Classification and hemodynamic characteristics of delayed intracerebral hemorrhage following stent-assisted coil embolism in unruptured intracranial aneurysms.

Background and objective: Stent-assisted coil (SAC) embolization is a commonly used endovascular treatment for unruptured intracranial aneurysms (UIAs) but can be associated with symptomatic delayed intracerebral hemorrhage (DICH). Our study aimed to investigate the hemodynamic risk factors contributing to DICH following SAC embolization and to establish a classification for DICH predicated on hemodynamic profiles. Methods: This retrospective study included patients with UIAs located in the internal carotid artery (ICA) treated with SAC embolization at our institution from January 2021 to January 2022. We focused on eight patients who developed postoperative DICH and matched them with sixteen control patients without DICH. Using computational fluid dynamics, we evaluated the hemodynamic changes in distal arteries [terminal ICA, the anterior cerebral artery (ACA), and middle cerebral artery (MCA)] pre-and post-embolization. We distinguished DICH-related arteries from unrelated ones (ACA or MCA) and compared their hemodynamic alterations. An imbalance index, quantifying the differential in flow velocity changes between ACA and MCA post-embolization, was employed to gauge the flow distribution in distal arteries was used to assess distal arterial flow distribution. Results: We identified two types of DICH based on postoperative flow alterations. In type 1, there was a significant lower in the mean velocity increase rate of the DICH-related artery compared to the unrelated artery (-47.25 ± 3.88% vs. 42.85 ± 3.03%; p < 0.001), whereas, in type 2, there was a notable higher (110.58 ± 9.42% vs. 17.60 ± 4.69%; p < 0.001). Both DICH types demonstrated a higher imbalance index than the control group, suggesting an association between altered distal arterial blood flow distribution and DICH occurrence. Conclusion: DICH in SAC-treated UIAs can manifest as either a lower (type 1) or higher (type 2) in the rate of velocity in DICH-related arteries. An imbalance in distal arterial blood flow distribution appears to be a significant factor in DICH development.

Carbon Nitride-Based siRNA Vectors with Self-Produced O2 Effects for Targeting Combination Therapy of Liver Fibrosis via HIF-1α-Mediated TGF-ß1/Smad Pathway.

Hypoxia is an important feature, which can upregulate the hypoxia-inducible factor-1α (HIF-1α) expression and promote the activation of hepatic stellate cells (HSCs), leading to liver fibrosis. Currently, effective treatment for liver fibrosis is extremely lacking. Herein, a safe and effective method is established to downregulate the expression of HIF-1α in HSCs via targeted delivery of VA-PEG-modified CNs-based nanosheets-encapsulated (VA-PEG-CN@GQDs) HIF-1α small interfering RNA (HIF-1α-siRNA). Due to the presence of lipase in the liver, the reversible release of siRNA can be promoted to complete the transfection process. Simultaneously, VA-PEG-CN@GQD nanosheets enable trigger the water splitting process to produce O2 under near-infrared (NIR) irradiation, thereby improving the hypoxic environment of the liver fibrosis site and maximizing the downregulation of HIF-1α expression to improve the therapeutic effect, as demonstrated in liver fibrosis mice. Such combination therapy can inhibit the activation of HSCs via HIF-1α-mediated TGF-ß1/Smad pathway, achieving outstanding therapeutic effects in liver fibrosis mice. In conclusion, this study proposes a novel strategy for the treatment of liver fibrosis by regulating the hypoxic environment and the expression of HIF-1α at lesion site.

Overview of the 2022 WHO Classification of Pituitary Adenomas/Pituitary Neuroendocrine Tumors: Clinical Practices, Controversies, and Perspectives.

The latest edition of the WHO classification of the central nervous system was published in 2021. This review summarizes the major revisions to the classification of anterior pituitary tumors. The most important revision involves preferring the terminology of pituitary neuroendocrine tumor (PitNET), even though the terminology of pituitary adenoma (PA) still can be used according to this WHO classification compared to the previous one. Moreover, immunohistochemistry (IHC) examination of pituitary-specific transcription factors (TFs), including PIT1, TPIT, SF-1, GATA2/3, and ERα, is endorsed to determine the tumor cell lineage and to facilitate the classification of PitNET/PA subgroups. However, TF-negative IHC staining indicates PitNET/PA with no distinct cell lineages, which includes unclassified plurihormonal (PH) tumors and null cell (NC) tumors in this edition. The new WHO classification of PitNET/PA has incorporated tremendous advances in the understanding of the cytogenesis and pathogenesis of pituitary tumors. However, due to the shortcomings of the technology used in the diagnosis of PitNET/PA and the limited understanding of the tumorigenesis of PitNET/PA, the application of this new classification system in practice should be further evaluated and validated. Besides providing information for deciding the follow-up plans and adjunctive treatment after surgery, this classification system offers no additional help for neurosurgeons in clinical practice, especially in determining the treatment strategies. Therefore, it is necessary for neurosurgeons to establish a comprehensive pituitary classification system for PitNET/PA that incorporates neuroimaging grading data or direct observation of invasiveness during operation or the predictor of prognosis, as well as pathological diagnosis, thereby distinguishing the invasiveness of the tumor and facilitating neurosurgeons to decide on the treatment strategies and follow-up plans as well as adjunctive treatment after surgery.

Surgical Technique and Efficacy Analysis of Extra-pseudocapsular Transnasal Transsphenoidal Surgery for Pituitary Microprolactinoma.

OBJECTIVE: To elucidate the role of transsphenoidal surgery in the treatment of pituitary microprolactinoma. METHODS: The clinical data of 107 prolactinoma cases treated by extra-pseudocapsular transnasal transsphenoidal surgery (ETTS) for different indications in our department since 2011 was retrospectively analyzed. RESULTS: The most common indication was the ineffectiveness of oral medication (41.1%), followed by the personal willingness of the patient (35.5%), and 20.6% of the patients were young women with clear tumor boundaries. The pseudocapsule was not observed in 63 cases (58.9%), incomplete pseudocapsule was observed in 26 cases (24.3%), and complete pseudocapsule in 18 cases (16.8%). A total of 97 patients (90.7%) obtained 1-year post-operation remission. According to the relative location of the adenoma and pituitary gland on the MRI scan, 46 patients were classified into a central type, 59 a lateral type, and 2 a supra-pituitary type. Two patients developed hypogonadism, one patient developed hypocortisolism, and one patient developed post-operative hypothyroidism. Two patients were administrated with hormone replacement treatment, and the treatment was stopped within one week. There was no permanent hypopituitarism. Further investigation demonstrated that the adenoma types could affect the remission rates of hyperprolactinemia and gross total resection rate in microprolactinoma. CONCLUSION: ETTS was an effective treatment for pituitary microprolactinomas. This could be the first choice for patients who presented enclosed adenoma on the MRI and were potentially curable in a preoperative evaluation. Maximal safe removal of the adenoma by ETTS with the aim to increase the sensitivity of the drugs was also recommended for patients with invasive dopamine agonist resistant prolactinomas and patients with difficulty in childbirth.

LINC00365 inhibited lung adenocarcinoma progression and glycolysis via sponging miR-429/KCTD12 axis.

This study researched the function of long non-coding RNA LINC00365 in lung adenocarcinoma (LAD) progression. LINC00365, miR-429, and KCTD12 expression in the LAD clinical tissues and cells were detcetd by qRT-PCR and Western blot. LINC00365, miR-429, and KCTD12 effects on H1975 cells malignant phenotype were detected by cell counting kit-8 assay, clone formation experiment, Transwell experiment, and glycolysis. Dual luciferase reporter gene assay and RNA pull-down assay were implemented. LINC00365 effect on H1975 cells in vivo growth was detected. LINC00365 was low expressed in the LAD patients and cells, associating with poor outcome. LINC00365 up-regulation attenuated H1975 cells proliferation, migration, invasion, glycolysis and in vivo growth. LINC00365 inhibited KCTD12 expression by sponging miR-429. miR-429 up-regulation and KCTD12 down-regulation partial reversed LINC00365 inhibition on H1975 cells malignant phenotype. Thus, LINC00365 inhibited LAD progression and glycolysis via targeting miR-429/KCTD12 axis. LINC00365 might be a potential candidate for LAD target treatment clinically.

Curcumin increases crizotinib sensitivity through the inactivation of autophagy via epigenetic modulation of the miR-142-5p/Ulk1 axis in non-small cell lung cancer.

Drug resistance is a critical factor responsible for the recurrence of non-small cell lung cancer (NSCLC). Previous studies suggest that curcumin acts as a chemosensitizer and radiosensitizer in human malignancies, but the underlying mechanism remains elusive. In the present study, we explored how curcumin regulates the expression of miR-142-5p and sensitizes NSCLC cells to crizotinib. We found that miR-142-5p is significantly downregulated in NSCLC tissue samples and cell lines. Curcumin could increase crizotinib cytotoxicity by epigenetically restoring the expression of miR-142-5p. Furthermore, curcumin treatment suppressed the expression of DNA methylation-related enzymes, including DNMT1, DNMT3A, and DNMT3B, in NSCLC cells. In addition, the upregulation of miR-142-5p expression increased crizotinib cytotoxicity and induced apoptosis in tumor cells in a similar manner to that of curcumin. Strikingly, miR-142-5p overexpression suppressed crizotinib-induced autophagy in A549 and H460 cells. Mechanistically, miR-142-5p inhibited autophagy in lung cancer cells by targeting Ulk1. Overexpression of Ulk1 abrogated the miR-142-5p-induced elevation of crizotinib cytotoxicity in A549 and H460 cells. Collectively, our findings demonstrate that curcumin sensitizes NSCLC cells to crizotinib by inactivating autophagy through the regulation of miR-142-5p and its target Ulk1.

Evaluation of the in vitro Activity and in vivo Efficacy of Anidulafungin-Loaded Human Serum Albumin Nanoparticles Against Candida albicans.

Recent decades have seen a significant increase in invasive fungal infections, resulting in unacceptably high mortality rates. Anidulafungin (AN) is the newest echinocandin and appears to have several advantages over existing antifungals. However, its poor water solubility and burdensome route of administration (i.e., repeated, long-term intravenous infusions) have limited its practical use. The objective of this study was to develop anidulafungin-loaded Human Serum Albumin (HSA) nanoparticles (NP) so as to increase both its solubility and antifungal efficacy. HSA was reduced using SDS and DTT, allowing liberation of free thiols to form the intermolecular disulfide network and nanoassembly. Reduced HSA was then added to MES buffer (0.1 M, pH 4.8) and magnetically stirred at 350 rpm and 25°C with AN (m/m 50:1) for 2 h to form nanoparticles (AN NP). We next performed routine antifungal susceptibility testing of Candida strains (n = 31) using Clinical and Laboratory Standards Institute (CLSI) methodologies. Finally, the in vivo efficacy of both AN and AN NP was investigated in a murine model of invasive infection by one of the most common fungal species-C. albicans. The results indicated that our carrier formulations successfully improved the water solubility of AN and encapsulated AN, with the latter having a particle size of 29 ± 1.5 nm with Polymer dispersity index (PDI) equaling 0.173 ± 0.039. In vitro AN NP testing revealed a stronger effect against Candida species (n = 31), with Minimum Inhibitory Concentration (MIC) values 4- to 32-fold lower than AN alone. In mice infected with Candida and having invasive candidiasis, we found that AN NP prolonged survival time (P < 0.005) and reduced fungal burden in kidneys compared to equivalent concentrations of free drug (P < 0.0001). In conclusion, the anidulafungin nanoparticles developed here have the potential to improve drug administration and therapeutic outcomes for individuals suffering from fungal diseases.

Role of Neonatal Behavioral Neurological Assessment combined with magnetic resonance diffusion tensor imaging in evaluating white matter development in preterm infants. / NBNAè¯„åˆ†è”åˆç£å ±æŒ¯å¼¥æ•£å¼ é‡æˆåƒåœ¨æ—©äº§å„¿è„‘ç™½è´¨å‘è‚²è¯„ä»·ä¸­çš„ä½œç”¨åŠç›¸å ³æ€§åˆ†æž.

OBJECTIVES: To study the correlation of fractional anisotropy (FA) on magnetic resonance diffusion tensor imaging with Neonatal Behavioral Neurological Assessment (NBNA) score in preterm infants, and to study the role of FA in evaluating white matter development from the perspective of imaging. METHODS: A prospective study was performed for 98 preterm infants who were admitted to the Neonatal Intensive Care Unit of the Third Affiliated Hospital of Zhengzhou University within 24 hours after birth from October 2016 to January 2020. According to the results of NBNA, they were divided into an abnormal group with 51 infants (NBNA score <37) and a normal group with 47 infants (NBNA score ≥37). The FA values of 10 regions of interest were collected and compared between the two groups. The correlations of FA value and umbilical arterial blood gas pH value with the NBNA score were analyzed. RESULTS: Compared with the normal group, the abnormal group had significantly lower FA value of the posterior limb of the internal capsule and umbilical arterial blood pH (P<0.05). The FA value of the posterior limb of the internal capsule and umbilical arterial blood pH were positively correlated with the NBNA score (r=0.584 and 0.604 respectively, P<0.001), and the FA value of the posterior limb of the internal capsule was positively correlated with umbilical arterial blood pH (r=0.426, P<0.05). CONCLUSIONS: The FA value of the posterior limb of the internal capsule can quantitatively reflect white matter development in preterm infants and is correlated with the NBNA score. The combination of the two indices can help to evaluate white matter development in preterm infants more accurately and objectively. Citation.

Diagnostic Value of Diffusion Tensor Imaging for Infants' Brain Development Retardation Caused by Pre-Eclampsia.

Objective: Pre-eclampsia (PE) can cause brain development delay in infants. This work aims to characterize the pattern differences of brain white matter development in premature infants under PE conditions and those without. Methods: Eighty preterm infants delivered by women with PE were selected as the PE group, and ninety-six preterm infants of the same period born to women without high-risk perinatal factors were used as control. All infants underwent diffusion tensor imaging (DTI) examination. The fractional anisotropy (FA) was measured in five regions of interests (ROIs), including posterior limbs of internal capsule (PLIC), splenium of the corpus callosum (SCC), superior frontal gyrus (SFG), superior parietal lobule (SPL), and superior occipital gyrus (SOG). The relationship between the FA values and postmenstrual age (PMA) was analyzed. Results: After adjusting for the birth weight and gestational ages, in the SCC and PLIC, the PMA and FA values showed a low-to-medium intensity positive correlation in the control group (r = 0.30, p=0.003; r = 0.53, p < 0.0001), while no positive relevance was detected in the PE group (r = 0.08, p=0.47; r = 0.19, p < 0.08). In the PE and control groups, in the SPL and SOG, the PMA and FA values showed a near-consistent positive correlation (r = 0.57, r = 0.55 vs. r = 0.31, r = 0.55; all p < 0.05). In the control group, in SFG, the PMA and FA values had a medium intensity positive correlation (r = 0.47, p < 0.0001), but there was no statistical difference in correlation in PE (r = 0.10, p=0.39). Conclusion: PE may cause lagging brain development in the SCC, PLIC, and SFG during infancy. DTI may be an effective and sensitive detection tool.

T217-Phosphorylation Exacerbates Tau Pathologies and Tau-Induced Cognitive Impairment.

BACKGROUND: Recent studies show that an increased T217-phosphorylation of tau in plasma could diagnose AD at an early stage with high accuracy and high specificity, while the potential toxic role of tau T217-phosphorylation is not known. OBJECTIVE: To study the potential toxic role of tau T217-phosphorylation. METHODS: We performed stereotactic brain injection, behavioral testing, immunohistochemistry and immunofluorescence, western blotting, Golgi staining, in vitro recombinant tau polymerization, and other measurements. RESULTS: We first constructed tau T217-wild-type (T217), T217-phospho-mimic (T217E), and T217-non-phospho-mimic (T217A) plasmids or their virus vectors on the basis of wild-type tau. We found that expressing tau-T217E induced a significantly increased tau phosphorylation at multiple AD-associated sites with inhibited proteolysis and increased cleavage/fibrillization of tau, while expressing tau-T217A abolished the above changes of tau both in vitro and in vivo. By mutating T217E on tau-P301L, a dominant mutation identified in patients with frontotemporal dementia, we did not observe significant exacerbation of tau-P301L phosphorylation and cognitive impairment although the increased tau cleavage and propagation were shown. CONCLUSION: T217-phosphorylation exacerbates wild-type tau hyperphosphorylation with aggravated tau cleavage/fibrillization and cognitive impairments, while overexpressing T217E on the basis P301L does not exacerbate tau phosphorylation or the P301L-induced cognitive deficits, although it aggravates tau cleavage and propagation.

Brain Development in Infants of Mothers With Gestational Diabetes Mellitus: A Diffusion Tensor Imaging Study.

OBJECTIVE: The objective of this study was to investigate clinical neurocognitive performance and microstructural white matter (WM) alterations in infants of mothers with gestational diabetes mellitus (GDM) using diffusion tensor imaging. MATERIALS AND METHODS: Infants (corrected gestational age, 33.42-36.00 weeks) of mothers with GDM (n = 31) and gestational age- and sex-matched unexposed controls (n = 31) accomplished 3-T diffusion tensor imaging scans and neurocognitive tests. Diffusion tensor imaging measures, mainly referring to fractional anisotropy (FA) values, were compared between 2 groups, and within-group analysis of correlation between FA values and neurocognitive testing outcomes in GDM-exposed infants was conducted subsequently. RESULTS: Fractional anisotropy was significantly decreased in the splenium of corpus callosum, posterior limb of internal capsule, thalamus in infants of mothers with GDM when compared with controls (P < 0.05), reflecting microstructural WM abnormalities in the GDM group. Decreased FA was associated with worse neurocognitive performance in the exposed group (P < 0.05). CONCLUSIONS: Individuals of mothers with GDM showed microstructural WM abnormalities in different brain regions, which were significantly related to worse neurocognitive performance. This might reveal that GDM directly insults the brain development of the offspring.

[An assessment of white matter development in preterm infants with bronchopulmonary dysplasia using diffusion tensor imaging].

OBJECTIVE: To assess white matter development in preterm infants with bronchopulmonary dysplasia (BPD) using fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of diffusion tensor imaging (DTI). METHODS: Ninety-six infants with a gestational age of ≤32 weeks and a birth weight of <1 500 g who were admitted to the neonatal intensive care unit within 24 hours after birth from August 2016 to April 2019 and underwent head MRI and DTI before discharge were enrolled. According to the discharge diagnosis, they were divided into BPD group with 48 infants and non-BPD group with 48 infants. The two groups were compared in terms of FA and ADC values of the same regions of interest on DTI image. RESULTS: There were no significant differences in the incidence rates of periventricular/intraventricular hemorrhage, periventricular leukomalacia, and punctate white matter lesions between the two groups (P>0.05). Compared with the non-BPD group, the BPD group had significantly lower FA values and significantly higher ADC values of the posterior limb of the internal capsule, the splenium of the corpus callosum, the occipital white matter, the cerebellum, and the cerebral peduncle (P<0.05). Compared with the non-BPD group, the BPD group had a significantly higher frequency of apnea, a significantly higher proportion of infants with pneumonia or mechanical ventilation, and a significantly longer duration of assisted ventilation (P<0.05). CONCLUSIONS: BPD may has potential adverse effects to white matter development in preterm infants, leading to delayed white matter development. Therefore, it is necessary to pay attention to the neurological function of these infants.

Tau Acetylation in Entorhinal Cortex Induces its Chronic Hippocampal Propagation and Cognitive Deficits in Mice.

BACKGROUND: Increased tau acetylation at K174, K274, K280, and K281 has been observed in the brains of Alzheimer's disease (AD) patients or in transgenic mice, but the role of acetylation in tau propagation is elusive. OBJECTIVE: To study the effect of tau acetylation in entorhinal cortex on tau transmission and learning and memory. METHODS: Stereotactic brain injection, behavioral test, electrophysiological recording, immunohistochemistry, and immunofluorescence were used. RESULTS: We constructed the hyperacetylation mimics of tau (AAV-Tau-4Q), the non-acetylation tau mutant (AAV-Tau-4R), and the wild-type tau (AAV-Tau-WT). By overexpressing these different tau proteins in the entorhinal cortex (EC) of 2-month-old mice, we found that overexpressing Tau-4Q in EC for 3 or 6 months (to 5 or 8 months of age) neither induces tau propagation to dentate gyrus (DG) nor glial activation in DG, nor spatial memory deficit. However, overexpressing Tau-WT and Tau-4Q in EC for 13.5 months (15.5 months of age) at 2 months promoted tau propagation respectively to granulosa and hilus of DG with glial activation, synaptic dysfunction, and memory deficit, while overexpressing Tau-4R abolished tau propagation with improved cellular pathologies and cognitive functions. Furthermore, overexpressing Tau-4Q in unilateral DG of 2-month-old mice for 8 weeks also promoted its contralateral transmission with glial activation, and mice with tau (Tau-WT, Tau-4Q, and Tau-4R) overexpression in DG showed cognitive deficits compared with the empty vector controls. CONCLUSION: Tau acetylation induces a time-dependent propagation from EC to DG, and only hippocampus but not EC tau accumulation induces cognitive deficits.

Isotactic Polybutene-1/Bamboo Powder Composites with Excellent Properties at Initial Stage of Molding.

Isotactic polybutylene-1 (iPB) has lots of advantages and is best used as hot water pipe. However, to transform into stable crystal form I, the iPB needs as long as 7 days. In this process, the irreversible damage brings great difficulties to the use of the iPB. The method which convert it directly into crystal I has shortcomings such as being requiring complex operation and being expensive. In this study, an innovative idea was put forward, not paying attention to the crystal transformation of iPB but only focusing on reducing the time it can be applied. In this study, bamboo powder was modified by the silane coupling agent KH570 (KBP) to prepare iPB/KBP composite. The infiltration test and Fourier transform infrared (FTIR) analysis showed that the hydrophilicity of KBP is greatly reduced, which can greatly improve the compatibility of the iPB and KBP. The tensile strength, tensile modulus, flexural strength, and flexural modulus of the composites storage for 3 days is equal to the pure iPB with storage 7 days with the KBP additions of 3%, 3%, 7%, and 5%, respectively. The heat deformation temperature (HDT) of the composite with 3% KBP after 1-day storage reached the value of pure iPB storage for 7 days. This provides more space and possibilities for the industrialization of the iPB. The crystallization behavior of iPB/KBP composites proves that the addition of KBP accelerates the crystallization rate of iPB, but the crystallinity of the iPB/KBP composites is not changed. The SEM photograph of iPB/KBP composites showed that when the KBP addition was low the compatibility between KBP and iPB was good. When the KBP addition was increased the agglomeration of KBP in the iPB was very obvious, which leads to the poor mechanical properties of the composite.

Tau accumulation triggers STAT1-dependent memory deficits by suppressing NMDA receptor expression.

Intracellular tau accumulation forming neurofibrillary tangles is hallmark pathology of Alzheimer's disease (AD), but how tau accumulation induces synapse impairment is elusive. By overexpressing human full-length wild-type tau (termed hTau) to mimic tau abnormality as seen in the brain of sporadic AD patients, we find that hTau accumulation activates JAK2 to phosphorylate STAT1 (signal transducer and activator of transcription 1) at Tyr701 leading to STAT1 dimerization, nuclear translocation, and its activation. STAT1 activation suppresses expression of N-methyl-D-aspartate receptors (NMDARs) through direct binding to the specific GAS element of GluN1, GluN2A, and GluN2B promoters, while knockdown of STAT1 by AAV-Cre in STAT1flox/flox mice or expressing dominant negative Y701F-STAT1 efficiently rescues hTau-induced suppression of NMDAR expression with amelioration of synaptic functions and memory performance. These findings indicate that hTau accumulation impairs synaptic plasticity through JAK2/STAT1-induced suppression of NMDAR expression, revealing a novel mechanism for hTau-associated synapse and memory deficits.

The sequence and de novo assembly of Oxygymnocypris stewartii genome.

Animal genomes in the Qinghai-Tibetan Plateau provide valuable resources for scientists to understand the molecular mechanism of environmental adaptation. Tibetan fish species play essential roles in the local ecology; however, the genomic information for native fishes was still insufficient. Oxygymnocypris stewartii, belonging to Oxygymnocypris genus, Schizothoracinae subfamily, is a native fish in the Tibetan plateau living within the elevation from roughly 3,000 m to 4,200 m. In this report, PacBio and Illumina sequencing platform were used to generate ~385.3 Gb genomic sequencing data. A genome of about 1,849.2 Mb was obtained with a contig N50 length of 257.1 kb. More than 44.5% of the genome were identified as repetitive elements, and 46,400 protein-coding genes were annotated in the genome. The assembled genome can be used as a reference for future population genetic studies of O. stewartii and will improve our understanding of high altitude adaptation of fishes in the Qinghai-Tibetan Plateau.

Biomarkers for Early Diagnostic of Mild Cognitive Impairment in Type-2 Diabetes Patients: A Multicentre, Retrospective, Nested Case-Control Study.

BACKGROUND: Both type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are common age-associated disorders and T2DM patients show an increased risk to suffer from AD, however, there is currently no marker to identify who in T2DM populations will develop AD. Since glycogen synthase kinase-3ß (GSK-3ß) activity, ApoE genotypes and olfactory function are involved in both T2DM and AD pathogenesis, we investigate whether alterations of these factors can identify cognitive impairment in T2DM patients. METHODS: The cognitive ability was evaluated using Minimum Mental State Examination (MMSE) and Clinical Dementia Rating (CDR), and the mild cognitive impairment (MCI) was diagnosed by Petersen's criteria. GSK-3ß activity in platelet, ApoE genotypes in leucocytes and the olfactory function were detected by Western/dot blotting, the amplification refractory mutation system (ARMS) PCR and the Connecticut Chemosensory Clinical Research Center (CCCRC) test, respectively. The odds ratio (OR) and 95% confidence intervals (95% CI) of the biomarkers for MCI diagnosis were calculated by logistic regression. The diagnostic capability of the biomarkers was evaluated by receiver operating characteristics (ROC) analyses. FINDINGS: We recruited 694 T2DM patients from Jan. 2012 to May. 2015 in 5 hospitals (Wuhan), and 646 of them met the inclusion criteria and were included in this study. 345 patients in 2 hospitals were assigned to the training set, and 301 patients in another 3 hospitals assigned to the validation set. Patients in each set were randomly divided into two groups: T2DM without MCI (termed T2DM-nMCI) or with MCI (termed T2DM-MCI). There were no significant differences for sex, T2DM years, hypertension, hyperlipidemia, coronary disease, complications, insulin treatment, HbA1c, ApoE ε2, ApoE ε3, tGSK3ß and pS9GSK3ß between the two groups. Compared with the T2DM-nMCI group, T2DM-MCI group showed lower MMSE score with older age, ApoE ε4 allele, higher olfactory score and higher rGSK-3ß (ratio of total GSK-3ß to Ser9-phosphorylated GSK-3ß) in the training set and the validation set. The OR values of age, ApoE ε4 gene, olfactory score and rGSK-3ß were 1.09, 2.09, 1.51, 10.08 in the training set, and 1.06, 2.67, 1.47, 7.19 in the validation set, respectively. The diagnostic accuracy of age, ApoE ε4 gene, olfactory score and rGSK-3ß were 0.76, 0.72, 0.66, 0.79 in the training set, and 0.70, 0.68, 0.73, 0.79 in the validation set, respectively. These four combined biomarkers had the area under the curve (AUC) of 82% and 86%, diagnostic accuracy of 83% and 81% in the training set and the validation set, respectively. INTERPRETATION: Aging, activation of peripheral circulating GSK-3ß, expression of ApoE ε4 and increase of olfactory score are diagnostic for the mild cognitive impairment in T2DM patients, and combination of these biomarkers can improve the diagnostic accuracy.

Treatment of giant/large internal carotid aneurysms: parent artery occlusion or stent-assisted coiling.

PURPOSE: Treatment of giant/large internal carotid aneurysm is a challenge for neurologists. Previously, parent artery occlusion was the classic therapy; now the stent-assisted coil embolization has become available in recent years, but the optimal therapy is under debate. The goal of the present study was to compare two endovascular treatment modalities in terms of safety, efficacy and short-term outcomes. METHODS: All the patients were divided into two groups: Group A: patients who underwent parent artery occlusion, and Group B: patients who underwent stent-assisted coil embolization. Follow-up outcomes were evaluated using the modified Rankin Scale (mRS). RESULTS: After 12 months of follow-up, the favorable outcome (mRS: 0-2) had no statistical significance in both groups (p = 1.00). Patients in group A had greater ischemia compared with patients in group B, but the difference did not reach statistical significance (p = 0.421). In group B, patients had a higher rate of partial occlusion (p = 0.255) and recurrence (10% vs. 0%; p = 0.586). CONCLUSIONS: Stent-assisted coiling may not be superior to parent artery occlusion in selected patients after short-term follow-up. Parent artery occlusion is a simple, safe and effective treatment for large/giant internal carotid aneurysms.

Treatment of unruptured vertebral dissecting aneurysms: internal trapping or stent-assisted coiling.

PURPOSE: Endovascular treatment is an attractive approach for the treatment of unruptured vertebral dissecting aneurysms, and includes internal trapping and stent-assisted coil embolization. However, the optimal therapy remains debatable. We reviewed our experience with both endovascular treatment modalities and compared the safety, efficacy, and short-term outcomes for each approach. MATERIALS AND METHODS: We retrospectively reviewed 65 consecutive patients with unruptured vertebral dissecting aneurysms who underwent endovascular treatment between January 2003 and January 2014. 24 patients underwent endovascular internal trapping (group A) while 41 patients underwent stent-assisted coiling (group B). Thirteen patients underwent single stent with coiling while 28 patients underwent double or three stent-assisted coiling. Short-term outcomes were evaluated using the modified Rankin Scale. RESULTS: A favorable clinical outcome was achieved in 58 of 65 patients. Procedure-related complications included ischemic symptoms (n = 6) and recurrence (n = 4). There was no statistical difference in modified Rankin Scale scoring between groups. Group A patients had more ischemia symptoms compared with group B patients (p = 0.043), Group B patients had higher recurrence rates compared with group A patients, but the difference had no statistical significance (p = 1.00). However, recurrence only occurred in patients who underwent stent-assisted coiling alone (p = 0.046). CONCLUSION: Stent-assisted coiling for unruptured vertebral dissecting aneurysms may maintain artery patency. Multilayer disposition of stents with coils may decrease complications and facilitate aneurysm occlusion. Larger, prospective studies are necessary to determine the long-term outcomes of reconstructive therapy.

The recovery time of traumatic carotid-cavernous fistula-induced oculomotor nerve paresis after endovascular treatment with detachable balloons.

PURPOSE: The recovery time of traumatic carotid-cavernous fistula-induced oculomotor nerve paresis (ONP) after endovascular embolization with detachable balloons has not yet been adequately evaluated. This study was performed to make a deep analysis of the factors, which affect the prognosis of ONP after endovascular treatment of traumatic carotid-cavernous fistula (TCCF). MATERIALS AND METHODS: We retrospectively evaluated the clinical characteristics and the outcome of oculomotor nerve function in a series of 98 consecutive patients with ONP due to traumatic carotid-cavernous fistula which were endovascular treated with detachable balloons. Univariate analysis was applied to test the association between the time of ONP recovery and clinical variables. RESULTS: Ninety-eight consecutive patients (62 males, 36 females, mean age 34.2±12.7years) having presented with ONP underwent endovascular treatment with detachable balloons were enrolled in this study. ONP was complete in 22 (22.4%) patients and partial in 76 (77.6%) patients. Ninety (91.8%) patients were successfully occluded by single-session endovascular embolization. Retreatments by transarterial routes had to be performed in 8 (8.2%) patients because of recurrent fistula having occurred within 4weeks after embolization. ONP was recovered completely in all the patients, among who 4 (4.1%) were treated with occlusion of internal carotid artery. Factors showing significant association with the recovery time of ONP were the location of the fistula (P=0.007), the degree of preoperative ONP (P=0.003), the number of detachable balloon used (P=0.000) and the length of ONP before endovascular treatment (P=0.000). CONCLUSION: Endovascular treatment of traumatic carotid-cavernous fistula-induced ONP with detachable balloons is a safe and effective method. The length of ONP before endovascular treatment, the location of the fistula, the degree of preoperative ONP, the number of detachable balloons used were the statistically significant predictors of the length of ONP complete recovery.