Objective: To analyze the relationship between asthma and nocturia in women based on the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2018,so as to provide reference for the prevention and treatment of female nocturia. Methods: Female respondents aged ≥20 years with nocturia or asthma were selected from the 2005-2018 NHANES database.Those with both diabetes stroke and obstructive sleep apnea syndrome were excluded.A weighted analysis was conducted using a complex sampling design.The association between asthma and nocturia in women was evaluated with univariate analysis，propensity score matching (PSM)，and multivariate logistic regression models. Results: A total of 14 718 respondents were selected，of whom 1426 (9.7%) were diagnosed with asthma，and 4664 (31.7%) with nocturia.There is a significant correlation between asthma and nocturia (χ =39.846，P<0.01). Age，body mass index (BMI)，smoking and race were also associated with nocturia (P<0.01).Multivariate logistic regression analysis showed that，the age，BMI，smoking，race and asthma were correlated with the risk of nocturia，before PSM matching (P<0.05).To eliminate confounding bias，PSM was applied，and generalized linear mixed model analysis after matching showed that the risk of nocturia remained high in asthma patients (OR=1.540，95% CI：1.320-1.800，P<0.01). Conclusion: Asthma is associated with nocturia in women，indicating that it may be an important risk factor for female nocturia.

Objective:To investigate the risk factors of skin adverse events associated with immune checkpoint inhibitor (ICI) therapy in patients with urologic neoplasms, and establish a predictive model.Methods:A single-center retrospective case-control study enrolled 91 advanced urologic neoplasms patients who received ICI therapy at the Department of Urology, Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2025. Patients were divided into the skin lesion group ( n=44) and the control group ( n=47). Patients in the skin lesion group experienced related skin adverse events during ICI treatment, while patients in the control group did not experience such events during ICI treatment. The general data and laboratory indicators were compared between the two groups. The normally distributed measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; the non-normally distributed measurement data were expressed as the median (interquartile range) [ M ( Q1, Q3)], and the Kruskal-Wallis test was used for comparison between groups. The count data were expressed as the number of cases and percentages, and the Chi-test was used for comparison between groups. First, a univariate analysis was conducted on the influencing factors of skin adverse events in patients with urologic neoplasms after ICI treatment. Then, the indicators with statistically significant differences in the univariate analysis were further included in the multivariate Logistic regression model to screen the independent risk factors for predicting skin adverse events. The R software was used to incorporate the factors with significant differences from multivariate analysis into the prediction model and construct a Nomogram. The calibration curve was utilized to evaluate the consistency between predicted values and actual observed results. Meanwhile, the discrimination of the model was verified by the receiver operating characteristic (ROC) curve and the area under the curve (AUC), so as to comprehensively verify the reliability and clinical application value of the prediction model. Results:The results of univariate analysis showed that there were statistically significant differences between the skin lesion group and the control group in terms of the proportion of other immune responses, serum albumin level, absolute eosinophil count, and C-reactive protein (CRP) levels ( P<0.05). These factors were included in multivariate Logistic regression, which identified elevated absolute eosinophil count and elevated CRP as the independent risk factors for related skin adverse events in patients with urologic neoplasms after ICI treatment. A predictive nomogram was built based on these factors. The calibration curve showed high consistency between predicted and actual probabilities, and ROC analysis confirmed the combined model had high predictive value (AUC=0.883, P<0.001). Conclusions:Elevated absolute eosinophil count and elevated CRP level are independent predictors of immune-related skin adverse events in urologic neoplasms patients after ICI treatment. The prediction model constructed based on these two factors facilitates early clinical screening and identification of high-risk patients.

Objective To identify potential drug target genes associated with idiopathic pulmonary fibrosis(IPF)and predict therapeutic candidates using a two-sample Mendelian randomization(MR)approach across the druggable genome.Methods Druggable genome data from the DGIdb database and Finan were integrated to identify overlapping genes.A two-sample MR analysis was performed to infer causal relationships between genes and IPF.Functional enrichment analyses,including Gene Ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG),were conducted to explore biological pathways.Drug-target interactions were predicted via DSigDB database screening,followed by molecular docking simulations to evaluate binding affinities.Results Among the 2588 overlapping druggable genes,thirty exhibited significant causal associations with IPF(P＜0.05).Four hub genes(NOD2,LATS2,LTA,and TCF7L2)were enriched in IPF-related pathways,notably Hippo and TNF signaling.Six potential therapeutics were identified:oxyphenbutazone,moexipril,α-galactosylceramide,GSK429286A,CGP74514A,and JW-7-24-1.Molecular docking confirmed strong binding affinities between these drugs and their targets.Conclusion This study has identified thirty druggable gene targets and six candidate drugs for IPF.The enrichment of hub genes in key pathways and validated drug-target interactions provide insights into IPF therapies.

OBJECTIVE To investigate the acute lung injury effects of pulmonary phospholipids and their phospholipase A2(PLA2)decomposition products-lysophospholipids and fatty acids-on mice.METHODS Mice were randomly assigned to the following groups:① solvent control(PBS)and PLA2;② solvent control and glycerol phospholipid groups:1,2-dioleoyl-sn-glycero-3-phosphoserine(DOPS),1,2-dipalmitoyl-sn-glycero-3-phosphoserine(DPPS),1,2-dioleoyl-sn-glycero-3-phosphoethanol-amine(DOPE),1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine(DPPE),1,2-dipalmitoyl-sn-glycero-3-phosphocholine(DPPC),and 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine(SOPC);③ solvent con-trol and fatty acid groups:palmitic acid(PA),oleic acid;④ solvent control and lysophospholipid groups:1-oleoyl-2-hydroxy-sn-glycero-3-phosphoserine(18∶1 LysoPS),1-stearoyl-sn-glycero-3-phosphoserine(18∶0 LysoPS),1-palmitoyl-sn-glycero-3-phosphoserine(16∶0 LysoPS),1-palmitoyl-sn-glycero-3-phos-phoethanolamine(16∶0 LysoPE),1-palmitoyl-sn-glycero-3-phosphocholine(16∶0 LysoPC);⑤ solvent control,PLA2,DPPC,PA,16∶0 LysoPC,16∶0 LysoPS,and 18∶1 LysoPS.Following anesthesia,mice were administered nebulized PBS in the solvent control group,2.1 ug·kg-1 PLA2 in PBS in the PLA2 group and 2.5 mg·kg-1 of the corresponding substance in PBS in other experimental groups.For group①,survival times were recorded and survival curves were plotted.At 1 h post-treatment,lung tissues from groups ①②③④ were collected,photographed to obtain white light images,and subjected to HE staining to assess histopathological changes and pathological scoring.At 2 h post-treatment,pulmonary blood flow in group ⑤ was assessed using laser speckle contrast imaging,arterial blood gas was analyzed with a blood gas analyzer,and lung function was evaluated using whole-body pleth-ysmography.At 6 hours post-treatment,blood cells from group ⑤ were analyzed using an automated hematology analyzer.RESULTS Compared with the solvent control group,severe pathological changes were observed in lung tissues of the PLA2 group,accompanied by extensive inflammatory infiltration and interstitial thickening,with all mice succumbing within 240 min.In mice treated with glyc-erol phospholipids,alveolar structures remained clear,alveolar walls were intact and continuous,and alveolar spaces were translucent,with only occasional minor inflammatory cell infiltration in the septa.No significant pathological alterations were detected in the fatty acid groups.Minor inflammatory cell infiltration was seen in the 16∶0 LysoPE and 16∶0 LysoPC groups.However,such pathological changes as patchy hemorrhage,alveolar interstitial edema,increased alveolar wall thickness,and elevated neutrophil counts were observed in the 18∶1 LysoPS,18∶0 LysoPS,and 16∶0 LysoPS groups.Pathological scores based on HE staining were significantly increased in the 16∶0 LysoPS and 18∶1 LysoPS groups com-pared with the solvent control.The percentage of the lung tissue injury area was also markedly higher in the 16∶0 LysoPS group.A significant decrease in the mean fluorescence intensity of blood flow was observed in the 16∶0 LysoPS group.Arterial partial pressure of oxygen(pO2)was significantly reduced in the PLA2 group,while arterial partial pressure of carbon dioxide(pCO2)was markedly elevated in the 16∶0 LysoPS and 18∶1 LysoPS groups.Lung function tests revealed that the 16∶0 LysoPS group exhibited significant increases in expiratory time,end-expiratory pressure,and enhanced pause,in contrast to significant decreases in tidal volume,expired volume,and minute volume.The 18∶1 LysoPS group also exhibited a significant decline in minute volume.No significant changes in inflammatory cell concentrations were detected in blood,with the exception of neutrophils in the 16∶0 LysoPS group,which showed a significant but physiologically normal increase.CONCLUSION Pulmonary phospholipids and their PLA2-derived fatty acid metabolites do not induce severe lung injury in mice while the lyso-phospholipid metabolites,particularly lysophosphatidylserine,are found to cause significant lung injury.

Objective:To construct a dual performance management model based on data envelopment analysis (DEA),so as to assess the quality of metrological management of medical equipment,and formulate management countermeasures. Methods:The dual performance management model was constructed by adopting data envelopment analysis-banker-charnes-cooper (DEA-BCC). The evaluation indicator system was built from two dimensionalities included input performance and output performance,which can perform comprehensive evaluation meterring performance of equipment,so as to formulate three dimensional measure included improvement of management team,optimization of metrological process,and routine monitor and management for improving metrological management of equipment. A total of 183 used medical equipment of International Peace Maternity & Child Health Hospital of China welfare institute (IPMCH) from 2022 to 2023 were selected. The metrological management of 176 medical equipment from January to December 2022 adopted formulation of management countermeasures on the basis of subjective evaluation to perform management (subjective evaluation),and the metrological management of 177 medical equipment (included 170 equipment that were used in subjective evaluation) from January to December 2023 adopted formulation of management countermeasures on the basis of dual performance evaluation (dual performance evaluation). The self-made online survey questionnaire was used to investigate the recognition degree of 104 operators of clinical department,who used the equipment. Among of them,48 operators received the management method of subjective evaluation,and 56 operators received the dual performance evaluation. The metrological management performance,management effectiveness and clinical recognition degree of the two kinds of management methods for medical equipment were compared. Results:The values of standardized input performance,output performance and comprehensive performance of equipment,which adopted dual performance evaluation management,were respectively 87.74±3.61,97.19±1.70 and 1.11±0.04. Input performance of dual performance evaluation management was lower than that of subjective evaluation management method,and output performance and comprehensive performance of dual performance evaluation management were higher than these of subjective evaluation management method,and the differences of them between two methods were statistically significant (t=4.866,4.457,7.793,P<0.05). The average metrological pass rates of mechanics,thermodynamics,thermology,textiles and medical equipment of medical laboratory of using dual performance evaluation management were (97.99±1.14)％,(97.39±2.08)％,(97.43±1.87)％,(98.06±0.92)％ and (96.77±2.03)％,respectively. All of them were higher than these of using subjective evaluation management method,and the differences of them between two methods were statistically significant (t=4.431,3.232,3.324,4.928,3.352,P<0.05). The satisfaction rates of 56 operators of equipment,who adopted dual performance evaluation management,were respectively 98.21％,94.64％,96.43％,100.00％ and 98.21％ for the management system,metrological frequency,metrological items,metrological effect and service quality of metrological staffs of equipment,which were higher than these of subjective evaluation management method,and the differences of them between two methods were statistically significant (x2=7.240,5.660,6.296,6.128,12.735,P<0.05). Conclusion:The dual performance management model can control the input of metrological management of medical equipment,and enhance the output of metrological management of medical equipment,and promote the operation quality of medical equipment,and improve the level of clinical service of medical equipment.

OBJECTIVE To investigate the biodistribution of lipid nanoparticles(LNPs)with different surface charges and different particle sizes in mice.METHODS LNPs were prepared using microfluidic technology by incorporating positively charged phospholipids,negatively charged phospholipids,ioniz-able phospholipids,and neutral phospholipids into the formulation to create LNPs with corresponding surface charges.The particle size of the LNPs was controlled by polyethylene glycol(PEG)modifica-tion and measured using dynamic light scattering(DLS)and transmission electron microscopy(TEM),while the surface charge was analyzed using a zeta potential analyzer.The LNPs were labeled with a fluorescent dye,and the mice were intravenously injected with 0.625 μmol·kg-1 of LNPs.At 1,4,12 and 24 h post-injection,the brain,heart,livers,spleen,lungs and kidneys were collected.The fluorescence distribution in different organs was detected using an in vivo imaging system to reflect the distribution of LNPs in various organs.RESULTS Particle size analysis showed that,except the ionizable lipid nanoparticles without PEG modification(LNP-MC3),which had a particle size>200 nm,the particle sizes of positively charged LNPs without PEG modification(LNP-Pos),PEG-modified positively charged LNPs(LNP-Pos-P),PEG-modified neutral LNPs(LNP-Neu-P),PEG-modified ionizable LNPs(LNP-MC3-P),and PEG-modified negatively charged LNPs(LNP-Neg-P)were all<200 nm.Zeta potential analysis revealed that the surface charges of the LNPs were the highest in LNP-Pos,followed by LNP-Pos-P,LNP-MC3-P,LNP-Neu-P,LNP-MC3 and LNP-Neg-P.In vivo imaging results indicated that LNP-Pos-P,LNP-Pos and LNP-MC3-P were primarily distributed in the livers,lungs and kidneys,respectively,while LNP-Neu-P and LNP-Neg-P in the livers,kidneys,and lungs,respectively.The distribution of LNP-MC3-P in the brain,heart,spleen and kidneys peaked at 12 h post-injection,but at 24 h in the livers.The distribution of LNP-Pos-P in the lungs peaked at 1 h post-injection.CONCLUSION LNPs are primarily distributed in the livers.Surface charges influence the second most highly-distributed organs.LNP-Pos-P and LNP-MC3-P are the second most highly-distributed in the lungs,and LNP-Neu-P and LNP-Neg-P in the kidneys.

OBJECTIVE To construct novel central nervous system(CNS)-targeted lipid nanoparti-cles for the treatment of organophosphorus-induced brain injury in mice.METHODS(1)Preparation,screening,and characterization of lipid nanoparticles.① Lipid nanoreactivators were prepared using the thin-film hydration method,with asoxime(HI-6)as the therapeutic drug and lipid carriers composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine(POPS),1,2-dipalmitoyl-sn-glycero-3-phospho-choline(DPPC),and cholesterol(CHOL)(PDC)at varying molar ratios(1∶6∶3,3∶4∶3,5∶2∶3 and 7∶0∶3)(HI-6@PDC 1∶6∶3,3∶4∶3,5∶2∶3 and 7∶0∶3).② FLU-labeled lipid nanocarriers(FLU@PDC 1∶6∶3,3∶4∶3,5∶2∶3,and 7∶0∶3)were prepared and physically mixed with phospholipase A2(PLA2)solution(at the final PLA2 concentration of 10 kU·L-1)to obtain FLU@PDC+PLA2.Male KM mice were randomly divided into normal control(PBS),FLU,and FLU@PDC+PLA2(1∶6∶3,3∶4∶3,5∶2∶3,and 7∶0∶3)groups(n=7 per group).After intravenous(iv)administration(FLU dose:1 mg·kg-1,carrier dose:80 mg·kg-1),brain tissues were collected at 1 h,homogenized,centrifuged,and analyzed via fluorescence spectrophotom-etry to screen the optimal CNS-targeted lipid carrier composition.③ The morphology of HI-6@PDC 5∶2∶3 was characterized by transmission electron microscope(TEM).The particle size,polydispersity index(PDI),and zeta potential of HI-6@PDC 5∶2∶3 were measured using a Zeta potential and particle size analyzer.Encapsulation efficiency and loading efficiency of HI-6@PDC 5∶2∶3 were determined using an ultrafiltration centrifugation method combined with high-performance liquid chromatography(HPLC).In vitro release kinetics of HI-6@PDC 5∶2∶3 and HI-6@PDC+PLA2 5∶2∶3 were assessed using a dialysis bag diffusion method combined with fluorescence spectrophotometry.(2)Validation of CNS targeting.① Cyanine7(Cy7)-labeled PDC 5∶2∶3(Cy7@PDC)was prepared and mixed with PLA2 solution(Cy7@PDC+PLA2 5∶2∶3).Mice were divided into normal control,Cy7,Cy7@PDC 5∶2∶3 and Cy7@PDC+PLA2 5∶2∶3 groups(n=3 per group).After iv injection(Cy7 dose:1 mg·kg-1,carrier dose:80 mg·kg-1),brain fluorescence was visualized at 3 h using a small animal in vivo imaging(IVIS)system.② Cyanine 3(Cy3)-labeled PDC 5∶2∶3(Cy3@PDC 5∶2∶3)was prepared and mixed with PLA2 solution(Cy3@PDC+PLA2 5∶2∶3).Mice were divided into Cy3@PDC 5∶2∶3 and Cy3@PDC+PLA2 5∶2∶3 groups(n=3 per group).After iv injection(Cy3 dose:1 mg·kg-1,carrier dose:80 mg·kg-1),brain tissues were collected at 2 h for fluorescent staining and Cy3 fluorescence observation.(3)Therapeutic efficacy eval-uation.① Male KM mice were randomly divided into normal control,brain injury,HI-6 treatment,and HI-6@PDC+PLA2 5∶2∶3 treatment groups(n=6 per group).Except for the normal control,all the mice were subcutaneously(sc)injected with soman(120 μg·kg-1),followed by immediate iv treatment(HI-6 dose:22 mg·kg-1,carrier dose:80 mg·kg-1).At 10 min,orbital blood and brain tissues were collected before brain weight was recorded.Acetylcholinesterase(AChE)reactivation in blood and brain was measured using the Ellman method.② Grouping and treatment were identical to ①(n=3 per group).At 24 h,brain tissues were collected for HE staining to assess histopathological damage.③ Mice were divided into brain injury and HI-6@PDC+PLA2 5∶2∶3 treatment groups(n=10 per group)and treated as in ①(soman dose:220 ug·kg-1).Survival rates,neurotoxic symptoms(tremors,salivation),and seizure latency were recorded,and survival curves were plotted.RESULTS(1)PDC 5∶2∶3 exhibited the highest brain fluorescence,indicating optimal CNS targeting.HI-6@PDC 5∶2∶3 appeared in regular spherical shapes,and were negatively charged,with a size of(219.4±3.1)nm,PDI of 0.4±0.02,entrapment effi-ciency of 72.9％and loading efficiency of 49.7％.HI-6@PDC+PLA2 5∶2∶3 showed a cumulative release of 43.5％at 60 min,which was lower than that of rhodamine B(RB)but sufficient for CNS therapeutic timelines.(2)In vivo fluorescence and pathological fluorescence confirmed PLA2-mediated CNS delivery.(3)HI-6@PDC+PLA2 5∶2∶3 significantly enhanced AChE reactivation in the blood and brain compared to HI-6.Histopathology revealed mitigated brain injury in treated mice.HI-6@PDC+PLA2 5∶2∶3 prolonged survival,reduced convulsions,alleviated neurotoxicity,and extended seizure latency.CONCLUSION HI-6@PDC 5∶2∶3 can effectively cross the blood-brain barrier via PLA2 mediation,demonstrating strong CNS targeting.It can significantly improve AChE reactivation in peripheral and central tissues and offers potent therapeutic efficacy against organophosphate-induced brain injury.

OBJECTIVE To investigate the biodistribution of lipid nanoparticles(LNPs)with different surface charges and different particle sizes in mice.METHODS LNPs were prepared using microfluidic technology by incorporating positively charged phospholipids,negatively charged phospholipids,ioniz-able phospholipids,and neutral phospholipids into the formulation to create LNPs with corresponding surface charges.The particle size of the LNPs was controlled by polyethylene glycol(PEG)modifica-tion and measured using dynamic light scattering(DLS)and transmission electron microscopy(TEM),while the surface charge was analyzed using a zeta potential analyzer.The LNPs were labeled with a fluorescent dye,and the mice were intravenously injected with 0.625 μmol·kg-1 of LNPs.At 1,4,12 and 24 h post-injection,the brain,heart,livers,spleen,lungs and kidneys were collected.The fluorescence distribution in different organs was detected using an in vivo imaging system to reflect the distribution of LNPs in various organs.RESULTS Particle size analysis showed that,except the ionizable lipid nanoparticles without PEG modification(LNP-MC3),which had a particle size>200 nm,the particle sizes of positively charged LNPs without PEG modification(LNP-Pos),PEG-modified positively charged LNPs(LNP-Pos-P),PEG-modified neutral LNPs(LNP-Neu-P),PEG-modified ionizable LNPs(LNP-MC3-P),and PEG-modified negatively charged LNPs(LNP-Neg-P)were all<200 nm.Zeta potential analysis revealed that the surface charges of the LNPs were the highest in LNP-Pos,followed by LNP-Pos-P,LNP-MC3-P,LNP-Neu-P,LNP-MC3 and LNP-Neg-P.In vivo imaging results indicated that LNP-Pos-P,LNP-Pos and LNP-MC3-P were primarily distributed in the livers,lungs and kidneys,respectively,while LNP-Neu-P and LNP-Neg-P in the livers,kidneys,and lungs,respectively.The distribution of LNP-MC3-P in the brain,heart,spleen and kidneys peaked at 12 h post-injection,but at 24 h in the livers.The distribution of LNP-Pos-P in the lungs peaked at 1 h post-injection.CONCLUSION LNPs are primarily distributed in the livers.Surface charges influence the second most highly-distributed organs.LNP-Pos-P and LNP-MC3-P are the second most highly-distributed in the lungs,and LNP-Neu-P and LNP-Neg-P in the kidneys.

Objective:To construct a dual performance management model based on data envelopment analysis (DEA),so as to assess the quality of metrological management of medical equipment,and formulate management countermeasures. Methods:The dual performance management model was constructed by adopting data envelopment analysis-banker-charnes-cooper (DEA-BCC). The evaluation indicator system was built from two dimensionalities included input performance and output performance,which can perform comprehensive evaluation meterring performance of equipment,so as to formulate three dimensional measure included improvement of management team,optimization of metrological process,and routine monitor and management for improving metrological management of equipment. A total of 183 used medical equipment of International Peace Maternity & Child Health Hospital of China welfare institute (IPMCH) from 2022 to 2023 were selected. The metrological management of 176 medical equipment from January to December 2022 adopted formulation of management countermeasures on the basis of subjective evaluation to perform management (subjective evaluation),and the metrological management of 177 medical equipment (included 170 equipment that were used in subjective evaluation) from January to December 2023 adopted formulation of management countermeasures on the basis of dual performance evaluation (dual performance evaluation). The self-made online survey questionnaire was used to investigate the recognition degree of 104 operators of clinical department,who used the equipment. Among of them,48 operators received the management method of subjective evaluation,and 56 operators received the dual performance evaluation. The metrological management performance,management effectiveness and clinical recognition degree of the two kinds of management methods for medical equipment were compared. Results:The values of standardized input performance,output performance and comprehensive performance of equipment,which adopted dual performance evaluation management,were respectively 87.74±3.61,97.19±1.70 and 1.11±0.04. Input performance of dual performance evaluation management was lower than that of subjective evaluation management method,and output performance and comprehensive performance of dual performance evaluation management were higher than these of subjective evaluation management method,and the differences of them between two methods were statistically significant (t=4.866,4.457,7.793,P<0.05). The average metrological pass rates of mechanics,thermodynamics,thermology,textiles and medical equipment of medical laboratory of using dual performance evaluation management were (97.99±1.14)％,(97.39±2.08)％,(97.43±1.87)％,(98.06±0.92)％ and (96.77±2.03)％,respectively. All of them were higher than these of using subjective evaluation management method,and the differences of them between two methods were statistically significant (t=4.431,3.232,3.324,4.928,3.352,P<0.05). The satisfaction rates of 56 operators of equipment,who adopted dual performance evaluation management,were respectively 98.21％,94.64％,96.43％,100.00％ and 98.21％ for the management system,metrological frequency,metrological items,metrological effect and service quality of metrological staffs of equipment,which were higher than these of subjective evaluation management method,and the differences of them between two methods were statistically significant (x2=7.240,5.660,6.296,6.128,12.735,P<0.05). Conclusion:The dual performance management model can control the input of metrological management of medical equipment,and enhance the output of metrological management of medical equipment,and promote the operation quality of medical equipment,and improve the level of clinical service of medical equipment.

OBJECTIVE To investigate the acute lung injury effects of pulmonary phospholipids and their phospholipase A2(PLA2)decomposition products-lysophospholipids and fatty acids-on mice.METHODS Mice were randomly assigned to the following groups:① solvent control(PBS)and PLA2;② solvent control and glycerol phospholipid groups:1,2-dioleoyl-sn-glycero-3-phosphoserine(DOPS),1,2-dipalmitoyl-sn-glycero-3-phosphoserine(DPPS),1,2-dioleoyl-sn-glycero-3-phosphoethanol-amine(DOPE),1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine(DPPE),1,2-dipalmitoyl-sn-glycero-3-phosphocholine(DPPC),and 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine(SOPC);③ solvent con-trol and fatty acid groups:palmitic acid(PA),oleic acid;④ solvent control and lysophospholipid groups:1-oleoyl-2-hydroxy-sn-glycero-3-phosphoserine(18∶1 LysoPS),1-stearoyl-sn-glycero-3-phosphoserine(18∶0 LysoPS),1-palmitoyl-sn-glycero-3-phosphoserine(16∶0 LysoPS),1-palmitoyl-sn-glycero-3-phos-phoethanolamine(16∶0 LysoPE),1-palmitoyl-sn-glycero-3-phosphocholine(16∶0 LysoPC);⑤ solvent control,PLA2,DPPC,PA,16∶0 LysoPC,16∶0 LysoPS,and 18∶1 LysoPS.Following anesthesia,mice were administered nebulized PBS in the solvent control group,2.1 ug·kg-1 PLA2 in PBS in the PLA2 group and 2.5 mg·kg-1 of the corresponding substance in PBS in other experimental groups.For group①,survival times were recorded and survival curves were plotted.At 1 h post-treatment,lung tissues from groups ①②③④ were collected,photographed to obtain white light images,and subjected to HE staining to assess histopathological changes and pathological scoring.At 2 h post-treatment,pulmonary blood flow in group ⑤ was assessed using laser speckle contrast imaging,arterial blood gas was analyzed with a blood gas analyzer,and lung function was evaluated using whole-body pleth-ysmography.At 6 hours post-treatment,blood cells from group ⑤ were analyzed using an automated hematology analyzer.RESULTS Compared with the solvent control group,severe pathological changes were observed in lung tissues of the PLA2 group,accompanied by extensive inflammatory infiltration and interstitial thickening,with all mice succumbing within 240 min.In mice treated with glyc-erol phospholipids,alveolar structures remained clear,alveolar walls were intact and continuous,and alveolar spaces were translucent,with only occasional minor inflammatory cell infiltration in the septa.No significant pathological alterations were detected in the fatty acid groups.Minor inflammatory cell infiltration was seen in the 16∶0 LysoPE and 16∶0 LysoPC groups.However,such pathological changes as patchy hemorrhage,alveolar interstitial edema,increased alveolar wall thickness,and elevated neutrophil counts were observed in the 18∶1 LysoPS,18∶0 LysoPS,and 16∶0 LysoPS groups.Pathological scores based on HE staining were significantly increased in the 16∶0 LysoPS and 18∶1 LysoPS groups com-pared with the solvent control.The percentage of the lung tissue injury area was also markedly higher in the 16∶0 LysoPS group.A significant decrease in the mean fluorescence intensity of blood flow was observed in the 16∶0 LysoPS group.Arterial partial pressure of oxygen(pO2)was significantly reduced in the PLA2 group,while arterial partial pressure of carbon dioxide(pCO2)was markedly elevated in the 16∶0 LysoPS and 18∶1 LysoPS groups.Lung function tests revealed that the 16∶0 LysoPS group exhibited significant increases in expiratory time,end-expiratory pressure,and enhanced pause,in contrast to significant decreases in tidal volume,expired volume,and minute volume.The 18∶1 LysoPS group also exhibited a significant decline in minute volume.No significant changes in inflammatory cell concentrations were detected in blood,with the exception of neutrophils in the 16∶0 LysoPS group,which showed a significant but physiologically normal increase.CONCLUSION Pulmonary phospholipids and their PLA2-derived fatty acid metabolites do not induce severe lung injury in mice while the lyso-phospholipid metabolites,particularly lysophosphatidylserine,are found to cause significant lung injury.