Brain Protection Effects of Mild Hypothermia Combined with Distant Ischemic Postconditioning and Thrombolysis in Patients with Acute Ischemic Stroke.

To assess the effectiveness and molecular mechanisms of mild hypothermia and remote ischemic postconditioning (RIPC) in patients with acute ischemic stroke (AIS) who have undergone thrombolysis therapy. A total of 58 AIS patients who received recombinant tissue plasmin activator (rt-PA) intravenous thrombolysis were included in this prospective study. Participants were randomly allocated to the experimental group (rt-PA intravenous thrombolysis plus mild hypothermic ice cap plus remote ischemic brain protection, n = 30) and the control group (rt-PA intravenous thrombolysis plus 0.9% saline, n = 28). The RIPC was performed for 14 consecutive days on both upper limb arteries spaced 2 minutes apart. Five cycles of ischemia-reperfusion were performed sequentially (2-2, 3-3, 4-4, 5-5, 5-0 minutes, respectively). The outcome measures of the National Institute of Health stroke scale (NIHSS) score, volume of cerebral infarction, serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1ß, tumor necrosis factor α, nuclear factors kappa B (NF-κB), and NOD-1ike receptor pyrin 3 (NLRP3) were evaluated at different time points after treatment. Similarly, the 90-day modified Rankin Scale (mRS) scores were compared between the two groups. After treatment, the NIHSS score, MDA, NF-κB, and NLRP3 levels in the experimental group were significantly lower than those in the control group (p < 0.05). While the SOD in the experimental group was significantly higher than in the control group (p < 0.05), the NIHSS scores decreased within groups (all p < 0.05) in both experimental and control groups. The 90-day mRS score (0-2 points) in the experimental group was significantly higher than that in the control group (73.33% vs. 53.57%, p < 0.05) and no significant differences were observed in the safety indices between the two groups (all p > 0.05). Our study shows that combining mild hypothermia and RIPC has a positive effect on brain protection and can significantly reduce the oxidative stress and associated outburst of inflammatory response. The Clinical Trial Registration number is ChiCTR2300073136.

HNSC exosome-derived MIAT improves cognitive disorders in rats with vascular dementia via the miR-34b-5p/CALB1 axis.

OBJECTIVE: To explore the molecular mechanism by which hippocampal neural stem cell (HNSC) exosome (exo)-derived MIAT improves cognitive disorders in rats with vascular dementia (VD). METHODS: Rat hippocampal tissues were collected, and HNSCs and hippocampal neuronal cells (HNCs) were isolated, purified, and identified. Then the exosomes (exo) of the HNSCs were extracted and identified. A VD rat model was constructed. HE staining was used to evaluate the hippocampal pathology in each group. The expressions of the RNAs in the HNSCs were intervened, and the cells were then grouped. ELISA was used to measure the of TNF-α, IL-1, and Aß1-42 expression levels. The kits were used to determine the oxidative stress factor levels. The targeting relationships among MIAT, miR-34b-5p, and CALB1 were measured using dual-luciferase assays. The MIAT expressions in exo were measured using qRT-PCR. The proliferation and apoptosis of the HNCs were determined using CCK-8 and Annexin V-FITC/PI staining, respectively. The CALB1, TH, and Bcl-2 protein expressions were determined using Western blot. The Morris water maze test was used for the spatial learning and memory testing. RESULTS: The hippocampal tissues in the model group were clearly damaged, but the pathological characteristics were significantly improved in the exo group. The exo group also showed an increased SOD level, decreased MDA and ROS levels, and down-regulated TNF-α, IL-1, and Aß1-42 expressions (all P<0.05). MiR-34b-5p had a targeting relationship with both MIAT and CALB1, and MIAT was found to be expressed in exo. The oe-MIAT-exo group and the miR-34b-5p inhibitor group showed significantly up-regulated CALB1, TH, and Bcl-2 protein expressions in the HNCs, increased cell viability, as well as reduced apoptosis, but the si-MIAT-exo group showed the opposite results (all P<0.05). The MiR-34b-5p inhibitor partially reversed the effect on the si-MIAT-exo group. The miR-34b-5p mimic group showed significantly down-regulated CALB1, TH, and Bcl-2 protein expressions in the HNCs, inhibited cell viability, as well as increased apoptosis, but the oe-CALB1 group showed the opposite results (all P<0.05). Oe-CALB1 partially reversed the effect on the miR-34b-5p mimic group. The memory and learning abilities of the rats in the oe-MIAT-exo group and the model + exo group were significantly improved but not as much as they were in the normal rats. CONCLUSION: MIAT-containing exo from HNSCs can improve cognitive disorders in VD rats via the miR-34b-5p/CALB1 axis.

Effects of argatroban therapy for stroke patients: A meta-analysis.

BACKGROUND: The therapeutic efficacy and safety of argatroban for stroke patients remain controversial. The purpose of this study was to collect all evidence and perform a meta-analysis to comprehensively evaluate the effects of argatroban for stroke patients compared with no-argatroban regimens. METHODS: The databases of PubMed, EMBASE and the Cochrane library were searched from their inception up to December 2020. Categorical outcomes were summarized as odds ratio (OR) and 95% confidence interval (CI); while continuous data were pooled as standardized mean difference (SMD) and 95%CI. RESULTS: A total of 11 studies were enrolled. Overall meta-analysis showed infusion of argatroban significantly improved neurological functions of stroke patients compared with control treatment, showing increased National Institutes of Health Stroke Scale (NIHSS) score change (SMD = 1.02; 95% CI, 0.58-1.46, p < 0.001), modified Barthel Index (SMD = 3.81; 95% CI, 2.72-4.89, p < 0.001) as well as a decreased incidence of early neurological deterioration (OR = 0.48; 95% CI: 0.28-0.84, p = 0.01). Argatroban treatment did not increase the risk of symptomatic intracerebral hemorrhage (p = 0.733), asymptomatic intracranial hemorrhage (p = 0.608), gastrointestinal bleeding (p = 0.601), major systemic hemorrhage (p = 0.582) and mortality (p = 0.797), except minor systemic hemorrhage (OR = 2.40; 95% CI: 1.15-5.02, p = 0.020). Subgroup analyses for NIHSS score change and complications obtained the similar conclusions. CONCLUSION: Argatroban infusion may be an effective and safe therapeutic option to improve functional outcomes of stroke patients.

Clinical effect of vestibular rehabilitation on benign paroxysmal positional vertigo: A protocol for systematic review.

BACKGROUND: This study will evaluate the clinical effect of vestibular rehabilitation (VR) on benign paroxysmal positional vertigo (BPPV). METHODS: In this study, we will identify relevant trials on the topic published in MEDLINE, EBASE, Web of Science, Cochrane Library, Scopus, CINAHL, CBM, and CNKI from inception to the present. We will also search conference proceedings, thesis/dissertation, ongoing trials in clinical trial registry, and reference lists of included studies. Two researchers will independently carry out record selection, data extraction, and study quality assessment, respectively. Any disagreement will be arbitrated and solved with the help of a third researcher. If necessary, we will conduct random-effects meta-analysis to pool the effect estimates of included trials determined to be acceptable heterogeneity. RESULTS: We will summarize the latest evidence to assess the effect of VR for the treatment of patients with BPPV. CONCLUSION: The findings of this study will help determine whether or not VR is effective in treating BPPV. OSF REGISTRATION: osf.io/k83y5.

Effect of DPP-4 inhibitor on elderly patients with T2DM combined with MCI.

The aim of this study was to investigate the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor on blood sugar level and cognitive ability in elderly patients with type 2 diabetes mellitus (T2DM) combined with post-stroke mild cognitive impairment (MCI). Thirty patients received DPP-4 inhibitor (study group), while another thirty received sulfonylurea (control group). Six months after treatment, markers regarding blood sugar were improved in both groups (all P<0.05) without intergroup differences (all P>0.05); scores regarding cognitive ability improved in the study group (both P<0.05) and were higher versus the control group (both P<0.01); the study group had higher Aß1-42/Aß1-40 value versus the pretreatment value (P<0.001), which differed from the control group (P<0.05); tumor necrosis factor-α and interleukin-6 concentrations decreased in both groups, while the study group had greater reductions; C-reactive protein value decreased after treatment in the study group (all P<0.05). Using DPP-4 inhibitor in elderly patients with T2DM combined with post-stroke MCI can lower blood sugar and improve cognitive ability. The mechanism may be associated with the improvement of Aß gathering and reduction in inflammatory response.