Objective To investigate the effect and mechanism of Ginkgo biloba extract(EGB761)on acute lung injury(ALI)induced by sepsis in mice.Methods Fifty male Kunming mice were selected,they were randomly divided into sham operation group(intraperitoneal injection of equal amount of normal saline after operation),model group(intraperitoneal injection of equal amount of normal saline after operation),low-dose EGB761 group(intraperitoneal injection of 20 mg/kg EGB761 immediately after operation)and high-dose EGB761 group(intraperitoneal injection of 50 mg/kg EGB761 immediately after operation)and high-dose EGB761+nuclear factor E2-related factor 2(Nrf2)inhibitor ML385 group(intraperitoneal injection of ML385 30 mg/kg 1 hour before modeling and 50 mg/kg EGB761 immediately after operation),with 10 mice in each group.ALI model of sepsis was established by cecal ligation and puncture(CLP),and the sham operation group only underwent open-closed abdominal surgery.Serum and lung tissue were taken at 12 hours after operation,and the pathological changes of lung tissue were observed under light microscope after hematoxylin-eosin(HE)staining,and the lung injury score was made.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of interleukin(IL-6,IL-1β)and tumor necrosis factor-α(TNF-α)in serum of mice in each group.Western blotting test and real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)were used to detect the protein expression levels of glutathione peroxidase 4(GPX4),Nrf2,member 11 of solute carrier family 7(SLC7A11)and the mRNA expression levels of Nrf2 and GPX4 mRNA the lung tissues of mice in each group.The content of malondialdehyde(MDA)in the lung tissues of mice in each group was detected by the thiobarbituric acid method.The activity of superoxide dismutase(SOD)in the lung tissues of mice in each group was detected by xanthine oxidase method.Results Compared with the sham operation group,in the model group,a large number of inflammatory cells infiltrated in the lung tissue,the alveolar structure was destroyed,the lung injury score was significantly increased(3.71±0.29 vs.0.33±0.10),and serum pro-inflammatory factors IL-1β,IL-6,TNF-α and the content of oxidation index MDA in lung tissue all increased significantly[IL-1β(ng/L):0.410±0.002 vs.0.351±0.007,IL-6(ng/L):0.650±0.010 vs.0.560±0.010,TNF-α(ng/L):0.320±0.010 vs.0.290±0.002,MDA(nmol/mg):2.49±0.31 vs.1.77±0.02,all P<0.05],while SOD activity in lung tissue decreased significantly(U/mg:20.20±4.61 vs.61.47±8.10,P<0.05),the expression levels of Nrf2,GPX4,SLC7A11 protein,GPX4,and Nrf2 mRNA all decreased[NRF2 protein expression(Nrf2/β-actin):0.33±0.11 vs.0.63±0.17,GPX4 protein expression(GPX4/β-actin):1.19±0.08 vs.2.50±0.17,SLC7A11 protein expression(SLC7A11/β-actin):0.41±0.03 vs.0.67±0.08;GPX4 mRNA(2-ΔΔCt):0.32±0.00 vs.1.02±0.21,NRF2 mRNA(2-ΔΔCt):0.44±0.04 vs.1.01±0.20,all P<0.05].Compared with the model group,the degree of lung injury in the low-dose EGB761 group and the high-dose EGB761 group was reduced to varying degrees,and the lung injury score in the high-dose EGB761 group was significantly reduced(0.96±0.40 vs.3.71±0.29,P<0.05).The contents of MDA in lung tissue and serum proinflammatory factors IL-1β,IL-6 and TNF-α were significantly decreased[MDA(nmol/mg):1.53±0.09 vs.2.49±0.31,IL-1β(ng/L):0.350±0.004 vs.0.410±0.002,TNF-α(ng/L):0.280±0.003 vs.0.320±0.010,all P<0.05],SOD activity,proteins of Nrf2,GPX4 and SLC7A11,and expression levels of GPX4 and Nrf2 mRNA all increased significantly[SOD activity(U/mg):63.78±8.74 vs.20.20±4.61,the expression of Nrf2 protein(NRF2/β-actin):0.71±0.06 vs.0.33±0.11,the expression of GPX4 protein(GPX4/β-actin):2.03±0.10 vs.1.19±0.08,and the expression of SLC7A11 protein(SLC7A11/β-actin)0.65±0.07 vs.0.41±0.03;GPX4 mRNA(2-ΔΔCt):0.80±0.10 vs.0.32±0.00,NRF2 mRNA(2-ΔΔCt):0.84±0.07 vs.0.44±0.04,all P<0.05].Compared with high-dose EGB761 group,Nrf2 inhibitor ML385 can obviously reverse the above-mentioned effects of high-dose EGB761 after intervention.Conclusion Ginkgo biloba extract EGB761 can improve the sepsis ALI induced by CLP in mice,and it may play a protective role by activating Nrf2 and up-regulating SLC7A11 to inhibit ferroptosis.

Bronchial asthma is a kind of heterogeneous respiratory disease, and its emergency diagnosis and treatment face multiple challenges. This article, based on the evolution of domestic and international guidelines and consensus, explores the current confusions and shortcomings in the emergency treatment of asthma, considering the clinical specifics of emergency medicine. Due to the limited applicability of classifications such as "refractory asthma" and "severe asthma" in emergency settings, as well as the complex diagnostic process that makes clinical operations difficult, it is proposed to unify the diagnostic terminology as "acute exacerbation of bronchial asthma" (mild, moderate, severe, critical severe) in emergency work. Assessment indicators, such as arterial oxygen partial pressure (PaO₂), partial pressure of arterial carbon dioxide (PaCO₂), arterial oxygen saturation (SaO₂), peak expiratory flow (PEF). Simplified were simplified. The clinical diagnosis and emergency management should prioritize the approach outlined in the Chinese guidelines for the prevention and treatment of bronchial asthma (basic version). For mild-to-moderate and severe exacerbations, a tiered treatment strategy is recommended, focusing on rapid symptom relief, standardized glucocorticoid use, and dynamic efficacy assessment. Additionally, the urgent need for formulating a Chinese expert consensus on emergency diagnosis and treatment of bronchial asthma is highlighted, along with promoting multicenter prospective studies to optimize emergency protocols and improve patient prognosis.
Humans ; Asthma/therapy* ; Practice Guidelines as Topic

Objective To investigate the effect and mechanism of Ginkgo biloba extract(EGB761)on acute lung injury(ALI)induced by sepsis in mice.Methods Fifty male Kunming mice were selected,they were randomly divided into sham operation group(intraperitoneal injection of equal amount of normal saline after operation),model group(intraperitoneal injection of equal amount of normal saline after operation),low-dose EGB761 group(intraperitoneal injection of 20 mg/kg EGB761 immediately after operation)and high-dose EGB761 group(intraperitoneal injection of 50 mg/kg EGB761 immediately after operation)and high-dose EGB761+nuclear factor E2-related factor 2(Nrf2)inhibitor ML385 group(intraperitoneal injection of ML385 30 mg/kg 1 hour before modeling and 50 mg/kg EGB761 immediately after operation),with 10 mice in each group.ALI model of sepsis was established by cecal ligation and puncture(CLP),and the sham operation group only underwent open-closed abdominal surgery.Serum and lung tissue were taken at 12 hours after operation,and the pathological changes of lung tissue were observed under light microscope after hematoxylin-eosin(HE)staining,and the lung injury score was made.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of interleukin(IL-6,IL-1β)and tumor necrosis factor-α(TNF-α)in serum of mice in each group.Western blotting test and real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)were used to detect the protein expression levels of glutathione peroxidase 4(GPX4),Nrf2,member 11 of solute carrier family 7(SLC7A11)and the mRNA expression levels of Nrf2 and GPX4 mRNA the lung tissues of mice in each group.The content of malondialdehyde(MDA)in the lung tissues of mice in each group was detected by the thiobarbituric acid method.The activity of superoxide dismutase(SOD)in the lung tissues of mice in each group was detected by xanthine oxidase method.Results Compared with the sham operation group,in the model group,a large number of inflammatory cells infiltrated in the lung tissue,the alveolar structure was destroyed,the lung injury score was significantly increased(3.71±0.29 vs.0.33±0.10),and serum pro-inflammatory factors IL-1β,IL-6,TNF-α and the content of oxidation index MDA in lung tissue all increased significantly[IL-1β(ng/L):0.410±0.002 vs.0.351±0.007,IL-6(ng/L):0.650±0.010 vs.0.560±0.010,TNF-α(ng/L):0.320±0.010 vs.0.290±0.002,MDA(nmol/mg):2.49±0.31 vs.1.77±0.02,all P<0.05],while SOD activity in lung tissue decreased significantly(U/mg:20.20±4.61 vs.61.47±8.10,P<0.05),the expression levels of Nrf2,GPX4,SLC7A11 protein,GPX4,and Nrf2 mRNA all decreased[NRF2 protein expression(Nrf2/β-actin):0.33±0.11 vs.0.63±0.17,GPX4 protein expression(GPX4/β-actin):1.19±0.08 vs.2.50±0.17,SLC7A11 protein expression(SLC7A11/β-actin):0.41±0.03 vs.0.67±0.08;GPX4 mRNA(2-ΔΔCt):0.32±0.00 vs.1.02±0.21,NRF2 mRNA(2-ΔΔCt):0.44±0.04 vs.1.01±0.20,all P<0.05].Compared with the model group,the degree of lung injury in the low-dose EGB761 group and the high-dose EGB761 group was reduced to varying degrees,and the lung injury score in the high-dose EGB761 group was significantly reduced(0.96±0.40 vs.3.71±0.29,P<0.05).The contents of MDA in lung tissue and serum proinflammatory factors IL-1β,IL-6 and TNF-α were significantly decreased[MDA(nmol/mg):1.53±0.09 vs.2.49±0.31,IL-1β(ng/L):0.350±0.004 vs.0.410±0.002,TNF-α(ng/L):0.280±0.003 vs.0.320±0.010,all P<0.05],SOD activity,proteins of Nrf2,GPX4 and SLC7A11,and expression levels of GPX4 and Nrf2 mRNA all increased significantly[SOD activity(U/mg):63.78±8.74 vs.20.20±4.61,the expression of Nrf2 protein(NRF2/β-actin):0.71±0.06 vs.0.33±0.11,the expression of GPX4 protein(GPX4/β-actin):2.03±0.10 vs.1.19±0.08,and the expression of SLC7A11 protein(SLC7A11/β-actin)0.65±0.07 vs.0.41±0.03;GPX4 mRNA(2-ΔΔCt):0.80±0.10 vs.0.32±0.00,NRF2 mRNA(2-ΔΔCt):0.84±0.07 vs.0.44±0.04,all P<0.05].Compared with high-dose EGB761 group,Nrf2 inhibitor ML385 can obviously reverse the above-mentioned effects of high-dose EGB761 after intervention.Conclusion Ginkgo biloba extract EGB761 can improve the sepsis ALI induced by CLP in mice,and it may play a protective role by activating Nrf2 and up-regulating SLC7A11 to inhibit ferroptosis.

OBJECTIVE: To evaluate the efficacy and safety of magnesium sulfate in the treatment of acute severe asthma in adults. METHODS: Literature searches were conducted on PubMed, Cochrane, CNKI, VIP and Wanfang databases to screen randomized controlled trial (RCT) of magnesium sulfate in the treatment of acute severe asthma in adults, starting from the establishment of the database and ending on May 22, 2024. The control group received conventional treatment. The observation group was given intravenous magnesium sulfate on the basis of routine treatment. The outcome indexes included total effective rate, peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and other pulmonary function indexes, and incidence of adverse reactions. The selection of relevant literature, the collection of data needed for the study and the risk assessment of bias in the included study were all conducted independently by 2 researchers. Stata 12.0 software was used for Meta-analysis, and funnel plot was used to evaluate publication bias. RESULTS: Sixteen RCT studies with a total of 2 601 patients were included. Meta-analysis results showed that the total effective rate in the observation group was significantly higher than that in the control group [risk ratio (RR) = 1.11, 95% confidence interval (95%CI) was 1.03-1.20, P = 0.008]. In pulmonary function examination, PEF [weighted mean difference (WMD) = 0.70, 95%CI was 0.24-1.15, P = 0.003], FEV1 (WMD = 0.48, 95%CI was 0.29-0.68, P = 0.000) and FVC (WMD = 0.72, 95%CI was 0.47-0.97, P = 0.000) were significantly better than those in the control group. There was no significantly difference in the incidence of adverse reactions between the two groups (RR = 0.51, 95%CI was 0.17-1.55, P = 0.419). The funnel plot was drawn for the total effective rate, which showed that each study presented a symmetrical distribution, and the Begg's test (Z = 1.31, P = 0.189) and Egger's test (t = 1.18, P = 0.261) were combined to consider the small possibility of publication bias. CONCLUSIONS Current evidence shows that the use of magnesium sulfate in the treatment of acute severe asthma in adults increases the total response rate and improves lung function without increasing the incidence of adverse reactions. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies high-quality studies.
Humans ; Magnesium Sulfate/administration & dosage* ; Asthma/drug therapy* ; Adult ; Randomized Controlled Trials as Topic ; Forced Expiratory Volume ; Peak Expiratory Flow Rate/drug effects* ; Treatment Outcome

Background: Insulin regulates glucose homeostasis and has important effects on metabolism, cell growth, and differentiation. Depending on the cell type and physiological context, insulin signal has specific pathways and biological outcomes in different tissues and cells. For studying the signal pathway of insulin on glycolipid metabolism in porcine embryonic fibroblast (PEF), we used high-throughput sequencing to monitor gene expression patterns regulated by insulin. Objectives: The goal of our research was to see how insulin affected glucose and lipid metabolism in PEFs. Methods: We cultured the PEFs with the addition of insulin and sampled them at 0, 48, and 72 h for RNA-Seq analysis in triplicate for each time point. Results: At 48 and 72 h, 801 and 1,176 genes were differentially expressed, respectively. Of these, 272 up-regulated genes and 264 down-regulated genes were common to both time points. Gene Ontology analysis was used to annotate the functions of the differentially expressed genes (DEGs), the biological processes related to lipid metabolism and cell cycle were dominant. And the DEGs were significantly enriched in interleukin-17 signaling pathway, phosphatidylinositol-3-kinase-protein kinase B signaling pathway, pyruvate metabolism, and others pathways related to lipid metabolism by Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Conclusions These results elucidate the transcriptomic response to insulin in PEF. The genes and pathways involved in the transcriptome mechanisms provide useful information for further research into the complicated molecular processes of insulin in PEF.

Objective To explore the roles of Th17 cells in paraquat-induced acute lung injury(ALI)in a murine models through investigating the expression of Th17 type cytokine IL-17 and the specific transcription factor of Th17 cells-RORγt mRNA. Methods Male Kunming mice were randomly divided into the normal control group and the poisoned group. The ALI model induced by PQ poisoning was produced by intraperitoneal injection PQ solu-tion (20 mg/kg),and the normal control group was given normal saline solution with the same volume. After treatment for 48 hours,the animals were sacrificed. H&E staining and TUNEL staining were done to measure histo-logical changes and apoptosis. Serum level of Th17 related-cytokines was assayed by ELISA. The mRNA ex-pression of RORγt and the protein expression of IL-17 in the lung tissue were detected by real time-PCR assay and western blot,respectively. Results Compared with the normal control group,the lung inflammation and apopto-sis were significantly higher in the poisoned group. The serum level of IL-17A was significantly increased (P <0.05) and the lung parenchyma RORγt mRNA and IL-17 protein levels were significantly increased. Conclu-sion IL-17 plays an important role in the pathogenesis of ALI induced by paraquat poisoning.

Aim To establish and compare asthma models among different strains of obese mice. Methods Different strains of SPF female mice, namely Kunming ( KM ) , C57BL/6J and BALB/c mice, were randomly divided into four groups ( control group, asthma group, obesity group and obese asthma group). The mice were fed a high-fat diet or a normal diet for 12 weeks, following which they were sensitized and challenged with ovalbu-min ( OVA) or phosphate-buffered saline ( PBS) . Body weight, fat weight, liver weight, Lee′s index, OVA-specific IgE concen-tration in bronchoalveolar lavage fluid ( BALF) , serum total cho-lesterol ( TC) and triglyceride ( TG) levels, and lung and adi-pose morphologies were evaluated. The specific airway resistance ( sRaw) was measured using double-chamber plethysmography. Results The mice on a high-fat diet showed a more rapid in-crease in body weight compared with those on a normal diet. Af-ter 12 weeks of feeding, body, fat, and liver weights and Lee′s index were higher for the obese mice than for the lean mice. The adipocyte cross-sectional area was significantly greater in the obese BALB/c and KM mice than in their lean counterparts;the C57BL/6J groups showed no significant differences. The BALB/c mice demonstrated more significant symptoms of acute asthma, local inflammation and airway hyper-responsiveness ( AHR ) . Conclusion Compared with C57BL/6J and KM mice, BALB/c mice fed a high-fat diet and sensitized and challenged with OVA provide the most suitable model for evaluating the relationship between obesity and asthma.

Objective To investigate the differences in position and volume between planning target volumes (PTV) based on positron emission tomography?computed tomography (PET?CT) images with an standardized uptake value ( SUV) no less than 2?5, 20% of the maximum SUV ( SUVmax ), or 25% of SUVmax , three?dimensional ( 3D ) CT, and four?dimensional ( 4D ) CT in thoracic esophageal cancer. Methods Eighteen patients with thoracic esophageal cancer sequentially received chest 3DCT, 4DCT, and [18F]fluoro?2?deoxy?D?glucose (FDG) PET?CT scans. PTV3D was obtained by conventional expansion of 3DCT images;PTV4D was obtained by fusion of target volumes from 10 phases of 4DCT images. The internal gross tumor volumes ( IGTV) , IGTVPET2.5 , IGTVPET20%, and IGTVPET25%, were generated based on PET?CT images with an SUV no less than 2?5, 20% of SUVmax , and 25% of SUVmax , respectively. These IGTVs were expanded longitudinally by 3?5 cm and radically by 1 cm to make PTVPET2.5 , PTVPET20%, and PTVPET25%, respectively. Results PTV3D was significantly larger than both PTV4D and PTVPET(P=0?000 -0?044), while there was no significant difference between PTV4D and PTVPET ( P= 0?216 -0?633 ) . The mutual degrees of inclusion ( DIs ) between PTV3D and PTV4D were 0?70 and 0?95, respectively, which were negatively correlated with 3D?Vector ( P=0?039). The mutual DIs between PTVPET2.5, PTVPET20%, and PTVPET25% were 0?74, 0?72, 0?78, 0?73, 0?77, and 0?70, respectively, which showed no correlation with 3D?Vector (P=0?150 -0?822). The mutual DIs between PTV3D and PTVPET were 0?86, 0?84, 0?88, 0?63, 0?67, and 0?59, respectively. Conclusions It is difficult to achieve complete volumetric overlap of PTVs based on 3DCT, 4DCT and PET?CT in thoracic esophageal cancer due to different target volume information. PET scan during free breathing should be used with caution to generate PTVs in thoracic esophageal cancer.

Objective To compare the position,volume and matching index (MI) of esophagus between quiet end-inspiration and end-expiration in three dimensional CT (3D-CT) assisted with active breathing control (ABC) and the corresponding phases in four dimensional CT (4D-CT).Methods Eleven patients with peripheral lung cancer underwent 4D-CT simulation scan and 3D-CT simulation scans in end-inspiratory hold (CTEIH) and end-expiratory hold (CTEEH) in succession.The 0％ phase was defined as end-inspiratory phase (CT0),while the 50％ phase was defined as end-expiratory phase (CT50).The proximal,mid-,and distal thoracic esophagus were delineated separately on CT0,CT50,CTEIH and CTEEH images.The position,volume and MI of each segment esophagus between CT0 and CTEIH,CT50 and CTEEH were compared.Results In the left-right (x) direction,the position differences in the proximal,mid-,and distal thoracic esophagus between CT0and CTEIH were (-0.02 ±0.16)cm,(0.06 ± 0.26)cm and (0.10 ± 0.33) cm respectively,and in the anterior-posterior (y) direction,the position differences were (0.04 ±0.24)cm,(0.04 ±0.12) cm and (0.08 ±0.15) cm respectively,and the position differences in the same direction were not statistically significant.In the x direction,the position differences of the proximal,mid-,or distal thoracic esophagus between CT50 and CTEEH were (-0.02 ±0.24) cm,(0.12 ± 0.37) cm and (0.26 ± 0.33) cm respectively,and in the y direction,the position differences were (0.03 ±0.21)cm,(0.04 ±0.17)cm and (0.14 ±0.18)cm respectively,and the position differences in x and y directions of proximal and mid-thoracic esophagus between CT50 and CTEEH were not statistically significant,while the position differences in x and y directions of distal thoracic esophagus between CT50and CTEEH were both statistically significant (t =0.025,0.024,P ＜ 0.05).The volumes of the proximal,mid-and distal thoracic esophagus were all larger in CT0and CT50 than those in CTEIHand CTEEH,but without statistical differences.The MIs of the volumes of the proximal,mid-and distal thoracic esophagus between CT0 and CTEIH were (0.50 ± 0.17),(0.50 ± 0.19) and (0.56 ± 0.08),respectively,and those between CT50and CTEEH were (0.50 ±0.16),(0.47 ±0.14) and (0.51 ±0.15),respectively.The MI of each segment esophagus between CT0and CTEIHwas larger than that between CT50 and CTEEH,but without statistical differences.Conclusions The influence of breathing modes on the centroid positions of the proximal,mid-thoracic normal esophagus were not significant and there were spatial mismatches for any segment esophagus between 3D-CT assisted with ABC and 4D-CT.

Objective To analyze artifacts of gross tumor volume (GTV) and correlated factors in each phase images of four dimensional CT (4DCT) for peripheral lung cancer based on three dimensional CT (3DCT) assisted with active breathing control.Methods Nineteen patients with peripheral lung cancer underwent 3DCT (CTFB) and 4DCT simulation scans during free breathing and then underwent 3DCT simulation scans in end inspiration hold (CTEIH) and end expiration hold (CTEEH) assisted with active breathing control.The relative deviations (Devref) between the reference GTV (GTVref) and the GTVsdelineated based on CTFB (GTVFB) and all phases of 4DCT were calculated respectively.Correlations between GTVref and Devmax and between the tumor motion in the cranio-caudal (CC) direction and Devref were analyzed.Results The maximum median Devref of GTV was GTVFB with 17.83％,and the maximum median Devref of the GTV in all phases of 4DCT was GTV30 with 17.20％.A significant negative correlation was found between GTVEIH and Devmax (r =-0.691,P =0.001).The Devref was crrnelated with the tumor motion amplitude in the CC direction (r =0.323-0.617,P =0.005-0.150).The partial regression coefficient of influence of GTVref size and motion amplitude in the CC direction to the tumor Devmax were -0.500 and 0.583,P =0.002 and 0.001,respectively.Conclusions The GTV artifacts in different phase of 4DCT for the peripheral lung cancer were different to each other,and the influence of target displacement to artifacts was larger than that of target volume,so artifacts could be reduced by controlling breathing to reduce target displacement.