ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang （WDD） on mice with ischemic heart disease （IHD） presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group， WDD low-dose group （WDD-L）， WDD medium-dose group （WDD-M）， WDD high-dose group （WDD-H）， and atorvastatin calcium tablet group， with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91， 17.81， 35.62 g·kg^-1， and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg^-1， twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration， the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin （HE） staining. Serum N-terminal pro-B-type natriuretic peptide （pro-BNP） content was measured by enzyme-linked immunosorbent assay （ELISA）. Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL） were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group， model serum group， WDD-L drug-containing serum group， WDD-M drug-containing serum group， and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group， the model group showed a significantly increased cardiac index （P0.01）， significantly decreased fractional shortening （FS） （P0.01）， and significantly increased left ventricular end-diastolic internal diameter （LVDD） and left ventricular end-systolic internal diameter （LVDS） （P0.01）. Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated （P0.01）， and whole-blood viscosity （BV） at high， medium， and low shear rates was significantly increased （P0.01）. Compared with the model group， the WDD groups showed significantly reduced cardiac index （P0.05， P0.01）， significantly increased FS （P0.05， P0.01）， significantly decreased LVDD and LVDS （P0.01）， markedly improved cardiomyocyte morphology， significantly reduced inflammatory infiltration， significantly decreased serum pro-BNP levels （P0.01）， and significantly decreased BV at high， medium， and low shear rates （P0.01）， with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group， TC， TG， and LDL levels were significantly increased in the model group （P0.05， P0.01）， while HDL levels were significantly decreased （P0.05）. After WDD-H treatment， TC， TG， and LDL levels were significantly reduced and HDL levels were significantly increased in mice （P0.05， P0.01）. Compared with the sham-operation group， classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group （P0.01）， whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased （P0.01）. After WDD administration， all circulating monocyte subsets in blood and bone marrow were significantly alleviated （P0.05， P0.01）， with the WDD-M group showing the optimal effect. In vitro， compared with the blank group， CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group （P0.01）， and CD36 expression was significantly upregulated on RAW264.7 cells （P0.01）. Compared with the model serum group， all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation （P0.01）. WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines （P0.05， P0.01）， with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.

ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang （WDD） on mice with ischemic heart disease （IHD） presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group， WDD low-dose group （WDD-L）， WDD medium-dose group （WDD-M）， WDD high-dose group （WDD-H）， and atorvastatin calcium tablet group， with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91， 17.81， 35.62 g·kg^-1， and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg^-1， twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration， the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin （HE） staining. Serum N-terminal pro-B-type natriuretic peptide （pro-BNP） content was measured by enzyme-linked immunosorbent assay （ELISA）. Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL） were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group， model serum group， WDD-L drug-containing serum group， WDD-M drug-containing serum group， and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group， the model group showed a significantly increased cardiac index （P<0.01）， significantly decreased fractional shortening （FS） （P<0.01）， and significantly increased left ventricular end-diastolic internal diameter （LVDD） and left ventricular end-systolic internal diameter （LVDS） （P<0.01）. Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated （P<0.01）， and whole-blood viscosity （BV） at high， medium， and low shear rates was significantly increased （P<0.01）. Compared with the model group， the WDD groups showed significantly reduced cardiac index （P<0.05， P<0.01）， significantly increased FS （P<0.05， P<0.01）， significantly decreased LVDD and LVDS （P<0.01）， markedly improved cardiomyocyte morphology， significantly reduced inflammatory infiltration， significantly decreased serum pro-BNP levels （P<0.01）， and significantly decreased BV at high， medium， and low shear rates （P<0.01）， with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group， TC， TG， and LDL levels were significantly increased in the model group （P<0.05， P<0.01）， while HDL levels were significantly decreased （P<0.05）. After WDD-H treatment， TC， TG， and LDL levels were significantly reduced and HDL levels were significantly increased in mice （P<0.05， P<0.01）. Compared with the sham-operation group， classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group （P<0.01）， whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased （P<0.01）. After WDD administration， all circulating monocyte subsets in blood and bone marrow were significantly alleviated （P<0.05， P<0.01）， with the WDD-M group showing the optimal effect. In vitro， compared with the blank group， CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group （P<0.01）， and CD36 expression was significantly upregulated on RAW264.7 cells （P<0.01）. Compared with the model serum group， all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation （P<0.01）. WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines （P<0.05， P<0.01）， with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.

OBJECTIVE To study the mechanism of action of herb pair of Angelica sinensis-Poria cocos in intervening in allergic rhinitis. METHODS The core targets of herb pair of A. sinensis-P. cocos in intervening in allergic rhinitis were predicted through network pharmacology. Allergic rhinitis model of rats was established by intraperitoneal injection of aluminum hydroxide and ovalbumin mixture， and the rats were randomly divided into model group， loratadine group （positive control group， 0.9 mg/kg）， and low-， medium-， high-dose groups of herb pair of A. sinensis-P. cocos （3， 6 and 12 g/kg）， with 10 rats in each group. Another 10 healthy rats were used as the normal group. Each group of rats was intragastrically administered the corresponding liquid or normal saline once a day for 30 consecutive days. After the last administration， the behavioral scores of each group of rats were calculated， the levels of immunoglobulin E （IgE）， histamine， interleukin-4 （IL-4） in serum， and the protein expression levels of IL-6， tumor necrosis factor-α （TNF-α）， and prostaglandin-endoperoxide synthase 2 （PTGS2） in nasal mucosa tissue were detected. The pathological morphology changes of nasal mucosa tissue were observed. RESULTS Network pharmacology analysis revealed that IL-6， TNF and PTGS2 might play a key role in the intervention of allergic rhinitis by herb pair of A. sinensis-P. cocos， and the IL-17 and TNF signaling pathways might be the typical inflammatory signaling pathways intervened by herb pair of A. sinensis-P. cocos in allergic rhinitis. The results of animal experiments showed that compared with the model group， the behavioral score， the levels of IgE， histamine and IL-4， and the protein expressions of IL-6， TNF-α and PTGS2 in each administration group were decreased significantly （P＜0.05）， and there was a dose-dependent relationship with the herb pair of A. sinensis-P. cocos （P＜ 0.05）. CONCLUSIONS The herb pair of A. sinensis-P. cocos can effectively alleviate the symptoms of rats with allergic rhinitis， the mechanism of which may be related to the inhibition of the expressions of IL-6， TNF-α and PTGS2.

OBJECTIVE: To investigate the effects of using different filters in continuous renal replacement therapy (CRRT) on the mortality, inflammatory mediator level and hemodynamics in patients with sepsis-associated acute kidney injury (SA-AKI). METHODS: A prospective study was conducted. The patients with SA-AKI undergoing first CRRT admitted to the critical care medicine department of General Hospital of Ningxia Medical University from August 2022 to October 2023 were enrolled as the study objects, and they were divided into observation group and control group by random number table method. All patients received routine treatment including anti-infection, optimized volume management and organ function support. On this basis, the observation group was treated with oXiris filter for CRRT, while the control group was treated with ordinary filter for CRRT, and the first treatment time was ≥ 36 hours. General data of the two groups were collected and compared. At the same time, the inflammatory indicators [high-sensitivity C-reactive protein (hs-CRP), procalcitonin (PCT), interleukin-6 (IL-6)], sequential organ failure assessment (SOFA) score, mean arterial pressure (MAP), blood lactic acid (Lac), noradrenaline dosage and other related indicators were collected before CRRT treatment and 24 hours and 48 hours after treatment, and the 7-day and 28-day mortality of patients were recorded. RESULTS: Finally, 65 patients were enrolled, including 30 in the observation group and 35 in the control group. There were no significant differences in baseline data including age, gender, acute kidney injury (AKI) stage and infection source between the two groups. The 7-day mortality of observation group was significantly lower than that of control group [16.7% (5/30) vs. 42.9% (15/35), P < 0.05]. There was no significant difference in 28-day mortality between the observation group and the control group [36.7% (11/30) vs. 54.3% (19/35), P > 0.05]. There were no significant differences in inflammation indicators, SOFA score, MAP, Lac and norepinephrine dosage before treatment between the two groups. After 24-hour and 48-hour treatment, the hemodynamics of the two groups were stable compared with before treatment, the inflammatory indicators, SOFA score, Lac and norepinephrine dosage were reduced to varying degrees, and MAP was significantly increased. In the observation group, hs-CRP, PCT, IL-6, SOFA score, MAP, and norepinephrine dosage showed statistical significance at 24 hours after treatment as compared with before treatment [hs-CRP (mg/L): 125.0 (105.0, 171.2) vs. 280.5 (213.2, 313.8), PCT (μg/L): 51.0 (20.0, 62.8) vs. 71.0 (10.8, 100.0), IL-6 (ng/L): 1 762.2 (300.8, 4 327.5) vs. 4 447.5 (630.4, 5 000.0), SOFA score: 13.0 (12.0, 14.0) vs. 16.0 (15.0, 17.0), MAP (mmHg, 1 mmHg ≈ 0.133 kPa): 79.00±12.87 vs. 65.20±11.70, norepinephrine dosage (μg×kg^-1×min^-1): 0.82±0.33 vs. 1.63±0.51, all P < 0.05]. In the control group, PCT and MAP showed statistical significance after 48 hours of treatment as compared with before treatment. Compared with the control group, hs-CRP, SOFA score and norepinephrine dosage after 48 hours of treatment in the observation group were significantly decreased [hs-CRP (mg/L): 87.2 (74.2, 126.0) vs. 157.0 (88.0, 200.0), SOFA score: 11.0 (10.0, 12.0) vs. 12.0 (10.0, 14.0), norepinephrine dosage (μg×kg^-1×min^-1): 0.51±0.37 vs. 0.81±0.58, all P < 0.05], MAP was significantly increased (mmHg: 82.00±8.71 vs. 77.77±7.80, P < 0.05). CONCLUSION In the treatment of CRRT, oXiris filter can reduce the short-term mortality of SA-AKI patients, lower inflammatory mediators levels and improve hemodynamics, showing therapeutic advantages over conventional filters.
Humans ; Acute Kidney Injury/etiology* ; Sepsis/therapy* ; Prospective Studies ; Interleukin-6 ; Continuous Renal Replacement Therapy/methods* ; C-Reactive Protein ; Male ; Female ; Middle Aged ; Hemodynamics ; Procalcitonin ; Aged

OBJECTIVE: To investigate the predictive value of inflammatory indicator and serum cystatin C (Cys C) for the prognosis of patients with sepsis-associated acute kidney injury (SA-AKI). METHODS: A prospective observational study was conducted. Patients with SA-AKI admitted to the intensive care unit (ICU) of the General Hospital of Ningxia Medical University from January 2022 to December 2023 were selected as the study subjects. General patient data, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), inflammatory indicator, and serum Cys C levels were collected. The 28-day survival status of the patients was observed. A multivariate Logistic regression model was used to analyze the risk factors affecting the poor prognosis of SA-AKI patients. Receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive efficacy of each risk factor for the prognosis of SA-AKI patients. RESULTS: A total of 111 SA-AKI patients were included, with 65 patients (58.6%) in the survival group and 46 patients (41.4%) in the death group. The SOFA score, APACHE II score, interleukin-6 (IL-6), procalcitonin (PCT), hypersensitive C-reactive protein (hs-CRP), and serum Cys C levels in the death group were significantly higher than those in the survival group [SOFA score: 15.00 (14.00, 17.25) vs. 14.00 (11.00, 16.00), APACHE II score: 26.00 (23.75, 28.00) vs. 23.00 (18.50, 28.00), IL-6 (ng/L): 3 731.00±1 573.61 vs. 2 087.93±1 702.88, PCT (μg/L): 78.19±30.35 vs. 43.56±35.37, hs-CRP (mg/L): 266.50 (183.75, 326.75) vs. 210.00 (188.00, 273.00), serum Cys C (mg/L): 2.01±0.61 vs. 1.62±0.50, all P < 0.05]. Multivariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 1.273, 95% confidence interval (95%CI) was 1.012-1.600, P = 0.039], IL-6 (OR = 1.000, 95%CI was 1.000-1.001, P = 0.043), PCT (OR = 1.018, 95%CI was 1.002-1.035, P = 0.030), and Cys C (OR = 4.139, 95%CI was 1.727-9.919, P = 0.001) were independent risk factors affecting the 28-day prognosis of SA-AKI patients. ROC curve analysis showed that the area under the curve (AUC) of SOFA score, IL-6, PCT, and Cys C in predicting the 28-day prognosis of SA-AKI patients were 0.682 (95%CI was 0.582-0.782, P = 0.001), 0.753 (95%CI was 0.662-0.843, P < 0.001), 0.765 (95%CI was 0.677-0.854, P < 0.001), and 0.690 (95%CI was 0.583-0.798, P = 0.001), respectively. The combined predictive value of these four indicators for the prognosis of SA-AKI patients were superior to that of any single indicator, with an AUC of 0.847 (95%CI was 0.778-0.916, P < 0.001), a sensitivity of 95.7%, and a specificity of 56.9%. CONCLUSION The combination of SOFA score, IL-6, PCT, and Cys C provides a reliable predictive value for the prognosis of SA-AKI patients.
Humans ; Acute Kidney Injury/mortality* ; APACHE ; C-Reactive Protein ; Cystatin C/blood* ; Interleukin-6/blood* ; Logistic Models ; Predictive Value of Tests ; Procalcitonin/blood* ; Prognosis ; Prospective Studies ; Risk Factors ; ROC Curve ; Sepsis/mortality*

ObjectiveTo explore the protective effect and mechanism of Yangxin Dingji capsules on isoproterenol （ISO）-induced ventricular arrhythmia in SD rat cardiomyocytes based on the transforming growth factor-β activated kinase 1 （TAK1）-mitogen-activated protein kinase kinase 3 （MKK3）-p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodFifty male SPF-grade SD rats were randomly divided into a normal group， a model group， a propranolol group， a low-dose Chinese medicine group， and a high-dose Chinese medicine group. The ventricular arrhythmia model was constructed using the ISO "6+1" method. The propranolol group received propranolol at 0.015 g·kg^-1·d^-1. The Chinese medicine groups received Yangxin Dingji capsules at doses of 0.5、 2 g·kg^-1·d^-1， respectively. The normal and model groups were given an equal volume of 0.9% NaCl solution. Electrocardiogram （ECG） changes in SD rats were recorded using the BL-420F biological function experimental system. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the heart. Serum levels of cardiac troponin I （cTnI）， creatine kinase-MB （CK-MB）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and transforming growth factor-β₁ （TGF-β₁） were measured using enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of IL-1β and TNF-α was assessed using real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Reactive oxygen species （ROS） expression was detected using immunofluorescence. Protein expression levels of TAK1， phosphorylated TAK1 （p-TAK1）， MKK3， phosphorylated MKK3 （p-MKK3）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， IL-1β， and TNF-α were measured using Western blot or immunohistochemistry. ResultCompared with normal group， the model group showed significant ventricular arrhythmia in ECG， with an increased arrhythmia score （P<0.01）. Pathological damage to myocardial tissue was evident， and serum levels of cTnI， CK-MB， IL-1β， TNF-α， and TGF-β₁ were elevated （P<0.01）. The mRNA and protein expression of IL-1β and TNF-α in myocardial tissue was also increased （P<0.01）. ROS level and protein expression of p-TAK1， p-MKK3， p-p38 MAPK， and p-NF-κB were elevated in myocardial tissue （P<0.01）. In the propranolol and Chinese medicine groups， the incidence of sustained ventricular tachycardia （SVT） and arrhythmia scores were significantly reduced compared to model group （P<0.05， P<0.01）. Pathological damage to cardiomyocytes was alleviated， and levels of myocardial injury markers and inflammatory factors in serum and myocardial tissue were decreased. The ROS level in myocardial tissue was also reduced （P<0.01）， with a noticeable reduction in related molecules in the p38 MAPK pathway （P<0.05， P<0.01）. ConclusionThe expression of p38 MAPK pathway molecules was up-regulated in myocardial tissue of ISO-induced ventricular arrhythmia rats. Yangxin Dingji capsules may inhibit cardiac inflammation damage by regulating the expression of related molecules in the p38 MAPK pathway， thereby exerting a protective effect on myocardial cells， with TAK1 being a potential target.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

AIM:To investigate the regulatory role of retinoid X receptor(RXR)in oxidative stress response of rat type Ⅱ alveolar epithelial cells(AECII)induced by hypoxia/reoxygenation(HR).METHODS:The AECII were di-vided into control(C)group,HR group,HR+solvent dimethyl sulfoxide(DMSO)group(HD group),HR+RXR agonist 9-cis-retinoic acid(9-RA)group(RA group),and HR+RXR antagonist HX531 group(HX group).Cell Counting Kit-8(CCK-8)method was used to measure the cell viability.Immunofluorescence staining was used to detect the expression of surfactant protein A(SP-A)and RXRα in AECII.Kits were detected to the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in cells.Transmission electron microscopy was used to observe the ultrastructural changes of the cells.Western blot was used to detect the protein level of nuclear factor E2-related factor 2(Nrf2).RT-PCR was used to detect the expression level of Nrf2 mRNA.RESULTS:Compared with C group,the cell viability and SOD activity in HR,HD,RA and HX groups were decreased significantly(P<0.05),the MDA content were increased significantly(P<0.05),the Nrf2 mRNA and protein expression levels were decreased significantly(P<0.05 or P<0.01),and the immuno-fluorescence expression of RXRα was significantly increased(P<0.01).Compared with HR and HX groups,the cells in RA group showed significantly increased cell viability(P<0.05),increased SOD activity(P<0.05),decreased MDA con-tent(P<0.05),increased Nrf2 mRNA and protein expression levels(P<0.01),and significantly increased immunofluo-rescence expression of RXRα(P<0.01).CONCLUSION:Hypoxia/reoxygenation can aggravate the oxidative stress re-sponse of rat AECII,and RXR agonist intervention can alleviate HR-induced rat AECII injury by inhibiting oxidative stress.

Objective:To investigates the role and mechanism of ferroptosis in combined burn-blast injury with acute lung injury in rats.Methods:This study was an experimental study. Twenty-four 8-week-old male Sprague-Dawley rats were divided into control group and experimental group by random number table method, each containing 12 animals. The rats in experimental group were anesthetized and subjected to explosion treatment to create the model of combined burn-blast injury with acute lung injury, whereas the rats in control group underwent sham injury. At 24 hours post injury, the pathological morphology of lung tissue was observed by hematoxylin-eosin staining and immunohistochemical staining. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in the supernatant of bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay. The arterial partial pressure of oxygen (PaO 2) and arterial partial pressure of carbon dioxide (PaCO 2) of abdominal aortic blood were measured by automatic animal blood gas analyzer. The lung tissue was weighed and the wet-dry weight ratio was calculated. The total protein concentration in BALF was measured by bicinchoninic acid assay. Lung injury was scored based on hematoxylin-eosin staining. The levels of oxidative stress factors, such as reactive oxygen species, malondialdehyde, superoxide dismutase (SOD), glutathione, and ferrous ion in lung tissue homogenate of rats were detected by related kits. The expression levels of ferroptosis-related molecule glutathione peroxidase 4 (GPX4), lipid peroxidation-related molecule 4-hydroxynonenal (4-HNE), and oxidative DNA damage-related molecule 8-hydroxydeoxyguanosine (8-OHdG) in lung tissue were detected by immunofluorescence and immunohistochemistry methods. Mitochondrial morphology in lung tissue cells was observed under transmission electron microscopy. The sample number was all 6. Results:At 24 hours post injury, the lung tissue structure of rats in control group was clear and complete, and the alveolar wall was normal; in experimental group, the lung tissue edema of rats was obvious, the alveolar wall became thicker, and the structure was not clear. At 24 hours post injury, compared with those in control group, the levels of TNF-α, IL-1β, and IL-6 in BALF supernatant of rats in experimental group were significantly increased (with t values of 3.96, 9.84, and 10.60, respectively, P<0.05); the wet-dry weight ratio of lung tissue, lung injury score, and total protein concentration in BALF of rats in experimental group were significantly increased (with t values of 6.91, 6.64, and 10.04, respectively, P<0.05), PaO 2 of abdominal aortic blood decreased significantly ( t=8.85, P<0.05) while PaCO 2 did not change significantly ( P>0.05); the levels of SOD and glutathione in the lung tissue homogenate of rats in experimental group were significantly decreased (with t values of 4.36 and 8.56, respectively, P<0.05), while the levels of reactive oxygen species, malondialdehyde, and ferrous ion were significantly increased (with t values of 11.55, 9.78, and 14.77, respectively, P<0.05). At 24 hours post injury, immunofluorescence staining and immunohistochemical staining showed that the expression levels of GPX4 in lung tissue of rats in experimental group were 0.245±0.024 and 0.786±0.240, respectively, which were significantly lower than 1.000±0.305 and 1.000±0.200 in control group (with t values of 6.05 and 2.60, respectively, P<0.05); the expression levels of 4-HNE in lung tissue of rats in experimental group were 5.93±1.05 and 2.21±0.23, respectively, which were significantly higher than 1.00±0.29 and 1.00±0.23 in control group (with t values of 11.13 and 9.16, respectively, P<0.05); the expression levels of 8-OHdG in lung tissue of rats in experimental group were 2.08±0.40 and 1.61±0.29, respectively, which were significantly higher than 1.00±0.40 and 1.00±0.26 in control group (with t values of 4.72 and 3.87, respectively, P<0.05). At 24 hours post injury, compared with that in control group, the density of mitochondrial double-layer membrane in the lung tissue cells of rats in experimental group increased, the outer membrane ruptured, and the crista decreased. Conclusions:In rats with combined burn-blast injury with acute lung injury, there is oxidative DNA damage in lung tissue cells, the imbalance of antioxidant system in lung tissue, and a decrease in the expression of GPX4, the key molecule against ferroptosis, suggesting that ferroptosis is involved in the pathophysiological process of this disease.

Objective:To develop a predictive model for the intervention efficacy of lower extremity atherosclerotic occlusive disease (LEASO) and evaluate its performance to predict the outcomes of intervention therapy for patients with lower extremity atherosclerotic occlusive disease.Methods:This study retrospectively analyzed data from 238 patients with lower extremity atherosclerotic occlusive disease (LEASO), including 188 males and 50 females, aged between 35 and 88 years with a mean age of 68 years. These patients were randomly divided in a 7∶3 ratio into a training set ( n=166) and a testing set ( n=72) based on adverse outcomes, both training and test sets were divided into MALEs and non-MALEs groups. The training set had 67 MALEs and 99 non-MALEs, while the test set had 26 MALEs and 46 non-MALEs. Important variables related to outcome events were selected using LASSO regression in the training set and incorporated into a multifactorial logistic regression model to construct a predictive model. The model was visualized using forest plots and its performance was evaluated using data from both the training and testing sets. Results:Through LASSO regression, SIIRI(Systemic immune inflammatory response index, SIIRI), Rutherford >4, IP(Infrapopliteal, IP)>1, and P(Pedal, P)≥1 were selected as predictive indicators for the model. The area under the curve, sensitivity, and specificity of the model in the training set and testing set were 0.813, 80.6%, 72.7%, and 0.764, 65.4%, 80.4%. The calibration curve was consistent with expectations. The decision curves of the model had the highest accuracy, net benefit rate for clinical application of the model when the threshold probabilities of the training set and test set were in the range of 0~0.79 and 0~0.66.Conclusions:The predictive model built using preoperative Rutherford classification, IP classification, P classification, and SIIRI can identify high-risk individuals for early detection of MALEs and provide targeted intensified treatment. This model has practical significance in improving the prognosis of such patients and can be applied in clinical practice.