Although amyloid-β (Aβ) peptide accumulation is considered as a key early event in the pathogenesis of Alzheimer’s disease (AD), the precise pathophysiology of this deadly illness remains unclear and no effective remedies capable of inhibiting disease progression have been discovered. In addition to deposition of extracellular Aβ plaques and intracellular neurofibrillary tangles, neuroinflammation has been identified as the third core characteristic crucial in the pathogenesis of AD. More and more evidence from laboratory and clinical studies have suggested that anti-inflammatory treatments could defer or prevent the occurrence of AD. In this review, we will discuss multifaceted evidence of neuroinflammation presented in AD and the newly emerged anti-inflammatory targets both in pre-clinical and clinical AD.
Background: Although studies have reported an increased risk for cognitive disorders in Hashimoto's thyroiditis (HT) patients, even in the euthyroid state, the mechanisms involved remain unclear. The hippocampus is a classic brain region associated with cognitive function, among which the formation of long-term potentiation (LTP) in the Schaffer collateral-CA1 pathway plays an important role in the process of learning and memory. Therefore, this study established a euthyroid HT model in mice and investigated whether and how HT itself has the ability to trigger LTP alterations accompanied by learning and memory abnormality. Methods: An experimental euthyroid HT model was established in NOD mice through immunization with porcine thyroglobulin (Tg). Morris water maze was measured to determine mice spatial learning and memory. We investigated the effect of HT on synaptic transmission and high-frequency stimulation-induced LTP in the Schaffer collateral-CA1 synapse of mice hippocampus in vivo. Then, animals were sacrificed for thyroid-related parameter measure as well as detection of cellular and molecular events associated with the induction of LTP. Results: HT mice showed intrathyroidal lymphocyte infiltration and rising serum thyroid autoantibody levels accompanied by normal thyroid function. The HT mice had poorer performance in Morris water maze than controls. These alterations were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. The integrity of the synaptic structure is the premise for the production of LTP. As detected by transmission electron microscopy, the ultrastructure of synapse and astrocyte in the hippocampus were impaired in euthyroid HT mice. Additionally, Western blot and real-time polymerase chain reaction analyses confirmed that in HT mice, GS, GLAST, and GLT-1, key elements in glutamate-glutamine circulation located in astrocyte, were downregulated, accompanied by elevated levels of glutamate in the hippocampus, which impaired the material basis for LTP induction. NMDR2B expression in the hippocampus was also downregulated. Conclusion: HT can induce damage of LTP in the hippocampal Schaffer collateral-CA1 pathway in the euthyroid state, and this can be attributed, at least partly, to astrocytes impairment, which may underlie the deleterious effects of HT itself on hippocampal-dependent learning and memory function.
Background Rapidly progressive dementia (RPD) is a syndrome originating from various diseases. Recent advances have allowed a better understanding of its categories and spectrum; however, it remains challenging to make an accurate differential diagnosis and prognosis prediction. Methods This study was a retrospective evaluation of all participants admitted to the neurology department of a single center in China from January 2015 to December 2019. The screened patients met the RPD criteria and their characteristics were collected to explore a diagnostic pattern of RPD. In addition, outcomes of RPD were evaluated with the Glasgow Outcome Scale (GOS), activities of daily living scale (ADL), and simplified Mini-Mental State Examination (MMSE), and different prognostic analysis methods were performed to determine the prognostic factors of RPD. Results A total of 149 RPD patients among 15,731 inpatients were identified with an average MMSE value of 13.0 ± 4.6 at baseline. Etiological epidemiology revealed infectious, neurodegenerative and toxic/metabolic diseases as the three largest groups, accounting for 26.2%, 20.8% and 16.8% of all cases, respectively. In particular, prevalence rates of Creutzfeldt–Jakob disease (13.4%), Alzheimer’s disease (11.4%), carbon monoxide poisoning (8.1%), neurosyphilis (5.4%) and dementia with Lewy bodies (5.4%) were highest in this series. A recommended diagnostic framework for RPD etiology was thus established. Follow-up evaluations showed a negative correlation between age and GOS scores (r=-0.421, P < 0.001), as well as age and simplified MMSE scores (rs =- 0.393, P < 0.001), and a positive correlation between age and ADL scores (rs =0.503, P < 0.001), and significantly different GOS, ADL and simplified MMSE scores across various etiologies (P = 0.003; F = 9.463, P < 0.001; F = 6.117, P < 0.001). Conclusion Infectious, neurodegenerative and toxic-metabolic entities were the most common RPD categories, and establishing a practical approach to RPD etiology would allow better disease management.
Several single-center studies have evaluated the predictive performance of mechanical power (MP) on weaning outcomes in prolonged invasive mechanical ventilation (IMV) patients. The relationship between MP and weaning outcomes in all IMV patients has rarely been studied. A retrospective study was conducted on MIMIC-IV patients with IMV for more than 24 h to investigate the correlation between MP and weaning outcome using logistic regression model and subgroup analysis. The discriminative ability of MP, MP normalized to dynamic lung compliance (Cdyn-MP) and MP normalized to predicted body weight (PBW-MP) on weaning outcome were evaluated by analyzing the area under the receiver-operating characteristic (AUROC). Following adjustment for confounding factors, compared with the reference group, the Odds Ratio of weaning failure in the maximum MP, Cdyn-MP, and PBW-MP groups increased to 3.33 [95%CI (2.04–4.53), P < 0.001], 3.58 [95%CI (2.27–5.56), P < 0.001] and 5.15 [95%CI (3.58–7.41), P < 0.001], respectively. The discriminative abilities of Cdyn-MP (AUROC 0.760 [95%CI 0.745–0.776]) and PBW-MP (AUROC 0.761 [95%CI 0.744–0.779]) were higher than MP (AUROC 0.745 [95%CI 0.730–0.761]) (P < 0.05). MP is associated with weaning outcomes in IMV patients and is an independent predictor of the risk of weaning failure. Cdyn-MP and PBW-MP showed higher ability in weaning failure prediction than MP.
Objective: To investigate the correlation between the left arcuate fasciculus (AF) segments and acute/subacute post-stroke aphasia (PSA). Methods: Twenty-six patients underwent language assessment and MRI scanning. The integrity of the AF based on a three-segment model was evaluated using diffusion tensor imaging. All patients were classified into three groups according to the reconstruction of the left AF: completely reconstructed (group A, 8 cases), non-reconstructed (group B, 6 cases), and partially reconstructed (group C, 12 cases). The correlations and intergroup differences in language performance and diffusion indices were comprehensively estimated. Results: A correlation analyses showed that the lesion load of the language areas and diffusion indices on the left AF posterior and long segments was significantly related to some language subsets, respectively. When controlled lesion load was variable, significant correlations between diffusion indices on the posterior and long segments and comprehension, repetition, naming, and aphasia quotient were retained. Multiple comparison tests revealed intergroup differences in diffusion indices on the left AF posterior and long segments, as well as these language subsets. No significant correlation was found between the anterior segment and language performance. Conclusions: The integrity of the left AF segments, particularly the posterior segment, is crucial for the residual comprehension and repetition abilities in individuals with acute/subacute PSA, and lesion load in cortical language areas is an important factor that should be taken into account when illustrating the contributions of damage to special fiber tracts to language impairments.
Background To explore and analyze the influence of psychological nursing and health education on depression, anxiety and life quality of elderly patients with lung cancer. Methods There were 84 elderly patients with lung cancer who were admitted and treated in our hospital since July 2018 till July 2019, serving as the objects of observation. The selected patients were divided into the control group (n = 42) and the observation group in principle of random allocation by computer numbers. Routine care was conducted to the control group, while psychological nursing and health education were implemented to the observation group, so as to compare the improvement effect of depression, anxiety, life quality and compliance on the two groups of patients before/after the two different nursing methods were adopted for intervention. Results Hamilton Depression Scale and Hamilton Anxiety Scale scores in the observation group were lower than those in the control group, and the levels of various pulmonary function indicators including degree of blood oxygen saturation, forced expiratory volume in 1 second, forced vital capacity and maximum ventilatory capacity and quality of life scores were significantly improved; compared with the control group, the total compliance of the observation group was significantly increased, and the difference between the two groups was statistically significant (P < 0.05). Conclusion The psychological nursing and health education implemented for elderly patients with lung cancer will improve patients' bad mood effectively, enhance life quality and perfect prognosis for patients, maintaining significant value in clinical application.
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