1.Risk factors of systolic dysfunction after isolated traumatic brain injury
Yuzhu MIAO ; Jungen LI ; Peng YANG ; Jiecheng XIAO ; Li DING ; Oiufang ZHANG ; Sisi SUN ; Xiaoqin LI ; Shiqi LU
Chinese Journal of Emergency Medicine 2020;29(7):954-958
Objective:To investigate the risk factors of systolic dysfunction early complicated in patients with isolated traumatic brain injury (iTBI) and to evaluate the influence of complicated systolic dysfunction on the prognosis of iTBI patients.Methods:From January 2017 to October 2018, 123 patients with moderate or severe iTBI admitted to Trauma Centre in our hospital were included in the study, and patients with previous cardiovascular diseases were excluded. Left ventricular systolic function was assessed by transthoracic echocardiography within 24 h after admission. The patients were divided into normal systolic function group ( n=100) and systolic dysfunction group ( n=23) according to the results of echocardiography. Data were collected from all patients on admission, including GCS score, systolic blood pressure, heart rate, high-sensitivity cardiac troponin T (hs-cTnT), clinical treatment variables (use of sedative drugs, vasoactive drugs, etc.), craniotomy or not and clinical outcomes (survival or death) during hospitalization. Logistic regression analysis was used to analyze the related factors for iTBI patients complicated with systolic dysfunction, and receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of each index for iTBI patients complicated with cardiac insufficiency. Results:The systolic blood pressure (147.3±23.3) mmHg, the heart rate (96.1±26.3) beats/min and the hs-cTnT level (16.48±8.17) pg/mL in the systolic dysfunction group were higher than those in the normal systolic function group on admission (all P<0.05); and the GCS score in the systolic dysfunction group was lower than that in the normal systolic function group ( P<0.05). Logistic regression analysis showed that the heart rate ( OR=1.129, 95% CI: 1.001-1.516; P=0.038), the GCS score ( OR=0.640, 95% CI: 0.445-0.920; P=0.016) and the hs-cTnT level ( OR=1.054, 95% CI: 1.009-1.101; P=0.002) on admission were independent risk factors for iTBI patients complicated with systolic dysfunction. The area under the ROC curve (AUC) of the hs-cTnT levelon admission was the largest (AUC=0.863, P<0.01). The in-hospital mortality of patients in the systolic dysfunction group was higher than that of patients in the normal systolic function group (52.5% vs 22%, P=0.004). Conclusions:The heart rate, the GCS score and the serum hs-cTnT level on admission were independent risk factors for iTBI patients complicated with systolic dysfunction. The hs-cTnT level could better predict the occurrence of cardiac systolic dysfuncion, and higher in-hospital mortality was found in iTBI patients complicated with systolic dysfunction. Therefore, early detection and timely intervention may improve the prognosis of these patients.
2.A BRD4 PROTAC nanodrug for glioma therapy via the intervention of tumor cells proliferation, apoptosis and M2 macrophages polarization.
Tingting YANG ; Yuzhu HU ; Junming MIAO ; Jing CHEN ; Jiagang LIU ; Yongzhong CHENG ; Xiang GAO
Acta Pharmaceutica Sinica B 2022;12(6):2658-2671
Glioma is a primary aggressive brain tumor with high recurrence rate. The poor efficiency of chemotherapeutic drugs crossing the blood‒brain barrier (BBB) is well-known as one of the main challenges for anti-glioma therapy. Moreover, massive infiltrated tumor-associated macrophages (TAMs) in glioma further thwart the drug efficacy. Herein, a therapeutic nanosystem (SPP-ARV-825) is constructed by incorporating the BRD4-degrading proteolytic targeting chimera (PROTAC) ARV-825 into the complex micelle (SPP) composed of substance P (SP) peptide-modified poly(ethylene glycol)-poly(d,l-lactic acid)(SP-PEG-PDLLA) and methoxy poly(ethylene glycol)-poly(d,l-lactic acid) (mPEG-PDLLA, PP), which could penetrate BBB and target brain tumor. Subsequently, released drug engenders antitumor effect via attenuating cells proliferation, inducing cells apoptosis and suppressing M2 macrophages polarization through the inhibition of IRF4 promoter transcription and phosphorylation of STAT6, STAT3 and AKT. Taken together, our work demonstrates the versatile role and therapeutic efficacy of SPP-ARV-825 micelle against glioma, which may provide a novel strategy for glioma therapy in future.