included studies, which still need our further validation.
Animals ; Acute Lung Injury/drug therapy* ; Aspirin/pharmacology* ; Respiratory Distress Syndrome/drug therapy* ; Disease Models, Animal ; Bronchoalveolar Lavage Fluid/chemistry* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-1beta/metabolism* ; Peroxidase/metabolism* ; Lung/metabolism* ; Neutrophils/drug effects*

PURPOSE: Patients with multiple traumas are at high risk of developing respiratory complications, including pneumonia and acute respiratory distress syndrome. Many pulmonary complications are associated with systemic inflammation and pulmonary neutrophilic infiltration. Leukotriene-receptor antagonists are anti-inflammatory and anti-oxidant drugs subsiding airway inflammation. The present study investigates the effectiveness of montelukast in reducing pulmonary complications among trauma patients. METHODS: This randomized, double-blind, placebo-control trial was conducted in patients with multiple blunt traumas and evidence of lung contusion detected via CT scan. We excluded patients if they met at least one of the following conditions: < 16 years old, history of cardiopulmonary diseases or positive history of montelukast-induced hypersensitivity reactions. Patients were allocated to the treatment (10 mg of montelukast) or placebo group using permuted block randomization method. The primary measured outcome was the volume of pulmonary contusion at the end of the trial. The secondary outcomes were intensive care unit and hospital length of stay, ventilation days, multi-organ failure, and the in-hospital mortality rate. RESULTS: In total, 65 eligible patients (treatment = 31, placebo = 34) were included for the final analysis. The treatment group had more pulmonary contusion volume (mean (SD), mm³) at the right (68726.97 (93656.54) vs. 59730.27 (76551.74)) and the left side (67501.71 (91514.04) vs. 46502.21 (80604.21)), higher initial C-reactive peptide level (12.16 (10.58) vs. 10.85 (17.87)) compared to the placebo group, but the differences were not statistically significant (p > 0.05). At the end of the study, the mean (SD) of pulmonary contusion volume (mm³) (right side = 116748.74 (361705.12), left side = 64522.03 (117266.17)) of the treatment group were comparable to that of the placebo group (right side = 40051.26 (64081.56), left side = 25929.12 (47417.13), p = 0.228 and 0.082, respectively). Moreover, both groups have statistically similar hospital (mean (SD), days) (10.87 (9.83) vs. 13.05 (10.12)) and intensive care unit length of stays (mean (SD), days) (7.16 (8.15) vs. 7.82 (7.48)). Of note, the frequency of the in-hospital complications (treatment vs. control group) including acute respiratory distress syndrome (12.9% vs. 8.8%, p = 0.71), pneumonia (19.4% vs. 17.6%, p = 0.85), multi-organ failure (12.9% vs. 17.6%, p = 0.58) and the mortality rate (22.6% vs. 14.7%, p = 0.41) were comparable between the groups. CONCLUSION Administrating montelukast has no preventive or therapeutic effects on lung contusion or its complications.
Humans ; Adolescent ; Thoracic Wall ; Pneumonia ; Wounds, Nonpenetrating ; Thoracic Injuries/drug therapy* ; Lung Injury ; Contusions ; Respiratory Distress Syndrome/etiology* ; Inflammation ; Tablets ; Treatment Outcome

OBJECTIVES: Sepsis is a critical dysregulated host response with high mortality and current treatment is difficult to achieve optimal efficacy. Ozone therapy has been revealed to protect infection and inflammation-related diseases due to its role in antibiotic and immunoregulatory effect. Ozonated triglyceride is a key component of ozonated oil that is one of ozone therapy dosage form. However, the potential role of ozonated triglyceride in sepsis remains unclear. This study aims to explore the effect of ozonated triglyceride on septic mouse model and the molecular mechanism. METHODS: Intraperitoneal injection of lipopolysaccharide (LPS), cecal ligation and puncture (CLP) were applied to construct septic mouse model. The mouse serum was obtained for detection of cytokines, and lung tissues were collected for hematoxylin and eosin (HE) staining to evaluate the extent of lung injury in septic mouse with ozonated triglyceride treatment at different time and doses. The survival of septic mice was observed for 96 h and Kaplan-Meier analysis was used to analyze the survival rates. In addition, primary peritoneal macrophages and human acute monocytic-leukemia cell line (THP-1) were treated with inflammasome activators with or without ozonated triglyceride. The level of cytokines was detected by enzyme-linked immunosorbent assay (ELISA). The cleavage of caspase-1 and gasdermin-D (GSDMD) was detected by Western blotting. RESULTS: Ozonated triglyceride at different time and doses reduced the release of inflammasome-related cytokines [interleukin (IL)-1β and IL-18] (all P<0.05) but not pro-inflammatory cytokines such as IL-6 and tumor necrosis factor-α (TNF-α) in septic mice (all P>0.05). Ozonated triglyceride significantly improved the survival rate of septic mice and reduced sepsis-induced lung injury (all P<0.05). Ozonated triglyceride significantly suppressed the canonical and non-canonical activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome (all P<0.05) but not affected absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasomes in vitro (all P>0.05). Ozonated triglyceride reduced the cleavage of caspase-1 and the downstream GSDMD. CONCLUSIONS Ozonated triglyceride presents a protect effect on sepsis lethality via reducing cytokines release and sepsis-related organ injury. The mechanism is that ozonated triglyceride specifically suppresses the activation of NLRP3 inflammasome. Ozonated triglyceride is a promising candidate for sepsis treatment.
Animals ; Humans ; Mice ; Caspase 1 ; Cytokines ; Disease Models, Animal ; Inflammasomes ; Lung Injury ; NLR Family, Pyrin Domain-Containing 3 Protein ; Ozone/therapeutic use* ; Sepsis/drug therapy*

Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Acute Kidney Injury

Ingestion of corrosive substances can severely burn the upper digestive tract leading to bleeding or perforation, and may even be life-threatening. Less commonly, damage to the trachea and bronchi is involved. In this paper, a case of corrosive digestive tract injury and lung injury after oral administration of pipeline dredging agent (the main components are hydroxide, sodium carbonate, sodium hypochlorite, etc.) was analyzed. After active rescue treatment, the patient died of massive hemoptysis. It is suggested that serious complications may occur after ingestion of corrosive substances. Timely diagnosis and reasonable medical management are needed to improve the level of recognition and treatment of such diseases.
Humans ; Caustics ; Lung Injury/chemically induced* ; Gastrointestinal Tract ; Burns, Chemical/therapy* ; Eating

Objective: To study the effects of Nintedanib associated with Shenfu Injection on lung injury induced by paraquat (PQ) intoxication. Methods: In September 2021, a total of 90 SD rats were divided into 5 groups in random, namely control group, PQ poisoning group, Shenfu Injection group, Nintedanib group and associated group, 18 rats in each group. Normal saline was given by gavage route to rats of control group, 20% PQ (80 mg/kg) was administered by gavage route to rats of other four groups. 6 hours after PQ gavage, Shenfu Injection group (12 ml/kg Shenfu Injection), Nintedanib group (60 mg/kg Nintedanib) and associated group (12 ml/kg Shenfu Injection and 60 mg/kg Nintedanib) were administered with medicine once a day. The levels of serum transforming growth factor beta1 (TGF-β1), interleukin-1 beta (IL-1β) were determined at 1, 3 and 7 d, respectively. The pathological changes of lung tissue, the ratio of wet weight and dry weight (W/D) of lung tissue, the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were observed and determined after 7 d. Western blot was used to analyse the expression levels of fibroblast growth factor receptor 1 (FGFR1), platelet derivation growth factor receptor alpha (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2) in lung tissue after 7 d. Results: The levels of TGF-β1, IL-1β in all poisoning groups went up first and then went down. The levels of TGF-β1, IL-1β in associated group at 1, 3, 7 d were lower than that of PQ poisoning group, Shenfu Injection group and Nintedanib group at the same point (P<0.05). Pathological changes of lung tissue under the light microscopes showed that the degrees of hemorrhage, effusion and infiltration of inflammatory cells inside the alveolar space of Shenfu Injection group, Nintedanib group and associated group were milder than that of PQ poisoning group, and the midest in associated group. Compared with control group, the W/D of lung tissue was higher, the level of MDA in lung tissue was higher, while the level of SOD was lower, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were higher in PQ poisoning group (P<0.05). Compared with PQ poisoning group, Shenfu Injection group and Nintedanib group, the W/D of lung tissue was lower, the level of MDA in lung tissue was lower, while the level of SOD was higher, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were lower in associated group (P<0.05) . Conclusion: Nintedanib associated with Shenfu Injection can relieve lung injury of rats induced by PQ, which may be related to Nintedanib associated with Shenfu Injection can inhibit the activation of TGF-β1 and the expressions of FGFR1, PDGFRα, VEGFR2 in lung tissue of rats.
Animals ; Rats ; Rats, Sprague-Dawley ; Paraquat ; Transforming Growth Factor beta1 ; Receptor, Platelet-Derived Growth Factor alpha ; Vascular Endothelial Growth Factor A ; Acute Lung Injury/drug therapy*