AimThe effectiveness of neuroprotective agents is still unclear. Here we analyzed the clinical outcomes of acute ischemic stroke (AIS) patients treated with human urinary kallidinogenase (HUK) or edaravone (Eda) combined with butylphthalide (NBP).MethodsFrom January 2016 to December 2017, a total of 165 AIS patients were enrolled in this open‐label, randomized controlled clinical study. Patients were randomly allocated into HUK group and Eda group in a ratio of 2:1. All the patients received basic treatments and NBP (200 mg p.o. qid) while HUK group received 0.15 PNA unit of HUK injection (ivgtt. qd) and Eda group received 30 mg Eda (ivgtt. bid) for 14 consecutive days. Independency rate [12‐month modified Rankin Scale (mRS) score ≤ 1] and related factors were compared between the two groups.ResultsTwelve‐month mRS score of the HUK group (1, IQR 0~1) was significantly lower compared with Eda group (2, IQR 1~3, p < .0001). The HUK treatment achieved an independency rate of 79.1% while the Eda treatment only had 45.3% (p < .0001). Further binary logistic regression showed that recurrent stroke (RR: 0.1, 95% CI: 0.0~0.1, p = .038) and HUK treatment (RR: 4.2, 95% CI: 1.1~16.5, p = .041) could significantly affect patients' 12‐month outcomes.ConclusionHuman urinary kallidinogenase combined with NBP can enhance AIS patients' long‐term independency rate, and the effectiveness of HUK combined therapy is better than Eda.

Objective: To evaluate the association between hyperhomocysteinemia (HHcy) and risk of cognitive decline. Methods: Electronic databases such as PubMed and EMBASE were searched for prospective cohort studies that involved the relationship between HHcy and risk of cognitive decline. Adjusted risk ratios (RRs) and corresponding 95% confidence intervals (95% CIs) were calculated by Review Manager 5.2.7. Subgroup analyses were conducted on stratification of some important variables. Results: Fourteen publications were included in the analysis. The pooled RR was 1.53 (95% CI, 1.23-1.91; p = 0.0002) for patients with HHcy compared to subjects without HHcy. Subgroup analyses indicated that the pooled RRs were 1.51 (95% CI, 1.10-2.05; p = 0.01) for more than five-year follow-up studies and 1. 56 (95% CI, 1.13-2.14; p = 0.007) for less than five-year follow-up studies. The pooled RRs were 1.66 (95% CI, 1.21-2.26; p = 0.001) for studies excluding the confounder of B vitamins and 1.34 (95% CI, 1.08-1.66; p = 0.008) for non-excluded studies. In terms of region, the pooled RR was 1.60 (95% CI, 1.21-2.13; p = 0.001) for European and American countries, while the pooled RR was 1.27 (95% CI, 1.02-1.59; p = 0.03) for other regions. Conclusion: As one of the independent risk factors, HHcy was associated with an increased risk of cognitive decline.

Following cerebral infarction, activated microglia cells can release a large amount of inflammatory cytokines, thereby exacerbating neuronal damage. It has been demonstrated that the long non-coding RNA small nucleolar RNA host gene 1 (SNHG1) exerts a protective effect against cerebral infarction. However, its specific role in cerebral infarction and underlying mechanism have yet to be fully elucidated. The present study aimed to investigate the effects of the SNHG1 and microRNA (miR)-329-3p in cerebral infarction and to determine the underlying molecular mechanisms. An in vitro oxygen-glucose deprivation (OGD) model was established using the BV-2 microglial cell line. The mRNA expression levels of SNHG1 and miR-329-3p were analyzed using reverse transcription-quantitative PCR and the protein expression levels of cleaved caspase-3 and caspase-3 were detected using western blotting. The binding relationship between SNHG1 and miR-329-3p was predicted using starBase and verified using a dual luciferase reporter assay. The release of TNF-α and nitric oxide, as well as caspase-3 activity, were detected using appropriate commercial kits. Flow cytometry analysis was performed to measure cell apoptosis. The results of the present study revealed that the expression levels of SNHG1 were upregulated in the OGD-induced BV-2 cell model. miR-329-3p was discovered to directly target SNHG1, and its mRNA expression levels were downregulated in the OGD-induced BV-2 cell model. The SNHG1-plasmid downregulated miR-329-3p expression levels, while this effect was reversed by transfection with the miR-329-3p mimic. The overexpression of SNHG1 or knockdown of miR-329-3p inhibited OGD-induced BV-2 cell activation. In conclusion, the results of the present study suggested that SNHG1 may reduce microglial cell activity by regulating the expression of miR-329-3p, indicating its potential protective role in cerebral infarction.