Transcutaneous auricular vagus nerve stimulation improves gait and cortical activity in Parkinson's disease: A pilot randomized study.

OBJECTIVE: In this randomized, double-blind, sham-controlled trial, we explored the effect of 20 Hz transcutaneous auricular vagus nerve stimulation (taVNS) on gait impairments in Parkinson's disease (PD) patients and investigated the underlying neural mechanism. METHODS: In total, 22 PD patients and 14 healthy controls were enrolled. PD patients were randomized (1:1) to receive active or sham taVNS (same position as active taVNS group but without releasing current) twice a day for 1 week. Meanwhile, all subjects were measured activation in the bilateral frontal and sensorimotor cortex during usual walking by functional near-infrared spectroscopy. RESULTS: PD patients showed instable gait with insufficient range of motion during usual walking. Active taVNS improved gait characteristics including step length, stride velocity, stride length, and step length variability compared with sham taVNS after completion of the 7-day therapy. No difference was found in the Unified Parkinson's Disease Rating Scale III, Timed Up and Go, Tinetti Balance, and Gait scores. Moreover, PD patients had higher relative change of oxyhemoglobin in the left dorsolateral prefrontal cortex, pre-motor area, supplementary motor area, primary motor cortex, and primary somatosensory cortex than HCs group during usual walking. Hemodynamic responses in the left primary somatosensory cortex were significantly decreased after taVNS therapy. CONCLUSION: taVNS can relieve gait impairments and remodel sensorimotor integration in PD patients.

Disrupted amplitude of low-frequency fluctuations and causal connectivity in Parkinson's disease with apathy.

Apathy is a common non-motor symptom in Parkinson's disease (PD). We aimed to explore its associated neural substrates changes via amplitude of low-frequency fluctuations (ALFF) and granger causality analysis (GCA). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed in 20 PD patients with apathy (PD-A), 22 PD patients without apathy (PD-NA) and 19 healthy volunteers. GCA, a new method exploring direction from one brain region to another, was based on brain regions showing alterations of neural activity as seeds, which were examined utilizing ALFF approach. The relationships between ALFF or GCA and apathetic symptoms were also assessed. Relative to PD-NA group, PD-A group indicated decreased ALFF in left orbital middle frontal gyrus and bilateral superior frontal gyrus (SFG). Only ALFF values in right SFG were negatively correlated with Apathy Scale (AS) scores. Then GCA with the seed of right SFG showed a positive feedback from right thalamus to ipsilateral SFG, which was positively correlated with AS scores. In conclusion, dysfunction in SFG and a positive feedback from thalamus to ipsilateral SFG contributed to presence of PD-related apathy, providing a new perspective for future studies on apathy in PD.

Metabolism and pharmacokinetics of major polyphenol components in rat plasma after oral administration of total flavonoid tablet from Anemarrhenae Rhizoma.

Total flavonoid tablet from Anemarrhenae Rhizoma (Zhimu tablet), which was made of total polyphenol components extracted from the dried rhizome of Anemarrhena asphodeloides Bge. (Zhimu in Chinese), is a novel traditional Chinese medicine prescribed for the treatment of diabetes. Mangiferin (MF) and neomangiferin (NMF) are the two main components detected and determined in Zhimu tablet, accounting for 8.9% of the total weight of each tablet. In the present study, high performance liquid chromatography (HPLC) coupled with time-of-flight (TOF) tandem mass spectrometry (MS) was applied to characterize the metabolites of MF and NMF in rat plasmas collected at different time points after oral administration of Zhimu tablet at a dose of 3.63g/kg (corresponding to 270mg/kg MF). Accurate mass measurement was used to determine the elemental composition of metabolites and thus to confirm the proposed structures of identified metabolites. Time points of appearance of some metabolites, such as isomers, were also taken into account during the structure confirmation. A total of 21 potential metabolites were found in rat plasma at different time points, and the metabolic pathways in vivo were involved in hydrolysis, methylation, glucuronide conjugation, glycoside conjugation, sulphation, dehydration and isomerisation. Furthermore, a selective and accurate LC-MS assay method was developed and validated for the quantification of MF in plasma. Semi-quantification of main conjugated metabolites was also performed in order to describe the dynamic metabolism profiles of polyphenol components in Zhimu tablet. MF concentration in plasma reached 1.36±0.47µgmL(-1) about 5.0h after oral administration of Zhimu tablet, which showed a 3.24- and 4.91-fold increase in plasma maximum concentration and area under the concentration-time curve (AUC) from 0 to 24h of MF compared with those for rats administered with free MF, respectively. The results indicated that the pharmacokinetic processes and bioavailability of MF in rats would be affected by other components in Zhimu tablet.

[Diagnosis of phosphorus nutrition in winter wheat based on first derivative spectra and radial basis function neural network].

The hyperspectral leaf reflectance in winter wheat was measured under 4 phosphorus levels at different growth stages, i.e. revival stage, jointing stage, tassel stage and grouting stage. And their first derivative of spectra were calculated and denoised by the threshold denoising method based on wavelet transform. After studying characteristics of the two kinds of spectra resulting from different phosphorus contents levels as well as correlations between leaf phosphorus contents and spectral values, sensitive wavebands and four kinds of absorption areas were extracted. Then the four kinds of absorption areas and their corresponding leaf phosphorus content were normalized and input to RBFNN. Results show that: (1) Sensitive wavebands for monitoring leaf phosphorus contents in original leaf spectra are 426-435 and 669-680 nm. (2) Sensitive wavebands in first derivative of spectra are 481-493 and 685-696 nm. (3) Trained RBFNN can learn and seize the linearity/non-linearity mapping between samples and output targets.