Songorine inhibits oxidative stress-related inflammation through PI3K/AKT/NRF2 signaling pathway to alleviate lipopolysaccharide-induced septic acute lung injury.

OBJECTIVE: The present study aimed to investigate the protective action and mechanism of songorine on sepsis-induced acute lung injury (ALI). METHODS: The sepsis-induced ALI mouse and cell models were established by lipopolysaccharide (LPS) induction. Lung injury was assayed by hematoxylin and eosin staining, lung injury score, and lung wet-to-dry (W/D) weight ratio. Apoptosis in lung tissues was evaluated by TUNEL assay, and the expression of apoptosis-related markers (Bcl2, Bax, and caspase-3) was measured by western blotting. Levels of pro-inflammatory factors and oxidative stress markers in the bronchoalveolar lavage fluid (BALF) of mice were measured by ELISA and RT-qPCR. The expression of PI3K/AKT/NRF2 pathway-related proteins was analyzed by western blotting. RESULTS: Songorine treatment at 40 mg/kg mitigated sepsis-induced ALI, characterized by improved histopathology, lung injury score, and lung W/D weight ratio (p < 0.05). Moreover, songorine markedly attenuated sepsis-induced apoptosis in lung tissues; this was evidenced by an increase in Bcl2 levels and a decrease in Bax and caspase-3 levels (p < 0.01). Also, songorine reduced levels of proinflammatory cytokines (TNF-α, IL-6, IL-1ß and MPO) and oxidative stress regulators (SOD and GSH) in the BALF of LPS-induced sepsis mice and RAW264.7 cells (p < 0.05). In addition, songorine upregulated the PI3K/AKT/NRF2 pathway-related proteins in LPS-induced sepsis mice and RAW264.7 cells (p < 0.05). Furthermore, LY294002 (a PI3K inhibitor) treatment reversed the protective effect of songorine on sepsis-induced ALI. CONCLUSION: Songorine inhibits oxidative stress-related inflammation in sepsis-induced ALI via the activation of the PI3K/AKT/NRF2 signaling pathway.

Development of the ARDS-derived gene panel for lung adenocarcinoma prognosis stratification and experiment validation of CCL20 expression.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by lung inflammation and high mortality rates. Lung cancer, specifically lung adenocarcinoma (LUAD), is a major cause of cancer-related deaths worldwide. Patients with LUAD, particularly those undergoing chemotherapy, are more likely to develop ARDS. ARDS inflicts major malfunctioning in the immune system. We suspected a certain shared pathogenic mechanism between these diseases. This study analyzed 503 LUAD patients from the TCGA-LUAD cohort as the training set, 85 LUAD cases from the GSE30219 cohort as the validation set, and 24 RNA-seq samples from ARDS mice model and control groups in the GSE2411 cohort. The differentially expressed genes (DEGs) of ARDS were analyzed using the limma package and screened by Cox and Lasso analysis. ssGSEA and xCell algorithms were utilized for immune landscaping. RT-qPCR analysis was used to determine the mRNA levels of key genes in both the LPS-induced ARDS model and human LUAD cell lines. We identified DEGs between ARDS and control groups, which were highly associated with cytokine production and leukocyte migration. A prognosis model for LUAD patients was developed based on the expressions of the key genes in the ARDS-derived DEGs, including FMO3, IL1R2, CCL20, CFTR, and GADD45G. A satisfactory efficacy was observed in both the training and validation cohorts. The model demonstrated increased effectiveness in predicting the intratumor immune profile and mutation status of LUAD. Moreover, we utilized LPS to induce the ARDS model, which resulted in elevated expressions of IL1R2 and CCL20. Additionally, CCL20 was upregulated in cancerous LUAD cell lines. We developed an ARDS-based model for stratifying LUAD prognosis. CCL20 was found to be elevated in both the ARDS model and LUAD, suggesting a shared underlying mechanism of these two diseases.

Development and Validation of a Nomogram to Predict the Risk of Special Uterine Leiomyoma Pathological Types or Leiomyosarcoma in Postmenopausal Women: A Retrospective Study.

Purpose: The aim of this study was to investigate the risk factors of postmenopausal special uterine leiomyoma pathological types or leiomyosarcoma and to develop a nomogram for clinical risk assessment, ultimately to reduce unnecessary surgical interventions and corresponding economic expenses. Methods: A total of 707 patients with complete information were enrolled from 1 August 2012 to 1 August 2022. Univariate and multivariate logistic regression models were used to analyse the association between variables and special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. A nomogram for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients was developed and validated by bootstrap resampling. The calibration curve was used to assess the accuracy of the model and receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were compared with the clinical experience model. Results: The increasing trend after menopause, the diameter of the largest uterine fibroid, serum carcinoembryonic antigen 125 concentration, Serum neutrophil to lymphocyte ratio, and Serum phosphorus ion concentration were independent risk factors for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. We developed a user-friendly nomogram which showed good diagnostic performance (AUC=0.724). The model was consistent and the calibration curve of our cohort was close to the ideal diagonal line. DCA indicated that the model has potential value for clinical application. Furthermore, our model was superior to the previous clinical experience model in terms of ROC and DCA. Conclusion: We have developed a prediction nomogram for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. This nomogram could serve as an important warning signal and evaluation method for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients.

Myrislignan Induces Redox Imbalance and Activates Autophagy in Toxoplasma gondii.

Toxoplasma gondii (T. gondii) is an important health problem in human and animals, and the highlighting side effects of launched therapeutic chemicals cannot be ignored. Thus, it is urgent to develop new drugs to against the infection. Myrislignan originated from nutmeg exhibited excellent anti-T. gondii activity in vitro and in vivo, and was able to destroy mitochondrial function. However, the exact mechanism of action is still unknown. In this study, combining RNAs deep-sequencing analysis and surface plasmon resonance (SPR) analysis, the differentially expressed genes (DEGs) and high affinity proteins suggested that myrislignan may affect the oxidation-reduction process of T. gondii. Furthermore, the upregulating ROS activity after myrislignan incubation verified that myrislignan destroyed the oxidant-antioxidant homeostasis of tachyzoites. Transmission electron microscopy (TEM) indicated that myrislignan induced the formation of autophagosome-like double-membrane structure. Moreover, monodansyl cadaverine (MDC) staining and western blot further illustrated autophagosome formation. Myrislignan treatment induced a significant reduction in T. gondii by flow cytometry analysis. Together, these findings demonstrated that myrislignan can induce the oxidation-reduction in T. gondii, lead to the autophagy, and cause the death of T. gondii.

[Relationship between the prediction of the opening angle and the increased value of cross-sectional area in single open-door laminoplasty].

OBJECTIVE: To evolve the formula of relationship between opening angle of laminoplasty and the increased value of cross-sectional area, and to predict the opening angle according to the opening size of lanminoplasty. METHODS: From January 2013 to December 2015, 26 patients underwent single open-door laminoplasty in C3-C7. Among them, 10 patients with ossification of posterior longitudinal ligament, there were 6 males and 4 females, aged from 39 to 58 years old with an average of 49.2 years; and 16 patients with cervical spondylotic myelopathy, there were 10 males and 6 females, aged from 40 to 58 years old with an average of 50.2 years. Through the changes of spinal canal shape between preoperation and postoperation to set up the regular geometric model, and to deduce the formula of the relationship between the opening angle of laminoplasty and the increased value of cross-sectional area, and predict the formula of opening angle. According to the preoperative and postoperative CT scan, the needed parameters were measured, and were substituted in the above formula to get the change of cross-sectional area before and after operation, predicting the opening angle of laminoplasty. The differences between the change of cross-sectional area before and after operation, predictive the opening angle of laminoplasty and practical measured data were analyzed by statistical methods, thus to verify the feasibility of formula in practical application. RESULTS: All imaging data of 26 patients were obtained. There were significant differences in changes of cross-sectional areas in every patients (laminoplasty in C3 to C7) before and after operation in the same segment(P<0.01). The increasing extent in cross-sectional areas was gradually diminished following the opening angle increasing. There was no significant difference between the opening angle attained by formula and the data measured by software in the same segment(P>0.05). CONCLUSIONS: Increment of cross-sectional areas following C3-C7 laminoplasty can be accurately attained and the opening angle can also be predicted by a certain formula, which can help surgeons to attain the accurate opening angle and reduce the postoperative complications.

The positive correlation between upper adjacent vertebral fracture and the kyphosis angle of injured vertebral body after percutaneous kyphoplasty: An in vitro study.

OBJECTIVE: To investigate the correlation between the kyphosis angle of injured vertebral body and the risk of upper adjacent vertebral fracture after percutaneous kyphoplasty (PKP) using an osteoporotic vertebral compressed fracture model. MATERIALS AND METHODS: 24 functional spinal units (FSUs, T9 to L4) were selected from 6 elderly formalin preserved vertebral specimens to build the vertebral compressed fracture model. According to the kyphosis angle between the upper plate of upper vertebral body and the horizontal plane, group A (0°) and group B (20°) were defined, with each group comprised with 12 FSUs. The stiffness and fracture load were measured in both groups. RESULTS: After PKP, the stiffness was (571.513 ± 83.373)N/mm and the fracture load was (1751.659 ± 112.291)N in group A, with both significantly higher than those of group B (stiffness, (307.706 ± 46.723)N/mm; fracture load, (1128.011 ± 125.417)N). CONCLUSIONS: To reduce the risk of upper adjacent vertebral fracture, it is better to restore the height of injured vertebral body and decrease the angle of kyphosis to increase the capability of upper adjacent vertebral body against fracture.

[Clinical application of dynamic neutralization system (K-Rod) in treating multisegmental lumbar degenerative disease].

OBJECTIVE: To evaluate the clinical effects of dynamic neutralization system (K-Rod) in treating multisegmental lumbar degenerative disease. METHODS: From October 2011 to October 2013, 20 patients with multisegmental lumbar degenerative disease were treated with dynamic neutralization system (K-Rod). There were 8 males and 12 females with an average age of 45.4 years old (ranged from 31 to 65) and an average course of 3.8 years (ranged from 9 months to 6.25 years). All patients had the history of low back and legs pain. Among them, 10 cases were far lateral lumbar disc herniation, 7 cases were lumbar spinal stenosis, 3 cases were lumbar spondylolisthesis (degree I in 2 cases and degree II in 1 case). Every patient had only one responsible segment which causing the symptom would have to be rigidly fixed during operations, and the adjacent intervertebral disc of the responsible segments at least 1 segment has already obvious degenerated. All patients underwent the operation to relieve compressed nerves and reconstruct spinal stability with K-Rod system (the responsible segments were fixed with interbody fusion, and the adjacent segments were fixed with dynamic stabilization). Visual analogue scale (VAS), Japanese Orthopaedic Association Scores (JOA) and Oswestry Disability Index (ODI) were used to evaluate the clinical effects. Imaging data were used to analyze the range of motion (ROM), intervertebral disc height and intervertebral disc signal (according to modified Pfirrmann grading system) in degenerative adjacent segment. RESULTS: All patients were followed up for more than 1 year, and preoperative symptoms obviously relieved. There were significant differences in VAS, JOA, ODI between preoperative and postoperative (postoperative at 1 week and 1 year) (P<0.05). Radiological examination showed that all responsible segments had already fused, and no looseness, displacement and breakage of internal fixations were found. Postoperative at 1 year, the ROM of adjacent segments were decreased (P<0.05). There was no significant difference in intervertebral disc height between preoperative and postoperative at 1 year (P>0.05). According to modified Pfirrmann grading system to classification for the 25 disks of adjacent segment, 8 disks (32%) got improvement, 15 disks (60%) got no change and 2 disks (8%) got aggravation at 1 year after operation. CONCLUSION: Dynamic neutralization system (K-Rod) combined with interbody fusion could obtain short-term clinical effects in the treatment of multisegmental lumbar degenerative disease.