Alzheimer''s disease (AD) is the most common cause of senile dementia, accounting for an estimated 60% to 80% of cases, but there are no approved drugs to slow or stop the progressive clinical decline in the past years.Amyloid cascade hypothesis is recognized as the major etiologic basis for AD, however, the failures of several amyloid plaque-targeted programs have led many to dismiss the amyloid beta (Aβ) hypothesis of AD. Several reports show that soluble oligomers of Aβ (AβOs), which appear in brains more than 10 years before the clinical syndrome, are more toxic than Aβ plaque, causing synaptic dysfunction and neuronal apoptosis. Some agents that can effectively inhibit Aβ oligomer formation or block their toxicity made significant efficacy in clinical 2 and 3 trials, with the potential to be approved for the treatment of AD. This article reviews the recent development of AD drugs targeting Aβ oligomers, analyzes their structural characteristics, mechanism of action, preclinical and clinical data, and discusses the future direction of AD treatment, thus providing new strategies for AD drug research.

Objective To investigate the expression of LncRNA LINC00857 in pancreatic cells and the effect of lncRNA LINC00857 down-regulation on proliferation, migration and apoptosis of pancreatic cancer PANC-1 cells and possible mechanism. Methods The lentiviral vector GV112 was constructed and infected PANC-1 cells to obtain experimental group, while the blank plasmid was transfected as a negative control group and the cells without intervention were taken as normal control group. CCK-8 assay, Transwell assay, scratch test, flow cytometry, Western blot were used to detect the effect of LINC00857 down-regulation on cell proliferation, migration, apoptosis, cell cycle and EMT-related proteins. Results LINC00857 expression in pancreatic cancer cells were significantly higher than that in normal pancreatic epithelial cells (P < 0.001). Knockdown of LINC00857 could significantly inhibit the proliferation and migration of PANC-1 cells (P < 0.0001); compared with the negative control group, the apoptosis rates of cells in the experimental groups were significantly increased (P < 0.05), the number of cells in G₀/G₁ phase increased (P < 0.01), the number of cells in S phase decreased (P < 0.05), and the cells were blocked in the G₁ phase, E-cadherin expression was significantly up-regulated (P < 0.05) and N-cadherin and Vimentin expression were significantly down-regulated (N-cadherin: P < 0.01, Vimentin: P < 0.05). Conclusion LINC00857 can promote proliferation and migration of PANC-1 cells and inhibit its apoptosis by regulating G₁/S phase transition and EMT signaling pathway.

Based on the theory of qi， blood and fluids， and taking into account of the pathogenesis evolution process from constraint to phlegm， stasis and then mass in pulmonary nodules， an attempt has been made to construct a three-dimensional differentiation system for pulmonary nodules from the dimensions of time and space. The temporal progression of the early， middle， and late stages of pulmonary nodules reflects the pathological changes from constraint to phlegm and then stasis in the metabolism disorders of qi， blood and fluid. The spatial structures such as size， density， and morphology of pulmonary nodules reflect the pathological states of the duration， severity， and primary and secondary conditions of qi， blood and fluid metabolism disorders. Based on the temporal progression， the therapeutic principles have been proposed， which are dispelling pathogenic factors and promoting the use of beneficial factors to interrupt the growth momentum in the early stage， removing turbidity and dispersing phlegm to reduce the degree of nodules in the middle stage， and dispersing nodulation and eliminating abnormalities in the late stage. Based on the spatial structures， the suggested therapeutic methods are using wind herbs， employing multiple approaches to treat phlegm， and promoting blood circulation to resolve stasis， so as to provide theoretical reference for the systematic diagnosis and treatment of pulmonary nodules in traditional Chinese medicine.