Yishen Huazhuo Decoction Induces Autophagy to Promote the Clearance of Aß1-42 in SAMP8 Mice: Mechanism Research of a Traditional Chinese Formula Against Alzheimer's Disease.

BACKGROUND: Studies have found that autophagy could promote the clearance of Aß. To promote and maintain the occurrence of autophagy in Alzheimer's Disease (AD) might be a potential way to reduce neuronal loss and improve the learning and memory of AD. OBJECTIVE: To investigate the possible mechanisms of Yishen Huazhuo Decoction (YHD) against AD model. METHODS: Forty 7-month-old male SAMP8 mice were randomly divided into model (P8) group and YHD group, 20 in each group, with 20 SAMR1 mice as control (R1) group. All mice were intragastrically administered for 4 weeks, YHD at the dosage of 6.24g/kg for YHD group, and distilled water for P8 group and R1 group. Morris Water Maze (MWM) test, Nissl's staining, TEM, TUNEL staining, immunofluorescence double staining, and western blot analysis were applied to learning and memory, structure and ultrastructure of neurons, autophagosome, apoptosis index, Aß, LAMP1, and autophagy related proteins. RESULTS: The escape latency time of YHD group was significantly shorter on the 4th and 5th day during MWM test than those in P8 group (P=0.011, 0.008<0.05), and the number of crossing platform in YHD group increased significantly (P=0.02<0.05). Nissl's staining showed that the number of neurons in YHD group increased significantly (P<0.0001). TEM showed in YHD group that the nucleus of neurons was slightly irregular, with slightly reduced organelles, partially fused and blurred cristae and membrane of mitochondria. The apoptosis index of YHD group showed a decreasing trend, without statistically significant difference (P=0.093>0.05), while Caspase3 expression in YHD group was significantly lower (P=0.044<0.05). YHD could promote the clearance of Aß1-42 protein, improve the expression of Beclin-1 and p-Bcl2 proteins, reduce mTOR and p62 proteins. CONCLUSION: YHD could induce autophagy initiation, increase the formation of autophagosomes and autolysosome, promote the degradation of autophagy substrates, thereby regulating autophagy, and promoting the clearance of Aß1-42 to improve memory impairment in SAMP8 mice.

Correction: Cognitive Improvement during Treatment for Mild Alzheimer's Disease with a Chinese Herbal Formula: A Randomized Controlled Trial.

[This corrects the article DOI: 10.1371/journal.pone.0130353.].

Quantifying traditional Chinese medicine patterns using modern test theory: an example of functional constipation.

BACKGROUND: The study aimed to validate a scale to assess the severity of "Yin deficiency, intestine heat" pattern of functional constipation based on the modern test theory. METHODS: Pooled longitudinal data of 237 patients with "Yin deficiency, intestine heat" pattern of constipation from a prospective cohort study were used to validate the scale. Exploratory factor analysis was used to examine the common factors of items. A multidimensional item response model was used to assess the scale with the presence of multidimensionality. RESULTS: The Cronbach's alpha ranged from 0.79 to 0.89, and the split-half reliability ranged from 0.67 to 0.79 at different measurements. Exploratory factor analysis identified two common factors, and all items had cross factor loadings. Bidimensional model had better goodness of fit than the unidimensional model. Multidimensional item response model showed that the all items had moderate to high discrimination parameters. Parameters indicated that the first latent trait signified intestine heat, while the second trait characterized Yin deficiency. Information function showed that items demonstrated highest discrimination power among patients with moderate to high level of disease severity. CONCLUSIONS: Multidimensional item response theory provides a useful and rational approach in validating scales for assessing the severity of patterns in traditional Chinese medicine.

Senses make sense: An individualized multisensory stimulation for dementia.

Nonpharmacologic interventions have been recommended as first-line treatments for dementia, and multisensory stimulation environment has been used as a non-pharmacological treatment to dementia patients in the last decade. However, the clinical effect of multisensory stimulation environment remains temporary and uncertain. Individualized medicine has been suggested to hold great promise in medicine, and it should be equally important for dementia. Reminiscence integrating individual experiences into therapeutic schemes has shown potential in the field of improving cognitive functions and depressive symptoms for dementia patients, and interactive music also demonstrated a positive outcome by using individualized music for the hearing aspect. We therefore hypothesize that an individualized multisensory stimulation in a natural and realistic environment integrating personal experience may be an effective intervention for patients suffering from dementia.

Cognitive Improvement during Treatment for Mild Alzheimer's Disease with a Chinese Herbal Formula: A Randomized Controlled Trial.

OBJECTIVES: To explore the efficacy of Chinese herbal formula compared with donepezil 5 mg/day in patients with mild Alzheimer's disease (AD). METHODS: Patients with mild AD meeting the criteria were randomized into Chinese herbal formula Yishen Huazhuo decoction (YHD) group and donepezil hydrochloride (DH) group during the 24-week trial. The outcomes were measured by ADAS-cog, MMSE, ADL, and NPI with linear mixed-effect models. RESULTS: 144 patients were randomized. The mean scores of ADAS-cog and MMSE in both YHD group and DH group both improved at the end of the 24-week treatment period. The results also revealed that YHD was better at improving the mean scores of ADAS-cog and MMSE than DH. Linear mixed-effect models with repeated measures showed statistical significance in time × group interaction effect of ADAS-cog and also in time × group interaction effect of MMSE. The data showed YHD was superior to DH in improving the scores and long term efficacy. CONCLUSIONS: Our study suggests that Chinese herbal formula YHD is beneficial and effective for cognitive improvement in patients with mild AD and the mechanism might be through reducing amyloid-ß (Aß) plaque deposition in the hippocampus. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-12002846.