OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

To investigate body composition and associated factors in adolescents undergoing long-term regular sports training.

The incidence rate of thyroid cancer has been rising in recent years. How to accurately distinguish malignant and benign thyroid nodules before surgery has become an important research direction. Ultrasound, as a non-invasive and fast examination method, has been widely used in clinical practice. Some typical ultrasound features, such as calcification, unclear boundaries, multiple lesions, low echo, and aspect ratio>1, can indicate the occurrence of thyroid cancer before surgery. Further analysis of these ultrasound features is still a focus of current research. This article will review the expression and distribution of calcification, a typical ultrasound feature, in benign and malignant thyroid nodules, in order to provide a basis for predicting the malignancy of thyroid nodules based on the characteristics of calcification under preoperative ultrasound.

Objective:To assess the predictive value of acute liver failure (ALF) for sepsis-free survival (SFS) in burn patients and to identify associated risk factors.Methods:A retrospective cohort study was conducted on burn patients meeting inclusion criteria from the 2014 Kunshan aluminum dust explosion disaster (August 2, 2014 - April 13, 2015). Eligible patients were stratified into ALF and non-ALF groups based on the development of ALF. Demographic characteristics, total burn surface area, organ dysfunction, time to sepsis onset, and clinical outcomes were collected and compared between groups. Kaplan-Meier survival analysis and multivariate Cox regression were performed to assess the impact of ALF on SFS. A nomogram model was constructed for individualized risk prediction.Results:Among 185 enrolled patients (ALF group:21, non-ALF group:164), ALF incidence was 11.35%. The ALF group demonstrated higher mortality (85.71% vs. 34.15%, P<0.001) and SFS failure rates (100.00% vs. 61.59%, P<0.001) compared to non-ALF patients. Multivariate Cox analysis identified ALF as an independent sepsis predictor ( HR=1.68, 95% CI: 1.00-2.80, P<0.05). Time-dependent ROC analysis showed AUCs of 0.626, 0.714, 0.703, and 0.706 for SFS prediction at 2, 4, 8, and 12 weeks respectively. The nomogram model demonstrated that ALF combined with other parameters effectively predicted sepsis risk within 2-12 weeks post-injury. ALF development showed significant associations with concurrent organ dysfunction including acute kidney injury, acute heart failure, and acute respiratory distress syndrome (all P<0.001). A higher proportion of ALF patients received hemodialysis ( P<0.001) and pre-hospital central venous catheterization ( P=0.017). Conclusions:ALF independently predicts SFS failure and correlates strongly with poor prognosis in burn patients. Early ALF recognition and targeted interventions may facilitate sepsis risk stratification and precision prevention strategies.

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 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 establish an ultrasound radiomics model by integrating clinical, pathological, and conventional ultrasound features with radiomics characteristics, and to explore its clinical value in predicting endocrine resistance in hormone receptor(HR)-positive breast cancer.Methods:A retrospective analysis was performed on 478 patients with HR-positive breast cancer from January 2017 to December 2021 in the Second Affiliated Hospital of Harbin Medical University, of which 430 were resistant and 48 were sensitive. The clinical, pathological and immunohistochemical data and ultrasound images were collected.Firstly, the propensity score was used to process and match the data. Secondly, Logistic regression was used to screen clinical, pathological, and conventional ultrasound features associated with endocrine resistance. Then, PyRadiomics was used to extract the radiomic features of grayscale ultrasound images, and a series of methods such as Lasso regression were used to screen the radiomic features related to endocrine resistance. Seven machine learning methods such as random forest were used to build a radiomics model. Finally, clinical, pathological and ultrasound features were added to establish a clinical pathological model, a clinical pathological ultrasound model, a clinical pathological radiomics model and a combined model of the four features, and the model effectiveness was evaluated.Results:①Propensity score matching: 96 patients were matched, including 48 patients in the drug-resistant group and 48 patients in the sensitive group. ②Screening clinical pathological conventional ultrasound features related to endocrine resistance: lymph node metastasis, tumor diameter, posterior echo attenuation, and growth orientation were independent predictors of endocrine resistance (all P<0.05). ③Screening radiomics features related to endocrine resistance: 18 features such as Dependence Entropy. ④Establishing radiomics model: the machine learning model of random forest method (AUC=0.80) performed best. ⑤Radiomics model integrating clinical, pathological and conventional ultrasound features: the AUC of the clinical pathological model was 0.70, the AUC of the clinical pathological ultrasound model was 0.78, the AUC of the clinical pathological radiomics model was 0.82, and the AUC of the combined model was 0.86. Conclusions:The radiomics model established by the random forest method performs best in predicting endocrine resistance in HR-positive breast cancer. The model that integrates multiple features performs best in assessing endocrine resistance.which is expected to provide an objective basis for clinicians to predict endocrine resistance in HR-positive breast cancer.