Risk factors associated with malignant vasovagal syncope in children / 中华儿科杂志

Objective: To analyze the clinical characteristics and risk factors of malignant vasovagal syncope (VVS) in children. Methods: This was a case-control study. The data of 368 VVS patients who were treated in the Department of Cardiology, Children's Hospital, Capital Institute of Pediatrics from June 2017 to December 2021 was collected and analyzed. They were divided into malignant VVS group and non-malignant VVS group according to the presence of sinus arrest, and then their demographic characteristics were compared. The children with malignant VVS and complete clinical information were recruited into the case group and were matched by age and sex (1∶4 ratio) with non-malignant VVS patients during the same period.Their clinical characteristics and lab tests were compared. Independent sample t test, Mann Whitney U or χ2 test was used for comparison between groups.Logistic regression was used to analyze the risk factors for malignant VVS in children. Results: Eleven malignant VVS and 342 non-malignant VVS met the inclusion and exclusion critera. Eleven malignant VVS and 44 non-malignant children were recruited in the case-control study. Ten patients of the 11 malignant VVS had a cardiac arrest occurring at 35 (28, 35) minutes of the head-up tilt test, and the duration of sinus arrest was (9±5) s. One patient had syncope occurring while waiting for drawing blood, and the duration of sinus arrest was 3.4 s. The children with malignant vasovagal syncope were younger than non-malignant VVS patients (9 (7, 10) vs. 12 (10, 14) years old, P<0.05), and had higher mean corpuscular hemoglobin concentration (MCHC) and standard deviation of the mean cardiac cycle over 5-minute period within 24 hours ((347±9) vs. (340±8) g/L, (124±9) vs. (113±28) ms, both P<0.05). Logistic regression analysis showed that MCHC was an independent risk factor for malignant VVS in pediatric patients (OR=1.13, 95%CI 1.02-1.26, P=0.024). Conclusions: The onset age of malignant VVS was younger, with no other special clinical manifestations. MCHC was an independent risk factor for malignant VVS.

Mechanism of Berberis atrocarpa anthocyanin against Alzheimer's disease based on network pharmacology and experimental verification / 中国中药杂志

This study aimed to explore the potential mechanism of Berberis atrocarpa Schneid. anthocyanin against Alzheimer's disease(AD) based on network pharmacology, molecular docking technology, and in vitro experiments. Databases were used to screen out the potential targets of the active components of B. atrocarpa and the targets related to AD. STRING database and Cytoscape 3.9.0 were adopted to construct a protein-protein interaction(PPI) network and carry out topological analysis of the common targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed on the target using the DAVID 6.8 database. Molecular docking was conducted to the active components and targets related to the nuclear factor kappa B(NF-κB)/Toll-like receptor 4(TLR4) pathway. Finally, lipopolysaccharide(LPS) was used to induce BV2 cells to establish the model of AD neuroinflammation for in vitro experimental validation. In this study, 426 potential targets of active components of B. atrocarpa and 329 drug-disease common targets were obtained, and 14 key targets were screened out by PPI network. A total of 623 items and 112 items were obtained by GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking results showed that NF-κB, NF-κB inhibitor(IκB), TLR4, and myeloid differentiation primary response 88(MyD88) had good binding abilities to the active components, and malvidin-3-O-glucoside had the strongest binding ability. Compared with the model group, the concentration of nitric oxide(NO) decreased at different doses of malvidin-3-O-glucoside without affecting the cell survival rate. Meanwhile, malvidin-3-O-glucoside down-regulated the protein expressions of NF-κB, IκB, TLR4, and MyD88. This study uses network pharmacology and experimental verification to preliminarily reveal that B. atrocarpa anthocyanin can inhibit LPS-induced neuroinflammation by regulating the NF-κB/TLR4 signaling pathway, thereby achieving the effect against AD, which provides a theoretical basis for the study of its pharmacodynamic material basis and mechanism.

Effect of acetylalkannin from Arnebia euchroma on proliferation, migration, and invasion of human melanoma A375 cells / 中国中药杂志

This study aimed to explore the effect and mechanism of acetylalkannin from Arnebia euchroma on the proliferation, migration, and invasion of human melanoma A375 cells. A375 cells were divided into a blank group, and low-, medium-, and high-dose acetylalkannin groups(0.5, 1.0, and 2.0 μmol·L~(-1)). The MTT assay was used to detect cell proliferation. Cell scratch and transwell migration assays were used to detect cell migration ability, and the transwell invasion assay was used to detect cell invasion ability. Western blot was used to detect the protein expression of migration and invasion-related N-cadherin, vimentin, matrix metalloproteina-se-9(MMP-9), and Wnt/β-catenin pathway-related Wnt1, Axin2, glycogen synthase kinase-3β(GSK-3β), phosphorylated GSK-3β(p-GSK-3β), β-catenin, cell cycle protein D_1(cyclin D_1), and p21. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) was used to detect the mRNA expression of E-cadherin, matrix metalloproteinase-2(MMP-2), N-cadherin, vimentin, β-catenin, snail-1, and CD44. MTT results showed that the cell inhibition rates in the acetylalkannin groups significantly increased as compared with that in the blank group(P<0.01). The results of cell scratch and transwell assays showed that compared with the blank group, the acetylalkannin groups showed reduced cell migration and invasion, and migration and invasion rates(P<0.05, P<0.01) and weakened horizontal and vertical migration and invasion abilities. Western blot results showed that compared with the blank group, the high-dose acetylalkannin group showed increased expression of Axin2 protein(P<0.05), and decreased expression of N-cadherin, vimentin, MMP-9, Wnt1, p-GSK-3β, β-catenin, cyclin D_1, and p21 proteins(P<0.05, P<0.01). The expression of GSK-3β protein did not change significantly. PCR results showed that the overall trend of MMP-2, N-cadherin, vimentin, β-catenin, snail-1, and CD44 mRNA expression was down-regulated(P<0.01), and the expression of E-cadherin mRNA increased(P<0.01). Acetylalkannin can inhibit the proliferation, migration, and invasion of human melanoma A375 cells, and its mechanism of action may be related to the regulation of Wnt/β-catenin signaling pathway.

Mechanism of Arnebia euchroma Against Melanoma： An Exploration Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo preliminarily predict the active components， action targets， and signaling pathways of Arnebia euchroma in the treatment of melanoma based on network pharmacology and molecular docking， and to verify its possible mechanism of action in in vitro experiments. MethodThe active components and related targets of A. euchroma were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）SwissTargetPrediction and literature， and the targets related to melanoma from the GeneCards， Online Mendelian Inheritance in Man （OMIM）， and Comparative Toxicogenomics Database （CTD）. Following the construction of the protein-protein interaction （PPI） network of active components and related targets of A. euchroma and melanoma-related targets using STRING， Cytoscape 3.8.2 was used for screening and analyzing the nodes in the network of A. euchroma against melanoma. The intersections were subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis using DAVID 6.8. Acetyl alkannin， the active component in A. euchroma， was docked to the target by AutoDock Vina 1.1.2. The in vitro experiments were then carried out to verify the anti-melanoma effect of A. euchroma. ResultA total of 271 common targets of A. euchroma and melanoma were harvested， among which 23 were key targets， including matrix metalloproteinase-9 （MMP-9） and Janus kinase 2 （JAK2）. As revealed by KEGG enrichment analysis， A. euchroma mainly acted on Janus kinase/signal transduction and activator of transcription （JAK/STAT）， tyrosine kinase receptor （ErbB）， and vascular endothelial growth factor （VEGF） signaling pathways to resist melanoma. According to molecular docking， acetyl alkannin exhibited a good docking activity with JAK2， STAT3， VEGF， MMP-9， and E-cadherin receptors. The results of Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） showed that acetyl alkannin at different doses inhibited the protein and gene expression of JAK2， STAT3， VEGF， MMP-9， and E-cadherin in A375 cells （P<0.05）. ConclusionA. euchroma alleviates melanoma via multiple targets and multiple pathways， and it may exert the therapeutic effects by affecting the expression of such key target proteins as JAK2， STAT3， VEGF， MMP-9， and E-cadherin and inhibiting the invasion and metastasis of melanoma cells. This study has provided an experimental basis for the treatment of tumor with A. euchroma.

Protective Mechanism of Lavender Against Skin Photodamage Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo predict the active ingredients and mechanism of action of lavender in protecting skin photodamage based on network pharmacology and molecular docking technology，and further verify possible signal pathways via animal experiments. MethodThe active ingredients and potential targets of lavender were obtained by SwissTargetPrediction，PharmMapper， and literature. Skin photodamage-related targets were searched from GeneCards，Online Mendelian Inheritance in Man （OMIM），DrugBank and DisGeNET databases. After common targets of the two were screened out，STRING was adopted to analyze the protein-protein interaction （PPI） network，where topological analysis and core target screening were performed by CytoNCA plug-in of Cytoscape 3.8.2. Based on DAVID， gene ontology （GO） annotations and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out among the intersection targets， and the active ingredients of lavender and the signal pathway proteins were selected and verified via molecular docking with AutoDock vina 1.1.2. Finally， mouse photodamage model was established by UVB irradiating the bare skin of mouse back， and the skin condition was observed by naked eyes. Hematoxylin-eosin （HE） and picric acid-acid fuchsin staining （Van Gieson， VG） were used to observe the pathological changes of mouse skin tissues. Western blot was employed to detect the protein expression in mouse skin tissues to further validate the key signal pathways. ResultIn this study，6 active ingredients of lavender，526 potential targets，2 688 disease-related targets，and 258 intersection targets were screened out， and 16 core targets were obtained by PPI network. Additionally， 113 related signal pathways were obtained by KEGG pathway analysis，among which phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） pathway and nuclear transcription factor-κB （NF-κB） signal pathway might play a key role in skin photodamage protection by lavender. Molecular docking showed that the active ingredients and the signal pathway proteins were well docked. Animal experiments indicated that the total flavonoids of lavender improved the appearance and histopathological condition of mouse skin， reduced the relative expression levels of phosphorylated（p）-PI3K，p-Akt，and B cell lymphoma 2 （Bcl-2） proteins （P<0.05，P<0.01）， and increased relative expression level of Bcl-2-associated X protein（Bax） （P<0.05）. ConclusionLavender exerts synergistic effect in resisting skin photodamage，with the characteristics of multi-components，multi-targets，and multi-pathways， which provides a basis for subsequent in-depth research on the complex mechanism of lavender against skin photodamage.

Overview of systematic reviews on Shenmai Injection in prevention and treatment of diseases / 中国中药杂志

To summarize and evaluate the efficacy and safety of Shenmai Injection in the treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy, so as to provide supportive evidences for clinical rational use of Shenmai Injection. By searching literatures about studies on the systematic reviews on Shenmai Injection in treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy from the main Chinese and English databases. Primary efficacy and safety outcome measures were selected for comparative analysis and summary, and the appraisal tool of AMSTAR 2 was used to evaluate the included studies.A total of 36 systematic reviews(published from 2005 to 2020) were included, involving viral myocarditis, shock, pulmonary heart disease, malignant tumor and coronary heart disease. The number of cases included in each type of the above diseases was 3 840, 2 484, 12 702, 28 036 and 27 082, respectively. The comparison results showed that, Shenmai Injection combined with conventional/western medicine treatment groups had better efficacy than conventional/western medicine groups alone in the prevention and treatment of the above five diseases. The main adverse reactions of Shenmai Injection reported in the included studies were facial flushing, rash, palpitation, etc., but the incidence was low and the general symptoms were mild, so no special treatment was needed. Therefore, the application of Shenmai Injection on the basis of conventional treatment or western medicine treatment had better prevention and treatment efficacy of the diseases. It was suggested that more multi-center and larger sample-size randomized controlled trials should be carried out in the future, and the relevant reporting standards should be strictly followed in systematic reviews, so as to improve the scientificity and transparency of the study.