Objective:To analyze the mechanism of Chaiqin Qingning capsule in the treatment of upper respiratory tract infection by network pharmacology.Methods:Baicalin, radix bupleuri and artificial bezoar were selected as the main ingredients of Chaiqin Qingning capsules. The active ingredients were screened in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Chinese Traditional Medicine Integrated Database (TCMID) databases, and the target prediction and analysis were carried out through Drugbank and TCMSP databases. Genecards, Online Mendelian Inheritance in Man (OMIM) and MalaCards databases were used to screen out the genes related to upper respiratory tract infection. Omicshare platform was employed to gene ontology (GO) enrichment analysis of the targets. Uniprot database and Cystoscope software were used to construct protein interaction network. The network diagram of " compound-target-action pathway" was constructed with Cytoscape software to analyze the biological function and metabolism pathway of the key targets of Chaiqin Qingning capsule.Results:A total of 20 pharmacodynamic compounds in Chaiqin Qingning capsules were extracted, corresponding to 215 targets. 102 genes related to upper respiratory tract infection. A total of 18 common target genes were obtained by intersecting the corresponding targets of the compounds with disease-related targets. There were 986 protein interactions among 56 targets in the interaction network of Chaiqin qingning capsule in the treatment of upper respiratory tract infection, of which 673 were ≥0.9, which was a highly reliable interaction. According to the analysis of topological parameters, 18 genes were identified as the target of Chaiqin Qingning capsule in the treatment of upper respiratory tract infection. Using GO analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis, it was found that Chaiqin Qingning capsule may exert the pharmacological effect in the treatment of upper respiratory tract infection by regulating biological processes and related signaling pathways such as immune system, inflammatory response, cell apoptosis and proliferation process.Conclusions:Through multiple components, multiple targets and multiple pathways, Chaiqin Qingning capsule can affect immune system activation, stress response, inflammatory factor release, apoptosis process, cell proliferation, intracellular oxidation metabolism and other signal pathways and pathophysiological process, thus playing a role in the treatment of upper respiratory tract infection.

Objective:To investigate the effect of homocysteine (Hcy) on cerebral perfusion and cognitive function in patients with arteriosclerotic cerebral small vessel disease (aCSVD).Methods:A total of 117 patients with aCSVD who visited the First Affiliated Hospital of Anhui Medical University from June 2020 to September 2022 were enrolled and divided into the aCSVD cognitive impairment group (aCSVD-CI, n=57) and aCSVD non-cognitive impairment group (aCSVD-NCI, n=60) according to the Montreal Cognitive Assessment score. Serum Hcy measurement, cognitive function assessment, and three-dimensional pseudo-continuous arterial spin labeling perfusion imaging scan were performed in all patients, and multivariate Logistic regression analysis was used to explore risk factors for cognitive impairment in patients with aCSVD. The cerebral blood flow and perfusion differential brain regions of the whole brain, grey matter, and white matter were compared between the two groups. Partial correlation analyses were performed between the serum Hcy, overall cognitive function scores and cerebral blood flow in grey matter, as well as between the cerebral blood flow in the perfusion differential brain area and cognitive function scores. The mediating effect model was used to analyze the role of grey matter blood flow in the relationship between serum Hcy and overall cognition. Results:The serum Hcy level in the CSVD-CI group was higher than that in the CSVD-NCI group [16.38(14.02, 18.58) μmol/L vs 14.40 (11.93, 15.73) μmol/L, Z=-3.81, P<0.001]. In terms of cerebral perfusion, compared with the aCSVD-NCI group, the aCSVD-CI group had significantly lower cerebral blood flow in grey matter ( Z=-3.22, P=0.001), left middle frontal gyrus ( t=-4.91, P<0.05), right middle frontal gyrus ( t=-5.14, P<0.05), and right orbital medial frontal lobe ( t=-4.38, P<0.05). In contrast, the left hippocampus ( t=4.58, P<0.05) had increased cerebral blood flow. Multivariate Logistic regression analysis showed that serum Hcy level was independent risk factor for cognitive impairment in aCSVD after controlling for multiple risk factors. Partial correlation analysis showed that left middle frontal gyrus blood flow ( r=-0.39, P=0.006), right middle frontal gyrus blood flow ( r=-0.44, P=0.002), and right orbital medial frontal lobe cerebral blood flow ( r=-0.43, P=0.002) were negatively correlated with the Stroop Color Word Test-C results. Left hippocampal cerebral blood flow was negatively correlated with Auditory Word Learning Test-long-delayed recall ( r=-0.43, P=0.002). Further mediation analysis showed that the effect of Hcy on cognitive function was partly mediated by grey matter cerebral blood flow (indirect effect=-0.11, P<0.001). Conclusion:Hcy is an independent risk factor for cognitive impairment in aCSVD, and part of the effect of elevated Hcy on cognitive impairment in aCSVD may be mediated by decreased gray matter cerebral perfusion.

Objective:To investigate the impact of altering brain gray matter volume (GMV) on cognition and gait disorder in patients with amnestic mild cognitive impairment (aMCI).Methods:Thirty-six patients with aMCI, who admitted to the First Affiliated Hospital of Anhui Medical University from July 2018 to August 2020, were collected, and 33 normal controls (NC) matched with age, sex and education level were included in the same period. The neuropsychological assessment was done in all the subjects using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment scale (MoCA), Cambridge Cognitive Examination-Chinese version (CAMCOG-C), Geriatric Depression Scale (GDS) and Activities of Daily Living scale (ADL). The timed up and go test (TUG), dual task of timed up and go test (D-TUG) and Berg Balance Scale (BBS) were used in the subjects for assessment. The parameters such as stride length, gait speed, gait frequency were collected by intelligent device for energy expenditure and activity. All the subjects received 3.0 T magnetic resonance imaging scan to obtain high-resolution T 1 structural images. Voxel-based morphometry (VBM) was used to compare the difference of GMV between aMCI patients and NC. Partial correlation analysis was performed among altering GMV in the regions of interest (ROI), cognitive score and gait parameters, respectively. Linear regression analysis was used between whole brain GMV and gait parameters. Results:The scores of MMSE, MoCA, CAMCOG-C and the subitems of CAMCOG-C in aMCI group were significantly lower than those in NC group ( P<0.05). In aMCI patients, both the test time of TUG and D-TUG increased, gait speed slowed down, stride length shortened, and stride frequency and BBS score decreased ( P<0.05).VBM analysis showed that the whole brain GMV in aMCI patients was obviously lower than that of NC. In the aMCI group, GMV in ROI1 (right hippocampus, right parahippocampal gyrus, right amygdala and right fusiform gyrus), ROI2 (right middle temporal gyrus), ROI3 (right angular gyrus), ROI4 (right occipital lobe), ROI5 (bilateral orbital frontal lobe), ROI6 (left middle frontal gyrus and rectus gyrus), ROI7 (left fusiform gyrus and left parahippocampal gyrus) was significantly decreased compared with the NC group [Gaussian random field (GRF) correction, two-tailed test, voxel level P<0.001, cluster level P<0.05). In the aMCI group, GMV in ROI1 was positively correlated with orientation ( r=0.437, P=0.012), memory ( r=0.360, P=0.043), execution ( r=0.414, P=0.019), and negatively correlated with ADL score ( r=-0.529, P=0.002). GMV in ROI2 was negatively correlated with ADL score ( r=-0.400, P=0.023). GMV in ROI4 and in ROI5 was positively correlated with the calculation ( r=0.370, P=0.037) and execution ( r=0.360, P=0.043), respectively. GMV in ROI6 was positively correlated with MMSE score ( r=0.357, P=0.045), CAMCOG-C total score ( r=0.503, P=0.003) and calculation ( r=0.395, P=0.025), and negatively correlated with ADL score ( r=-0.387, P=0.028). GMV in ROI5 was positively correlated with gait speed ( r=0.391, P=0.027). In the aMCI group, CAMCOG-C total score was negatively correlated with D-TUG results ( r=-0.387, P=0.035), executive function was negatively correlated with TUG results ( r=-0.450, P=0.013) and D-TUG results ( r=-0.553, P=0.002), and positively correlated with gait speed ( r=0.379, P=0.039). Attention was positively correlated with gait speed ( r=0.590, P=0.001), and computing was positively correlated with gait speed ( r=0.371, P=0.044). The linear regression of whole brain GMV and gait parameters showed negative correlation between the GMV of left occipital lobe and TUG results in the aMCI group. The GMV of bilateral prefrontal cortex, right occipital lobe and surrounding cortex was positively correlated with gait speed (GRF correction, two-tailed test, voxel level P<0.001, cluster level P<0.05). Conclusions:Patients with aMCI presented with gray matter atrophy, cognition impairment, and gait disorders. The cognition impairment was closely related to the atrophy of medial temporal lobe. Gait disorders were not only associated with cognition impairment but also with gray matter volume in the prefrontal lobe, occipital lobe and its surrounding cortex, and anterior central gyrus.

Objective:To investigate the global and local changes of neurovascular coupling in arteriosclerotic cerebral small vessel disease (aCSVD) and the correlation with cognitive function.Methods:Forty-three patients with confirmed aCSVD from the outpatient department or ward of the Department of Neurology, the First Affiliated Hospital of Anhui Medical University between June 2020 and June 2021 were enrolled in this study. Meanwhile, 48 healthy subjects were selected as controls. Cognitive evaluation, resting-state functional magnetic resonance imaging and 3D pseudo-continuous arterial spin labeling magnetic resonance imaging scanning were performed in all subjects. The global cerebral blood flow-regional homogeneity (ReHo) correlation coefficient and the cerebral blood flow/ReHo ratio were used to evaluate global and local neurovascular coupling. Meanwhile, correlations between the cerebral blood flow/ReHo ratio and neuropsychological assessments were explored in aCSVD patients.Results:Global cerebral blood flow-ReHo coupling was decreased in aCSVD patients compared to healthy controls [aCSVD patients: 0.942(0.933, 0.950), healthy controls: 0.947(0.939, 0.954), Z=-2.11, P=0.035]. aCSVD patients showed decreased cerebral blood flow/ReHo ratio in the right lingual gyrus ( t=-4.45, P<0.05) and increased cerebral blood flow/ReHo ratio in the left ( t=4.91, P<0.05) and right ( t=4.72, P<0.05) inferior parietal lobule. Cerebral blood flow/ReHo ratio of the right inferior parietal lobule was negatively correlated with total score ( r=-0.33, P=0.031) and praxis score ( r=-0.43, P=0.004) in Cambridge Cognitive Examination-Chinese Version subitems and positively correlated with scores of Stroop Color Word Test (SCWT)-color ( r=0.33, P=0.032), SCWT-word ( r=0.34, P=0.025) and Trail Making Test-B ( r=0.31, P=0.043) in aCSVD patients. While the cerebral blood flow/ReHo ratio of the right lingual gyrus was negatively correlated with Visual Replicate-Immediate Recall score ( r=-0.36, P=0.017). Conclusion:aCSVD patients showed abnormal global and local neurovascular coupling, which was associated with attention, executive function, and visual space function.