Toxic amyloid-ß oligomers induced self-replication in astrocytes triggering neuronal injury.

BACKGROUND: Soluble amyloid-ß oligomer (AßO) induced deleterious cascades have recently been considered to be the initiating pathologic agents of Alzheimer's disease (AD). However, little is known about the neurotoxicity and production of different AßOs. Understanding the production and spread of toxic AßOs within the brain is important to improving understanding of AD pathogenesis and treatment. METHODS: Here, PS1V97L transgenic mice, a useful tool for studying the role of AßOs in AD, were used to identify the specific AßO assembly that contributes to neuronal injury and cognitive deficits. Then, we investigated the production and spread of toxic Aß assemblies in astrocyte and neuron cultures, and further tested the results following intracerebroventricular injection of AßOs in animal model. FINDINGS: The results showed that cognitive deficits were mainly caused by the accumulation of nonameric and dodecameric Aß assemblies in the brains. In addition, we found that the toxic AßOs were duplicated in a time-dependent manner when BACE1 and apolipoprotein E were overexpressed, which were responsible for producing redundant Aß and forming nonameric and dodecameric assemblies in astrocytes, but not in neurons. INTERPRETATION: Our results suggest that astrocytes may play a central role in the progression of AD by duplicating and spreading toxic AßOs, thus triggering neuronal injury. FUND: This study was supported by the Key Project of the National Natural Science Foundation of China; the National Key Scientific Instrument and Equipment Development Project; Beijing Scholars Program, and Beijing Brain Initiative from Beijing Municipal Science & Technology Commission.

[Effects of minimally invasive versus open esophagectomy on circulating tumor cells in patients with esophageal cancer].

OBJECTIVE: To investigate the effects of minimally invasive esophagectomy (MIE) and open esophagectomy (OE) on the level of circulating tumor cells (CTCs) in patients with esophageal cancer (EC). METHODS: A total of 73 patients with EC undergoing MIE (n=38) or OE (n=35) in our department between October, 2015 and October, 2017 were enrolled, with 10 patients with benign esophagus disease and 10 healthy volunteers as controls. The levels of CTCs in the peripheral blood of the participants were detected using CanPatrolTM technique and analyzed for their association with the operation methods and perioperative complications. RESULTS: CTCs were detected in 60.3% (44/73) of the EC patients but in none of the control subjects. CTC level after the surgery was significantly higher than that during the surgery, and CTC level during the surgery was significantly higher than that before surgery (P<0.001). The preoperative and intra-operative CTC levels were not significantly different between MIE and OE groups (P>0.05), but the postoperative CTC level was significantly lower in MIE group than in OE group, and postoperative increment of CTC level (from the preoperative level) was significantly lower in MIE group than in OE group (P<0.001). The total incidence of postoperative complications was significantly lower in MIE group than in OE group (28.9% vs 54.3%, P=0.023), and in both groups, CTC levels in patients with complications were significantly higher than those in patients without complications (P=0.001 and P=0.005 in MIE and OE groups, respectively). CONCLUSION: MIE may help to reduce the number of peripheral blood CTCs early after the operation, and dynamic monitoring CTCs level assists in evaluation of the prognosis of EC patients. CTC level may serve as an indicator for monitoring the prognosis of EC.

Changes of gray matter volume and amplitude of low-frequency oscillations in amnestic MCI: An integrative multi-modal MRI study.

BACKGROUND: Numerous studies have reported that the amnestic-type mild cognitive impairment (aMCI) patients have impaired brain structural integrity and functional alterations separately. PURPOSE: To investigate the changes of gray matter and amplitude of low-frequency oscillations in patients with aMCI by combining structural and functional magnetic resonance imaging (fMRI). MATERIAL AND METHODS: Thirty-four patients with aMCI and 34 controls were recruited. We adopted optimized voxel-based morphometry to detect regions with gray matter volume (GMV) loss induced by aMCI. Then regional differences in amplitude of slow-4 band (0.027-0.073 Hz) oscillations among these regions between patients and healthy controls were examined. Both slow-4 amplitude of low-frequency fluctuations (ALFF) and slow-4 fractional ALFF (fALFF; the relative amplitude that resides in the low frequencies) were employed. RESULTS: Patients with aMCI demonstrated significant GMV loss in the ventral medial prefrontal cortex (vMPFC), posterior cingulate cortex (PCC), bilateral hippocampus, right superior parietal gyrus, left insula and left middle temporal gyrus (P < 0.01). The patients exhibited significant decreases of slow-4 ALFF in the left hippocampus (P = 0.05) and PCC (P = 0.02), while the decreased slow-4 fALFF was detected in PCC (P = 0.01) and increased slow-4 fALFF in vMPFC (P = 0.03). In PCC, aMCI and controls exhibited significant different GMV-fALFF correlation (P < 0.05), with opposite correlation trend. CONCLUSION: The correlates between anatomical deficits and functional alterations in aMCI suggest that anatomical and functional deficits are linked to each other. The differences of GMV-fALFF correlations demonstrated altered anatomical-functional relationship in aMCI.

[Association between polymorphisms of Pen2 gene and late onset Alzheimer's disease].

OBJECTIVE: To explore the association between single nucleotide polymorphisms (SNPs) in Pen2 gene and late onset Alzheimer's disease (LOAD) in North Chinese population. METHODS: The genotypes of ApoE and Pen2 gene were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing respectively in 480 LOAD patients and 480 healthy controls. The strength of association between polymorphisms and AD was estimated with odds ratios (OR). RESULTS: The genotype of IVS2 + 335T < A was obtained. There was an association between IVS2 + 335T < A and apolipoprotein E (ApoE) genotypes (P = 0.002). In the subjects with APOEε 4 allele, there were significant differences in the distribution of alleles (P = 0.003) and genotypes (P = 0.007) between AD and control groups. The ORs (95% confidence interval (CI)) of allele A and T/A + A/A genotypes were 4.720 (1.517 - 10.654) and 3.886 (1.381 - 10.932) respectively with allele T and genotype T/T as references. CONCLUSION: An association exists between IVS2 + 335T < A and the development of LOAD in ApoEε 4 carriers within the northern Chinese population. And allele A of Pen 2 gene may increase the risk for LOAD.

Awareness of secondary stroke prevention guidelines among neurologists in China: a cross-sectional online survey.

BACKGROUND: Recurrent stroke following a transient ischemic attack or minor stroke is frequent but potentially preventable. The prevention outcome is, by and large, dependent on how well physicians understand and implement prevention guidelines. Yet, little is known about the scope of physicians' awareness and implementation of secondary stroke prevention guidelines in the mainland of China. This study aimed to identify the gaps between physicians' clinical practice and guidelines for secondary stroke prevention in China. METHODS: A nation-wide online survey with a 16-item questionnaire that reflects major components of the Chinese National Secondary Stroke Prevention Guidelines was performed between September 1, 2009 and October 31, 2009. RESULTS: A total of 3489 neurologists from third tier hospitals completed the survey. The percentage of the physicians who were aware of the control targets and prevention measures recommended in the Chinese national guidelines was generally lower than reported for developed countries. CONCLUSIONS: Physicians in the mainland of China lack sufficient awareness of secondary stroke prevention guidelines. Continuing education is highly recommended.