Study on the Composition and Mechanism of Santiao Decoction in Treating Insomnia Based on UPLC and Network Pharmacology and Molecular Docking Technology.

OBJECTIVE: To identify the chemical components of Santiao Decoction (STD) using Ultra Performance Liquid Chromatography (UPLC) and to conduct a network pharmacological study of STD for the treatment of insomnia based on this technique. METHODS: An ACQUITY UPLC BEH C18 column (2.1 mm×100 mm, 1.7 µm) was used to identify the chemical components of STD by relative molecular weight, mass spectrometry information, and comparison with the control. The active ingredients of the formula and their corresponding gene targets and targets for insomnia were retrieved from several databases, and a visual network diagram of "drug-active ingredient-target-disease" was constructed using Cytoscape 3.8.2 software, and GO functional annotation and KEGG pathway enrichment analysis were performed using various databases such as DAVID. RESULTS: Five active ingredients were identified from STD by UPLC technique, 268 active ingredients of STD were screened from the TCMSP database, and 109 genes related to STD for insomnia were screened by network pharmacology, among which IL6, MMP9, VEGFA, IL10, CCL2 may be the key targets of STD for insomnia. KEGG pathway analysis showed that STD acts on membrane rafts, plasma membrane micro-regions, and other related pathways, such as Toll-like receptor signaling pathway, prolactin signaling pathway, dopaminergic synapse, relaxin signaling pathway, ErbB signaling pathway, steroid hormone biosynthesis and NF-kappa B signaling pathway for regulation. CONCLUSION: The active ingredients in STD, such as (+)-catechin, Swertisin, quercetin, baicalein, and wogonin, may act on IL6, CCL2, VEGFA, MMP9, and other targets to regulate Toll-like receptor signaling pathway, ErbB signaling pathway, NF-kappa B and other signaling pathways, and exert certain therapeutic effects on insomnia, which provide a reference and basis for further research on the mechanism of action of STD.

[The comorbid mechanism of vestibular migraine and persistent postural-perceptual dizziness].

Vestibular migraine and persistent postural-perceptual dizziness both involve the vestibular system and are similar in clinical manifestations. After acute attack of vestibular migraine, it can gradually evolve into persistent posture-perceptual dizziness; persistent posture-perceptual dizziness caused by various factors can be combined with symptoms similar to vestibular migraine. Studies have shown that abnormal multi-sensory signal integration, abnormal neurotransmitters and genetic factors may be the co-disease mechanism of the two.

[Research progress on the mechanism of comorbidities of vestibular migraine and sleep disorders].

Vestibular migraine （VM） is one of the common vestibular diseases characterized by recurrent vertigo and migraine. Studies have shown that the sleep structure of VM patients is similar to that of migraine patients, and they have a common pathophysiological pathogenesis. There is a strong correlation between VM and the clinical symptoms of sleep disorders. Sleep disorders can trigger VM. On the contrary, VM can affect sleep regulatory centers and lead to structural sleep disorders. In addition, there is a common relationship between VM and sleep disorders in neuroanatomy, neurotransmitters and neural pathways. A correct understanding of the relationship between vestibular migraine and sleep disorders can provide some help for clinical diagnosis and treatment. This article reviews the relationship between vestibular migraine and the pathogenesis of sleep disorders.

Study on Mechanism of Jiawei Chaiqin Wendan Decoction in Treatment of Vestibular Migraine Based on Network Pharmacology and Molecular Docking Technology.

OBJECTIVE: To predict the main active ingredients, potential targets, and key pathways of Jiawei Chaiqin Wendan decoction treatment in vestibular migraine and explore possible mechanisms by network pharmacology and molecular docking technology. METHODS: The active ingredients and related targets of Jiawei Chaiqin Wendan decoction were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The corresponding genes of the target were queried by UniProt database, and the "drug-compound-target-disease" network was constructed by Cytoscape 3.7.2 software. GO functional enrichment analysis and KEGG pathway enrichment analysis were carried out by R software and Bioconductor, and column chart and bubble chart were drawn by Prism software and OmicShare database for visualization. Finally, the mechanism and potential targets of Jiawei Chaiqin Wendan decoction in the treatment of vestibular migraine were predicted. RESULTS: The "drug-compound-target-disease" network contains 154 active ingredients and 85 intersection targets. The key targets include AKT1, IL6, MAPK3, VEGFA, EGFR, CASP3, EGF, MAPK1, PTGS2, and ESR1. A total of 1939 items were obtained by GO functional enrichment analysis (P < 0.05). KEGG pathway enrichment analysis screened 156 signal pathways (P < 0.05), involving PI3K-Akt signal pathway, AGE-RAGE signal pathway in diabetes complications, MAPK signal pathway, HIF-1 signal pathway, IL-17 signal pathway, etc. Molecular docking results showed that quercetin, luteolin, kaempferol, tanshinone IIa, wogonin, naringenin, nobiletin, dihydrotanshinlactone, beta-sitosterol, and salviolone have good affinity with core target proteins IL6, PTGS2, MAPK1, MAPK3, and CGRP1. CONCLUSION: The active ingredients in Jiawei Chaiqin Wendan decoction may regulate the levels of inflammatory factors and neurotransmitters by acting on multiple targets such as IL6, MAPK3, MAPK1, and PTGS2, so as to play a therapeutic role in vestibular migraine.

[Systematic evaluation and trial sequential analysis of Tianma Gouteng Granules combined with anti-hypertensive drugs in treatment of essential hypertension].

To systematically evaluate the efficacy and safety of Tianma Gouteng Granules combined with conventional anti-hypertensive drugs in the treatment of essential hypertension. The clinical randomized controlled trials(RCTs) on the treatment of essential hypertension with Tianma Gouteng Granules combined with conventional anti-hypertensive drugs were searched in PubMed, EMbase, Cochrane Library, VIP, CNKI, Wanfang, SinoMed since the establishment of the databases to April 2020 based on inclusion and exclusion criteria, and Meta-analysis was conducted by using RevMan 5.3 software. A total of 15 RCTs were included, involving a total of 1 508 patients. Meta-analysis results showed that Tianma Gouteng Granules combined with conventional Western medicine were supe-rior to the control group in reducing systolic blood pressure(MD=-10.24, 95%CI[-13.54,-6.95], P<0.000 01), diastolic blood pressure(MD=-5.33, 95%CI[-7.21,-3.45], P<0.000 01), improving the clinical efficacy of patients(RR=1.22, 95%CI[1.15, 1.28], P<0.000 01) and curative effect of traditional Chinese medicine syndrome(RR=1.26, 95%CI[1.02, 1.57], P=0.04), increasing nitric oxide content(MD=9.59, 95%CI[7.23, 11.96], P<0.000 01), reducing endothelin-1(MD=-10.74, 95%CI[-15.74,-5.75], P<0.000 1), tumor necrosis factor(MD=-0.28, 95%CI[-0.36,-0.19], P<0.000 01), and interleukin-6(MD=-39.71, 95%CI[-43.40,-36.03], P<0.000 01). There was no statistically significant difference between the test group and the control group in the incidence of adverse reactions. No liver and kidney dysfunction occurred. The results of the subgroup analysis showed that the effect of Tianma Gouteng Granules combined with ARB drugs was more obvious in reducing the systolic and diastolic pressure. Trial sequential analysis showed that the studies accumulatively included for clinical efficacy crossed the traditional threshold and the TSA threshold, further affirming its clinical efficacy. The clinical application of Tianma Gouteng Granules combined with conventional Western medicine in the treatment of primary hypertension and accompanying symptoms has clear efficacy and certain safety, so it is recommended for clinical application.

Rectangular illumination method using LED arrays for machine vision.

Machine vision image quality is significantly affected by illumination. Uniform illumination of a rectangular target surface requires a function for evaluating the illumination system. In this study, based on an LED array light source illuminance model, such an evaluation function was established. Further, the influence of the light source's structure on illumination was analyzed using a single-factor analysis method to determine the boundary conditions, and it was then solved using a genetic algorithm to finalize the structural design. An experimental platform was built to measure the illuminance uniformity. The experimental results were consistent with the numerical results, verifying the effectiveness and feasibility of the proposed illumination method. Thus, this research provides a theoretical reference for the illumination of a rectangular target surface for vision-based detection.

[Analysis of anti-fatigue mechanism and potential targets of ginseng].

Ginseng has effects in reinforcing vital energy,invigorating health effectively and relieving fatigue symptoms,and ginsenoside( GS) is the main component of its anti-fatigue effect. Totally 17 active components and 92 drug targets of ginseng compounds were screened from Traditional Chinese Medicine Systems Pharmacology; and 78 intersecting genes of diseases and drug targets were obtained based on R Language Technology. The protein-protein interaction( PPI) network was constructed by STRING 11. 0 software,and Matthews Correlation Coefficient( MCC) algorithm was used to screen core target genes. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyze the major genes and their roles in regulatory networks. The results indicated that ginseng could regulate the core target genes,including AKT serine/threonine kinase( AKT1),interleukin-1ß,Toll-like receptor binding molecule 1( ICAM1),mitogen-activated protein kinase 8( MAPK8),AP-1 transcription factor subunit( JUN),transducer and activator of transcription 1( STAT1) and prostaglandin peroxidase synthase 2( PTGS2). It could participate in the functions of cytokine receptor binding,cell adhesion molecule binding and tumor necrosis factor receptor superfamily binding,and also regulate the signal pathways of tumor necrosis factor,interleukin 17 and c-type lectin receptor,so as to exert an anti-fatigue effect. Based on the results of network analysis,32 four-week-old male SPFACR mice were randomly divided into control group,low-dose ginsenoside group,middle-dose ginsenoside group and high-dose ginsenoside group. The corresponding drugs were administrated for 3 weeks. The results showed that GS could significantly up-regulate the expressions of STAT1 and AKT1( P<0. 01,P<0. 05),and downregulate the expressions of PTGS2 and JUN( P<0. 01). However,there was no significant effect on MAPK8,IL-1ß and ICAM1. Ginseng's anti-fatigue regulation network was constructed through network pharmacology,and the results were verified by experiments,in order to reveal the anti-fatigue mechanism of ginseng and provide scientific basis for its clinical application.

Paeoniflorin augments systemic Candida albicans infection through inhibiting Th1 and Th17 cell expression in a mouse model.

Paeoniflorin (PF), a Chinese herbal medicine, has been widely used in clinical practice in China because of its dual immunoregulatory effects. A previous study found that PF inhibited the biofilm formation of Candida albicans (C. albicans) in vitro; however, whether PF plays an antifungal role in vivo is still unexplored. In this study, we sought to examine the effect of PF alone or in combination with an antifungal agent, fluconazole (FCZ), using a mouse model of systemic candidiasis. The results showed that the survival time of mice treated with PF alone or PF + FCZ decreased compared with the Infected alone and FCZ treated groups, respectively (8.20 ±â€¯1.75 vs 10.40 ±â€¯2.50 days, P < 0.05; 24.60 ±â€¯6.55 vs 29.00 ±â€¯3.16 days, P < 0.05). The fungal burden in the kidney of mice increased in the PF alone and PF + FCZ treated groups compared with the Infected alone or FCZ treated group. Furthermore, it was found that the PF and PF + FCZ treated groups showed significantly decreased levels of serum interferon gamma (IFN-γ), interleukin (IL)-17, and IL-22, and an increased level of serum IL-4; PF had no effect on the production of tumor necrosis factor alpha (TNF-α). PF alone or in combination with FCZ decreased the proliferation of Th1 (IFN-γ+CD4+) and Th17 cells (IL-17+CD4+) and increased the expression of Th2 cells (IL-4+CD4+). These results suggested that PF treatment could be detrimental to the host response to systemic C. albicans infection in mice. Thus, caution might be required for clinical use of PF in patients with fungal infection.

Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne.

Severe acne is a chronic inflammatory skin disorder characterized by widespread inflammatory lesions including nodules, cysts and potential scarring. Here we perform the first genome-wide association study of severe acne in a Chinese Han population comprising 1,056 cases and 1,056 controls using the Illumina HumanOmniZhongHua-8 BeadChip. In an independent cohort of 1,860 cases and 3,660 controls of Chinese Han, we replicate 101 SNPs of which 3 showed consistent association. We identify two new susceptibility loci at 11p11.2 (DDB2, rs747650, P(combined)=4.41 × 10⁻9 and rs1060573, P(combined)=1.28 × 10⁻8) and 1q24.2 (SELL, rs7531806, P(combined)=1.20 × 10⁻8) that are involved in androgen metabolism, inflammation processes and scar formation in severe acne. These results point to new genetic susceptibility factors and suggest several new biological pathways related to severe acne.

Inhibition of PI3Kδ improves systemic lupus in mice.

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanying excessive inflammatory responses. Phosphoinositide 3-kinase p110δ (PI3Kδ) is reported to associate with autoimmune conditions. We here aimed to determine whether selective inhibition of PI3Kδ is effective in a lupus model of BXSB mice, using the selective PI3Kδ inhibitor IC87114, which was intraperitoneally administrated to BXSB mice aged from 14 to 22 weeks. We showed that IC87114 improved renal function by decreasing the levels of proteinuria and serum creatinine, ameliorating the pathologic changes of kidneys and IgG and C3 deposition. Serum anti-autoantibody to nuclear antigen, anti-dsDNA, IL-1ß, and IL-17 were markedly reduced by IC87114 therapy. Hepatic damage was also inhibited by administration of IC87114. Expression of phosphorylated AKT (p-AKT) and monocyte chemoattractant protein-1 was inhibited and mouse survival improved. In sum, PI3Kδ activation may be a critical factor for escalating autoimmune renal and hepatic damage, and its inhibition may alleviate the autoimmune damage. Our study reveals that the selective blockade of PI3Kδ is effective for mouse SLE.

Myeloid-derived suppressor cells protect mouse models from autoimmune arthritis via controlling inflammatory response.

Myeloid-derived suppressor cells (MDSCs) have been reported to participate in immune suppression and autoimmune disorders. However, its role in autoimmune arthritis remains to be determined. We explored whether adoptive transfer of MDSCs in vivo would block joint inflammation and histological damage using collagen-induced arthritis (CIA) and antigen-induced arthritis (AIA) models. CD11b(+) Gr-1(+) MDSCs were isolated from the single cells from the spleens of CIA mice on day 41 or AIA mice on day 35. MDSCs (2 × 10(6)) were then transferred to AIA and CIA mice via tail vein before arthritis establishment at indicated time points. Phosphate buffered saline (PBS) was injected as control. Arthritis was evaluated by severity score and histology. The levels of TNF-α, IL-6, IL-17 and IL-10 in the serum and joints were detected by enzyme-linked immunosorbent assay (ELISA). The number of Th17 cells and macrophages in draining lymph nodes and joint tissues was assessed by flow cytometric analysis. Adoptive transfer of MDSCs significantly reduced the clinical score of arthritis, alleviated joint inflammation and histological damage both in AIA and CIA models compared with PBS-treated control groups. The levels of TNF-α, IL-6, IL-17, and IL-10 in the serum and joints were down-regulated by transfer of MDSCs. In addition, adoptive transfer of MDSCs significantly reduced the number of Th17 cells and macrophages in draining lymph nodes and joint tissues. Altogether, we demonstrate that adoptive transfer of MDSCs prevented autoimmune arthritis in mouse models of RA through inhibiting Th17 cells and macrophages. These new findings provide insights into the inhibitory functions of MDSCs and MDSCs may be used as a cell-based biotherapy in RA.

Treatment of depression based on differentiation of the Shaoyang Channels.

Depression is a disease with which man would be in a low mental state and have decreased physiological vitality. The author thinks that this disease is located in the Shaoyang Channels, with the heart, liver, kidney, spleen and stomach involved. However, the affection always centers in the Shaoyang Channels. The functional activities, the ascending and descending, in and out of qi in the other organs, all depend on the generation and development of gallbladder-qi and the function of the gallbladder in pivoting qi. "The qi activities in the twelve channels must be inspired by the qi activities of the liver and gallbladder, and can disease only be avoided when qi in these organs has got free flow." Abnormal distribution of the ministerial fire constitutes the basic mechanism for the onset of depression. According to the pathogeneses and clinical manifestations, the syndrome of depression can be divided into three types, namely, flaming-up of gallbladder-fire, stagnation in Shaoyang and failure of ministerial fire in dispersing, and stagnation in Shaoyang and insufficiency of ministerial fire. The deficiency and excess of vital-qi and pathogenic factors of the three types are different. Based on the principle of 'soothing the depressed liver, and dispersing the depressed fire', removing stagnation and promoting unrestrained flow of qi should be taken as the main principle in the treatment of depression. Xiao Chaihu Tang should be used as the main prescription for its action of qi-pivoting and Shaoyang-dispersing. Based on the actual condition of the vital-qi and the pathogenic-qi, symptomatologic modifications can be done in the prescription for directly removing the pathogenic factors, or for reinforcing and reducing at the same time by using herbs of cold and warm natures.