Development of a novel immune infiltration-related diagnostic model for Alzheimer's disease using bioinformatic strategies.

Background: The pathogenesis of Alzheimer's disease (AD) is complex and multi-factorial. Increasing evidence has shown the important role of immune infiltration in AD. Thus the current study was designed to identify immune infiltration-related genes and to explore their diagnostic value in AD. Methods: The expression data of AD patients were downloaded from the GEO database. The limma R package identified differentially expressed genes (DEGs) between AD and controls. The CIBERSORT algorithm identified differentially infiltrated immune cells (DIICs) between AD and controls. DIIC-correlated DEGs were obtained by Pearson correlation analysis. WGCNA was employed to identify DIIC-related modules. Next, LASSO, RFE, and RF machine learning methods were applied to screen robust DIIC-related gene signatures in AD, followed by the construction and validation of a diagnostic nomogram. Detection of the expression of related genes in the peripheral blood of Alzheimer's disease and healthy volunteers by RT-PCR. In addition, the CTD database predicted chemicals targeting DIIC-related gene signatures in the treatment of AD. Results: NK cells, M0 macrophages, activated myeloid dendritic cells, resting mast cells, CD8+ T cells, resting memory CD4+ T cells, gamma delta T cells, and M2 macrophages were differentially infiltrated between AD and controls. Pearson analysis identified a total of 277 DIIC-correlated DEGs between AD and controls. Thereafter, 177 DIIC-related genes were further obtained by WGCNA analysis. By LASSO, RFE and RF algorithms, CMTM2, DDIT4, LDHB, NDUFA1, NDUFB2, NDUFS5, RPL17, RPL21, RPL26 and NDUFAF2 were identified as robust gene signature in AD. The results of RT-PCR detection of peripheral blood samples from Alzheimer's disease and healthy volunteers showed that the expression trend of ten genes screened was consistent with the detection results; among them, the expression levels of CMTM2, DDIT4, LDHB, NDUFS5, and RPL21 are significantly different among groups. Thus, a diagnostic nomogram based on a DIIC-related signature was constructed and validated. Moreover, candidate chemicals targeting those biomarkers in the treatment of AD, such as 4-hydroxy-2-nonenal, rosiglitazone, and resveratrol, were identified in the CTD database. Conclusion: For the first time, we identified 10 immune infiltration-related biomarkers in AD, which may be helpful for the diagnosis of AD and provide guidance in the treatment of AD.

Successful mechanical thrombectomy in acute bilateral M1 middle cerebral artery occlusion: a case report and literature review.

BACKGROUND: Acute bilateral occlusion of the middle cerebral artery (MCA) is a very rare condition, and most cases are accompanied by a poor prognosis. However, mechanical thrombectomy (MT) for bilateral MCA is challenging. Here, we report a case of acute unilateral MCA occlusion with sequential acute occlusion of the bilateral MCA during intravenous thrombolysis (IVT). We urgently performed bilateral MT of the MCA and effective recanalization. CASE PRESENTATION: The patient is a 73-year-old man who complained of a sudden adverse influence on speech and an inability to move his left limb for 2 h. He had a history of paroxysmal atrial fibrillation, but had never used any anticoagulants before. Head and neck computed tomography angiography (CTA) showed embolism in the right M1 MCA. During intravenous alteplase thrombolytic therapy, the patient suddenly became unconscious. Cerebral angiography showed occlusion of the M1 segment of the bilateral MCA in the patients. MT of the bilateral MCA was performed using a combination of a stent retriever and an aspiration catheter with mTici 3 revascularization. On the second day, the patient became conscious, although he had remaining symptoms of speech insufficiency and weakness of the left limb. The mRS score was 2 90 days after the operation. CONCLUSIONS: Acute bilateral occlusion of the M1 segment of the MCA is extremely rare and is accompanied by high morbidity and high mortality. Intravenous alteplase thrombolysis can increase the risk of atrial thrombus shedding in patients with atrial fibrillation, so patients with acute bilateral MCA occlusion in the M1 segment chose direct MT or bridging therapy, which remains controversial, and the sequence of MT remains to be discussed. Nevertheless, early endovascular treatment can decrease the morbidity and mortality of such patients.

Epigenetic transcripts of LINC01311 and hsa-miR-146a-5p regulate neural development in a cellular model of Alzheimer's disease.

Emerging evidence has shown that Long noncoding RNAs (LncRNAs) are aberrantly expressed and functionally involved in the development of neurodegenerative disorders. In this work, we investigated the regulatory effects of lncRNA of LINC01311 and its competing endogenous RNA target of hsa-miR-146a-5p in a cellular model of Alzheimer's disease (AD). SH-SY5Y cells were treated with synthetic Βeta-Amyloid Peptide (1-42) (AB1-42) in vitro to induce AD-like neural injuries. Expressions of LINC01311 and hsa-miR-146a-5p were monitored by qRT-PCR. LINC01311 was upregulated and hsa-miR-146a-5p downregulated to examine their functional regulations on AB1-42-induced apoptosis, proliferation slowdown, autophagy, and amyloid precursor protein (APP) accumulations. Hsa-miR-146a-5p was also overexpressed in LINC01311-upregulated SH-SY5Y cells to examine their correlated regulations on AB1-42-induced neural injuries. LINC01311 was downregulated whereas hsa-miR-146a-5p upregulated in AB1-42 treated SH-SY5Y cells. LINC01311 upregulation and hsa-miR-146a-5p downregulation protected AB1-42-induced apoptosis, proliferation slowdown, autophagy, and APP accumulations in SH-SY5Y cells. Hsa-miR-146a-5p overexpression reversed the protection of LINC01311 on AB1-42-induced neural injuries. Our work demonstrated that the epigenetic axis of LINC01311/hsa-miR-146a-5p was involved in the functional regulation of human-lineage neurons in a cellular model of AD, thus suggesting a clinical potential of exploring epigenetic network for treating AD patients.

First-Principles Study on Self-Activated Luminescence and 4f → 5d Transitions of Ce3+ in M5(PO4)3X (M = Sr, Ba; X = Cl, Br).

The origin of the self-activated luminescence in the apatite-type M5(PO4)3X (MPOX; M = Sr or Ba; X = Cl or Br) samples and the spectral assignment for cerium-doped Sr5(PO4)3Cl (SPOC) phosphors are determined from first-principles methods combined with hybrid density functional theory (DFT) calculations, using the standard PBE0 hybrid functional, with wave function-based embedded-cluster ab initio calculations (at the CASSCF/CASPT2/RASSI-SO level). Electronic structure calculations are performed in order to accurately derive the band gaps of the hosts, the locations of impurity states in the energy bands that are caused by native defects and doped Ce3+ ions, and the charge-compensation mechanisms of aliovalent doping. The calculations of defect formation energies under O-poor conditions demonstrate that the native defects are easily generated in the undoped MPOX samples prepared under reducing atmospheres, from which thermodynamic and optical transition energy levels, as well as the corresponding energies, are derived in order to interpret the luminescence mechanisms of the undoped MPOX as previously reported. Our calculations reveal that the self-activated luminescence is mainly attributed to the optical transitions of the excitons bound to the oxygen vacancies (VO), along with their transformation of the charge states 0 ↔ 1+. Furthermore, the eight excitation bands observed in the synchrotron radiation excitation spectra of SPOC: Ce3+, Na+ phosphors are successfully assigned according to the ab initio calculated energies and relative oscillator strengths of the 4f1 → 5d1-5 transitions for the Ce3+ ions at both the Sr(1) and Sr(2) sites in the host. It is hoped that the feasible first-principles approaches in this work are applied in order to explore the origins of the luminescence in undoped and lanthanide-doped phosphors, complementing the experiments from the perspective of chemical compositions and the microstructures of materials.

Effectiveness of Revive SE in the RAPID registry : Revive Acute Ischemic Stroke Patients ImmeDiately (RAPID) Prospective Multicenter Trial.

PURPOSE: The prospective, multicenter Revive Acute ischemic stroke Patients ImmeDiately (RAPID) trial was carried out to evaluate the real-world safety and efficacy of the Revive SE stent retriever. METHODS: From January 2017 the study planned to enroll 100 patients with acute ischemic stroke who were treated with the Revive SE as a first pass. The study primary outcomes were rates of favorable reperfusion using the modified thrombolysis in cerebral infarction score [mTICI] 2b/3 and rates of favorable outcome with the modified Rankin Scale (mRS) ≤2 at 3 months. The secondary outcomes were time interval from puncture to vascular reperfusion, number of passes by Revive SE stent-retriever, incidence of distal embolization and into new territories and rate of symptomatic intracranial hemorrhage (SICH) within 24 h post intervention. RESULTS: A total of 100 treated patients (mean age: 65.6 ± 11.3 years) were enrolled. The median National Institutes of Health Stroke Scale before the procedure was 16. Target vessel occlusions were as follows: middle cerebral artery (MCA) M1 in 48, M2 in 6, anterior cerebral artery (ACA) in 3, internal carotid artery (ICA) in 22, basilar artery (BA) in 17, and vertebral artery (VA) in 4. Reperfusion rate with Revive SE without rescue devices was 69%. Reperfusion rate with Revive SE only was 83.3% in MCA M2, followed by 82.4% in BA. Thromboembolic complications and SICH developed in 10% and 2% of patients, respectively. Overall, a satisfactory reperfusion was achieved in 92% and a favorable outcome at 90 days in 48%. CONCLUSION: Use of the Revive SE for thrombectomy appeared to be effective and safe but these findings need be confirmed in larger clinical trials (RAPID ClinicalTrials.gov number, NCT03007082).

Impaired Center-Surround Suppression in Patients with Alzheimer's Disease.

Alzheimer's disease (AD) is often associated with declined visual processing abilities. Here we tested whether the functions of center-surround suppression- a hallmark property in the visual system- are altered by AD. To this end, we recruited three groups of participants (AD, elderly, and young) in a motion direction discrimination task, in which we measured the temporal duration threshold of a  drifting Gabor with varying stimulus sizes. We first replicated the phenomena of center-surround suppression that the required duration for discriminating a high contrast grating decreases with increasing stimulus size. We then showed that the magnitudes of suppression varied among the three groups. There was progressive reduction of suppression in the elderly and AD groups compared with the young group. Interestingly, we found that the levels of suppression can predict the severity of dementia in the AD group. Our results suggest that AD is associated with impaired center-surround functions in the visual motion processing pathway.

Local thrombolytic therapy in severe cerebral venous sinus thrombosis during puerperium.

This study is to explore and evaluate the efficacy and safety of local thrombolytic therapy in superior sagittal sinus in patients with severe cerebral venous sinus thrombosis during puerperium, as well as the efficacy and safety of anti-platelet aggregation treatment for preventing recurrence. Twelve patients during postpartum period with cerebral venous sinus thrombosis were received local thrombolytic therapy by placing a micro-catheter at the distal end of superior sagittal sinus from January 2008 to December 2013. All the patients accepted mechanical thrombus maceration before local intrasinus thrombolytic therapy, and were treated with low molecular weight heparin in the acute phase. After local thrombolytic therapy, anti-platelet aggregation treatment was performed for 6 months. Follow-up data included lumber puncture, fundus examination and magnetic resonance venography (MRV) once per half year for 6-70 months. At discharge, the intracranial pressure of 12 patients reduced to below 200 mmH2O. DSA or MRV confirmed that superior sagittal sinus of 9 patients were smooth. The cortex venous and deep venous were recovered to normal. Superior sagittal sinus of 3 patients recanalized partly. Cortex venous and deep venous was compensated. The follow-up study indicated that no thrombosis and new neurological symptoms occurred among all patients. Local thrombolytic treatment is safe and effective in patients with severe cerebral venous sinus thrombosis during puerperium. The collateral circulation compensation is the main recovery factor. And it is also safe and effective for anti-platelet aggregation treatment to prevent recurrence of cerebral venous sinus thrombosis.

Combining transarterial chemoembolization with radiofrequency ablation for hepatocellular carcinoma.

The aim of this study was to compare the effectiveness of combination of radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) with that of RFA alone in patients with hepatocellular carcinoma (HCC). All possible trials comparing RFA plus TACE with RFA alone for HCC were included into this meta-analysis. We estimated the summary odds ratio (OR) with its 95% confidence interval (95% CI) to assess the effects. Nineteen eligible studies matched the selection criteria, including 1,728 patients. Meta-analysis showed that the combination of TACE and RFA (OR(1 year) = 2.14, 95% CI = 1.57-2.91, P < 0.001; OR(3 years) = 1.98, 95% CI = 1.28-3.07, P = 0.001; OR(5 years) = 2.70, 95% CI = 1.42-5.14, P = 0.003) were associated with higher survival rates. No evidence of publication bias was observed. High-quality evidence suggests that TACE plus RFA improve the survival rates compared with RFA alone for patients with HCC.