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Abstract Objectives Both hyposmia and substania nigra (SN) hyperechogenicity on trascranial sonography (TCS) were risk markers for idiopathic Parkinson’s disease (PD), which was beneficial to the differential diagnosis of the disease. However, each of their single diagnostic value is often limited. The purpose of present study was to explore whether the combination of olfactory test and TCS of SN could enhance the differential diagnostic power in Chinese patients with PD. Methods Thirty-seven patients with PD and twenty-six patients with essential tremor (ET) were evaluated on 16-item odor identification test from extended version of sniffin’ sticks and TCS of SN. The frequency of hyposmia and SN hyperechogenicity in each group was compared. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the two clinical biomarkers were analyzed. Results The frequency of hyposmia in patients with PD was significantly higher than in patients with ET (62.2% VS. 3.8%, P = 0.000). The frequency of SN hyperechogenicity in patients with PD was significantly higher than in ET subjects (48.6% VS. 15.4%, P = 0.006). The combination of hyposmia and SN hyperechogenicity (if either one or both present) discriminated patients with PD from ET with a sensitivity of 78.4% and 29.7%, specificity of 80.8% and 100%, PPV of 85.3% and 100%, and NPV of 72.4% and 50.0%, respectively. Conclusions Our preliminary data suggested that the combination of hyposmia and SN hyperechogenicity could improve the diagnostic potential for discriminating Chinese patients with PD from ET.

To explore the effect of Hei Xiaoyaosan on autophagy levels in Alzheimer's disease(AD). A total of 100 4-month-old Wistar male rats were randomly selected as a blank group, and 10 rats were taken as a sham operation group and injected with 1 μL of normal saline on both sides of the hippocampus. The other rats were injected with Aβ_(1-42) solution in the hippocampus to replicate the AD model. Fifty successfully modeled rats were selected and randomly divided into the model group, Aricatio group(0.5 mg·kg~(-1)), and high, medium, and low dose groups of Hei Xiaoyaosan(15.30, 7.65, and 3.82 g·kg~(-1)), with 10 rats in each group. The rats were administered by continuous gavage for 42 days. Morris water maze was used to detect the learning and memory ability of rats, and Hoechst staining was used to observe the pathological changes of nerve cells in the hippocampal CA1 region. The mRNA expression of p38MAPK, Beclin-1, and Bcl-2 was detected by RT-qPCR.Western blot was used to detect the expressions of p38MAPK, Beclin-1, Bcl-2, APP, and related proteins. The level of Aβ_(1-42) in the hippocampus was detected by ELISA, and the expression level of LC3Ⅱ in the hippocampus was detected by immunohistochemistry. The experimental results showed that compared with the blank group, the learning and memory ability of rats in the model group decreased(P<0.01). The nuclei in the CA1 region of the hippocampus showed blue bright spots and were closely arranged. The mRNA expression of p38MAPK was up-regulated, and the mRNA expressions of Beclin-1 and Bcl-2 were down-regulated(P<0.01). The expressions of p38MAPK, p-p38MAPK, and APP were increased, while those of Beclin-1, Bcl-2, and p-Bcl-2 were decreased(P<0.01). The expression of Aβ_(1-42) was increased(P<0.01). The relative expression of LC3Ⅱ decreased(P<0.01). Compared with the model group, the learning and memory ability of rats in each administration group was improved(P<0.05 or P<0.01). The nuclei in the CA1 region of the hippocampus gradually became clear, showing light blue. The mRNA expression of p38MAPK was down-regulated(P<0.01), and that of Beclin-1 and Bcl-2 was increased(P<0.05 or P<0.01). The expressions of p38MAPK, p-p38MAPK, and APP were down-regulated, while those of Beclin-1, Bcl-2, and p-Bcl-2 were up-regulated(P<0.05 or P<0.01). The expression of Aβ_(1-42) was decreased(P<0.01). The relative expression of LC3Ⅱ was increased(P<0.01). It can be concluded that Hei Xiaoyaosan can improve the cognitive ability of AD model rats, and its potential mechanism may be related to regulating the p38MAPK/Beclin-1/Bcl-2 signaling pathway, increasing the level of autophagy, and reducing the accumulation of Aβ_(1-42).

The effect and mechanism of Heixiaoyao Powder on the polarization of microglia(MG) in APP/PS1 double transgenic mice were explored based on NADPH oxidase 2(NOX2)/reactive oxygen species(ROS)/nuclear factor kappaB(NF-κB) signaling pathway. Fifty 4-month-old male APP/PS1 mice were randomly divided into a model group, an MCC950 group(10 mg·kg~(-1)), and low-, medium-, and high-dose Heixiaoyao Powder groups(6.45, 12.89, and 25.78 g·kg~(-1)). Thirty male C57BL/6J mice of the same age and strain were randomly divided into a blank group, a blank + intragastric intervention group, and a blank + intraperitoneal injection group. Drug intervention lasted 90 days. Morris water maze test was used to detect learning and cognitive ability. Nissl staining and transmission electron microscopy were used to observe the pathological morphology and ultrastructure of hippocampal neurons. Immunofluorescence was used to detect the positive expression of M1-type marker CD16/32~+/Iba-1~+, M2-type marker CD206~+/Iba-1~+ of MG and the expression of hippocampal ROS. The colorimetric method was used to detect the content of malondialdehyde(MDA) and superoxide dismutase(SOD) in the hippocampus. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory factors, including interleukin-6(IL-6), interleukin-8(IL-8), and tumor necrosis factor-α(TNF-α), in the hippocampus. Western blot was used to detect the protein expression of β-amyloid protein(Aβ), Iba-1, CD16/32, CD206, NOX2, NF-κB, p-NF-κB, NF-κB inhibitor alpha(IκBα), and p-IKBα in the hippocampus. The results showed that as compared with the blank group, the model group showed prolonged target quadrant movement distance and escape latency(P<0.01), shortened target quadrant retention time and percentage(P<0.01), disorganized neuronal cells with swelling, nuclear disappearance or bias, reduced number of cells, dissolved or absent Nissl bodies, and a clear area in the cytoplasm, damaged and shrunk cell membrane with abnormal cell morphology, few organelles in the cytoplasm, reduced and swollen mitochondria, increased MG M1-type marker CD16/32~+/Iba-1~+(P<0.01), decreased M2-type marker CD206~+/Iba-1~+(P<0.01), increased ROS activity and MDA content(P<0.01), decreased SOD level(P<0.01), elevated inflammatory factors IL-6, IL-8, and TNF-α(P<0.01), up-regulated protein expression and phosphorylation of Aβ, CD16/32, Iba-1, NOX2, NF-κB, and IKBα(P<0.01), and down-regulated CD206(P<0.01). There was no statistically significant difference between the blank group, the blank + intragastric intervention group, and the blank + intraperitoneal injection group. After the intervention of Heixiaoyao Powder, the Heixiaoyao Powder groups showed shortened target quadrant movement distance and escape latency(P<0.01), prolonged target quadrant retention time and percentage(P<0.01), increased and neatly arranged cells with relieved swelling, increased Nissl bodies, regular cell morphology, and intact cell membrane, relieved swelling of mitochondria, slightly expanded endoplasmic reticulum, decreased CD16/32~+/Iba-1~+(P<0.05 or P<0.01), increased CD206~+/Iba-1~+(P<0.01), decreased ROS activity and MDA content(P<0.01), increased SOD level(P<0.01), decreased content of inflammatory factors IL-6, IL-8, and TNF-α(P<0.01), down-regulated protein expression and phosphorylation of Aβ, CD16/32, Iba-1, NOX2, NF-κB, and IKBα(P<0.01), and up-regulated CD206(P<0.01). In conclusion, Heixiaoyao Powder can alleviate neuronal damage and improve the learning and memory abilities of APP/PS1 mice. The mechanism of action may be related to the inhibition of NOX2/ROS/NF-κB signaling pathway, regulating the polarization of MG, increasing the expression of M2 type, inhibiting the expression of M1 type, and reducing the release of inflammatory factor.

Juniperus przewalskii is important for water and soil conservation. It is one of the native tree species suitable for afforestation and greening in high-cold and arid areas of Qinghai Province. Predicting the potential geographic distribution of J. przewalskii in Qinghai Province under the climate change scenario will provide theoretical guidance for its management, introduction, and cultivation. In this study, the current potential distribution of J. przewalskii was simulated firstly based on 88 effective distributional records from field investigation and data collection via Maxent model and ArcGIS spatial analysis. We analyzed dominant factors affecting the potential distribution of J. przewa-lskii by Jackknife test and correlation coefficient. The distribution of J. przewalskii under three climate change scenarios (SSP126, SSP245, SSP585) with the climate model data of the sixth phase of the Coupled Model Intercomparison Projects (CMIP6) were predicted for 2061-2080. The results showed that the area under the receiver operating characteristic curve (AUC) of the Maxent model was greater than 0.92, suggesting a good predictive performance. Under current climatic condition, the suitable distribution area of J. przewalskii was mainly located in the eastern part of Qinghai Province, with the suitable area accounted for 11.2% of the total. The dominant factors affecting the distribution of J. przewalskii were altitude, annual precipitation, the minimum temperature of coldest month, and slope, with a cumulative contribution rate of 85.9%. The suitable areas of J. przewalskii altered under the three future climate scenarios. The suitable areas would shrink under the SSP245 scenario and expand under the SSP126 and SSP585 scenarios. The sui-table area of J. przewalskii would have the most obvious expansion under the SSP126 climate situation, with the expanding areas being mainly located in Zeku County, the north-central part of Henan Mongolian Autonomous County, and the southeast of Qilian County. Under three climatic scenarios, the suitable area of J. przewalskii would gradually migrate to high altitudes, but without clear altitudinal and longitudinal shifts.