Molecular mechanism of Danggui Niantong Decoction in the treatment of gouty arthritis based on network pharmacology and molecular docking / 国际中医中药杂志

Objective:To explore the molecular mechanism of Danggui Niantong Decoction in the treatment of gouty arthritis (GA) based on network pharmacology and molecular docking.Methods:By selecting for the active components and targets of Danggui Niantong Decoction with TCMSP, and retrieving the GeneCards, OMIM, PharmGKB and DrugBank databases to obtain GA related targets. The potential targets of Danggui Niantong Decoction in the treatment of GA were obtained by the intersection of mappings. The regulation network of Chinese medicine compound and protein-protein interaction network of Danggui Niantong Decoction were constructed by Cytoscape software, and the targets of Danggui Niantong Decoction in the treatment of GA were analyzed by GO and KEGG enrichment by David Database. Finally, molecular docking was performed by using Autodock software.Results:There are 198 active components that could treat GA in Danggui Niantong Decoction. The key active components are Quercetin and Kaempferol. There are 46 key targets, the core targets are NFE2L2, HMOX1, PPARA, PTGS2, IL1β, CXCL8. GO enrichment suggests that the key genes are primarily involved in many biological processes such as Inflammatory response regulation, response to oxidative stress, Fatty acid metabolism process, steroid metabolism, lipopolysaccharide response and reactive oxygen species metabolism. KEGG pathway indicates that Danggui Niantong Decoction mainly acted on IL-17 signal pathway, HIF-1 signal pathway, TNF signal pathway and AGE-RAGE signal pathway. Molecular docking shows that the active components of Danggui Niantong Decoction and action target of GA can combine toghether with high efficiency, and the structure is stable.Conclusion:Danggui Niantong Decoction has multi-component, multi pathway and multi-protein characteristics. Danggui Niantong Decoction can treat GA by regulating immune inflammatory reaction and oxidative stress reaction.

Mechanism of transforming growth factor- β1 induce renal fibrosis based on transcriptome sequencing analysis / 浙江大学学报·医学版

OBJECTIVES@#To explore the mechanism of transforming growth factor-β1 (TGF-β1) induce renal fibrosis.@*METHODS@#Renal fibroblast NRK-49F cells treated with and without TGF-β1 were subjected to RNA-seq analysis. DESeq2 was used for analysis. Differentially expressed genes were screened with the criteria of false discovery rate<0.05 and l o g 2 F C >1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Genes encoding transcription factors were further screened for differential expression genes. Then, the expression of these genes during renal fibrosis was verified using unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis model and a public gene expression dataset (GSE104954).@*RESULTS@#After TGF-β1 treatment for 6, 12 and 24 h, 552, 1209 and 1028 differentially expressed genes were identified, respectively. GO analysis indicated that these genes were significantly enriched in development, cell death, and cell migration. KEGG pathway analysis showed that in the early stage of TGF-β1 induction (TGF-β1 treatment for 6 h), the changes in Hippo, TGF-β and Wnt signaling pathways were observed, while in the late stage of TGF-β1 induction (TGF-β1 treatment for 24 h), the changes of extracellular matrix-receptor interaction, focal adhesion and adherens junction were mainly enriched. Among the 291 up-regulated differentially expressed genes treated with TGF-β1 for 6 h, 13 genes (Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Ahr, Foxo1, Myc, Tcf7, Foxc2, Glis1) encoded transcription factors. Validation in a cell model showed that TGF-β1 induced expression of 9 transcription factors (encoded by Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Myc, Tcf7), while the expression levels of the other 4 genes did not significantly change after TGF-β1 treatment. Validation results in UUO-induced mouse renal fibrosis model showed that Snai1, Irf8, Bhlhe40, Junb, Arid5a, Myc and Tcf7 were up-regulated after UUO, Vdr was down-regulated and there was no significant change in Lef1. Validation based on the GSE104954 dataset showed that IRF8 was significantly overexpressed in the renal tubulointerstitium of patients with diabetic nephropathy or IgA nephropathy, MYC was highly expressed in diabetic nephropathy, and the expressions of the other 7 genes were not significantly different compared with the control group.@*CONCLUSIONS@#TGF-β1 induces differentially expressed genes in renal fibroblasts, among which Irf8 and Myc were identified as potential targets of chronic kidney disease and renal fibrosis.

Effect of mechanical stimulation by rubbing abdomen by interfering with Th17 cell function on intestinal homeostasis in IBS-C model mice / 国际生物医学工程杂志

Objective:To investigate the possible mechanism of rubbing abdomen to regulate intestinal homeostasis in irritable bowel syndrome with constipation (IBS-C) mouse models.Methods:IBS-C mouse models of intestinal immune dysfunction were established using trinitrobenzene sulfonic acid (TNBS)-induced C57BL/J6 male mice. Thirty C57BL/J6 mice were randomly divided into three groups: the control group, the model group, and the mogul group. After 7 days of modeling, mice in the mogul group were given a mogul mechanical stimulation intervention once per day for 2 weeks, while mice in the control and model groups were not given any intervention. Changes in serum levels of interleukin-6 (IL-6) and IL-17A were detected by enzyme-linked immune sorbent assay (ELISA) and immunohistochemistry. The gene expression and protein levels of IL-17A and IL-23 were detected by quantitative real-time fluorescence PCR (qRT-PCR) and Western Blot, respectively. The morphological changes were observed by HE staining. The CD44 and CD62L expression changes were observed by immunofluorescence staining.Results:Compared with the model group, the levels of IL-6 and IL-17A in the serum of mice in the mogul group were decreased, and the expression of IL-6 and IL-7A in the tissues was down-regulated (all P<0.001). In addition, the gene expression and protein expression levels of IL-17A and IL-13 in the tissues of mice in the mogul group were decreased (all P<0.001). HE staining results showed that the mogul mechanical stimulation intervention could repair colonic tissues and reduce the inflammatory response. Immunofluorescence staining results showed that mogul mechanical stimulation intervention could downregulate the expression of CD44 but had no modulating effect on the expression of CD62L. Conclusions:Rubbing abdomen can improve intestinal homeostasis in IBS-C model mice by regulating changes in Th17 cell function.

Analysis of acupoint selection rules of Tuina in the treatment of infantile autumn diarrhea based on Traditional Chinese Medicine Inheritance Support Platform / 国际中医中药杂志

Objective:To analyze the rules and distribution of acupuncture points used in pediatric tuina treatment for autumn diarrhea, and to provide a theoretical basis for the promotion and application of Tuina treatment techniques for pediatric diarrhea.Methods:We searched the literature on Tuina treatment of pediatric autumn diarrhea in the Chinese academic journals full-text database (CNKI), Chinese science and technology journals full-text database (VIP), Wanfang database and Chinese biomedical database (SinoMed), and collected the Tuina prescriptions on children's autumn diarrhea disease from the database to March 2021,with the help of the Traditional Chinese Medicine Inheritance Support Platform (V 2.0) software,and Data mining technology was applied to analyze the common acupoints and acupoint distribution of pediatric Tuina treatment of autumn diarrhea to form the core acupoints used in pediatric Tuina treatment of autumn diarrhea.Results:A total of 101 pediatric autumn diarrhea Tuina prescriptions were screened, involving 61 acupoints, among them 18 acupoints used more frequently, and 35 acupoint combinations were obtained, including 15 two-acupoint combinations, 11 three-acupoint combinations, and 2 four-acupoint combinations, and 7 new acupoint combinations were obtained.Conclusion:The core points mainly belong to the spleen meridian, large intestine meridian, abdomen, seven knotted bones, turtle tail, spine, and umbilicus, which can be used as a basic Tuina prescription for clinical reference.

Modulating gut miocrobiota: A new strategy in the treatment of gout / 中国临床药理学与治疗学

Gout is a persistent increase in blood uric acid caused by purine and uric acid metabolism disorders, resulting in monosodium urate crystal deposition induced by recurrent inflammatory diseases, mainly manifested as elevated uric acid and inflammatory attacks. Studies have shown that gout and changes in the gut miocrobiota are mutually causal, and the gut miocrobiota can not only affect purine and uric acid metabolism but also regulate inflammatory response. Therefore, regulating the gut miocrobiota is expected to become a new strategy for the treatment of gout. This article starts from the regulation of purine and uric acid metabolism and inflammatory response by gut miocrobiota, so as to clarify the specific application of gut miocrobiota regulation as a new strategy for gout treatment.

Neutrophil extracellular traps and its role in gouty diseases / 中国临床药理学与治疗学

Neutrophil extracellular traps (NETs) are an important part of the innate immunity. They are mainly involved in the occurrence of gout disease through NADPH oxidase 2-dependent pathways and it is related to the spontaneous remission of gouty arthritis and the formation of tophi. These pathological features can be analyzed by methods such as electron microscopy and immunohistochemical staining. In order to further explore the molecular mechanism of NETs and discover potential drug targets for gouty arthritis, this article summarizes its role in gouty diseases and related detection techniques.

Effect of abdominal mechanical stimulation on nervous system in irritable bowel syndrome-Diarrehea / 国际生物医学工程杂志

Objective:To observe the effect of abdominal mechanical stimulation on rats with irritable bowel syndrome-Diarrehea (IBS-D), and to explore the possible mechanism of abdominal massage mechanical stimulation to improve IBS-D.Method:60 newborn Wistar rats were randomly divided into blank group, model group and abdominal massage group, 20 rats for each group. The IBS-D rat model was established by separating the mother rats and newborn rats. In the abdominal massage group, the IBS-D rats were treated with abdominal rubbing once a day for 14 days. In the model group, the IBS-D rats were only bound to the experimental platform once a day for 5 min for 14 days. The rats in blank group were not made model and with no intervention. The intestinal motility and visceral sensitivity of rats were measured by the time of glass bulb expulsion and the abdominal lift volume threshold. The pathological changes of rat colon tissue were observed by hematoxylin-eosin staining. The changes of mast cells in colon tissue were observed by toluidine blue staining. The ultramicrostructure of intestinal glial cells was observed by transmission electron microscope. The content of proinflammatory factors IL-6 and IL-1β in rat plasma was determined by ELISA.Results:Compared with the model group, mechanical stimulation of the abdominal massage can significantly prolong the discharge time of the glass beads [(2.5±0.2) min vs (1.6±0.2) min], increase the abdominal lift volume threshold of rats [(0.5±0.1) ml vs (0.4±0.1) ml], improve the pathological state of the colon tissue, and reduce the number of mast cells [(2.64±0.22) per field vs (5.61±0.12) per field], reduce the number of mitochondria in the intestinal glial cells and increase the density of heterochromatin, and can also reduce the secretion of proinflammatory factors IL-6 [(189.4±4.7) pg/ml vs (224.8±8.6) pg/ml] and IL-1β [(178.4±7.1) pg/ml vs (191.4±8.4) pg/ml], and the differences were statistically significant (all P<0.05). Conclusions:Mechanical stimulation of abdominal massage can increase the visceral sensitivity of IBS-D rats, regulate intestinal glial cells and reduce the secretion of proinflammatory factors. The mechanism may be related to the intestinal-brain axis.

Effects of abdominal massage on the structure and function of affective loop in rats with generalized anxiety disorder / 国际生物医学工程杂志

Objective:To observe the structural and functional changes of each nucleus group in generalized anxiety disorder(GAD) rat models before and after the massage therapy, and to explore the central regulating mechanism of the massage therapy in GAD.Methods:60 Wistar male rats were randomly divided into blank group, model group and abdominal rubbing group, 20 rats for each group. GAD rat models were established by chronic emotional stress, and the models were evaluated by the elevated cross maze experiment. In the abdominal rubbing group, the GAD rats were treated with abdominal rubbing once a day for 10 min for 14 days. In the control group, the GAD rats were only bound to the experimental platform once a day for 10 min for 14 days. Horseradish peroxidase (HRP) retrograde tracking marker method was used to detect the changes of the structure of each nuclear cluster in the affective loop of the GAD rats in each group. The liquid-mass spectrometry quantitative analysis was used to determine the relative concentrations of N-acetyl aspartate (NAA), glutamic acid, choline and creatine in nuclear cluster of the GAD rats in each group.Results:Compared with the blank group, the HRP labeled cells in the rats of model group were less expressed and the activity of the emotional circuit in the brain was weak. The NAA/creatine ratio in the left hippocampal tissue of the rats in the model group was significantly increased than that of the blank group(0.94±0.08 vs 0.79±0.10, P<0.05), the glutamic acid/creatine ratio in the right hippocampal tissue was significantly decreased (0.95±0.10 vs 1.12±0.13, P<0.01), and the NAA/creatine andglutamic and acid/creatineratios in the left cortical tissue were all significantly decreased (1.04±0.05 vs 1.41±0.23, and 1.21±0.04 vs 1.57±0.11, all P<0.01). Compared with the model group, the hippocampal tissues of the GAD rats in the abdominal rubbing group had a large number of HRP aggregation and spread to the surrounding tissues, the NAA/creatine and glutamic acid/creatine ratios in the left hippocampal tissue of the abdominal rubbing group were significantly decreased (0.74±0.21 vs 0.94±0.09 and 0.92±0.20 vs 1.21±0.12, all P<0.01). The differences between the model group and the abdominal rubbing group in the ratio of glutamic acid/creatine in the right hippocampal tissue (1.01±0.23 vs 0.95±0.10), the ratio of NAA/creatine in the left cortical tissue (1.12±0.09 vs 1.04±0.05), and the ratio of glutamic acid/creatine in the left cortical tissue (1.22±0.12 vs 1.21±0.04) were not statistically significant ( P>0.05). Conclusions:Abdominal rubbing can effectively enhance the activity of affective loop and improve the relative concentration of neuron metabolites in hippocampal and cortical tissues in the affective loop, suggesting that the mechanism of GAD treatment by abdominal rubbing may be closely related to the structure and function of regulating affective loop.

Effect of -induced changes in tumor tissue acoustic properties on efficacy of high-intensity focused ultrasound ablation / 南方医科大学学报

OBJECTIVE@#To investigate the effects of on the acoustic characteristics of tumor tissue and how such acoustic changes affect the efficacy of high-intensity focused ultrasound (HIFU) ablation in nude mice.@*METHODS@#Forty mice bearing human breast cancer cell (MDA-MB-231) xenograft were randomized into experimental group (=20) and control group (=20) for intravenous injection of suspension (200 μL, 4 × 10 cfu/mL) and PBS (200 μL) for 3 consecutive days, respectively. Before and at 3 and 7 days after the first injection, shear wave elastography was used to evaluate the hardness of the tumor tissue. On day 7 after the first injection, 10 mice from each group were sacrificed and the sound velocity and sound attenuation of the tumor tissues were measured. The changes in the collagen fibers in the tumors were evaluated using Masson staining, and neovascularization in the tumor was assessed with immunohistochemistry for platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31). The remaining 10 tumor-bearing mice in each group were subjected to HIFU ablation, and the ablation efficiency was evaluated by assessing the changes in irradiation gray values, coagulative necrosis volume, energy efficiency factor (EEF) and irradiation area and by pathological examination with HE staining.@*RESULTS@#In the experimental group, the collagen fibers in the tumor tissues were strong and densely aligned, and the tumors contained fewer new blood vessels showing strip-or spot-like morphologies. In the control group, the collagen fibers in the tumors were thin and loosely arranged, and the tumors showed abundant elongated or round new blood vessels. colonized in the tumor 7 days after the injection, and the tumor hardness was significantly greater in the experimental group than in the control group (=0.01); the acoustic velocity (=0.001) and the acoustic attenuation (=0.000) of the tumor tissues were also greater in the experimental group. HIFU irradiation resulted in significantly greater changes in the gray scale of tumor (=0.0006) and larger coagulative necrosis volume (=0.0045) in the experimental group than in the control group, and the EEF was significantly smaller in the experimental group (=0.0134).@*CONCLUSIONS@# can cause changes in collagen fiber content, acoustic velocity and attenuation in the tumor tissue and reduce the EEF of HIFU irradiation, thereby improving the efficacy of HIFU irradiation.

Mechanism of Acupuncture for Recovery of Neurological Function after Spinal Cord Injury and Role of Related Signal Pathway (review) / 中国康复理论与实践

This article introduced the main biological mechanisms of acupuncture promoting nerve function recovery after spinal cord injury, which include inhibition of inflammation and oxidative stress, alleviation of neuropathic pain, increase of neurotrophic active sub-stance, regulation of cell survival/apoptosis gene and neural regeneration pathway.

Anti-inflammatory mechanism of low dose methotrexate and its application in spinal cord injury / 中国药理学通报

Methotrexate (MTX)has dual effects of anti-inflam-matory and immune suppression,and its pharmacological mecha-nism is complex,diverse and synergistic.This paper summari-zes the main anti-inflammatory mechanism of low-dose MTX,in-cluding inhibition of JAK/STAT pathway,inhibition of inflam-matory reaction and immune response,increasing the accumula-tion of adenosine and the function of intracellular metabolites (methotrexate polyglutamate).In addition,low-dose MTX can inhibit oxidation by decreasing the level of lipid peroxidation, suppress the inflammatory response to secondary spinal cord in-jury,reduce spinal cord ischemia reperfusion injury and neuro-pathic pain,thus playing a neuroprotective role by a series of pharmacological mechanism.The anti-inflammatory mechanism of low-dose MTX and its application in spinal cord injury were reviewed,to guide the further research on the anti-inflammatory effect of MTX,and provide a theoretical basis for new drugs for clinical treatment of spinal cord injury.

Bridge role of Jingming (BL 1) for VDT asthenopia and brainfag based on human instinct / 中国针灸

To explore the bridge role of Jingming (BL 1) for video display terminal (VDT) asthenopia and brainfag. Ancient literature and modern scientific research on the acupoint have been analyzed and summarized so as to explore pressing the acupoint the instinct feedback of brain after asthenopia. It is demonstrated that Jingming (BL 1) is a key channel between eyes, brain and the outside world, and it is one of major feedback points of brain after asthenopia. In this paper we try to establish a new research thinking and ascertain it, namely Jingming (BL 1) reflecting the relationship between asthenopia and brainfag. We hope that it can provide some references for further research on cognizing brain through eye.

Evoked potential examination after spinal cord injury and its application in evaluating animal models / 中国药理学通报

Evoked potentials can reflect the integrity of spinal sensory and motor conduction pathway.Evoked potential exami-nation not only provides relatively objective index for patients with spinal cord injury in preoperative diagnosis,intraoperative monitoring and prognosis judging,but also plays an irreplaceable role in evaluating animal models for spinal cord injury.This pa-per systematically reviews evoked potential in the clinical exami-nation of spinal cord injury and its application in evaluating ani-mal models.

“Tongmai songjin yigu” massage therapy for lumbar spinal stenosis：a randomized controlled trial / 中国组织工程研究

BACKGROUND:Chinese medicine therapy is effective for patients with mild-to-moderate lumbar spinal stenosis and also has a better long-term effect than surgical patients, which can enhance perioperative efficacy and prevent spinal restenosis. OBJECTIVE:To evaluate the clinical efficacy of “Tongmai songjin yigu” massage therapy on lumbar spinal stenosis. METHODS:Eighty-four patients with degenerative lumbar spinal stenosis were randomly and equaly divided into treatment group and control group. Treatment group were treated with “Tongmai songjin yigu” massage therapy; patients in the control group were treated according to the guidelines for diagnosis and treatment of common disease in orthopedics and traumatology promulgated by China Association of Chinese Medicine, once a day, continuous for 2 weeks. RESULTS AND CONCLUSION:After treatment, the visual analog scale score in the treatment group was improved significantly (P < 0.05), and there was a significant difference in the Japanese Orthopaedic Association Scores on subjective symptom and daily life between the treatment and control groups (P < 0.05). The effective rate of the treatment group was higher than that of the control group (P< 0.05). These findings indicate that “Tongmai songjin yigu” massage therapy is better than traditional massage, but clinical large-sample studies are required.

Inflammatory response and anti-inflammatory therapy after acute spinal cord injury / 中国药理学通报

Acute spinal cord injury can lead to severe motor,sen-sory and sphincter muscle dysfunction.Inflammatory response caused by inflammatory cytokines plays a crucial role in the oc-currence and development of secondary damage.Maintaining the body balance between inflammaion and anti-inflammation through an appropriate anti-inflammatory intervention will be an important strategy for drug therapy of spinal cord injury.This paper mainly introduces the cause,process and participation of inflammatory response in the pathophysiological mechanism of acute spinal cord injury,and also reviews the latest progress of experimental research of anti-inflammatory drugs,aiming to provide reference for finding the safe and effective drugs.

Therapeutic Effect of Abdominal Kneading Massage for Chronic Superficial Gastritis / 广州中医药大学学报

Objective To observe the therapeutic effect of abdominal kneading massage in treating chronic superficial gastritis. Methods Forty-six cases of chronic superficial gastritis were randomly divided into test group and control group, 23 cases in each group. The patients of the test group were treated by the abdominal kneading massage, once a day, 7 times for a course of treatment, and the treatment lasted 2 courses. The patients of the control group took the western medicine Domperidone tablets orally, 10 mg each time, 3 times a day, for 2 continuous weeks. After treatment, we compared the clinical efficacy on syndromes and gastroscopy detection results in both groups. Results ( 1) After treatment, the scores of syndromes were decreased in both groups ( P<0.01 compared with those before treatment) , and the decrease was more obvious in the test group ( P<0.05 compared with the control group). ( 2) The total efficiency of test group was 91.30%, and that of the control group was 60.87%, the difference being significant ( P<0.01). ( 3) The results of gastroscopy showed that the relief of the gastritis lesions of the test group was significantly better than that in the control group, and the difference was significant ( P < 0.01). Conclusion Abdominal kneading massage can effectively relieve the symptom and gastric mucosa inflammatory manifestations of the chronic superficial gastritis patients, and this treatment can be recommended in clinical application.

Potential Biological Mechanism Underlying Rehabilitation Training after Spinal Cord Injury (review) / 中国康复理论与实践

Spinal cord injury is a kind of disease with high disability rate and poor prognosis. According to the degree of injury and damage plane, adopting appropriate rehabilitation measures can effectively enhance the patient's sensory and motor function, and ultimately improve the quality of life. This article briefly introduced the content of rehabilitation training corresponding with various periods, and sum-marized that relieving the secondary injury, improving the regenerative microenvironment, promoting proliferation and differentiation of en-dogenous neural stem cells differentiation and inducing plasticity were the biological mechanisms underlying the effect of rehabilitation training.

Duplication of animal models for spinal cord injury and its application in experimental therapeutics / 中国药理学通报

The mechanism of spinal cord injury and repair therapy after nerve injury is currently a hotspot of neuroscience research.Duplicating animal models plays a key role in experimental therapeutics of spinal cord injury.This review systematically describes the progress in animal models for spinal cord injury including contusion, compression, transection, ischemic,distraction and chemical-mediated injury,which have been established at home and abroad.Based upon the aforementioned models,some applications in experimental therapeutics are simultaneously enumerated.All these information provides scientific guidance for the experimental novel drugs′screening.