Objective. To study the role of endogenous carbon monoxide (CO) in endotoxin shock. Methods. The changes of CO levels and the effects of zinc protoporphyrin IX (ZnPP),an inhibitor of heme-oxygenase (HO), in endotoxin shock and the efficacy of hemin,an inducer of HO were investigated.Results. The plasma CO levels were found to be significantly increased during the course of endotoxin shock. Injection of ZnPP was shown to abrogate the endotoxin-induced hypotension and metabolic derangements markedly. Administration of hemin to healthy rabbits revealed the hypotension and metabolic derangements similar to the animals given endotoxin.Conclusion.CO is a newly found endogenously produced mediator which may play an important role in the pathogenesis of endotoxin shock.

Objective:To investigate the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) in meningioma tissue and its effect on the growth and metastasis of human meningioma cell line IOMM-Lee cells.Methods:The specimens of 34 patients with meningioma were collected. Methylation-specific polymerase chain reaction (MSP) method was used to detect MGMT methylation in meningioma tissue and normal brain tissue; immunohistochemical staining was used to detect the expression of MGMT in meningioma tissue and normal brain tissue. The cultured human glioma cell line IOMM-Lee cells were divided into blank control group (normal cultured IOMM-Lee cells), negative control group (empty vector virus transfected IOMM-Lee cells) and RNAi lentivirus transfection group (transfected with RNAi lentivirus vector to down-regulate the expression of MGMT). The expression of MGMT in IOMM-Lee cells was silenced by RNAi technology. The expression levels of MGMT mRNA and protein in cells were detected by real-time fluorescence quantitative PCR and Western blot. The proliferation activity of cells was detected by cell counting kit-8 (CCK-8) test, the colony forming ability was detected by cell clone formation test, and the invasion and migration ability of cells in each group were detected by Transwell test and cell scratch test.Results:The methylation of MGMT in meningioma tissue reached 88.23% (30/34). MGMT methylation was not detected in normal brain tissue; the staining intensity of MGMT in meningioma tissue was significantly higher than that in normal brain tissue. Compared with the blank control group and the negative control group, the relative expression of MGMT mRNA and protein in IOMM-Lee cells of the RNAi lentiviral transfection group were significantly decreased (all P<0.05). After 24, 48 and 72 hours of transfection, the proliferation activity of IOMM-Lee cells decreased significantly (all P<0.05), with reduced number of cell clone formation and cell invasion (all P<0.05). The rate of scar healing decreased significantly ( P<0.05). Conclusions:MGMT is mostly hypermethylated in human meningiomas. Silencing the expression of MGMT in meningiomas can inhibit the growth and metastasis of meningiomas.

Objective:To investigate the role of miR-145 in inflammatory response and immune regulation after traumatic brain injury(TBI).Methods:Male C57BL/6 mice were randomly divided into sham operation group(Sham),model group(TBI),TBI+NC agomir group and TBI+miR-145 agomir group.Modified Nerve Injury Severity Score(mNSS)was used to evaluate neurological function after trauma.MWM test was used toevaluates neurocognitive function of mice after TBI.Flow cytometry was used to detect the number of Tregs in tbrain tissue of each group of mice.ELISA was used to detect expressions of inflammatory cytokines in hippocampus of each group of mice.Immunohistochemistry was used to detect expression of activated microglia/macrophage Iba-1 in hippocampus of each group of mice.RT-qPCR was used to detect expressions of M1/M2 microglia/macrophage marker genes iNOS,CD11b,CD206 and Arg1.TUNEL staining and neuronal nuclear immunity double staining with fluorescent label(NeuN)were used to detect neuronal apoptosis.Results:Compared with Sham group,expression of miR-145 in hippocampus of mice in TBI group was significantly decreased,the neurological damage was increased,and percentage of Tregs in CD4+T cell population in brain tissue was decreased.Expression levels of IL-1β,IL-6,TNF-α,IL-4,IL-10 and TGF-β in hippocampus were significantly increased,the number of activated microglia/macrophage IBA-1 was increased,expression levels of iNOS CD11b,CD206 and Arg1 were significantly increased,and the neuronal apoptosis was increased.Notch1,p21 and Hes1 mRNA and protein levels were significantly increased(all P<0.05).Compared with TBI+NC agomir group,expression of miR-145 in hippocampus of mice in TBI+miR-145 agomir group was significantly increased,and neurological damage was reduced.Percentage of Tregs in CD4+T cell population in brain tissue was significantly increased,expressions of pro-inflammatory cytokines IL-1β,IL-6,and TNF-α were decreased,while anti-inflammatory cytokines IL-4,IL-10 and TGF-β were significantly increased in hippocampus.The number of activated microglia/macrophage IBA-1 was significantly decreased,expression levels of iNOS and CD11b were decreased,while expression levels of CD206 and Arg1 were significantly increased.mRNA and protein levels of Notch1,p21 and Hes1 were significantly reduced(all P<0.05).Conclusion:Overexpression of miR-145 promotes M2 polarization of microglia to regulate post-traumatic neuroinflammatory response and improve behavioral dysfunction by increasing Treg level,which may be mediated by Notch signaling pathway.

Objective To explore the risk factors and potential mechanisms of hypertension events on the same day after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis. Methods Clinical data of patients who underwent TAVI for severe aortic stenosis at Department of Structural Heart Disease, Fuwai Hospital from December 2023 to February 2024 were retrospectively collected. According to the peak systolic blood pressure on the same day after surgery, patients were divided into a hypertension group (≥140 mm Hg) and a normal blood pressure group (<140 mm Hg). Logistic regression model was used to analyze the risk factors for hypertension on the same day after TAVI. Results A total of 54 patients after TAVI were included, with 41 patients in the hypertension group, including 18 males and 23 females, with an average age of (72.83±6.78) years; 13 patients in the normal blood pressure group, including 9 males and 4 females, with an average age of (70.00±7.57) years. Univariate analysis found that there were statistical differences in interventricular septal thickness [(13.71±1.98) mm vs. (12.23±1.59) mm, P=0.018], preoperative left ventricular ejection fraction (LVEF)>55% [33 (80.5%) vs. 6 (46.2%), P=0.040], and postoperative same-day LVEF>55% [33 (80.5%) vs. 4 (30.8%), P=0.003]. Multivariate logistic regression analysis found that postoperative same-day LVEF>55% [OR=10.173, 95%CI (1.044, 99.115), P=0.046] was an independent risk factor for hypertension on the same day after TAVI. Conclusion Myocardial contractility mainly participates in the occurrence of hypertension on the same day after TAVI. This study can not only improve our understanding of early hemodynamic changes after TAVI, but also provide a basis for the formulation of early hypertension treatment plans after TAVI to improve the short- and long-term prognosis of patients.