Improvement of cerebral ischemia-reperfusion injury by L-3-n-butylphthalide through promoting angiogenesis.

Cerebral ischemia/reperfusion (I/R) injury may lead to a poor prognosis for ischemic stroke patients after reperfusion therapy, and currently, lacks effective therapeutic intervention. This study aimed to investigate the effects of L-3-n-butylphthalide (L-NBP) on cerebral I/R injury in rats. Rat models of cerebral I/R injury were established using the middle cerebral artery occlusion/refusion (MACO/R) surgery and were administrated intragastrically with L-NBP or vehicle. We found that L-NBP attenuated the histological damages and reduced the brain hematoma in MACO/R rats. L-NBP also significantly improved the neurological function, alleviated the brain edema, and reduced the permeability of blood-brain barrier of MACO/R rats. Moreover, we detected that L-NBP considerably facilitated microvessel formation in the lesion area of brain in MACO/R rats. Finally, we found that L-NBP significantly increased the protein and mRNA expression levels of Nrf2, HIF-1α, and VEGF in the brain of MACO/R rats. In conclusion, our results demonstrated that L-NBP exerted significant beneficial effects on cerebral I/R injury in rats through promoting angiogenesis, which may be associated with the activation of Nrf2/HIF-1α/VEGF signaling pathway. Our results suggested that L-NBP could be a potential therapeutic drug for cerebral I/R injury.

Ischemic stroke/transient ischemic attack in adults with primary immune thrombocytopenia: a meta-analysis.

OBJECTIVE: To carry out a systematic review to help resolve the controversy of ischemic stroke (IS)/transient ischemic attack (TIA) in patients with primary immune thrombocytopenia (ITP). METHODS: A database search of PubMed and Ovid Embase was conducted for epidemiologic studies published up to December 17, 2019. The effective size was estimated by pooled prevalence, annualized incidence/risk, relative risk (RR), and their corresponding 95% confidence intervals (CIs). RESULTS: The systematic review included 14 eligible studies from 11 publications. The pooled annualized cumulative incidence was 0.15% (95% CI, 0.03-0.26%) per person-years. And the pooled annualized cumulative risk of IS/TIA of ITP was 0.86% (95% CI, 0.33-1.39%) per year based on 3 population-based cohort studies. There was a higher risk of incident IS/TIA in ITP patients than ITP-free subjects (pooled unadjusted or adjusted RR with 95% CI, 1.46 [1.22-1.74] or 1.50 [1.29-1.73]). CONCLUSIONS: IS/TIA was not uncommon in patients with primary ITP. ITP patients have a higher risk of IS/TIA compared with the reference cohorts. Healthcare professionals should take into account the risk of IS/TIA when treating ITP patients with or without a history of IS/TIA.

BDNF Val66Met polymorphism and cognitive impairment in Parkinson's disease-a meta-analysis.

BACKGROUND: Conflicting results identifying the association between Brain-derived neurotrophic factor (BDNF) polymorphism, Val66Met, and cognitive impairment in Parkinson's disease (PD) have been reported. METHODS AND RESULTS: To clarify whether Val66Met is related to cognitive impairment in PD, we carried out this meta-analysis by searching literature from PubMed, Web of Science, and Embase databases regarding this polymorphism. Six eligible studies involving 1467 PD patients were included in this meta-analysis. Our results showed statistically significant association between Val66Met and risk of cognitive impairment in PD patients in additive model (Met/Met vs. Val/Val: OR 3.82, 95%CI 1.32 to 11.08, p = 0.01) and recessive model (Met/Met vs. Val-carrier: OR 3.81, 95%CI 1.38 to 10.53, p = 0.01) except for dominant model. CONCLUSIONS: Our meta-analysis implicates Val66Met BDNF polymorphism may be associated with Parkinson's disease cognitive impairment, further well-designed studies with larger populations are required to validate these results owing to the limited research.

Lack of association between the Angiogenin (ANG) rs11701 polymorphism and amyotrophic lateral sclerosis risk: a meta-analysis.

To perform a meta-analysis to help resolve the controversy of whether the Angiogenin (ANG) rs11701 polymorphism is associated with amyotrophic lateral sclerosis (ALS) risk. A literature search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, Wanfang and SinoMed was conducted for eligible studies published up to Jun 5, 2015. The strength of the association between the polymorphism and ALS susceptibility was estimated by odds ratio (OR) and associated 95 % confidence interval (CI). The pooled ORs were assessed for the dominant model (TG + GG vs. TT), recessive model (GG vs. TG + TT), heterozygote model (TG vs. TT), homozygote model (GG vs. TT) and allele model (G vs. T). Ten eligible articles were identified, which reported 14 case-control studies and a total of 5807 cases and 3861 controls. Analysis of pooled ORs and 95 % CIs suggested lack of association between the ANG rs11701 polymorphism and risk for ALS, Familial ALS or Sporadic ALS (all p value for z test >0.05). A stratified analysis according to Caucasian or Han Chinese origin further showed that the rs11701 polymorphism was not associated with the disease risk in Caucasians or Han Chinese. There is no difference in the polymorphism frequencies between patients with FALS or SALS. The ANG rs11701 polymorphism was not associated with risk for ALS, FALS or SALS. There is no difference between the polymorphism frequencies in patients with FALS or SALS. Further well-designed studies with larger populations are required to validate these results.

Lack of association between the ATP13A2 A746T variant and Parkinson's disease susceptibility in Han Chinese: a meta-analysis.

PURPOSE: To perform a meta-analysis to help resolve the controversy of whether the ATP13A2 A746T variant is associated with Parkinson's disease (PD) susceptibility in Han Chinese. METHODS: Six literature databases were searched for case-control studies published up to October 2014: Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang and SinoMed. RESULTS: Five eligible articles were identified, which reported six case-control studies and a total of 1703 cases and 2050 controls. The overall results suggested low frequencies of the A746T variant in Han Chinese patients (9/1703, 0.55%) and controls (6/2050, 0.29%). We failed to find evidence of significant differences in variant frequencies among Han Chinese, Uyghur and Japanese patients (p = 0.263). Analysis of pooled odds ratios (ORs) and 95% confidence interval (CIs) revealed no association between the A746T variant and overall PD risk (GA vs. GG: OR 1.78, 95%CI 0.71-4.46, p = 0.216; allele A vs. G: OR 1.90, 95%CI 0.77-4.69, p = 0.167). CONCLUSION: The ATP13A2 A746T variant is rare in Han Chinese patients and controls and is not associated with PD susceptibility in this ethnic group. Variant frequencies do not differ significantly among Han Chinese, Uyghur and Japanese patients. Further well-designed studies with larger samples are needed to validate these results.

Association between the Angiogenin (ANG) K17I variant and amyotrophic lateral sclerosis risk in Caucasian: a meta-analysis.

The study purpose is to perform a meta-analysis to help resolve the debate of whether the Angiogenin (ANG) K17I variant is associated with amyotrophic lateral sclerosis (ALS) risk in Caucasian. Three literature databases were searched for eligible studies published up to January 8, 2015: PubMed, Embase and Web of Science using the following search terms: amyotrophic lateral sclerosis or ALS and Angiogenin or ANG. Five eligible articles were identified, which reported 6 case-control studies and a total of 2326 cases and 3799 controls. The overall results suggested low frequencies of the K17I variant in Caucasian patients (10/2326, 0.43 %) and controls (6/3799, 0.16 %). There is no difference in the variant frequencies between patients with FALS or SALS (p = 0.069). Analysis of pooled odds ratios (ORs) and 95 % confidence intervals (CIs) revealed that the ANG K17I variant increases the risk for ALS (AT vs. AA: OR 2.65, 95 % CI 1.05-6.66, p = 0.038) and familial ALS (FALS) (AT vs. AA: OR 11.81, 95 % CI 2.11-66.15, p = 0.005) but not for sporadic ALS (SALS) (AT vs. AA: OR 1.63, 95 % CI 0.55-4.82, p = 0.378). The ANG K17I variant is rare in Caucasian patients and controls and increases the risk for ALS and FALS but not for SALS in Caucasian populations. Further well-designed studies with larger samples are needed to validate these results.

Homocysteine, vitamin B12, and folate levels in patients with multiple sclerosis in Chinese population: A case-control study and meta-analysis.

BACKGROUND: Current studies suggested discrepancies on the correlations between multiple sclerosis (MS) and blood levels of homocysteine (Hcy), vitamin B12 (VB12), and folate. We performed a case-control study and meta-analysis to help resolve the controversy of these lab values in Chinese patients with MS. METHODS: We recruited 80 Chinese MS patients, 86 age/sex matched neurological controls (patients with peripheral vertigo or sleep disorders), and 80 age- and sex-matched healthy controls. Serum Hcy levels were measured using flourimetric high-performance liquid chromatography, serum levels of VB12 and folate using immune assay. A literature search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed was conducted for case-control studies with pure Chinese populations published up to March 16, 2019. The effective size was estimated by the pooled standardized mean difference (SMD) and associated 95% confidence interval (CI). RESULTS: The case-control study results suggest higher Hcy levels (mean ± SD) and frequency of hyperhomocysteinemia in the Chinese MS cases than control groups (all p < 0.001), lower for VB12 levels (mean ± SD, p = 0.043 or 0.039). No significant difference was observed for levels of folate (mean ± SD, both p > 0.05), and for frequency of folate or VB12 deficiency (all p > 0.05). Analysis of pooled SMDs and 95% CIs suggested increased Hcy levels in Chinese MS patients (SMD: 2.31, 95% CI: 1.33-3.28, p < 0.001), and in relapsing or remitting cases relative to controls (SMD: 0.94 or 0.85, 95% CI: 0.49-1.39 or 0.35-1.34, both p < 0.001). The meta-analysis results also suggested reduced VB12 levels in Chinese MS patients (SMD: -0.30, 95% CI: -0.46-0.14, p < 0.001), and in relapsing MS patients compared to controls (SMD: -0.31, 95% CI: -0.47-0.15, p < 0.001), while no statistical difference for cases in remission. No significant difference was observed for levels folate in all comparisons. CONCLUSION: Patients with MS tend to have increased blood Hcy levels compared to controls. MS patients of Chinese origin and those in relapse may have decreased levels of VB12. Hcy and VB12 may contribute to pathogenesis of the disease, and VB12 may correlate with MS relapse.