Objective To investigate the effect of dexamethasone on expressions of angiopoietin-1,2 (Ang-1,2) in rats with acute lung injury induced by phosgene.Methods A total of 36 SD rats were randomly (random number) divided into 3 groups:normal control group that consisted of the rats with air exposure,phosgene group that consisted of the rats with exposure to 8.33 mg/L phosgene (purity 100％,of the same volume as the inhaled air in the normal control group) for 5 minutes and dexamethasone group that consisted of the rats with caudal vein injection of 2.5 mg/kg dexamethasone an hour before exposure to the same dose of phosgene.Wet and dry ratio of the lung (W/D) was calculated,and leukocyte count and total protein content of bronchoalveolar lavage fluid (BALF) were recorded 2 hours later.The concentrations of Ang-1,2 in the serum and BALF were measured by enzyme-linked immunosorbent assay (ELISA).Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the mRNA levels of Ang-1,2 and Tie-2 in the lung tissue.The protein expression of Ang-1,2 and Tie-2 in the lung tissue were quantified by Western blot.Results Compared with phosgene group,the lung W/D,protein content of BALF and WBC count in dexamethasone group were significantly decreased (P ＜ 0.01).Compared with normal control group,Ang-1 and Tie-2 expressions in phosgene group were significantly decreased (P ＜ 0.01).Compared with phosgene group,the serum,BALF and lung tissue of Ang-1 and Tie-2 expressions in dexamethasone group was significantly increased (P ＜0.01).Compared with normal control group,the serum,BALF and lung tissue of Ang-2 expressions in phosgene group were significantly increased (P ＜ 0.01).Compared with phosgene group,the serum,BALF and lung tissue of Ang-2 expressions in dexamethasone group were significantly decreased (P ＜ 0.05,P ＜ 0.01).Conclusion Dexamethasone has a beneficial effect on acute lung injury induced by phosgene in rats by inhibition of Ang-2 and increase in Ang-1 and Tie-2 expressions.

Objective: To investigate changes of NLRP3 signal transduction pathway of acute lung injury induced by phosgene to analyze NLRP3-mediated IL-1β release inflammatory process in rats. Methods: Rats were randomly divided into two groups, 10 rats in the Air group that consists of the rats with air exposure, 10 rats in the Psg group that consists of the rats with phosgene exposure at 8.33 g/m³ for 5 min. The specimens of serum, bronchoalveolar lavage fluid (BALF) and lung were collected after 6h. Morphological changes were observed by HE staining. The expression of NLRP3 in the lung of two groups was detected by immunohistochemistry. NLRP3、ASC and caspase-1 expression in the lung tissue was quantified by Western blot. Reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the expression of NLRP3、ASC and caspase-1 mRNA in the lung tissue. The concentrations of IL-1β、IL-18 and IL-33 in the serum and BALF were measured by enzyme-linked immunosorbent assay. RT-PCR were used to detect the expression of IL-1β、IL-18 and IL-33 mRNA in the lung tissue. Results: We successfully replicated the model of phosgene-induced ALI in rats. Morphological of HE staining after phosgene exposure to 6 h observed inflammatory cell infiltration in lung tissue in Phosgene group. Immunohistochemical staining results showed that there were many NLRP3 positive cells in lung tissue in Phosgene group. The levels of NLRP3 and caspase-1 mRNA and protein expression in lung were significantly increased (P<0.05) in Phosgene group, but no significant change was observed in lung ASC mRNA and protein expression (P>0.05) . Compared with Air group, the serum, BALF and lung tissue of IL-1β、IL-18 and IL-33 mRNA and protein expression were significantly increased (P<0.01) in Phosgene group. Conclusion NLRP3-mediated inflammatory response probably involved in the process of the phosgene, so it maybe one of the pathogenesis of acute lung injury.

Abstract To understand the relationship between cardiovascular disease (CVD) and adverse childhood experiences (ACEs), the present review aims to describe the burden and influencing factors of CVD, epidemiological characteristics and burden of ACEs, current research on the relationship between ACEs and CVD, and the mechanism of ACEs leading to CVD. It is proposed that further assessment of the relationship is warranted through identifying blood biomarkers, conducting prospective cohort studies and intervention studies. Such efforts would provide valuable scientific insights for primary prevention strategies for cardiovascular disease.

Objective: To investigate the effects of methylprednisolone on NOD-like receptor hot protein domain-associated protein 3 (NLRP3) inflammasome in phosgene-induced acute lung injury. Methods: Rats were randomly divided into four groups, 10 rats in Air group (inhalation of air of the same volume as the phosgene group) , 10 rats in Phosgene group (inhalation of 8.33 mg/L with 100% purity phosgene for 5 min) , 10 rats in Saline control group (inhalation of the same dose of phosgene and 2 mg/kg saline via tail vein injection one hour later) , 10 rats in MP group (inhalation of the same dose of phosgene and 2 mg/kg MP via tail vein injection one hour later) . The specimens of serum, bronchoalveolar lavage fluid (BALF) and lung tissue were collected after 6h. Morphological changes were observed by HE staining. The expression of NLRP3 in the lung of four groups was detected by immunohistochemistry. NLRP3、ASC and caspase-1 expression in the lung tissue was quantified by Western blot. Reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the expression of NLRP3、ASC and caspase-1 mRNA in the lung tissue. The concentrations of IL-1β、IL-18 and IL-33 in the serum and BALF were measured by enzyme-linked immunosorbent assay. Results: We successfully replicated the model of phosgene-induced ALI in rats. Morphological of HE staining after phosgene exposure to 6 h observed inflammatory cell infiltration in lung tissue in Phosgene group. Immunohistochemical staining results showed that there were many NLRP3 positive cells in lung tissue in Phosgene group. The levels of NLRP3, caspase-1 mRNA and protein expression in lung were significantly increased (P<0.05) in Phosgene group compared with Air group; compared with Phosgene group, The levels of NLRP3 and caspase-1 mRNA and protein expression in MP group were significantly decreased (P<0.05) . Compared with Air group, The levels IL-1β、IL-18 and IL-33 mRNA protein expression in the serum and BALF were significantly increased (P<0.05) in Phosgene group. Compared with Phosgene group, The levels IL-1β、IL-18 and IL-33 mRNA protein expression in the serum and BALF were significantly decreased (P<0.05) in MP group. Conclusion Methylprednisolone can effectively protect the rats from phosgene-induced acute lung injury by inhibiting the expression of the NLRP3 inflammasome and reducing the release of inflammatory factors such as interleukin-1β (IL-1β) mediated by it.

Objective To observe the effect of signal transduction pathway of nuclear factor-kappa B (NF-κB) on Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and pyroptosis in rats with acute lung injury induced (ALI) by phosgene. Methods The rats were randomly(random number) divided into 3 groups: air exposure control group, phosgene exposure group and PDTC group with phosgene exposure after 100 mg/kg pyrrolidine dithiocarbamate (PDTC) administration. The specimens of serum, bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h after exposure. Morphological changes were observed by HE staining. The expression of NLRP3 in the lung of three groups was detected by immunohistochemistry. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expressions of NF-κB p65, NLRP3, ASC and caspase-1 mRNA in the lung tissue. NF-κB p65,NLRP3, ASC and caspase-1 protein levels in the lung tissue were quantified by Western blot. The concentrations of IL-1β, IL-18 and IL-33 in the serum and BALF were measured by enzyme-linked immunosorbent assay (ELISA). Pyroptosis was observed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). Results The model of phosgene-induced ALI was successfully established in rats. Morphological changes with inflammatory cell infiltration were observed in the lung tissues of phosgene group, in which NLRP3 positive cells also could be observed by immunohistochemical staining. The mRNA expressions and protein levels of NF-κB p65, NLRP3 and caspase-1 in lung tissues were significantly increased (P＜0.05) in phosgene group, compared with air control group. The mRNA expressions and protein levels of NF-κB p65,NLRP3 and caspase-1 in lung tissues were significantly decreased (P＜0.05) in PDTC group, compared with phosgene group. The IL-1β,IL-18 and IL-33 protein levels in serum and BALF were significantly increased (P＜0.05) in phosgene group, compared with air control group. The IL-1β,IL-18 and IL-33 protein levels in serum and BALF were significantly decreased (P＜0.05) in PDTC group, compared with phosgene group. TUNEL results showed that pyroptosis in the lung tissue obviously increased in phosgene group, while decreased in PDTC group. Conclusions NLRP3 inflammasome and lung cell pyroptosis were induced through NF-kB signal transduction pathway in rats with acute lung injury caused by phosgene inhalation. Blockade of NF-κB can alleviate acute lung injury by down-regulating the expression of NLRP3 inflammasome to inhibit pyroptosis.

Acute ammonia-induced intoxication is a kind of acute irritant gas poisoning, which mainly causes systemic inflammatory reaction and immune dysfunction through direct and indirect lung injury, leading to chemogenic pulmonary edema and acute respiratory distress syndrome (ARDS). The mechanism of its toxic injury is complex, and the fatality rate of patients increases significantly once ARDS occurs. In this paper, the patient with acute and severe ammonia-induced intoxication was successfully treated by extracorporeal membrane oxygenation (ECMO) combined with fiberoptic bronchoscopy and other critical technologies, and achieved good results. By analyzing the diagnosis and treatment process of severe ammonia-induced intoxication complicated with ARDS patients, this paper summarizes the clinical characteristics of ammonia-induced intoxication injury, and the application opportunities of ECMO and various critical medical technologies, so as to facilitate the efficient intervention and treatment of ammonia-induced intoxication according to the clinical opportunity and improve the survival rate of patients.

Objective:To investigate the expression level and clinical value of miR-28-5p in patients with aspiration pneumonia.Methods:This was a retrospective controlled study. A total of 60 patients with severe pneumonia in the Intensive Care Unit of Jinshan Hospital Affiliated to Fudan University were selected as the study group. According to the pathogenic factors, the patients were divided into the aspiration pneumonia group and other infectious pneumonia group. At the same time, 20 healthy physical examination patients in our hospital were selected as the healthy control group. Venous blood was collected from patients in the study group on days 1, 4, and 7. The expression level of miR-28-5p in serum was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the serum levels of interleukin-4 (IL-4), IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA) assay. The clinical detection results of C-reactive protein (CRP) and procalcitonin (PCT) in the study group were collected. Statistical analysis was conducted with SPSS 26.0. Then the diagnostic value of serum miR-28-5p for aspiration pneumonia was analyzed by receiver operating characteristic (ROC) curve, and the correlation between serum miR-28-5p and IL-4, IL-6, IL-8, IL-10, TNF-α, CRP and PCT was analyzed by Pearson method. According to the clinical effect of 10 days of treatment, the patients were divided into the good prognosis and poor prognosis groups, and the relationship between miR-28-5p and the expression levels of various inflammatory factors and prognosis was analyzed.Results:Compared with the healthy control group, the level of serum miR-28-5p in the study group was significantly increased, and the level of serum miR-28-5p in the aspiration pneumonia group was much lower than that in the other infectious pneumonia group ( P<0.05). Compared with day 0, the expression level of serum miR-28-5p in the aspiration pneumonia group was highly increased, with statistical significance ( P<0.05). ROC curve of serum miR-28-5p expression in aspiration pneumonia showed that AUC was 0.871. When the critical value was 1.211, the sensitivity was 76.67% and the specificity was 95%. Pearson correlation analysis showed that miR-28-5p was positively correlated with IL-6 ( P<0.05), and negatively correlated with IL-4 and IL-10 ( P<0.05). ROC curve analysis showed that the area under the curve of age, miR-28-5p, IL-8, IL-10, TNF-α, CRP, and PCT were 0.695, 0.813, 0.655, 0.668, 0.724, 0.651, and 0.661, respectively. Conclusions:Serum miR-28-5p has important reference significance for the diagnosis of aspiration pneumonia, and has certain value for distinguishing different types of aspiration pneumonia. The expression of miR-28-5p in serum is expected to be a new biomarker to judge the prognosis of patients with severe pneumonia. Age, TNF-α, IL-8, IL-10, CRP and PCT are correlated to the prognosis of severe pneumonia.

Acute ammonia-induced intoxication is a kind of acute irritant gas poisoning, which mainly causes systemic inflammatory reaction and immune dysfunction through direct and indirect lung injury, leading to chemogenic pulmonary edema and acute respiratory distress syndrome (ARDS). The mechanism of its toxic injury is complex, and the fatality rate of patients increases significantly once ARDS occurs. In this paper, the patient with acute and severe ammonia-induced intoxication was successfully treated by extracorporeal membrane oxygenation (ECMO) combined with fiberoptic bronchoscopy and other critical technologies, and achieved good results. By analyzing the diagnosis and treatment process of severe ammonia-induced intoxication complicated with ARDS patients, this paper summarizes the clinical characteristics of ammonia-induced intoxication injury, and the application opportunities of ECMO and various critical medical technologies, so as to facilitate the efficient intervention and treatment of ammonia-induced intoxication according to the clinical opportunity and improve the survival rate of patients.

OBJECTIVETo investigate the effects of adenovirus-delivered angiopoietin-1 siRNA (Ad. Ang-1siRNA) on the expression of matrix metalloproteinase-2, 9 (MMP-2, 9) and tissue inhibitor of metallopro-teinase-1 (TIMP-1) in rats with acute lung injury (ALI) induced by phosgene (Psg).

METHODSWe first established a rat model of Psg-induced acute lung injury (ALI). The rats were randomly divided into 6 groups: air control group with exposure to air, air+adenovirus (air+Ad) group with caudal vein injection of 1×10(8) pfu/ml adenovirus 1 h after air exposure, air+Ad/Ang1 group with caudal vein injection of 1×10(8) pfu/ml Ad.Ang-1siRNA 1 h after air exposure, Psg group with exposure to 8.33 mg/L Psg (purity 100%, of the same volume as the inhaled air in the air control group) for 5 min, Psg+Ad group with caudal vein injection of 1×10(8) pfu/ml adenovirus 1 h after exposure to the same dose of Psg, and Psg+Ad/Ang1 group with caudal vein injection of 1×10(8) pfu/ml Ad.Ang-1siRNA 1 h after exposure to the same dose of Psg. Serum, bronchoalveolar lavage fluid (BALF), and lung tissue were collected 36 h after exposure. The protein expression of Ang-1, MMP-2, 9, and TIMP-1 in serum and BALF was determined by double-antibody sandwich ELISA. RT-PCR was used to determine the mRNA levels of Ang-1, MMP-2, 9, and TIMP-1 in lung tissue. The protein expression of MMP-2, 9 and TIMP-1 in lung tissue was determined by Western blot.

RESULTSA rat model of Psg-induced ALI was successfully established. The levels of MMP-2, 9 in serum, BALF, and lung tissue were significantly increased in the Psg group and Psg+Ad/Ang1 group as compared with the control group (P<0.01); no significant change was observed in serum TIMP-1 protein expression (P>0.05); interestingly, TIMP-1 protein expression in BALF and lung tissue was significantly increased (P<0.01). Compared with the Psg group, the Psg+Ad/Ang1 group showed a significant decrease in MMP-2, 9 expression in BALF, serum, and lung tissue (P<0.05), but no significant change in protein expression of TIMP-1 was discovered (P>0.05).

CONCLUSIONAd.Ang-1siRNA has a potential beneficial effect in rats with Psg-induced ALI through inhibition of MMP-2, 9 expression, but has no significant effect on the expression of TIMP-1.

Acute Lung Injury ; chemically induced ; metabolism ; Adenoviridae ; genetics ; Angiopoietin-1 ; physiology ; Animals ; Bronchoalveolar Lavage Fluid ; Chemical Warfare Agents ; toxicity ; Disease Models, Animal ; Lung ; metabolism ; Matrix Metalloproteinase 2 ; genetics ; Matrix Metalloproteinases ; metabolism ; Phosgene ; toxicity ; RNA, Messenger ; genetics ; RNA, Small Interfering ; Rats ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism

OBJECTIVETo investigate the effect of melatonin (MT) on p38 mitogen-activated protein kinase (MAPK) signaling pathway in rats with phosgene-induced lung injury.

METHODSFifty specific pathogen-free male Sprague-Dawley rats were randomly divided into phosgene inhalation group, air control group, saline control group, MT treatment group, and SB203580 (specific inhibitor of p38 MAPK) group, with 10 mice in each group. All groups except the air control group were exposed to phosgene, and the animals were sacrificed 6 h later. Lung wet/dry weight (W/D) ratio and the content of malondialdehyde (MDA) and nitric oxide (NO) and activity of myeloperoxidase (MPO) in bronchoalveolar lavage fluid (BALF) were measured. The qualitative and quantitative expression of p38 MAPK and phospho-p38 MAPK (p-p38) was measured by immunohistochemistry (IHC) and Western blot, respectively. Inducible nitric oxide synthase (iNOS) level in lung tissue was determined by Western blot.

RESULTSCompared with the air control group, the phosgene inhalation group had significantly increased lung W/D ratio and neutrophil count in BALF (P < 0.01); the MT treatment group had significantly lower neutrophil count and lung W/D ratio than the phosgene inhalation group (P < 0.05). IHC demonstrated that the air control group had relatively weak expression of p-p38 in lung tissue; the expression of p-p38 was significantly up-regulated after phosgene inhalation, and it was mainly distributed in infiltrating inflammatory cells and vascular endothelial cells, positive in the cytoplasm and nucleus of many cells. The distribution of p-p38-positive cells in the MT treatment and SB203580 groups was similar to that in the phosgene inhalation group, but the MT treatment and SB203580 groups had a significantly reduced number of cells with p-p38-positive nuclei and a significantly reduced intensity of p-p38 expression signals. The phosgene inhalation group had significantly increased content of MDA and NO and activity of MPO compared with the air control group (P < 0.01); the MT treatment and SB203580 groups had significantly reduced content of MDA and NO and activity of MPO compared with the phosgene inhalation group (P < 0.05), but had higher content of MDA and NO and activity of MPO than the air control group. The Western blot showed that the phosgene inhalation group had significantly increased expression of iNOS and p-p38 compared with the air control group (P < 0.01); the MT treatment and SB203580 groups had lower expression of iNOS and p-p38 than the phosgene inhalation group (P < 0.05).

CONCLUSIONMT and SB203580 have a significant protective effect in rats with phosgene-induced lung injury, and the mechanism may be associated with scavenging free radicals and inhibiting activation of p38 MAPK and expression of iNOS.

Animals ; Bronchoalveolar Lavage Fluid ; Chemical Warfare Agents ; toxicity ; Imidazoles ; Lung ; drug effects ; Lung Injury ; chemically induced ; Male ; Malondialdehyde ; adverse effects ; Melatonin ; physiology ; Mice ; Nitric Oxide ; adverse effects ; Nitric Oxide Synthase Type II ; metabolism ; Phosgene ; toxicity ; Pyridines ; Rats, Sprague-Dawley ; Respiratory Distress Syndrome, Adult ; metabolism ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases ; metabolism