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 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.

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 possible action mechanism of the micro ribonucleic acid-1-3p(miR-1-3p)/Annexin A2(AnxA2)molecular axis in high glucose(HG)-induced neovascularization of human retinal microvascular en-dothelial cells(HRMECs).Methods A cell injury model was established by culturing HRMECs in vitro and treating them with HG.The HRMECs were divided into the Con group(DMEM medium containing fetal bovine serum in volume fraction of 10％),HG group(cultured in 25 mmol·L-1 D-glucose),HG+miR-NC group(transfected with miR-NC),HG+miR-1-3p group(transfected with miR-1-3p mimics),HG+sh-NC group(transfected with sh-NC),HG+sh-AnxA2 group(transfect-ed with sh-AnxA2),HG+miR-1-3p+pcDNA group(transfected with miR-1-3p mimics+pcDNA),and HG+miR-1-3p+pcDNA-AnxA2 group(transfected with miR-1-3p mimics+pcDNA-AnxA2).After 48 h of transfection,cells were collected and cultured in 25 mmol·L-1 D-glucose medium for 24 h.Cell viability and number of migrating cells were detected using MTT and Transwell chamber experiments,respectively.The number of lumen formations was detected by the lumen forma-tion experiment.The dual luciferase reporter assay was adopted to detect the targeting relationship between miR-1-3p and AnxA2.Western blot was used to detect the protein levels of vascular endothelial growth factor(VEGF)and matrix metal-loproteinase-2(MMP-2).Results Compared with the Con group,the expression level of miR-1-3p in the HG group de-creased,while the levels of AnxA2 messenger ribonucleic acid(mRNA)and protein increased,with statistically significant differences(all P＜0.05).Compared with the Con group,the HG group showed an increase in cell viability,number of mi-grating cells,lumen formation and protein levels of VEGF and MMP-2,with statistically significant differences(all P＜0.05).Compared with the HG+miR-NC group,the HG+miR-1-3p group showed a decrease in cell viability,number of migrating cells,lumen formation and protein levels of VEGF and MMP-2,with statistically significant differences(all P＜0.05).Compared with the HG+sh-NC group,the HG+sh-AnxA2 group showed a decrease in cell viability,number of mi-grating cells,lumen formation and protein levels of VEGF and MMP-2,with statistically significant differences(all P＜0.05).Compared with the HG+miR-1-3p+pcDNA group,the HG+miR-1-3p+pcDNA-AnxA2 group showed an increase in cell viability,number of migrating cells,lumen formation and protein levels of VEGF and MMP-2,with statistically signifi-cant differences(all P＜0.05).Conclusion Overexpression of miR-1-3p can inhibit proliferation,migration and neovas-cularization of HRMECs by targetedly regulating AnxA2 expression.

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*