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 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 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 evaluate the role of distortion product otoacoustic emissions (DPOAE) testing in evaluating early hearing loss among noise-exposed workers. Methods A total of 174 noise-exposed workers in a metal shipbuilding enterprise were selected as the research subjects by the convenience sampling method. Pure tone audiometry (PTA), DPOAE and the level of noise exposure were conducted on the workers. The rank correlation analysis was used to analyze the correlation between DPOAE amplitude and PTA threshold. The multilevel model was used to analyze the effects of gender, age, noise exposure intensity, cumulative noise exposure (CNE), hearing loss classification and PTA threshold on DPOAE results. Results At the frequencies of 0.50, 1.00, 2.00, 3.00, 4.00, 6.00 and 8.00 kHz, the DPOAE amplitude was negatively correlated with the PTA threshold (rank correlation coefficients were -0.12, -0.48, -0.47, -0.18, -0.23, -0.44, -0.19, respectively, all P<0.01). At the most frequencies, DPOAE amplitude was negatively correlated with age and CNE (all P<0.05). The results of multilevel model analysis showed that there were significant differences in DPOAE amplitudes at certain frequencies across gender, age, noise intensity, CNE, and hearing loss classification (all P<0.05). Significant differences in DPOAE responses were found among different CNE and hearing loss groups (all P<0.01). Conclusion DPOAE testing can objectively reflect the hearing status of noise-exposed workers and could be considered for inclusion in routine hearing monitoring to facilitate early detection of noise-induced hearing loss.

Objective:To evaluate the clinical value of peripheral blood monocyte subset analysis in the diagnosis and treatment of chronic myelomonocytic leukemia (CMML) .Method:We retrospectively enrolled 51 patients newly diagnosed with CMML at Guangdong Provincial People's Hospital between June 1, 2020, and December 31, 2024, according to the WHO 2022 diagnostic criteria. Twenty-three patients with other myeloid neoplasms (excluding CMML) and peripheral monocytosis (absolute count ≥0.5×10 9/L and percentage ≥10%) were included as the control group. All patients underwent bone marrow aspiration for examinations including bone marrow smears, biopsies, cytogenetics, and gene mutation analysis to establish a definitive diagnosis. Concurrently, flow cytometry was used to determine the proportions of peripheral blood monocyte subsets: classical (MO1, CD14 +CD16 -) , intermediate (MO2, CD14 +CD16 +) , and non-classical (MO3, CD14 lowCD16 +) . Differences between the groups were compared, and diagnostic efficacy was evaluated using receiver operating characteristic (ROC) curves. Result:Among the 51 CMML patients, the proportion of the peripheral blood MO1 subset was significantly higher than that in patients with other myeloid neoplasms ( P=0.027) , whereas there were no significant differences in the MO2 and MO3 subsets (all P>0.05) . Further analysis revealed that 43 (84.31%) of the CMML patients met the WHO diagnostic threshold for the MO1 subset (≥94%) , while the remaining 8 patients did not; 46 patients (90.20%) had MO3 subset proportions below the threshold proposed by Hudson (≤1.13%) , while the remaining 5 patients were above this threshold. In-depth analysis showed that among the 8 patients who did not meet the WHO criteria, 7 were experiencing inflammation. Similarly, all 5 patients who did not meet the Hudson criteria were in an inflammatory state. Subsequent ROC curve analysis of this cohort identified a cut-off value for the MO1 subset of 97.55% [Area Under the Curve (AUC) =0.661, P=0.027], which aligns with the WHO criteria. Conclusion:Peripheral blood monocyte subset analysis, particularly MO1 subset analysis, can effectively assist in CMML diagnosis, but exclusion of inflammatory conditions is required.

Objective:To evaluate the clinical value of peripheral blood monocyte subset analysis in the diagnosis and treatment of chronic myelomonocytic leukemia (CMML) .Method:We retrospectively enrolled 51 patients newly diagnosed with CMML at Guangdong Provincial People's Hospital between June 1, 2020, and December 31, 2024, according to the WHO 2022 diagnostic criteria. Twenty-three patients with other myeloid neoplasms (excluding CMML) and peripheral monocytosis (absolute count ≥0.5×10 9/L and percentage ≥10%) were included as the control group. All patients underwent bone marrow aspiration for examinations including bone marrow smears, biopsies, cytogenetics, and gene mutation analysis to establish a definitive diagnosis. Concurrently, flow cytometry was used to determine the proportions of peripheral blood monocyte subsets: classical (MO1, CD14 +CD16 -) , intermediate (MO2, CD14 +CD16 +) , and non-classical (MO3, CD14 lowCD16 +) . Differences between the groups were compared, and diagnostic efficacy was evaluated using receiver operating characteristic (ROC) curves. Result:Among the 51 CMML patients, the proportion of the peripheral blood MO1 subset was significantly higher than that in patients with other myeloid neoplasms ( P=0.027) , whereas there were no significant differences in the MO2 and MO3 subsets (all P>0.05) . Further analysis revealed that 43 (84.31%) of the CMML patients met the WHO diagnostic threshold for the MO1 subset (≥94%) , while the remaining 8 patients did not; 46 patients (90.20%) had MO3 subset proportions below the threshold proposed by Hudson (≤1.13%) , while the remaining 5 patients were above this threshold. In-depth analysis showed that among the 8 patients who did not meet the WHO criteria, 7 were experiencing inflammation. Similarly, all 5 patients who did not meet the Hudson criteria were in an inflammatory state. Subsequent ROC curve analysis of this cohort identified a cut-off value for the MO1 subset of 97.55% [Area Under the Curve (AUC) =0.661, P=0.027], which aligns with the WHO criteria. Conclusion:Peripheral blood monocyte subset analysis, particularly MO1 subset analysis, can effectively assist in CMML diagnosis, but exclusion of inflammatory conditions is required.

Objective To understand the characteristics of occupational noise hazards in key industries in Huizhou City. Methods A total of 247 enterprises from 13 key industries in Huizhou City were selected as the research subjects using the stratified judgment sampling method. The worksite survey of occupational health and workplace noise intensity and spectrum monitoring were conducted at key work sites using "questionnaires and on-site inspections" method. Results The rate of noise intensity exceeding national standards was 53.4% (132/247). The median, 25th and 75th percentile of noise pressure levels in workplaces and worksites were 85.1 (81.2, 91.2)and 82.5 (78.8, 86.3) dB(A), respectively. The high-noise workplaces accounted for 50.0% (479/958). The rate of noise intensity exceeding national standard at work sites was 32.9% (303/921). The sound pressure level of noise at work sites was positively correlated with sound pressure level of noise sources (Spearman correlation coefficient=0.73, P<0.01). The top three high-risk work sites for exceeding national noise standards were grinding, frame nailing, and material cutting, with exceedance rates of 84.6%, 81.3%, and 62.8%, respectively. The frequency characteristics of the top ten high-risk work sites were mainly high-frequency noise. There were significant differences in noise spectrum characteristics among different workpiece materials used in similar types of work sites (all P<0.05), though high-frequency noise remained dominant. Conclusion Noise hazards in workplaces of key industries in Huizhou City are relatively severe. Continuous attention should be given to key work sites with high over-standard rate, such as grinding, frame nailing, and material cutting, and noise control strategies should be developed based on frequency spectrum characteristics.

Objective To explore the effects of fecal microbiota transplantation on blood uric acid(UA)metabolism,adverse reactions,and gout control in patients with refractory gout.Methods A total of 102 patients with refractory gout in the First Affiliated Hospital of Medical College of Shantou University from June 2020 to June 2023 were randomly divided into two groups,with 51 cases in each group.Control group received benzbromarone and febuxostat treatment,while the observation group re-ceived fecal microbiota transplantation.The gout control status and occurrence of adverse reactions were observed in both groups;intestinal flora,UA,levels of C-reactive protein(CRP),interleukin-18(IL-18),interleukin-6(IL-6),and scores of joint pain,swelling and limited mobility were compared between the two groups before and after treatment.Results Five patients in each group were lost to follow-up.The total gout control rate in the observation group was 89.13％,which was significantly higher than 69.57％ in the control group(P＜0.05).At 4 and 12 weeks after treatment,the levels of Escherichia coli,UA,CRP,IL-18 and IL-6 as well as the scores of joint swelling,pain and limited mobility in the observation group were significantly lower than those in the control group,while the lev-els of Bifidobacterium,Lactobacillus and Bifidobacterium to Escherichia coli(B/E)ratio were signifi-cantly higher than those in the control group(P＜0.01).The total incidence of adverse reactions was 10.87％ in the observation group and 6.52％ in the control group,with no significant between-group difference(P＞0.05).Conclusion Fecal microbiota transplantation has a definite therapeutic effect for patients with refractory gout,which can significantly reduce UA level and control clinical symptoms,and its mechanism may be related to the correction of intestinal flora imbalance.

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.