Identification of immune-related molecular markers in intracranial aneurysm (IA) based on machine learning and cytoscape-cytohubba plug-in.

BACKGROUND: Intracranial aneurysm (IA) is a common cerebrovascular disease. The immune mechanism of IA is more complicated, and it is unclear so far. Therefore, it is necessary to continue to explore the immune related molecular mechanism of IA. METHODS: All data were downloaded from the public database. Limma package and ssGSEA algorithm was used to identify differentially expressed mRNAs (DEmRNAs) and analyze immune cell infiltration, respectively. Machine learning and cytoscape-cytohubba plug-in was used to identify key immune types and multicentric DEmRNAs of IA, respectively. Multicentric DEmRNAs related to key immune cells were screened out as key DEmRNAs by Spearman correlation analysis. Diagnostic models, competing endogenous RNA (ceRNA) regulatory network and transcription factor regulatory network were constructed based on key DEmRNAs. Meanwhile, drugs related to key DEmRNAs were screened out based on DGIdb database. The expression of key DEmRNAs was also verified by real time-PCR. RESULTS: In this study, 7 key DEmRNAs (NRXN1, GRIA2, SLC1A2, SLC17A7, IL6, VEGFA and SYP) associated with key differential immune cell infiltration (CD56bright natural killer cell, Immature B cell and Type 1 T helper cell) were identified. Functional enrichment analysis showed that VEGFA and IL6 may be involved in the regulation of the PI3K-Akt signaling pathway. Moreover, IL6 was also found to be enriched in cytokine-cytokine receptor interaction signaling pathway. In the ceRNA regulatory network, a large number of miRNAs and lncRNAs were found. In the transcription factor regulatory network, the transcription factor SP1 was correlated with VEGFA, SYP and IL6. It is also predicted that drugs related to key DEmRNAs such as CARBOPLATIN, FENTANYL and CILOSTAZOL may contribute to the treatment of IA. In addition, it was also found that SVM and RF models based on key DEmRNAs may be potential markers for diagnosing IA and unruptured intracranial aneurysm (UIA), respectively. The expression trend of key DEmRNAs verified by real-time PCR was consistent with the bioinformatics analysis results. CONCLUSION: The identification of molecules and pathways in this study provides a theoretical basis for understanding the immune related molecular mechanism of IA. Meanwhile, the drug prediction and diagnosis model construction may also be helpful for clinical diagnosis and management.

Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion.

BACKGROUND: Data from trials investigating the effects and risks of endovascular thrombectomy for the treatment of stroke due to basilar-artery occlusion are limited. METHODS: We conducted a multicenter, prospective, randomized, controlled trial of endovascular thrombectomy for basilar-artery occlusion at 36 centers in China. Patients were assigned, in a 2:1 ratio, within 12 hours after the estimated time of basilar-artery occlusion to receive endovascular thrombectomy or best medical care (control). The primary outcome was good functional status, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]), at 90 days. Secondary outcomes included a modified Rankin scale score of 0 to 2, distribution across the modified Rankin scale score categories, and quality of life. Safety outcomes included symptomatic intracranial hemorrhage at 24 to 72 hours, 90-day mortality, and procedural complications. RESULTS: Of the 507 patients who underwent screening, 340 were in the intention-to-treat population, with 226 assigned to the thrombectomy group and 114 to the control group. Intravenous thrombolysis was used in 31% of the patients in the thrombectomy group and in 34% of those in the control group. Good functional status at 90 days occurred in 104 patients (46%) in the thrombectomy group and in 26 (23%) in the control group (adjusted rate ratio, 2.06; 95% confidence interval [CI], 1.46 to 2.91, P<0.001). Symptomatic intracranial hemorrhage occurred in 12 patients (5%) in the thrombectomy group and in none in the control group. Results for the secondary clinical and imaging outcomes were generally in the same direction as those for the primary outcome. Mortality at 90 days was 37% in the thrombectomy group and 55% in the control group (adjusted risk ratio, 0.66; 95% CI, 0.52 to 0.82). Procedural complications occurred in 14% of the patients in the thrombectomy group, including one death due to arterial perforation. CONCLUSIONS: In a trial involving Chinese patients with basilar-artery occlusion, approximately one third of whom received intravenous thrombolysis, endovascular thrombectomy within 12 hours after stroke onset led to better functional outcomes at 90 days than best medical care but was associated with procedural complications and intracerebral hemorrhage. (Funded by the Program for Innovative Research Team of the First Affiliated Hospital of USTC and others; ATTENTION ClinicalTrials.gov number, NCT04751708.).

Endovascular Treatment Versus Best Medical Management in Acute Basilar Artery Occlusion Strokes: Results From the ATTENTION Multicenter Registry.

BACKGROUND: The authors compare the effectiveness and safety of endovascular treatment (EVT) versus best medical management (BMM) in strokes attributable to acute basilar artery occlusion (BAO). METHODS: The present analysis was based on the ongoing, prospective, multicenter ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion) trial registry in China. Our analytic sample comprised 2134 patients recruited at 48 sites between 2017 and 2021 and included 462 patients who received BMM and 1672 patients who received EVT. We performed an inversed probability of treatment weighting analysis. Qualifying patients had to present within 24 hours of estimated BAO. The primary clinical outcome was favorable functional outcome (modified Rankin Scale score, 0-3) at 90 days. We also performed a sensitivity analysis with the propensity score matching-based and the instrumental variable-based analysis. RESULTS: In our primary analysis using the inversed probability of treatment weighting-based analysis, there was a significantly higher rate of favorable outcome at 90 days among EVT patients compared with BMM-treated patients (adjusted relative risk, 1.42 [95% CI, 1.19-1.65]; absolute risk difference, 11.8% [95% CI, 6.9-16.7]). The mortality was significantly lower (adjusted relative risk, 0.78 [95% CI, 0.69-0.88]; absolute risk difference, -10.3% [95% CI, -15.8 to -4.9]) in patients undergoing EVT. Results were generally consistent across the secondary end points. Similar associations were seen in the propensity score matching-based and instrumental variable-based analysis. CONCLUSIONS: In this real-world study, EVT was associated with significantly better functional outcomes and survival at 90 days. Well-designed randomized studies comparing EVT with BMM in the acute BAO are needed. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR2000041117.

Uncovering of Key Pathways and miRNAs for Intracranial Aneurysm Based on Weighted Gene Co-Expression Network Analysis.

BACKGROUND: Intracranial aneurysm (IA) is a serious cerebrovascular disease. The identification of key regulatory genes can provide research directions for early diagnosis and treatment of IA. METHODS: Initially, the miRNA and mRNA data were downloaded from the Gene Expression Omnibus database. Subsequently, the limma package in R was used to screen for differentially expressed genes. In order to investigate the function of the differentially expressed genes, a functional enrichment analysis was performed. Moreover, weighted gene co-expression network analysis (WGCNA) was performed to identify the hub module and hub miRNAs. The correlations between miRNAs and mRNAs were assessed by constructing miRNA-mRNA regulatory networks. In addition, in vitro validation was performed. Finally, diagnostic analysis and electronic expression verification were performed on the GSE122897 dataset. RESULTS: In the present study, 955 differentially expressed mRNAs (DEmRNAs, 480 with increased and 475 with decreased expression) and 46 differentially expressed miRNAs (DEmiRNAs, 36 with increased and 10 with decreased expression) were identified. WGCNA demonstrated that the yellow module was the hub module. Moreover, 16 hub miRNAs were identified. A total of 1,124 negatively regulated miRNA-mRNA relationship pairs were identified. Functional analysis demonstrated that DEmRNAs in the targeted network were enriched in vascular smooth muscle contraction and focal adhesion pathways. In addition, the area under the curve of 16 hub miRNAs was >0.8. It is implied that 16 hub miRNAs may be used as potential diagnostic biomarkers of IA. CONCLUSION: Hub miRNAs and key signaling pathways were identified by bioinformatics analysis. This evidence lays the foundation for understanding the underlying molecular mechanisms of IA and provided potential therapeutic targets for the treatment of this disease.

Angioplasty and/or stenting after thrombectomy in patients with underlying intracranial atherosclerotic stenosis.

PURPOSE: To investigate the imaging and clinical outcomes of emergent angioplasty and/or stenting or neither in patients of emergent large-vessel occlusion (ELVO) with underlying severe intracranial atherosclerotic stenosis (ICAS). METHODS: In this multicenter prospective cohort study, we included patients of ELVO with underlying ICAS. Patients received emergent angioplasty and/or stenting or neither after mechanical thrombectomy at the interventionists' discretion. The primary outcome was recanalization rate at 24 h, which was defined as a modified arterial occlusive lesion score of 2 or 3. RESULTS: A total of 113 consecutive patients with underlying ICAS > 70% in anterior cerebral circulation were enrolled in this study. Of these, 81 (71.7%) received emergent angioplasty and/or stenting after thrombectomy. Patients in the emergent angioplasty and/or stenting group were significantly more likely to have recanalization at 24 h (adjusted OR [aOR], 3.782; 95% confidence interval [CI], 1.821-9.125; P = 0.02) and less likely to have early neurologic deterioration (aOR, 0.299; 95% CI, 0.110-0.821; P = 0.01). However, emergent angioplasty and/or stenting was not significantly associated with symptomatic intracranial hemorrhage (aOR, 0.710; 95% CI, 0.199-2.622; P = 0.67), asymptomatic intracranial hemorrhage (aOR, 1.325; 95% CI, 0.567-3.031; P = 0.81), death at 90 days (aOR, 0.581; 95% CI, 0.186-2.314; P = 0.41), and functional independence at 90 days (aOR, 1.752; 95% CI, 0.774-3.257; P = 0.16), compared with patients that received neither. CONCLUSION: Emergent angioplasty and/or stenting is possible in patients of ELVO with ICAS and may reduce the risk of reocclusion and early neurologic deterioration with no increased risk of intracranial hemorrhage and death than those received neither.

Aminophylline for treatment of postdural puncture headache: A randomized clinical trial.

OBJECTIVE: To investigate the efficacy and safety of IV aminophylline for patients with postdural puncture headache (PDPH). METHODS: We randomly assigned patients to groups receiving either 250 mg IV aminophylline or a placebo within 3 hours of symptom onset once daily for 2 consecutive days. The primary endpoint was headache severity 8 hours after treatment. We assessed this using visual analog scale (VAS) scores taken from patients in a standing position. We also recorded posttreatment VAS score changes, Patient Global Impression of Change (PGIC) scores, and adverse events. We performed an intention-to-treat analysis. RESULTS: We enrolled 126 patients with PDPH at 5 centers in China (62 assigned to the aminophylline group and 64 to the placebo group). The median age was 37 years, and 96 (76.2%) patients were women. Compared to the placebo-treated patients, the aminophylline-treated patients had significantly lower mean VAS scores 8 hours after treatment (5.34 vs 2.98, p < 0.001) and were significantly more likely to report improvements on the PGIC (39.1% vs 72.6%, p < 0.01). This therapeutic effect was already evident at the 30-minute time point and persisted for 2 days. There was no significant difference in the incidence of adverse events (4.8% vs 1.6%, p = 0.589). CONCLUSIONS: IV aminophylline is an effective and safe early-stage treatment for patients with PDPH. CLINICALTRIALSGOV IDENTIFIER: NCT02522013. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for people with PDPH, IV aminophylline reduces headache severity.

Enhanced bioconversion of ethylene glycol to glycolic acid by a newly isolated Burkholderia sp. EG13.

Burkholderia sp. EG13 with high ethylene glycol-oxidizing activity was isolated from soil, which could be used for the synthesis of glycolic acid from the oxidation of ethylene glycol. Using the resting cells of Burkholderia sp. EG13 as biocatalysts, the optimum reaction temperature and pH were 30 °C and 6.0, respectively. After 24 h of biotransformation, the yield of glycolic acid from 200 mM ethylene glycol was 98.8 %. Furthermore, an integrated bioprocess for the production of glycolic acid which involved in situ product removal (ISPR) was investigated. Using fed-batch method with ISPR, a total of 793 mM glycolic acid has been accumulated in the reaction mixture after the 4th feed.

[Pilot-plant testing for flue gas desulfurization and dust removal by activated coke].

A developed flue gas desulfurization and dust removal process with a cross-flow moving bed filled with activated coke (AC) was tested on a pilot scale with the gas treatment capacity of 1000 mg x h(-t). The results show that a easy-operating and stable-running pilot-scale testing equipment can be reached, and under the conditions of testing space velocity, the feed gas temperature of 120 degrees C, SO2 concentrations of 3232-6006 mg x m(-3) and dust concentration of 89.3-1599.7 mg x m(-3), the high efficiency of flue gas desulfurization and dust removal is reached with the purity of dust less than 50 mg x m(-3). In the technology, the spent AC was regenerated by heating, and the SO2 concentration in the desorption gas is about 40.1%, which can be efficiently recovered as a sulfur resource. Favorable economy benefit can be reached by using the process.