Diagnosis and Drug Prediction of Parkinson's Disease Based on Immune-Related Genes.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Immune mechanisms play an important role in the development of PD. The purpose of this study was to identify potential differentially expressed immune-related genes (IRGs), signaling pathways, and drugs in PD, which may provide new diagnostic markers and therapeutic targets for PD. Differentially expressed genes (DEGs) and IRGs were respectively obtained from the Gene Expression Omnibus (GEO) dataset and the ImmPort database. Weighted gene co-expression network analysis (WGCNA) was utilized to further identify hub IRGs. Core IRGs were obtained by intersection of DEGs and hub genes in the module of WGCNA, followed by construction of diagnostic models and regulation network establishment of long non-coding RNAs (lncRNAs)-miRNAs-diagnostic IRGs. Analysis of functional enrichment and protein-protein interaction (PPI) network and identification of related drugs of DEGs was performed. LILRB3 and CSF3R were identified as potential diagnostic markers for PD. Two regulatory pairs were identified based on LILRB3 and CSF3R, including XIST-hsa-miR-214-3p/hsa-miR-761-LILRB3 and XIST-hsa-miR-485-5p/hsa-miR-654-5p-CSF3R. LEP and IL1A were drug targets of Olanzapine. MMP9 and HSP90AB1 were drug targets of Bevacizumab. In addition, LEP and MMP9 were respectively drug targets of Lovastatin and Celecoxib. Herpes simplex infection (involved TNFRSF1A) and cytokine-cytokine receptor interaction (involved CSF3R, LEP, and IL1A) were the most remarkably enriched signaling pathways of DEGs. Identified IRGs and related signaling pathways may play critical roles in the development of PD. Additionally, LILRB3 and CSF3R can be considered as potential immune-related diagnostic markers for PD. LEP, IL1A, MMP9, and HSP90AB1 may be regarded as immune-related therapeutic targets for PD.

Thrombolysis and embolectomy in treatment of acute stroke as a bridge to open-heart resection of giant cardiac myxoma: A case report.

BACKGROUND: Cardiac embolism is a common cause of ischemic stroke in young adults. Neurological complications associated with atrial myxoma most frequently include cerebral infarct due to embolus. Early complete resection of giant cardiac myxoma is the key to its treatment and prevention of stroke recurrence. CASE SUMMARY: A 42-year-old, previously healthy woman was admitted to the hospital with sudden-onset inability to speak and right-sided hemiplegia. While sweeping the floor 2 h prior to hospital admission, the patient developed sudden inability to express herself or understand what others were saying, accompanied by dyskinesia of the right limb, inability to walk or hold objects, and involuntary choreiform movements of the left upper limb. The patient was diagnosed with cerebral embolism and cardiac myxoma, complicated by left middle cerebral artery occlusion. The acute stroke was treated with intravenous thrombolytic therapy and arterial embolectomy as a bridging therapy to open resection of left atrial cardiac myxoma. The patient condition improved remarkably following initial thrombolysis and embolectomy and subsequently underwent emergency open resection of the atrial cardiac myxoma. She had no recurrence during 1-year follow-up. CONCLUSION: Strong consideration should be given to urgent intravenous thrombolysis (rt-PA, alteplase) in young adult stroke patients at the time of hospital admission. The present case demonstrated a highly successful outcome that combined thrombolysis and arterial embolus retrieval as a bridge to early complete resection of a giant cardiac myxoma for both stroke treatment and recurrence prevention.

Assessing the Efficacy and Safety of Tirofiban in Combination With Dual-antiplatelet Therapy in Progressive Ischemic Stroke Patients.

ABSTRACT: This study assessed the efficacy and safety of tirofiban in combination with dual-antiplatelet therapy (DAPT) in progressive ischemic stroke. One hundred and four patients equally divided into a tirofiban group or DAPT group were enrolled from June 2018 to December 2019. Efficacy outcomes included National Institutes of Health Stroke Scale score for 14 days, and modified Rankin scale (mRs) scores as excellent (mRs 0-1) or favorable (mRs 0-2) measured 90 days after stroke. At 14 days, the tirofiban group had a lower National Institutes of Health Stroke Scale score compared with the DAPT group (F = 14.959, P = 0.000). The mRS scores of the 2 groups at 90 days after treatment were significantly different from those before treatment. At 90 days, excellent favorable functional outcome (mRS ≤ 2) was achieved in 33 of 52 (63.43%) patients in the tirofiban group compared with 25 of 52 (48.08%) patients in the DAPT group. The incidence of bleeding was 5.77% in the tirofiban group, compared with 0% in DAPT group. Intravenous (IV) tirofiban alone or combined with DAPT was shown to be safe and effectively improved clinical outcome in progressive ischemic stroke patients. IV tirofiban was shown to be superior to the DAPT regimen.

Uncovering the Potential Differentially Expressed miRNAs and mRNAs in Ischemic Stroke Based on Integrated Analysis in the Gene Expression Omnibus Database.

INTRODUCTION: Ischemic stroke is the third leading cause of death. There is no known treatment or cure for the disease. Moreover, the pathological mechanism of ischemic stroke remains unclear. OBJECTIVE: We aimed to identify potential microRNAs (miRNAs) and mRNAs, contributing to understanding the pathology of ischemic stroke. METHODS: First, the data of miRNA and mRNA were downloaded for differential expression analysis. Then, the regulatory network between miRNA and mRNAs was constructed. Third, top 100 differentially expressed mRNAs were used to construct a protein-protein interaction network followed by the function annotation of mRNAs. In addition, in vitro experiment was used to validate the expression of mRNAs. Last, receiver operating characteristic diagnostic analysis of differentially methylated genes was performed. RESULTS: Totally, up to 26 differentially expressed miRNAs and 1,345 differentially expressed mRNAs were identified. Several regulatory interaction pairs between miRNA and mRNAs were identified, such as hsa-miR-206-HMGCR/PICALM, hsa-miR-4491-TMEM97, hsa-miR-3622b-5p/hsa-miR-548k-KLF12, and hsa-miR-302a-3p/hsa-miR-3145-3p-CTSS. MAPK signaling pathway (involved DUSP1) and the Notch signaling pathway (involved NUMB and CREBBP) were identified. The expression validation of KLF12, ARG1, ITGAM, SIRT4, SERPINH1, and DUSP1 was consistent with the bioinformatics analysis. Interestingly, hsa-miR-206, hsa-miR-4491, hsa-miR-3622b-5p, hsa-miR-548k, hsa-miR-302a-3p, hsa-miR-3145-3p, KLF12, and ID3 had the potential diagnostic value of ischemic stroke. CONCLUSIONS: The identified differentially expressed miRNAs and mRNAs may be associated with the development of ischemic stroke.

Relationship between elevated plasma trimethylamine N-oxide levels and increased stroke injury.

OBJECTIVE: To investigate whether elevated plasma trimethylamine N-oxide (TMAO) levels are associated with initial stroke severity and infarct volume. METHODS: This cross-sectional study included 377 patients with acute ischemic stroke and 50 healthy controls. Plasma TMAO levels were assessed at admission. Stroke infarct size and clinical stroke severity were measured with diffusion-weighted imaging and the NIH Stroke Scale (NIHSS). Mild stroke was defined as an NIHSS score <6. RESULTS: Plasma TMAO levels were higher in patients with ischemic stroke than in healthy controls (median 5.1 vs 3.0 µmol/L; p < 0.001). Every 1-µmol/L increase in TMAO was associated with a 1.13-point increase in NIHSS score (95% confidence interval [CI] 1.04-1.29; p < 0.001) and 1.69-mL increase in infarct volume (95% CI 1.41-2.03; p < 0.001) after adjustment for vascular risk factors. At admission, 159 patients (42.2%) had experienced a mild stroke, and their plasma TMAO levels were lower compared to those with moderate to severe stroke (median 3.6 vs 6.5 µmol/L; p < 0.001). The area under the receiver operating characteristics curve of plasma TMAO level in predicting moderate to severe stroke was 0.794 (95% CI 0.748-0.839; p < 0.001), and the optimal cutoff value was 4.95 µmol/L. The sensitivity and specificity of TMAO levels ≥4.95 µmol/L for moderate to severe stroke were 70.2% and 79.9%, respectively. CONCLUSIONS: Patients with ischemic stroke had higher plasma TMAO levels compared to healthy controls. Higher plasma TMAO level at admission is an independent predictor of stroke severity and infarct volume in patients with acute ischemia.

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.

Genome-Wide Profiling of miRNA and mRNA Expression in Alzheimer's Disease.

BACKGROUND Our study aimed to identify key differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) which can serve as potential biomarkers for diagnosis and therapy of Alzheimer's disease (AD). MATERIAL AND METHODS We performed miRNA and mRNA integrated analysis (MMIA) to identify DEGs and DEmiRNAs of AD. The AD-specific DEmiRNAs-targets interaction network was contrasted. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed. Q-RT-PCR was used to verify the expression of selected DEGs and DEmiRNAs. RESULTS We conducted MMIA of AD based on 1 miRNA dataset and 3 mRNA datasets derived from the Gene Expression Omnibus (GEO) database; 1759 DEGs and 12 DEmiRNAs were obtained. DEGs of AD were significantly enriched in Huntington's disease and AD. LRP1, CDK5R1, PLCb2, NDUFA4, and DLG4 were 5 DEGs regulated by 4 DEmiRNAs, including miR-26b-5p, miR-26a-5p, miR-107, and miR-103a-3p. These 4 miRNAs were the top 4 miRNAs covering most DEGs. According to the qRT-PCR results, the expression of PLCß2, NDUFA4, DLG4, miR-107, and miR-103a-3p was consistent with our integrated analysis. CONCLUSIONS We concluded that LRP1, CDK5R1, PLCß2, NDUFA4, and DLG4 may play a role in AD regulated by miR-26b-5p, miR-26a-5p, miR-107, and miR-103a-3p. Our findings will contribute to identification of biomarkers and new strategies for drug design for AD treatment.

Botulinum toxin type A with or without needle electromyographic guidance in patients with cervical dystonia.

AIM: To investigate the efficacy and safety of electromyography (EMG)- and palpation-guided botulinum toxin type A injection in cervical dystonia (CD) patients. METHODS: In this randomized, controlled trial, 68 CD patients were randomly allocated to two groups, receiving botulinum toxin type A injections guided by either palpation (Group A) or EMG (Group B). The primary endpoint is defined as the difference in the Tsui score between groups at 16 weeks. The secondary endpoints were the visual analog scale (VAS) and Hospital Anxiety and Depression Scale (HADS) scores and Clinical and Patient Global Impression of Change (CGIC and PGIC). RESULTS: Sixty-five patients completed the study. No significant difference was observed in the Tsui score between groups A and B at 4, 8, and 12 weeks after treatment (p > 0.05). However, 16 weeks after treatment, the Tsui score of group A was significantly higher than that of group B. For both groups, the degree of pain at each time point during follow-up significantly reduced after treatment. However, no significant difference was observed in VAS scores between the two groups. Interestingly, the patient HADS score decreased without statistical significance 8 weeks following treatment. No significant difference in HADS scores was observed between the two groups. Additionally, there was no significant difference in PGIC and CGIC between the two groups. However, CGIC was significantly higher than PGIC. No significant difference in adverse reactions was observed between groups. CD patients treated with EMG guidance experienced a significantly more pain at the injection site but a significantly lower adverse event occurrence rate of dysphagia when compared to CD patients treated with palpation guidance only. CONCLUSIONS: CD patients treated with EMG guidance experienced a prolonged benefit as measured by the Tsui scale when compared to CD patients treated with palpation guidance alone. EMG-guided injection resulted in a lower incidence of dysphagia and higher incidence of discomfort at the injection site than palpation-guided injection.