miR-1297 sensitizes glioma cells to temozolomide (TMZ) treatment through targeting adrenomedullin (ADM).

BACKGROUND: Gliomas account for about 80% of all malignant brain and other central nervous system (CNS) tumors. Temozolomide (TMZ) resistance represents a major treatment hurdle. Adrenomedullin (ADM) has been reported to induce glioblastoma cell growth. METHODS: Cell viability was measured using the CCK-8 assay. The apoptosis analysis was performed using the Annexin V-FITC Apoptosis Detection Kit. The mitochondrial membrane potential was determined by JC-1 staining. A nude mouse tumor assay was used to detect tumor formation. Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were performed in tissue sections. Activation of Akt and Erk and expression of apoptosis-related proteins were determined by immunoblotting. RESULTS: ADM expression has been found upregulated in TMZ -resistant glioma samples based on bioinformatics and experimental analyses. Knocking down ADM in glioma cells enhanced the suppressive effects of TMZ on glioma cell viability, promotive effects on cell apoptosis, and inhibitory effects on mitochondrial membrane potential. Moreover, ADM knockdown also enhanced TMZ effects on Bax/Bcl-2, Akt phosphorylation, and Erk1/2 phosphorylation. Bioinformatics and experimental investigation indicated that miR-1297 directly targeted ADM and inhibited ADM expression. miR-1297 overexpression exerted similar effects to ADM knockdown on TMZ-treated glioma cells. More importantly, under TMZ treatment, inhibition of miR-1297 attenuated TMZ treatment on glioma cells; ADM knockdown partially attenuated the effects of miR-1297 inhibition on TMZ-treated glioma cells. CONCLUSIONS: miR-1297 sensitizes glioma cells to TMZ treatment through targeting ADM. The Bax/Bcl-2, Akt, and Erk1/2 signaling pathways, as well as mitochondrial functions might be involved.

Correlation analysis between TSP2, MMP-9 and perihematoma edema, as well as the short-term prognosis of patients with hypertensive intracerebral hemorrhage.

BACKGROUND: To analyze the correlation between thrombospondin-2 (TSP2), matrix metalloproteinase (MMP)-9, and perihematomal edema, as well as the short-term prognosis of patients with hypertensive intracerebral hemorrhage. METHODS: The clinical data of 114 patients with hypertensive intracerebral hemorrhage admitted to our hospital from January 2018 to February 2020 were collected and divided into groups according to the levels of TSP2 and MMP-9. We compared edema indexes in patients with different levels of TSP2 and MMP-9, and analyzed the correlation between TSP2, MMP-9 and relative edema volume index (REI), edema change index (AEI). We also assessed the TSP2 and MMP-9 levels in patients with different prognoses, and analyzed the predictive value of TSP2 and MMP-9 for poor prognosis of patients. RESULTS: (I) There was no difference in the REI and AEI values between the low and high TSP2 groups at admission and 24 h after admission (P>0.05), while the REI and AEI values of the high TSP2 group at 5 and 15 d after admission were significantly lower than those of the low TSP2 group (P<0.05); (II) the REI and AEI values of patients with different MMP-9 levels were not different between admission and 24 h after admission (P>0.05), while the REI and AEI values of the high MMP-9 group were significantly higher than those of the low MMP-9 group at 5 and 15 d after admission (P<0.05); (III) Pearson correlation analysis showed that MMP-9 was positively correlated with REI and AEI, while TSP2 was negatively correlated (P<0.05); (IV) among 114 patients, 39 had poor prognosis, 75 had good prognosis The MMP-9 levels of patients with a poor prognosis were significantly higher than those of patients with a good prognosis, and the TSP2 level was the opposite (P<0.05); (V) receiver operating characteristic (ROC) curve showed that the sensitivity, specificity and the area under the curve (AUC) of the TSP2 + MMP-9 combination in the diagnosis of hypertensive cerebral hemorrhage were significantly higher than when TSP2 and MMP-9 were tested separately (P<0.05). CONCLUSIONS: In patients with hypertensive intracerebral hemorrhage, TSP2 is negatively correlated with edema around the hematoma, while MMP-9 is positively correlated.

Systematic review and meta-analysis of the effect of continuous cerebrospinal fluid drainage on keyhole surgery during the perioperative period.

BACKGROUND: Lumbar continuous drainage of fluid (LCDF) has become more widely used in the diagnosis and treatment of neurological diseases in recent years. The use of LCDF can enable a better understanding of the patient's condition and reduce the incidence of related complications. LCDF can also affect complications of perforation surgery, including mortality during hospitalization, cerebral vasospasm (CVS), bleeding, and aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Articles published from library construction to April 2021 were searched for in the English-language databases PubMed, Cochrane Library, and Embase. All randomized controlled trials (RCTs) with LCDF and hole locking surgery were meta-analyzed using the Cochrane Collaboration's RevMan 5.3 software. RESULTS: Ten RCTs involving 1,092 patients (continuous drainage group, n=585; control group, n=507) were included in the meta-analysis. For the statistical different in incidence of perioperative cerebral infarction in the two groups, the odds ratio (OR) was 5.42 [95% confidence interval (CI): (2.71, 10.83); P<0.00001], and for the statistical difference in the incidence of cerebral hemorrhage, the OR was 4.76 [95% CI: (2.11, 10.76); P=0.0002]. Perioperative complications were fewer in the LCDF-treated drainage group than in the conventional group. DISCUSSION: This meta-analysis of 10 RCTs confirmed that LCDF compared with other treatments is associated with a lower incidence of perioperative complications, such as cerebral hemorrhage, hydrocephalus, and cerebral infarction, as well as increased Glasgow Outcome Scale (GOS).