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海南医科大学学报（英文版）
海南医科大学学报（英文版）

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海南医科大学学报（英文版）/Journal Journal of Hainan Medical University
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    Effect and mechanism of knockout RhoE on the protein expression profiles in cardiac tissues of diabetic rats based on 4D proteomics

    ZHAO YunSHI Kai-jiaWU Cai-xiaZOU Yuan...
    1-10页
    查看更多>>摘要：Objective: To analyze the effect of RhoE gene expression change on protein expression profiles in the cardiac tissue of diabetic rats, and analyse the possible underlying regulatory mechanism. Methods: Six-week-old male RhoE gene knockout (KO) and wild-type (WT) Sprague Dawley rats were injected intraperitoneally with streptozotocin (70 mg/kg) to establish the type 1 diabetes model (T1DM), with injection of the same amount of sodium citrate saline as the control group. A week later, the fasting blood glucose of the rats was measured daily, and blood glucose concentration 16.7 mmol/L was regarded as a successful model. Two additional weeks later, the hearts of the rats in each group were removed and four-dimensional label-free quantitative proteomics technology (4D-LFQ) was used to analyze the changes of protein profiles in the heart tissue. The related functions, enrichment signals, and protein-protein interaction network (PPI) of the differentially expressed proteins were analyzed. Results: T1DM rat models were successfully established. Taking a fold change > 1.5 and P < 0.05 as the threshold, a total of 2931 quantifiable proteins were identified. In the non-diabetic state, the KO group had 26 and 45 significantly up- and downregulated proteins, respectively, compared with the WT group; in the diabetic state, the KO group had 19 and 28 significantly up- and downregulated proteins, respectively, compared with the WT group. The GO annotation results showed that most of the differentially expressed proteins were located in the extracellular matrix, and their biological functions were mainly concentrated in the immune response and energy metabolism. KEGG analysis showed that the signaling pathways associated with the differentially expressed proteins in cardiac tissue after RhoE knockout were mainly related to ribosomes and fat digestion and absorption. Protein interaction network analysis showed that in the cardiac tissue of the KO group, there were more Col1α1- and Col1α2-interacting proteins among the upregulated proteins, and among the down-regulated proteins, related proteins involved in the ribosomal pathway interact more in the network. Conclusion: RhoE knockout significantly changes the protein expression profiles in diabetic cardiac tissue, affecting multiple signaling pathways closely related to diabetic cardiomyopathy. The results provide insights into the pathogenesis and therapeutic target screening of diabetic cardiomyopathy.
      原文链接:
    • 万方数据
    • 维普

    Four FDA-approved drugs exhibited inhibition effect on severe fever with thrombocytopenia syndrome virus in vitro

    WANG Tian-tianYIN Zhi-yunDENG Ya-liZHU Qiong...
    11-17页
    查看更多>>摘要：Objective: To screen the anti-SFTSV drugs from 1430 FDA-approved drugs via mini-genome system, and to investigate which stage of the infection process could be suppressed by the identified drugs. Methods: The SFTSV mini-genome system was used to screen drugs with inhibitory effect on SFTSV replication and transcription, and the 50％ inhibitory concentration (IC50) of each drug was calculated by drug concentration gradient inhibition experiment. Drugs were used to pre-incubate with virus and then incubate with cells, to incubate with virus and cells simultaneously, to incubate with cells after virus invading into cells, or to incubate during the whole infection process, and then qRT-PCR was used to measure the viral RNA copies in the culture supernatant. These experiments were performed to quantitatively determine the inhibition effects of drugs on SFTSV indifferent stages of the whole process including virion stability, entry and post-entry stages, so as to clarify the inhibition mechanism of these drugs. Results: Four drugs including Mycophenolate mofetil, Mycophenolic acid, Nitazoxanide, and Vidofludimus were identified having efficient inhibitory effects on SFTSV RNA replication via minigenome system, with the IC50 of 0.014 µmol/L, 0.627 µmol/L, 1.283 µmol/L, and 0.059 µmol/L, respectively. All four drugs showed effective inhibition when adding during the whole SFTSV infection process as well as the post-entry stage. Conclusion: Mycophenolate mofetil, Mycophenolic acid, Nitazoxanide and Vidofludimus show efficient anti-viral effects on SFTSV infection.
      原文链接:
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    • 维普

    Intervention and immune regulation of Fuzheng Xiaoying Decoction on experimental autoimmune thyroiditis model rats

    QIAO Jia-junZHANG Yu-yangSHI Jing-pingXIA Zhong-yuan...
    18-24页
    查看更多>>摘要：Objective: To investigate the effect of Fuzheng Xiaoying Decoction on experimental autoimmune thyroiditis (EAT) model rats and explore its possible mechanism of immune regulation. Methods: Among the 40 female SD rats, 10 were randomly selected as the blank group, and the rest were immunized with pig thyroglobulin and Freund's adjuvant combined with high iodine feeding to make the EAT model. After the model was established, they were randomly divided into three groups: the model group, the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group, which were continuously gavaged for 2 months. The anti thyroid autoantibodies, thyroid function, IL-38 and Th17/Treg distribution were measured. The pathological changes of thyroid tissue were observed by HE staining. Results: Compared with the blank group, the levels of TPOAb and TGAb in the model group were significantly higher(P<0.05). Lymphocyte infiltration was seen in the thyroid tissue of the model group,and also the thyroid follicles were partially destroyed, the shape was irregular, and the colloid distribution was uneven, indicating that the modeling was successful. Compared with the model group, the levels of TPOAb and TGAb in the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group decreased significantly(P<0.05). And the Fuzheng Xiaoying Decoction group had more significant improvement in thyroid follicle destruction and lymphocyte infiltration than the selenium yeast tablet group (P<0.05). Compared with the blank group, the levels of T3, T4, FT3 and FT4 in the model group increased, the level of IL-38 decreased, the proportion of Th17 increased, and the ratio of Th17/Treg increased (P<0.05). Compared with the model group, T4 level decreased, IL-38 level increased in the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group(P<0.05).But there was no statistically significant difference in the reduction of Th17 proportion and Th17/Treg ratio between the above two groups and the model group (P>0.05). There was no significant difference in Treg ratio among the groups. Conclusion: Fuzheng Xiaoying Decoction can significantly reduce the level of anti thyroid autoantibodies in EAT rats by regulating the immunity of EAT rats, and improve the follicular destruction and lymphocyte infiltration of thyroid tissue in rats.
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    • 维普

    Based on the theory of "Kidney-blood-bone" to explore the mechanism of GH/IGF-1 system in the prevention and treatment of osteoporosis in Qing 'e pill

    SUN XinYANG Qi-ningWANG Qing-yanLI Jia...
    25-31页
    查看更多>>摘要：Objective: To observe the changes of growth hormone (GH)/insulin-like growth factor-1(Igf-1) system in blood, kidney and bone tissue of rats, and to explore the preventive and therapeutic effect of Qing 'e pill on osteoporosis due to kidney deficiency and its mechanism, to provide the basis for studying the etiology and pathogenesis of osteoporosis due to kidney deficiency. Methods: The rat osteoporosis model was established by ovariectomy, they were randomly divided into normal group, model group, Western Medicine Group, Jianpi Group, high-dose group, middle-dose group and low-dose group, the levels of serum alkaline phosphatase (ALP) , tartrate acid phosphatase (TRACP), growth hormone (GH) and GHR (Ghr) in kidney, bone and blood were determined by Elisa, the contents of insulin-like growth factor-1(Igf-1) and insulin-like growth factor-1 receptor (IGF-1R) were analyzed by SPSS 25.0 software. Results: 1. Compared with the normal group, the contents of TRACP and ALP in serum of the model group were significantly increased, suggesting that the rats developed high-conversion osteoporosis. 2. The levels of serum, bone and renal GHR, Igf-1 and insulin-like growth factor-1 receptor (IGF-1R) in the model group were significantly lower than those in the control group. 3. Compared with the model group, the contents of TRACP and ALP in the high, middle and low dose groups were significantly decreased. 4. Compared with the model group, the contents of GHR, Igf-1 and IGF-1R in blood, bone and kidney tissue of the high, middle and low dose groups were increased. Conclusion: 1. Qing 'e pill can improve the bone metabolism of osteoporosis. 2. Qinge pill may prevent and cure osteoporosis by increasing the contents of GHR, Igf-1 and IGF-1R in blood, bone and kidney.
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    Exploring the key pathways of tetrandrine in the treatment of early silicosis based on bioinformatics and in vitro experiments

    LIANG ChaoZHOU Jia-weiLIU Ya-fengGUO Jian-qiang...
    32-42页
    查看更多>>摘要：Objective: Exploring the key pathways affecting the development of early silicosis based on bioinformatics and in vitro experiments. Method: Collecting differentially expressed genes in silicosis patients through literature mining; Collecting differentially expressed genes in silicon dioxide infusion mice by using a high-throughput gene expression database (GEO); Obtaining disease targets related to silicosis by means of online human Mendelian genetic database (OMIM), GeneCards and comparative toxicgenomics database (CTD); differentially expressed genes and disease targets were subjected to gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analysis via R-package and Metascape platforms, respectively. The Schrödinger and Pymol software were used for molecular docking and modification. Silicon dioxide-stimulated macrophages and epithelial cells were modeled and analyzed by PCR and western blot (WB). Result: 2065 differentially expressed genes in silicosis patients, 2291 differentially expressed genes in rat infused with silicon dioxide, and 803 targets for silicosis-related diseases were screened out. GO enrichment analysis mainly involves G protein-coupled receptor binding, the regulation of inflammatory response, and participation in immune response. The enrichment analysis of KEGG pathway mainly included ECM-receptor interaction, TNF signaling pathway, and IL-17 signaling pathway. IL-17 signaling pathway was screened out from different genes and disease targets, indicating that IL-17 signaling pathway might be the key pathway for the development of silicosis. Molecular docking results showed that the silicosis drug tetrandrine had good binding effect with the RAF/MEK/ERK pathway in the IL-17 signaling pathway. Cellular experiments showed that tetrandrine reduced the expression of inflammatory factors such as IL-6 and TGF-β in macrophages by regulating the RAF/MEK/ERKpathway, and inhibited the epithelial-mesenchymal transition and expression of inflammatory factors in epithelial cells. Conclusion: Tetrandrine regulates the inflammatory response and epithelial-mesenchymal transition (EMT) through the RAF/MEK/ERK pathway and thus affects the early progression of silicosis.
      原文链接:
    • 万方数据
    • 维普

    Experimental study of TGF-β1/Smads pathway inhibition of macrophage polarization based on miR145-5P negative feedback regulation

    WANG Qing-qingSHEN XiWAN LeiFAN Hai-xia...
    43-49页
    查看更多>>摘要：Objective: To investigate the effect of miR145-5P overexpression on the polarization imbalance of synovial macrophages in patients with rheumatoid arthritis (RA). Methods: Human mononuclear cells (THP-1) at logarithmic growth stage were induced into M1-type macrophages, and RA synovial fibroblasts M1-type macrophages were co-cultured into synovial macrophages. Synovial macrophages were divided into four groups :RA group (blank group), TGF-β1 group (model group) and miR145-5P overexpression group (TGF-β1+ miR145-5P mimics group) and miR145-5P overexpression negative control group (TGF-β1+ miR145-5P-mimics -NC group). The blank group did not receive any treatment, and the other three groups were induced by TGF-β1 in the medium for 48 h. Transfection miR145-5p mimic and miR145-5P-mimics-NC were added to co-culture medium, and IL-6, IL-6 and IL-6 of synovial macrophages were detected by ELISA.CD163 expression. Rt-qpcr was used to detect miR145-5p mRNA, TGF-β1mRNA, Smad3mRNA,Smad7mRNA expression level. The expression of TGF-β1/Smads pathway related proteins was detected by Western Blotting. Results: Compared with blank group, IL-6 level was up-regulated (P<0.01) ,and CD163 level was down-regulated in model group(P<0.05) , suggesting that TGF-β1 could induce intensified immune inflammatory response. Compared with the negative miR145-5P overexpression control group and model group, The expression of miR145-5P overexpression group molecule CD163 was significantly increased by ELISA(P<0.01), and the expression of inflammatory factor IL-6 was decreased (P<0.05). PCR showed that miR145-5P mRNA expression level was significantly increased in miR145-5P overexpression group,Smad3 mRNA and TGF-β1 mRNA were significantly decreased, and Smad7 mRNA was significantly increased (P<0.01). WB method showed that the anti-inflammatory protein Smad7 was significantly increased, while TGF-β1 and Smad3 were significantly decreased (P<0.01). Transwell chamber results confirmed that miR145-5P overexpression group significantly reduced macrophage invasion (P<0.01). Correlation analysis showed that miR145-5P was negatively correlated with Smad3 and positively correlated with Smad7 (P<0.01). Conclusion: miR145-5P may inhibit macrophage polarization in RA patients by targeting Smad3 protein, negatively regulating TGF-β1/Smads pathway, and alleviating immune inflammation.
      原文链接:
    • 万方数据
    • 维普

    Study on syndrome distribution and medication characteristics of patients with rectal cancer in the real world

    GAO FengGUO Li-junXIE Yan-mingLIU Huan...
    50-57页
    查看更多>>摘要：Objective: To explore the general characteristics, traditional Chinese medicine (TCM) syndromes and medication of patients with rectal cancer in China. Methods: The clinical data of inpatients with rectal cancer from the information system of 17 tertiary A-level traditional Chinese medicine hospitals in China were collected. After data standardization, descriptive analysis was performed on the general information, syndrome distribution and medication characteristics of the included patients, and association rule analysis was performed on the drug usage. Results: A total of 15424 hospitalized patients with rectal cancer were included. The ratio of male to female patients was 1.6:1, the average age was 60.87 years old, and the age was mainly in the range of 50 to 79 years old. Among the 12146 patients with rectal cancer, the top 5 TCM syndromes were Qi and Yin deficiency syndrome (25％), phlegm and blood stasis syndrome (19％), spleen deficiency syndrome (14％), Qi stagnation and blood stasis syndrome (7％) and Qi and blood deficiency syndrome (6％). After excluding the anti-tumor western medicine recommended by the guidelines, adrenal corticosteroids (43.55％), antibiotics (42.94％) and immunomodulatory drugs (42.66％) ranked the top three in the frequency of western medicine use. Dexamethasone (38.15％), metoclopramide tablets (20.51％) and furosemide injection (19.71％) were the three most commonly used western medicines. Among the three western medicines combined, cimetidine, granisetron hydrochloride dextrose injection + dexamethasone were the most common (support 8.23％, confidence 96.4％, and improvement 2.48％). Heat-clearing and detoxifying agents (53.72％), Yiqi-fuzheng agents (49.76％) and blood-activating and stasis-removing agents (15.68％) ranked the top 3 in the frequency of use of traditional Chinese medicine.Shenqi Fuzheng injection, Shenqi Fuzheng injection (21.59％), Compound Kushen injection (17.52％) and Aidi injection (11.96％) were the three most commonly used Chinese patent medicines. Conclusion: The main syndromes of patients with rectal cancer may be Qi and Yin deficiency syndrome, phlegm and blood stasis syndrome, and spleen deficiency syndrome, etc. The treatment needs to focus on the supplementation of vital essence, combination of dredging and tonifying method, and the integration of traditional Chinese and western medicine.
      原文链接:
    • 万方数据
    • 维普

    Meta-analysis of the clinical efficacy of Chinese herbal decoction combined with arthroscopy in the treatment of gouty arthritis

    XU Lu-chunWANG Jian-junYE ChaoWANG Yue...
    58-68页
    查看更多>>摘要：Objective: To systematically evaluate the efficacy of traditional Chinese medicine decoction combined with arthroscopy in the treatment of gouty arthritis. Methods: A systematic search of CNKI, CBM, WanFang, VIP, PubMed, Cochrane Library, and EMBASE databases, and the receipt of the database until February 2021. Randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) decoction combined with arthroscopy in the treatment of gouty arthritis. Two researchers independently read the title and abstract to screen and them read the full text to clarify whether it should be included. The method of Cochrane systematic review was used to evaluate the quality of the literature, and the RevMan 5.3 software was used to conduct meta-analysis of the data. Results: Nineteen RCTs were finally included. A total of 1383 patients, 697 cases in the treatment group were treated with traditional Chinese medicine decoction combined with arthroscopy, and 686 cases in the control group were treated with arthroscopy alone or combined with western medicine. Meta-analysis results showed that the total clinical effective rate (P<0.00001) of the treatment group was better than that of the control group. Visual analogue scoring (VAS) score (P=0.0005, P<0.00001, P=0.03) and erythrocyte sedimentation rate (ESR) level (P<0.00001, P<0.00001, P<0.00001)reduction in each subgroup was better than that of the control group. The Lysholm score of the treatment group increased (P<0.00001, P<0.00001, P=0.19), while for blood uric acid (UA) level (P<0.00001, P=0.18, P<0.0001) and C-reactive protein (CRP) levels (P<0.0001, P<0.00001, P=0.23) two subgroups were better than the control group, but there was no significant difference in one subgroup. Conclusion: Traditional Chinese medicine decoction combined with arthroscopy is effective in treating gouty arthritis, which can relieve pain, improve joint function, and reduce body inflammation and uric acid levels. However, in the future, clinical studies with larger sample sizes, more reasonable designs, and higher quality are still needed to demonstrate this conclusion.
      原文链接:
    • 万方数据
    • 维普

    Advances in the application of optical coherence tomography in the assessment of ischemic stroke

    XU Ding-jiZHAO Zhen-qiangCAI yi
    69-74页
    查看更多>>摘要：Ischemic stroke has high morbidity, mortality, disability rate and recurrence. It is the one of the main diseases that threaten people's health in China. Its etiology, pathogenesis, and reaction mechanism has been the research hotspot and difficulty of related studies have shown that the optical coherence tomography technology is an effective measure to evaluate ischemic cerebral apoplexy.Optical coherence tomography (OCT) is a gradually developed and mature imaging technology in recent years, and there are related studies on internal carotid artery, retina and coronary artery.Based on the above background, this paper reviews the research progress of optical coherence tomography in the assessment of the etiology, pathogenesis and response mechanism of ischemic stroke.
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    • 万方数据
    • 维普

    Research progress on pathogenesis of ulcerative colitis

    XIE Jing-riCHEN Shan-taoLIU Zhi-wei
    75-80页
    查看更多>>摘要：The incidence of ulcerative colitis is increasing year by year, yet the pathogenesis is still not clear. Many scholars have studied the genetic factors, environmental factors, intestinal microecological imbalance, intestinal mucosal barrier disorder, abnormal immune response and mitochondrial diseases, and abundant achievements have been made. In order to further understand the possible pathogenesis of ulcerative colitis, this paper reviews its research progress, in order to better guide clinical medication, and provide new ideas for further study of its pathogenesis.
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    • 维普