OBJECTIVES: Sepsis-associated acute lung injury (S-ALI) is one of the major causes of death in intensive care unit (ICU) patients, yet its mechanisms remain incompletely understood and effective therapies are lacking. Lytic cell death of macrophages is a key driver of the inflammatory cascade in S-ALI. PANoptosis, a newly recognized form of lytic cell death characterized by PANoptosome assembly and activation, involves plasma membrane rupture (PMR) mediated by ninjurin-1 (NINJ1), a recently identified pore-forming protein. Itaconic acid is known for its anti-inflammatory effects, but its role in macrophage PANoptosis during S-ALI is unclear. This study aims to investigate the protective effect of itaconic acid on macrophage PANoptosis in S-ALI to provide new therapeutic insights. METHODS: Male specific-pathogen-free C57BL/6J mice (6-8 weeks, 18-20 g) received intraperitoneal lipopolysaccharide (LPS) to establish a classical S-ALI model. Western blotting was used to assess PANoptosome-related proteins and enzymes involved in the itaconic acid metabolic pathway, while real-time reverse transcription polymerase chain reaction and metabolomics quantified itaconic acid levels. Primary peritoneal macrophages (PMs) were pretreated with the itaconate derivative 4-octyl itaconate (4-OI) and then exposed to tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ) to induce PANoptosis. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Western blotting was employed to quantify enzymes of the itaconate-metabolic pathway in PANoptotic macrophages, to evaluate the impact of 4-OI on PANoptosome-associated proteins, and to determine NINJ1 abundance in lung tissues from S-ALI mice and in PANoptotic macrophages. Fluorescent dye FM_4-64 was used to visualize 4-OI-mediated changes in PMR, whereas immunofluorescence staining mapped the effect of 4-OI on both the expression level and membrane localization of NINJ1 in PANoptotic macrophages. The effect of 4-OI on lactate dehydrogenase (LDH) release in culture supernatants and peripheal blood serum was assessed using a LDH assay kit, and non-denataring polyacylamide gel electrophoresis was used to assess the expression of NINJ1 in S-ALI mouse lung tissues and the impact of 4-OI on the expression of PANoptosis-associated NINJ1 multimeric reflected protein in macropahges. RESULTS: In S-ALI mouse lungs, PANoptosome components [NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Caspase-1, Z-DNA binding protein (ZBP1), and Caspase-3] and phosphorylated mixed lineage kinase domain-like protein (MLKL) S345 were significantly upregulated (all P<0.05), while metabolomics showed compensatory increases in itaconic acid and its key enzymes [aconitate decarboxylase 1 (ACOD1)/immunoresponsive gene 1 (IRG1)]. In macrophages, 4-OI obviously suppressed PANoptosome protein expression, reduced LDH release, restored plasma membrane integrity, and inhibited NINJ1 expression and oligomerization at the membrane (P<0.05). CONCLUSIONS Itaconic acid may alleviate macrophage PANoptosis in S-ALI by inhibiting NINJ1-mediated plasma membrane rupture. Targeting NINJ1 or enhancing itaconate pathways may offer a novel therapeutic strategy for S-ALI.
Animals ; Acute Lung Injury/pathology* ; Succinates/pharmacology* ; Sepsis/complications* ; Mice, Inbred C57BL ; Male ; Mice ; Macrophages/pathology* ; Cell Membrane/metabolism* ; Lipopolysaccharides ; Hydro-Lyases

Objective: To explore the intervention effect of aerobic step exercise on sleep quality of female college students, so as to provide a new perspective to improve the sleep quality of female college students. Methods: In the 2020 fall semester, a total of 41 female college students with mild or more severe sleep disorders were selected from Beijing Normal University through a questionnaire and were randomly divided into experimental group ( n =29) and control group ( n =12). The experimental group received 55 minutes/time step aerobic exercise intervention for 8 weeks, three times a week, while the control group received no exercise intervention from October to December. The two groups maintained the original learning and living habits, without additional physical activity. The Pittsburgh Sleep Quality Index Scale and portable sleep monitor were used to assess the subjects sleep quality from both subjective and objective aspects. Changes in energy metabolism were observed by triaxial accelerometer and standing body composition analyzer. Results: After exercise intervention, subjective sleep quality factor (1.24±0.43, 0.86±0.58), sleep efficiency factor (0.66±0.67, 0.07±0.25), sleep disorder factor (1.24± 0.51 , 1.03±0.18), daytime dysfunction factor (1.90±0.86, 1.48± 0.82 ) and PSQI score (7.21±1.85, 5.66±2.09) significantly improved ( t=3.64, 4.63, 2.27, 2.36, 3.29, P <0.05). The ratio of sleep to wakefulness decreased (25.54±7.86, 20.85± 5.13), the ratio of deep sleep (31.79±12.20, 38.32±10.19) and sleep efficiency (73.99±7.91, 78.68±5.12) increased significantly ( t=-2.12, -2.39, -2.21, P <0.05). Lean body mass [(38.55±2.95, 39.07±2.94)g] and basal metabolic rate [(1 257.45±41.14, 1 262.66 ±42.22)kcal] of the experimental group significantly increased after the intervention of medium high intensity aerobic pedal exercise ( F=5.95, 3.49, P <0.05). Total energy expenditure was positively correlated with subjective sleep quality and sleep efficiency ( r=-0.26, -0.44, P <0.05). Conclusions The 8 week aerobic step exercise intervention can increase the daytime energy consumption and basic metabolism of female college students. Improve the sleep depth and efficiency of female college students, reduce sleep disorders, and then effectively improve sleep quality.

To provide new ideas for clinical diagnosis and treatment of coronavirus disease 2019 (COVID-19), this study explore the expression level and prognostic value of platelet parameters in mild, moderate and severe COVID-19. This is a retrospective analysis. From January to May 2020, a total of 69 patients who were diagnosed with COVID-19 in the Third Central Hospital and the Jinnan Hospital (both situated in Tianjin) were enrolled in the disease group. According to the severity, these patients were divided into mild group (15 cases), moderate group (46 cases), and severe group (8 cases). In the same period, 70 non-infected patients were enrolled in control group. The level of white blood cell count (WBC), absolute neutrophil count (NEU#), absolute lymphocyte count (LY#), neutrophil-lymphocyte ratio (NLR), red blood cell count (RBC), hemoglobin (Hb), platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large contrast ratio (P-LCR) before and after treatment were analyzed. Binary logistic regression analysis is used to establish a mathematical model of the relationship between these indexes and the outcome of severe COVID-19 patients. The receiver operating characteristic(ROC) curve is used to further explore the prognosis value of MPV, P-LCR, NLR separately and jointly in COVID-19 patients. Compare to the control group, WBC and NE# increase ( Z=-5.63, P<0.01; Z=-9.19, P<0.01) and LY# decrease ( Z=-9.34, P<0.01) in the severe group; NLR increase with the aggravation of the disease, there is significant difference between groups ( Z=17.61, P<0.01); PLT, PDW, MPV and P-LCR decrease with the aggravation of the disease, there is significant difference between groups ( Z=9.47, P<0.01; Z=11.41, P<0.01; Z =16.76, P<0.01; Z=13.97, P<0.01). Binary logistic regression analysis shows MPV, P-LCR and NLR have predictive value for severe COVID-19 patients. There is a negative correlation between MPV, P-LCR and severe COVID-19 patients ( OR=1.004, P=0.034; OR=1.097, P=0.046). There is a positive correlation between NLR and severe COVID-19 patients ( OR=1.052, P=0.016). MPV and P-LCR of patients with good prognosis after treatment were significantly higher than those before treatment ( Z=-6.47, P<0.01; Z=-5.36, P<0.01). NLR was significantly lower than that before treatment ( Z=-8.13, P<0.01). MPV and P-LCR in poor prognosis group were significantly lower than those before treatment ( Z=-9.46, P<0.01; Z=-6.81, P<0.01). NLR was significantly higher than that before treatment ( Z=-3.24, P<0.01). There were significant differences between good and poor prognosis groups before and after treatment in MPV, P-LCR and NLR ( P<0.01). Combination of these three indexes, ROC shows the AUC is 0.931, the sensitivity is 91.5%, the specificity is 94.1%, the positive predictive value is 88.9%, and the negative predictive value is 87.4%, which is better than any of these indexes separately. Changes in these parameters are closely related to clinical stage of COVID-19 patients. MPV, P-LCR and NLR are of great value in the prediction and prognosis of severe COVID-19 patients.

To provide new ideas for clinical diagnosis and treatment of coronavirus disease 2019 (COVID-19), this study explore the expression level and prognostic value of platelet parameters in mild, moderate and severe COVID-19. This is a retrospective analysis. From January to May 2020, a total of 69 patients who were diagnosed with COVID-19 in the Third Central Hospital and the Jinnan Hospital (both situated in Tianjin) were enrolled in the disease group. According to the severity, these patients were divided into mild group (15 cases), moderate group (46 cases), and severe group (8 cases). In the same period, 70 non-infected patients were enrolled in control group. The level of white blood cell count (WBC), absolute neutrophil count (NEU#), absolute lymphocyte count (LY#), neutrophil-lymphocyte ratio (NLR), red blood cell count (RBC), hemoglobin (Hb), platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large contrast ratio (P-LCR) before and after treatment were analyzed. Binary logistic regression analysis is used to establish a mathematical model of the relationship between these indexes and the outcome of severe COVID-19 patients. The receiver operating characteristic(ROC) curve is used to further explore the prognosis value of MPV, P-LCR, NLR separately and jointly in COVID-19 patients. Compare to the control group, WBC and NE# increase ( Z=-5.63, P<0.01; Z=-9.19, P<0.01) and LY# decrease ( Z=-9.34, P<0.01) in the severe group; NLR increase with the aggravation of the disease, there is significant difference between groups ( Z=17.61, P<0.01); PLT, PDW, MPV and P-LCR decrease with the aggravation of the disease, there is significant difference between groups ( Z=9.47, P<0.01; Z=11.41, P<0.01; Z =16.76, P<0.01; Z=13.97, P<0.01). Binary logistic regression analysis shows MPV, P-LCR and NLR have predictive value for severe COVID-19 patients. There is a negative correlation between MPV, P-LCR and severe COVID-19 patients ( OR=1.004, P=0.034; OR=1.097, P=0.046). There is a positive correlation between NLR and severe COVID-19 patients ( OR=1.052, P=0.016). MPV and P-LCR of patients with good prognosis after treatment were significantly higher than those before treatment ( Z=-6.47, P<0.01; Z=-5.36, P<0.01). NLR was significantly lower than that before treatment ( Z=-8.13, P<0.01). MPV and P-LCR in poor prognosis group were significantly lower than those before treatment ( Z=-9.46, P<0.01; Z=-6.81, P<0.01). NLR was significantly higher than that before treatment ( Z=-3.24, P<0.01). There were significant differences between good and poor prognosis groups before and after treatment in MPV, P-LCR and NLR ( P<0.01). Combination of these three indexes, ROC shows the AUC is 0.931, the sensitivity is 91.5%, the specificity is 94.1%, the positive predictive value is 88.9%, and the negative predictive value is 87.4%, which is better than any of these indexes separately. Changes in these parameters are closely related to clinical stage of COVID-19 patients. MPV, P-LCR and NLR are of great value in the prediction and prognosis of severe COVID-19 patients.

Objective To discuss the efficacy of Compound Anisodine Injection combined with Iodized Lecithin Tablets in treatment of central serous chorioretinopathy.Methods Totally 60 patients with CSC were selected,and divided into two groups randomly.The patients in control group (29 cases) were given Iodized Lecithin Tablets.The patients in observation group (31 cases) were given Iodized Lecithin Tablets and Compound Anisodine Injection.The efficacy of Compound Anisodine Injection combined with Iodized Lecithin Tablets in treatment of central serous chorioretinopathy was evaluated by efficacy,visual acuity,light sensitivity,and adverse reaction during treatment.Results After treatment,the effective rates of observation and control groups were 93.5％ and 79.3％,and the observation group was significantly higher than control group (P ＜ 0.05).There were no statistical significance on visual acuity between two groups.After treatment,rhe visual acuity of two groups was increased and the visual acuity in the observation group was better (P ＜ 0.05).Before treatment,there were no statistical significance on light sensitivity between two groups.After 2 and 4 weeks treatment,the light sensitivity of two groups were increased and the light sensitivity in the observation group was higher (P ＜ 0.05).During treatment,there was no statistical significance on adverse reaction between two groups.Conclusion Compound Anisodine Injection combined with Iodized Lecithin Tablets has a curative effect on central serous chorioretinopathy.It could increase the visual acuity and improve the light sensitivity of eyes with good security.It is worthy of clinical use.