Glioma is the most common primary malignant brain tumor in the adult population,characterized by high incidence and low sur-vival rates.Current standard treatment options exhibit limited efficacy.In recent years,the crucial role of cGAS-STING signaling in tumor im-munity has garnered significant attention.This article systematically reviews the molecular mechanisms of cGAS-STING signaling in glioma and its potential tumor-suppressive effects,providing an in-depth exploration of various STING agonists and their delivery systems targeting this pathway.This review also summarizes the synergistic effects of combining cGAS-STING pathway activation with radiotherapy,chemo-therapy,and immune checkpoint inhibitors,providing substantial references for the development of multimodal comprehensive treatment strategies.

Glioma is the most common primary malignant brain tumor in the adult population,characterized by high incidence and low sur-vival rates.Current standard treatment options exhibit limited efficacy.In recent years,the crucial role of cGAS-STING signaling in tumor im-munity has garnered significant attention.This article systematically reviews the molecular mechanisms of cGAS-STING signaling in glioma and its potential tumor-suppressive effects,providing an in-depth exploration of various STING agonists and their delivery systems targeting this pathway.This review also summarizes the synergistic effects of combining cGAS-STING pathway activation with radiotherapy,chemo-therapy,and immune checkpoint inhibitors,providing substantial references for the development of multimodal comprehensive treatment strategies.

Objective To determine the extent of off-label antiepileptic drugs (AEDs) use in a tertiary pediatric epileptic center in China,so as to provide baseline data for getting acquainted with the extent of off-label AEDs use for the future.Methods Collected demographic information and prescriptions related to AEDs of all hospitalized children diagnosed with epilepsy from April 1st to September 30th 2016 were collected in Peking University First Hospital.According to person-time,prescriptions,different AEDs,various categories of off-label use,the incidence of off-label AEDs use was calculated respectively.Risk factors (age,gender,number of drug use,type of seizure and status epilepticus) were analyzed through the methods of single factor chi-square and muhi-factor Logistic regression analysis.Results A total of 291 person-times,749 prescriptions and involving 12 kinds of AEDs were collected.The rates of off-label drug use were 35.11％ (263/749 items) and 66.32％ (193/291 person-times) in prescriptions and person-times respectively.The main categories of off-label drug use were seizure types (38.40％,101/263 items),dosage (10.27％,27/263 items),mono/multidrug therapy (9.89％,26/263 items),scope of disease (0.76％,2/263 items) and age (72.62％,191/263 items),while 30.30％ (79/263 items) prescriptions were equal or more than 2 different categories of off-label drug use.The incidences of different drugs were different,with 100％ in Nitrazepam,Vigabatrin,Clobazam,Zonisamide,1.78％ (3/169 items) in Valproate but 0 in Clonazepam,Phenobarbital.According to the results of single factor chi-square and multi-factor Logistic regression,ages and seizure types were correlated with off-label AEDs use.The groups of infants and preschoolers had higher incidences of off-label AEDs use than the group of school and adolescence.The group of focal seizures only had lower incidences of off-label AEDs use.Conclusions Off-label AEDs use in the tertiary pediatric epileptic center in China is common.Younger patients (infant and preschool) have higher incidences of off-label AEDs use,while patients with focal seizures have lower incidences of off-label AEDs use.

Previous studies proposed that the synergistic effect of fibroblast growth factor-21 (FGF-21) and insulin may be due to the improvement of insulin sensitivity by FGF-21. However, there is no experimental evidence to support this. This study was designed to elucidate the mechanism of synergistic effect of FGF-21 and insulin in the regulation of glucose metabolism. The synergistic effect of FGF-21 and insulin on regulating glucose metabolism was demonstrated by investigating the glucose absorption rate by insulin resistance HepG2 cell model and the blood glucose chances in type 2 diabetic db/db mice after treatments with different concentrations of FGF-21 or/and insulin; The synergistic metabolism was revealed through detecting GLUT1 and GLUT4 transcription levels in the liver by real-time PCR method. The experimental results showed that FGF-21 and insulin have a synergistic effect on the regulation of glucose metabolism. The results of real-time PCR showed that the effective dose of FGF-21 could up-regulate the transcription level of GLUT1 in a dose-dependent manner, but had no effect on the transcription level of GLUT4. Insulin (4 u) alone could up-regulate the transcription level of GLUT4, yet had no effect on that of GLUT1. Ineffective dose 0.1 mg kg(-1) FGF-21 alone could not change the transcription level of GLUT1 or GLUT4. However, when the ineffective dose 0.1 mg x kg(-1) FGF-21 was used in combination with insulin (4 u) significantly increased the transcription levels of both GLUT1 and GLUT4, the transcription level of GLUT1 was similar to that treated with 5 time concentration of FGF-21 alone; the transcription level of GLUT4 is higher than that treated with insulin (4 u) alone. In summary, in the presence of FGF-21, insulin increases the sensitivity of FGF-21 through enhancing GLUT1 transcription. Vice versa, FGF-21 increases the sensitivity of insulin by stimulating GLUT4 transcription in the presence of insulin. FGF-21 and insulin exert a synergistic effect on glucose metabolism through mutual sensitization.