Abstract：ObjectiveTo explore the effects of Huanglian Wendantang （HLWDT） on pyroptosis of skeletal muscle in rats with impaired glucose tolerance （IGT） and to explain the mechanism based on NOD-like receptor protein 3 （NLRP3）/cysteine aspartate-specific protease-1 （Caspase-1）/gasdermin D （GSDMD）/interleukin-1β （IL-1β）/IL-18 signaling pathway.MethodThe SD male rats were fed with 45% high-fat diet for 20 weeks to induce the IGT model. After modeling， the rats were randomly divided into a blank group， a model group， a positive control group （metformin hydrochloride， 0.05 g·kg-1d-1）， and an HLWDT （7.8 g·kg-1d-1） group based on the body weight of rats. The blank group and the model group were fed with the same volume of distilled water. The dose for each group was set as 10 mL·kg-1d-1. After four weeks of continuous gavage， blood was collected and serum was separated. The skeletal muscles of rats were stored in liquid nitrogen. Subsequently， serum IL-1β and IL-18 were detected by the enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of NLRP3， Caspase-1， and GSDMD were detected by real-time quantitative PCR （Real-time PCR） and Western blot， respectively. The expression of GSDMD， IL-1β， and IL-18 proteins in skeletal muscle tissues was detected by immunofluorescence. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of skeletal muscles.ResultCompared with the blank group， the model group showed increased IL-1β and IL-18 in serum， and NLRP3， Caspase-1， and GSDMD gene and protein expression in skeletal muscle tissues （P<0.01）. Immunofluorescence assay showed that GSDMD， IL-18， and IL-1β protein expression in skeletal muscle tissues of the model group was significantly elevated （P<0.01）. HE staining showed obvious pathological changes in skeletal muscles. Compared with the model group， the HLWDT group and the positive control group could decrease IL-1β and IL-18 in serum and NLRP3， Caspase-1， and GSDMD gene and protein expression in skeletal muscle tissues （P<0.01）. In addition， immunofluorescence assay revealed that HLWDT could reduce protein expression levels of GSDMD， IL-1β， and IL-18 in skeletal muscles of IGT rats （P<0.01）. The results of HE staining showed that HLWDT could improve the pathological changes of skeletal muscles in IGT rats.ConclusionHLWDT can inhibit skeletal muscle pyroptosis of IGT rats， and the mechanism may be closely related to NLRP3/Caspase-1/GSDMD/IL-18/IL-1β signaling pathway.
Abstract：ObjectiveTo investigate the role of formyl peptide receptor 2 （FPR2） in the inhibitory effects of Buyang Huanwutang （BYHWT） on the oxidative stress and its protective effects on cerebral ischemia-reperfusion in rats.MethodForty-eight male SD rats were randomly divided into sham group， model group， BYHWT group and BYHWT combined with FPR2 inhibitor （Boc-2） group. In the sham group， only the vessels were isolated. In other groups， the middle cerebral artery occlusion （MCAO） model was constructed using the modified Longa method and reperfused after 2 h of ischemia. BYHWT （16 g·kg-1） was given by gavaged twice daily after reperfusion in BYHWT group and BYHWT+Boc-2 group. Boc-2 （0.4 mg·kg-1） was injected intraperitoneally 30 min before surgery. Equal volume of saline were given instead in sham and model group. After 24 h of reperfusion， Fluoro-Jade C （FJC） staining was performed to observe the changes in the number of FJC-positive cells. Western blot was performed to detect the expression of apoptosis-related B-cell lymphoma-2 (Bcl-2)， Bcl-2 associated X (Bax)， and cleaved aspartic acid cysteine proteolytic enzyme-3（Caspase-3）. Besides， superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）， and nitric oxide （NO） was measured. The mean fluorescence intensity of nicotinamide adenine dinucleotide phosphate Ⅱ（NADPH） oxidase 2 （NOX2） was examined by immunofluorescence.ResultCompared with sham group， the model group showed increased number of FJC-positive cells （P<0.01）， decreased Bcl-2 expression （P<0.01）， increased Bax and cleaved Caspase-3 expression （P<0.01）， increased NO and MDA content （P<0.05，P<0.01）， decreased GSH and SOD activities （P<0.05，P<0.01）， and increased NOX2 expression （P<0.01）. Compared with model group， there were decreased FJC-positive cells （P<0.01）， up-regulated Bcl-2 expression （P<0.01） with down-regulated cleaved Caspase-3 and Bax （P<0.05，P<0.01）， decreased NO and MDA （P<0.05，P<0.01） with increased GSH and SOD （P<0.01）， and decreased NOX2 expression （P<0.01） in the BYHWT group. All the above effects were partially blocked by Boc-2.ConclusionBYHWT can reduce oxidative stress injury and inhibit apoptosis in cerebral ischemia/reperfusion rats， which may be related with the down-regulation of NOX2 expression by FPR2.
Abstract：ObjectiveTo explore the action mechanism of medicinal pair Astragali Radix-Angelicae Sinensis Radix against diabetic cardiomyopathy （DCM） based on network pharmacology and in vivo animal experiment.MethodThe active ingredients and targets of Astragali Radix and Angelicae Sinensis Radix were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM）， and the relevant targets of DCM from the disease database. The common specific targets between the medicinal pair and DCM obtained via comparison were used for constructing the main active ingredients of Astragali Radix-Angelicae Sinensis Radix-DCM-target network， followed by protein-protein interaction （PPI） analysis of compound-DCM common targets and the screening of important modules using Molecular Complex Detection （MCODE） plugin. The gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis was carried out based on DAVID for exploring the possible molecular mechanisms， which were then subjected to experimental verification.ResultA total of 126 core targets of Astragali Radix-Angelicae Sinensis Radix for treating DCM were screened out based on network pharmacology. As indicated by KEGG pathway enrichment analysis， the above-mentioned key targets might be related to such pathways as inflammatory response， oxidative stress， insulin resistance， and apoptosis. The findings of in vivo animal experiments demonstrated that Astragali Radix-Angelicae Sinensis Radix delayed high glucose-induced cardiomyocyte injury of DCM rats， suggesting that this medicinal pair intervened in the pathological process to a certain extent.ConclusionAstragali Radix-Angelicae Sinensis Radix alleviates DCM possibly by acting on multiple targets including interleukin-6， vascular endothelial growth factor A， tumor necrosis factor， TP53 gene， and nuclear transcription factor， regulating apoptosis and glucolipid metabolism， and improving oxidative stress and inflammatory response. The research based on network pharmacology and experimental verification has provided new ideas for investigating the pathogenesis of DCM and its clinical treatment.
Abstract：ObjectiveTo explore the effect of Bushen Tongluo prescription （BSTLP） on the synaptic plasticity of hippocampal neurons in vascular dementia （VD） model rats and its mechanism.MethodSD male rats of SPF grade were selected. The rat model of VD was established by permanent bilateral ligation of the common carotid artery several times. The model rats were randomly divided into a model group， an insulin-like growth factor-1 （IGF-1， 20 μg·kg-1） group， high-dose （3 g·kg-1）， medium-dose （1.5 g·kg-1）， and low-dose （0.75 g·kg-1） BSTLP groups. A sham operation group was also set. Drugs were administered to rats by gavage once a day for four weeks. The model group and the sham operation group received the same volume of normal saline. After the last administration， all the rats were detected for spatial learning and memory by the Morris water maze. The apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase （TdT） dUTP nick-end labeling （TUNEL） assay. The changes in synaptic morphological structure and the number of dendritic spines in hippocampal neurons were detected by Golgi's method. The expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， mammalian target of rapamycin （mTOR）， synaptophysin （SYP）， and amyloid precursor protein （APP） in hippocampal neurons were detected by Western blot.ResultCompared with the sham operation group， the model group showed prolonged escape latency， lengthened swimming distance， dwindled the number of times for the platform crossing after platform removal （P<0.05）， increased apoptotic cells （P<0.05）， declining synaptic dendritic spines （P<0.05）， down-regulated expression levels of PI3K， Akt， mTOR， and SYP proteins， and up-regulated expression level of APP protein in hippocampal neurons （P<0.05）. Compared with the model group， the BSTLP groups and the IGF-1 group showed shortened escape latency and swimming distance， increased number of times for the platform crossing after platform removal （P<0.05），declining apoptotic cells （P<0.05）， up-regulated expression levels of PI3K， Akt， mTOR， and SYP proteins， and down-regulated expression level of APP protein in hippocampal neurons （P<0.05）. Compared with the IGF-1 group， the high-dose BSTLP group showed no significant difference in the escape latency， swimming distance， the number of times for the platform crossing after platform removal， apoptotic cells， synaptic dendritic spines， and expression levels of PI3K， Akt， mTOR， SYP， and APP proteins in hippocampal neurons. However， the differences were significant in the medium-dose and low-dose BSTLP groups （P<0.05）.ConclusionBSTLP can improve the learning and memory of rats with VD. The mechanism is presumedly related to the activation of thePI3K/Akt/mTOR pathway and improvement of synaptic plasticity of hippocampal neurons.
Keywords：vascular dementia （VD）;Bushen Tongluo prescription （BSTLP）;phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） pathway;synaptic plasticity
Abstract：ObjectiveTo explore the effects of Huatan Tongluo Decoction （HTTLD） on the morphology and function of brain tissues and intestine in rats with cerebral ischemia/reperfusion based on the gut-brain axis.MethodSixty SPF male rats were randomly divided into a sham operation group， a model group， high- （28.66 g·kg-1）， medium- （14.33 g·kg-1）， and low-dose （7.16 g·kg-1） HTTLD groups， and an edaravone （4 g·kg-1）+Clostridium butyricum （5.0×108 cfu·mL-1） group. The model was established by focal cerebral ischemia/reperfusion in rats. The drugs were administered by gavage. The brain tissue injury was determined by neurological deficit score and 2，3，5-triphenyl tetrazolium chloride （TTC） staining. The effect of cerebral ischemia/reperfusion on intestinal motility was assessed by the propulsion rate of small intestine. The intestinal mucosal cell damage was evaluated by the pathomorphological examination of the duodenal mucosa. Enzyme-linked immunosorbent assay （ELISA） was used to determine the content of D-lactate （D-LAC）， diamine oxidase （DAO）， and bacterial endotoxin （lipopolysaccharide， LPS） in serum. Western blot was used to detect the expression of Occludin， Claudin-5， and zonula occludens 1 （ZO-1） in the duodenum.ResultAfter cerebral ischemia/reperfusion， rats developed neurological deficit symptoms. The neurological deficit score in the model group was higher than that in the sham operation group （P<0.01）. Compared with the model group， the high- and medium-dose HTTLD groups could relieve the symptoms of neurological deficits and lower neurological deficit scores （P<0.01）. The results of TTC staining showed that the model group presented obvious infarcts in brain tissues compared with the sham operation group （P<0.01）. The cerebral infarction volumes of HTTLD groups were reduced compared with that in the model group （P<0.01）， especially the high-dose HTTLD group， and the effect was dose-dependent. Furthermore， the propulsion rate of small intestine in the model group was significantly reduced compared with that in the sham operation group （P<0.01）. Compared with the model group， HTTLD groups could increase propulsion rates of small intestine （P<0.01）， especially the high-dose HTTLD group， and the effect was dose-dependent. After cerebral ischemia/reperfusion， obvious duodenal mucosal damage could be observed， which was relieved after the administration of HTTLD. Western blot results showed that the protein expression of ZO-1， Occludin， and Claudin-5 in the model group was reduced compared with that in the sham operation group （P<0.01）. Compared with the model group， the HTTLD groups could up-regulate the expression of ZO-1， Occludin， and Claudin-5 to varying degrees （P<0.05， P<0.01）， especially the high-dose HTTLD group. ELISA showed that the serum D-LAC， DAO， and LPS of the model group were elevated compared with those in the sham operation group （P<0.01）. Compared with the model group， the HTTLD groups showed reduced D-LAC and DAO （P<0.05， P<0.01）， and the medium- and high-dose HTTLD groups showed reduced LPS （P<0.05， P<0.01）， especially the high-dose HTTLD group.ConclusionAfter cerebral ischemia/reperfusion， the rats showed damaged brain tissues， neurological dysfunction， intestinal mucosal injury， weakened intestinal motility， and destroyed the intestinal mucosal barrier. HTTLD can protect against brain-gut axis injury after cerebral ischemia/reperfusion by reducing the damage on brain tissues and gastrointestinal mucosa， relieving the symptoms of neurological deficits， promoting gastrointestinal motility， improving intestinal barrier function， and reducing the release of intestinal bacterial metabolites or poisons.
Abstract：ObjectiveTo explore the mechanism of Kangxian Yixin prescription in regulating mitochondrial permeability transition pore（mPTP）and inhibiting cardiomyocyte apoptosis.MethodH9c2 cardiomyocytes were cultured routinely. After 8 h of starvation，the cells were divided into the normal group，model group，Kangxian Yixin prescription（0.25 g·L-1） group，and cyclosporin A（CsA，10 μmol·L-1） group and treated with the corresponding drugs for 24 h for follow-up experiments. The H9c2 cardiomyocyte hypertrophy model was induced by norepinephrine（NE），whose optimal concentration was determined by real-time polymerase chain reaction （Real-time PCR）. The degree of mPTP opening was detected by flow cytometry， followed by the measurement of mRNA and protein expression levels of apoptosis-related factors cyclophilin D（Cyp-D），cytochrome C（Cyt-C），and cysteine aspartate-specific protease-3（Caspase-3） after mPTP opening and the quantification of mitochondrial membrane potential.ResultWhen the concentration of NE was 200 μmol·L-1， the mRNA expression levels of atrial natriuretic peptide（ANP） and brain natriuretic peptide（BNP） were the highest， implying that it was the optimal concentration to induce H9c2 cell hypertrophy. Compared with the normal group，the model group exhibited excessive opening of mPTP，weakened relative fluorescence intensity in mitochondria， decreased mitochondrial membrane potential（P<0.05，P<0.01），and elevated mRNA and protein expression of Cyp-D，Cyt-C，and Caspase-3（P<0.05）. Compared with the model group，both Kangxian Yixin prescription and CsA inhibited mPTP opening，enhanced the relative fluorescence intensity of mitochondria， increased mitochondrial membrane potential（P<0.05，P<0.01），and lowered the mRNA and protein expression of Cyp-D，Cyt-C，and Caspase-3 （P<0.05）.ConclusionKangxian Yixin prescription inhibits cardiomyocyte apoptosis possibly by regulating mPTP opening and inhibiting the expression of apoptosis-related factors Cyp-D，Cyt-C， and Caspase-3.
Abstract：ObjectiveTo observe the activation of microglia in hippocampus of depressed and anxious mice induced by maternal separation with acute restraint stress and the expression of interleukin-1β（IL-1β），interleukin-6（IL-6），tumor necrosis factor-α（TNF-α）， investigating the mechanism of Wenyang Jieyu prescription in treating anxiety and depression.MethodEighty four male C57BL offspring were randomly divided into control group， acute restraint stress group and model group on postnatal day 0（PD0）. Maternal separation combined with acute restraint stress was used to prepare anxious and depressed model mice， dividing the model mice into model group， Wenyang， Jieyu， Wenyang Jieyu and fluoxetine group according to random number table method. During the period of PD21-PD90， the control， acute restraint stress and model mice were fed with normal diet， with the other groups fed with corresponding medicine mixed diet. The Wenyang， Jieyu and Wenyang Jieyu groups were given 5.85， 12.03 and 16.71 g·kg-1·d-1 respectively. The fluoxetine group was given 2.60 mg·kg-1·d-1. Open field， zero maze test and social interaction tests were used to evaluate the anxiety and depression of model mice. The expression of Iba-1 in hippocampal microglia was detected by immunohistochemistry（IHC）. The mRNA expression of IL-1β， IL-6， TNF-α， Iba-1 and glucocorticoid receptor（GR）were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）.ResultCompared with the control group， total movement distance and time spent in central zone in 5 min of the model mice significantly decreased（P<0.01）， time spent in opened arm and total movement distance decreased significantly（P<0.05，P<0.01）， investigation time during testing and training increased significantly（P<0.01）. The expression of Iba-1 protein and mRNA，IL-1β，IL-6，TNF-α mRNA significantly increased（P<0.01）， the expression levels of GR mRNA significantly decreased（P<0.01）. The result of IHC staining showed that microglia were over activated. Compared with the model group， total movement distance and time spent in central zone in 5 min of mice in the Wenyang Jieyu and fluoxetine group significantly increased（P<0.05，P<0.01）.Time spent in opened arm significantly increased（P<0.01）. Investigation time during testing and training significantly decreased（P<0.05，P<0.01）. The expression of Iba-1 protein and mRNA，IL-1β，IL-6，TNF-α mRNA significantly decreased（P<0.05，P<0.01）. The expression of GR mRNA increased significantly（P<0.05，P<0.01）. IHC staining showed the microglia recovered. Time spent in opened arm of mice in the Wenyang group and Jieyu group significantly increased （P<0.01）， time spent investigating during testing decreased significantly （P<0.05）， the expression levels of Iba-1 protein and mRNA，IL-6 mRNA significantly decreased （P<0.05，P<0.01）. The expression of GR mRNA of mice in the Wenyang group significantly increased （P<0.05）， the expression of TNF-α mRNA significantly decreased （P<0.05）. Total movement distance of mice in the Jieyu group increased significantly （P<0.01）， time spent investigating during training decreased significantly （P<0.05），the expression level of IL-1β mRNA significantly decreased （P<0.05）. IHC staining showed that microglia recovered partly in both groups.ConclusionThe comprehensive curative effect and pharmacological action of Wenyang Jieyu prescription were better than Wenyang prescription and Jieyu prescription. Wenyang Jieyu prescription can treat anxiety and depression in maternal separation and acute restraint stress mice， its possible mechanism may be related to the decreased activation of microglia， down-regulation of IL-1β，IL-6，TNF-α expression and up-regulation of GR expression.
Abstract：ObjectiveTo investigate the renoprotective effects that Sanjiao Qushi prescription ameliorates cationic bovine serum albumin （C-BSA） induced membranous nephropathy（MN） in mice model and its influence on nuclear factor erythroid-2-related factor-2（Nrf2）/heme oxygenase-1（HO-1） signaling pathway.MethodSixty female BALB/c mice were randomly divided into the normal group（n=10） and the model group（n=50）. The mice in the model group received C-BSA injection via tail vein （6.5 mg·kg-1）. The mice that were successfully modeled were randomized into the model group， the low dose Sanjiao Qushi prescription group（3.71 g·kg-1）， the high dose Sanjiao Qushi prescription group（7.42 g·kg-1） and benazepril hydrochloride group（1.3 mg·kg-1）. And they were administered with the corresponding medicine by gavage once a day for four consecutive weeks. 24 hour-urine protein quantitation were performed before C-BSA injection and after C-BSA injection as well as the medicine gavage. When the treatment was finished， all of the mice were sacrificed and the biochemical indicators such as serum creatinine（SCr）， blood urea nitrogen（BUN）， triglyceride（TG）， total cholesterol（TC）， total protein（TP） and albumin（Alb） were measured. And the renal pathological morphology changes were observed by light microscope with hematoxylineosin（HE）， Masson and periodic acid-silver metheramine（PASM） staining. The deposition of immunoglobulin G（IgG） in the glomerulus was detected by fluorescence microscope. The expression of reactive oxygen species （ROS） of kidney was detected by fluorescence immunoassay. The protein expression levels of Nrf2 in cell nucleus and cytoplasm and the downstream protein factors HO-1 and NADH quinone acceptor oxidoreductase 1（NQO1） were detected by Western blot.ResultCompare to normal group， the levels of 24 hour-urine protein quantitation， TG and TC significantly increased in model group（P<0.01）， while TP and Alb levels significantly decreased（P<0.01）. The model group exhibited enlarged volume of glomerular， significantly thickened glomerular basement membrane（GBM）， fuchsinophilic protein deposition and spike formation through light microscope. Immunofluorescence staining for the model group exhibited granular deposition of IgG along the capillary wall. The expression of ROS in kidney significantly increased（P<0.01）. The protein expression levels of Nrf2 in cell nucleus significantly increased（P<0.01）， while Nrf2 in cytoplasm significantly decreased（P<0.01）.The protein expression levels of HO-1 and NQO1 significantly increased（P<0.01）. Compared to model group， the levels of 24 hour-urine protein quantitation， TG and TC significantly decreased in each treated group（P<0.01）， TP and Alb levels significantly increased（P<0.05，P<0.01）. The pathological damages alleviated obviously. The expression of ROS in kidney significantly decreased（P<0.01）. The protein expression levels of Nrf2 in cell nucleus significantly decreased（P<0.01）， while Nrf2 in cytoplasm significantly increased（P<0.05，P<0.01）. The protein expression levels of HO-1 and NQO1 significantly increased（P<0.01）.ConclusionSanjiao Qushi prescription worked on MN mice possibly by regulating related proteins in the Nrf2/HO-1 signaling pathway and relieving oxidative stress， thus decreasing 24 hour-urine protein and blood lipid， increasing serum protein， and alleviating the pathological damages to protect renal function and delay progress of the disease.
Abstract：ObjectiveTo observe the effect of modified Guilu Erxianjiao decoction combined with cisplatin on the immune function， resistance-related genes and interleukin-7（IL-7）-mediated Wnt/β-serial protein（β-catenin）signaling pathway in Lewis lung cancer mice by establishing a mouse model of Lewis lung cancer with deficiency of both Qi and Yin. And the anti-cancer mechanism of modified Guilu Erxianjiao decoction was clarified， so as to provide a basis for its clinical application.MethodA Lewis lung cancer mouse model （type of deficiency of both Qi and Yin） was established. Mice were divided into a normal group （no modeling）， a model group （saline solution）， a cisplatin group （cisplatin， 2 mg·kg-1）， a traditional Chinese medicine （TCM） group （modified Guilu Erxianjiao decoction， 19.63 g·kg-1·d-1）， and a combined group （modified Guilu Erxianjiao decoction， 19.63 g·kg-1·d-1 + cisplatin， 2 mg·kg-1）. The 10 mice in each group were administered separately for 21 days of intervention. The general conditions and organ indexes of mice were observed， and tumor inhibition rate was calculated. CD4+CD25+ regulatory T cell （CD4+CD25+ Treg） were detected by flow cytometry， the IL-7 level of cytokines in serum was detected by enzyme linked immunosorbent assay（ELISA）， and real-time quantitative polymerase chain reaction（Real-time PCR） was used to detect the gene expression level of drug resistance-related genes P-glycoprotein（P-gp）， and multidrug resistance protein1（MRP1）in tumor tissues. The protein expression of Wnt/β-serial protein（β-catenin）signaling pathway in tumor tissues were detected by Western blot.ResultIn the TCM group and the combined group， the food intake increased， the mental state was better， the response was sensitive， and the body weight increased. Compared with the cisplatin group， the thymus index and spleen index in the combined group were significantly increased （P<0.01）， and the tumor inhibition rate of the combined group was significantly increased （P<0.01）. Compared with the cisplatin group， the percentage of CD4+CD25+Treg/CD4+ in the TCM group and the combined group was significantly reduced （P<0.01）， and IL-7 in the TCM group and the combined group was significantly increased （P<0.01）. Compared with the cisplatin group， the expressions of P-gp and MRP1 genes in the TCM group and the combined group were significantly reduced （P<0.05， P<0.01）， and the protein expressions of secretory glycoprotein1（Wnt1）and β-serial protein（β-catenin）in the TCM group and the combined group were significantly reduced （P<0.01）.ConclusionThe combined use of modified Guilu Erxianjiao decoction and cisplatin can significantly inhibit the growth of tumors in mice with Lewis lung cancer， and its mechanism of action may be related to the efficacy of m odified Guilu Erxianjiao decoction in relieving the body's immunosuppressive state， promoting the body to produce IL-7， regulating IL-7-mediated Wnt/β-catenin signaling pathway and reducing the expression of resistance-related genes in lung cancer tissues.
Keywords：lung cancer;Wnt/β-serial protein（β-catenin）signal pathway;modified Guilu Erxianjiao decoction;cisplatin;Chinese medicine therapy
Abstract：ObjectiveTo observe the possible toxicity of long-term intravenous injection of Tanreqing injection in Beagle dogs， so as to provide experimental data for its clinical safe medication.MethodA total of 32 Beagle dogs （16 males and 16 females） were randomly divided into the low- （2.5 mL·kg-1）， medium- （5.0 mL·kg-1）， and high-dose （10.0 mL·kg-1） Tanreqing injection groups and control group according to their body mass indices， with eight dogs in each group. In the waking state， the dogs were treated with intravenous injection of corresponding drugs into the medial cephalic vein of forelimb for 13 weeks， followed by four-week drug withdrawal. After the observation of general condition， body mass， and food consumption， the Beagle dogs were subjected to electrocardiography， ophthalmoscopy， hematological examination， serum biochemistry， and blood coagulation test in the middle of medication （week 6）， at the end of medication （week 13）， and during recovery （week 17）. Then the gross anatomy was conducted for calculating the major organ coefficients and observing the histopathological changes.ResultNo obvious toxic reaction was found in each group， but the decreased fibrinogen and increased Kupffer's cells phagocytizing yellow-brown pigment in hepatic sinusoids were observed in the high-dose Tanreqing injection group following three months of medication. Reduction of fibrinogen was not observed in recovery period， but Kupffer's cells that phagocytized yellow-brown pigment still existed.ConclusionThe intravenous injection of Tanreqing injection at 2.50 mL·kg-1 （low dose）， 5.00 mL·kg-1 （medium dose） or 10.00 mL·kg-1 （high dose） for three months in Beagle dogs resulted in no obvious toxic reaction. However， it is still suggested to test the liver function and blood coagulation after long-term administration of high-dose Tanreqing injection.
Abstract：ObjectiveTo observe the therapeutic effect of modified Fuyuanwan combined with auricular acupressure bean on stage Ⅱ， Ⅲ diabetic nephropathy and its effect on serum janus kinase （JAK）/ signal transducer and activator of tranions （STAT） signaling pathway.MethodA total of 180 cases were randomly divided into control group and observation group， 90 cases in each group. Losartan potassium， modified Fuyuanwan combined with auricular acupressure bean were given respectively for 12 weeks. Renal function indexes ［blood urea nitrogen （BUN）， serum creatinine （SCr）， urinary albumin excretion rate （UAER）， 24 h urinary protein quantitative （24 h Upor）］， relative abundance of intestinal flora （verruca microflora， scleriobacteriae， deferribacter， proteobacteria）， oxidative stress indicators ［advanced oxidation protein products （AOPPs）， reactive oxygen species （ROS）， glutathione peroxidase （GSH-Px）， total superoxide dismutase （TSOD）］， renal blood flow index ［end-diastolic blood flow velocity （EDV）， peak systolic value （PSV）， pulse index （PI）， blood flow resistance index （RI）］， JAK/STAT signaling pathway ［JAK， phosphorylated JAK （p-JAK）， STAT， phosphorylated STAT （p-STAT） were observed before and after treatment. The safety indexes of two groups were evaluated after treatment. The efficacy was observed after treatment and followed up for 1 years and 2 years.ResultAfter treatment and follow-up for 1， 2 years， the total effective rates of patients in observation group were 97.8% （87/89）， 81.6% （71/87）， 59.8% （49/82）， respectively， observation group which were significantly higher than those in control group of 79.3%（69/87），57.8%（48/83），37.2%（29/78） （χ2=4.016， χ2=4.503， χ2=4.769， P<0.05）. Compared with control group after treatment， UAER， BUN， SCr， 24 h Upor， firmicutes， actinobacillus， proteobacteria， AOPPs， ROS， PI， RI， p-JAK， p-STAT3 in observation group were significantly decreased （P<0.05，P<0.01）， microflora verruca， GSH-PX， TSOD， JAK， STAT3 were significantly increased （P<0.05，P<0.01）， EDV and PSV were significantly accelerated （P<0.05，P<0.01）. The incidence of adverse reactions was 1.1% （1/89） in observation group， lower than 13.8% （12/87） in control group （χ2=5.127， P<0.05）.ConclusionModified Fuyuanwan combined with auricular acupressure bean can significantly improve the curative effect of stage Ⅱ， Ⅲ diabetic nephropathy， and its mechanism of action may be related to the serum JAK/STAT signaling pathway.
Keywords：modified Fuyuanwan;auricular point pressing with bean;losartan potassium;relative abundance of intestinal flora;janus kinase （JAK）/ signal transducer and activator of tranions （STAT） signaling pathway
Abstract：ObjectiveTo observe the clinical efficacy of modified Buyang Huanwutang combined with electroacupuncture （EA） in the treatment of traumatic spinal cord injury （TSCI） due to Qi deficiency and blood stasis.MethodEighty-seven TSCI patients who met the inclusion requirements were randomly divided into an observation group （n=44） and a control group （n=43）. On the basis of comprehensive western medical treatments， patients in the control group were further provided with Wuwei Tongshuan oral liquid，10 mL per time，three times per day， while those in the observation group received modified Buyang Huanwutang，one bag per day，for 12 consecutive weeks. Besides， EA was performed in both groups in the same way， once per day， six times per week， for six weeks in total. The American Spinal Injury Association （ASIA） motor score， modified Barthel index （MBI），visual analog scale （VAS） pain score，Berg balance scale （BBS） score，modified Ashworth scale （MAS） score， spinal cord independence measure-Ⅲ（SCIM-Ⅲ） score， lower limb range of motion （ROM）， and Qi deficiency and blood stasis syndrome score before and after treatment were evaluated， followed by the recording of the occurrence of complications during treatment. The brain-derived nerve growth factor （BDNF）， nerve growth factor （NGF）， vascular endothelial growth factor （VEGF）， neurotrophic factor-3 （NT-3）， malondialdehyde （MDA） and superoxide dismutase （SOD） levels before and after treatment were determined.ResultThe motor， light touch， needling sensation， MBI， and BBS scores of the observation group were higher than those of the control group （P<0.01）， while the AS and MAS scores were lower（P<0.01）. The angles of adductor and straight leg raising in the observation group were greater than those of the control group （P<0.01），but the Qi deficiency and blood stasis syndrome score was lower（P<0.01）. Both the scores of self-care， respiration， and sphincter management in SCIM-Ⅲ and the total score in the observation group were elevated as compared with those of the control group （P<0.01）. The cumulative incidence of complications in the observation group was 34.09%，significantly lower than 55.81% in the control group （χ2=4.149，P<0.05）. Compared with the control group， the observation group exhibited remarkably increased BDNF， NGF， VEGF， NT-3， and SOD （P<0.01） and decreased MDA （P<0.01）.ConclusionModified Buyang Huanwutang combined with EA is effective in alleviating spinal cord injury， promoting neural functional recovery， improving independence in activities of daily living， reducing the incidence of complications of patients with TSCI， which may be related to the amelioration of ischemia and hypoxia， inhibition of lipid peroxidation， and acceleration of nerve cell repair and regeneration.
Abstract：ObjectiveTo explore the curative effect and mechanism of modified Jiegeng Yuansentang combined with conventional therapy for postoperative mucosal edema in patients with cchronic rhinosinusitis with nasal polyps due to pulmonary Qi stagnation， and to explore its mechanism of action.MethodThe 90 patients were randomly divided into control group and observation group， 45 cases in each group.All patients were given conventional therapy after nasal endoscopy.Patients in control group were also given mometasone furoate combined with clarithromycin， and patients in observation group were given modified Jiegeng Yuansentang for internal administration and local irrigation.The course of the treatment was 6 weeks.The sino nasal outcome test-20 （SNOT-20）， nasal situation Lund-Kennedy， rhinoconjunctivitis quality of life questionnaire （RQLQ）， traditional Chinese medicine （TCM） syndrome， serum and nasal secretions inflammatory cytokines ［tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， interleukin-5 （IL-5），interleukin-17 （IL-17）］， serum protein ［aquaporin-1 （AQP-1）， aquaporin-3 （AQP-3）， aquaporin-5 （AQP-5）， fibronectin （Fn）］ were observed before and after treatment in two groups.The clinical symptoms， safety and recurrence after a follow-up of 12 months were compared between two groups.ResultThe total effective rate was 97.73% （43/44） in observation group， which was higher than 80.95% （34/42） in control group （χ2=4.726， P<0.05）.The patients were followed up for at least 12 months， and the recurrence rate was 4.65% （2/43） in observation group， which was lower than 32.35% （11/34） in control group （χ2=4.129， P<0.05）.Compared with control group after treatment， the SNOT-20， Lund-Kennedy， RQLQ， TCM syndrome， TNF-α， IL-1β， IL-5， IL-17， AQP-5 were significantly decreased in observation group （P<0.05）， while AQP-1， AQP-3， Fn were significantly increased in observation group （P<0.05）.The incidence of adverse reactions was 2.27% （1/44） in observation group， lower than 57.14% （24/42） in control group （χ2=5.243， P<0.05）.ConclusionModified Jiegeng Yuansentang can significantly improve postoperative mucosal edema in patients with chronic rhinosinusitis with nasal polyps due to pulmonary Qi stagnation， and the mechanism may be related to the regulation of inflammatory factors in serum and nasal secretions.
Keywords：modified Jiegeng Yuansentang;chronic rhinosinusitis with nasal polyps;pulmonary Qi stagnation;mechanism
Abstract：ObjectiveTo explore the clinical efficacy of modified Ditantang combined with acupuncture in the treatment of dysphagia after apoplexy （DAS） syndrome of phlegm and blood stasis blocking collaterals.MethodOne hundred and eight patients were randomly divided into control group （54 cases） and observation group （54 cases） by number table. Both groups underwent nutritional management，rehabilitation training and acupuncture. Patients in control group additionally took Tongluo Huatan capsules， 3 granules/time， 3 times/day， while patients in observation received modified Ditantang. Both groups had two weeks of treatment. The Kubota's drinking water test， swallowing contrast examination （VFSS）， and standard swallowing function assessment （SSA） were conducted. Swallowing disorder specific quality of life scale （SWAL-QOL） and sputum collateral stasis syndrome were scored before and after treatment. The levels of brain-derived neurotrophic factor （BDNF）， nerve growth factor （NGF） and neuron-specific enolase （NSE） before and after treatment. The occurrence of pneumonia， malnutrition， dehydration and aspiration were then recorded.ResultThe clinical effective rate was （47/49） 95.92%in the observation group， higher than （41/50） 82.00% in the control group's （χ2=4.854，P<0.05）. The grade of Kubota's drinking water test in observation group was lower than that in the control group（Z=2.211，P<0.05）. VFSS swallowing dysfunction in observation group was lighter than that in control group（Z=1.969，P<0.05）. The scores of Kubota's drinking water test， SSA and phlegm and blood stasis blocking collateral syndrome in the observation group were all lower than those in the control group（P<0.01）， while the VFSS score was higher than that in control group （P<0.01）. The swallowing symptom score， other symptom scores and total SWAL-QOL scores of the observation group were higher than those of the control group（P<0.01）. The levels of BDNF and NGF in the observation group were higher than those in the control group （P<0.01）， but the NSE level was lower than that in the control group（P<0.01）. The complication rate in the observation group was （6/49）12.24%， which was lower than （15/50）30.00% in the control group（χ2=4.668，P<0.05）.ConclusionOn the basis of nutrition management and rehabilitation training， modified Ditantang combined with acupuncture can reduce the risk of dysphagia and aspiration， improve the degree of neurological deficits， improve the quality of life， and reduce complications in treatment of DAS syndrome of phlegm and blood stasis， with significant clinical efficacy.
Keywords：cerebral stroke;dysphagia;syndrome of phlegm and blood stasis blocking collaterals;modified Ditantang;acupuncture;life quality
Abstract：ObjectiveTo observe clinical effect on chronic atrophic gastritis （CAG） with deficiency of stomach Yin when modified Shaoyao Gancaotang combined with Yiguanjian used on patients， and to study influence to prognostic risk.MethodOne hundred and ten cases patients were randomly divided into control group 54 cases and observation group 56 cases. Two groups got treatment of eradication of Helicobacter pylori （Hp）. Patients in control group got Yangweishu capsules， 3 grains/time， 2 times/day. Patients in observation groups when Shaoyao Gancaotang combined with Yiguanjian modified， 1 dose/day. The treatment continued for 16 weeks. Before and after treatment， gastroscope was discussed and operative link for gastritis assessment （OLGA） and operative link on intestinal-metaplasia assessment （OLGIM） were recorded， scores of atrophic degree， intestinal metaplasia degree， Hp infection， chronic inflammatory reaction， activity， endoscopic mucosal signs， dyspepsia symptoms， reported outcome patients reported outcomes （PRO） of patients with gastrointestinal diseases were graded. And to test levels of pepsinogenⅠ （PG Ⅰ），PGⅡ， gastrin-17 （G-17）， cytotoxin associated gene A （CagA） and vacuolar cytotoxin （VacA）.ResultThe effect of patients treated in observation group was better than the effect of patients received measures in control group （Z=2.068， P<0.05）. Scores of atrophic degree， intestinal metaplasia degree， chronic inflammatory reaction and activity were lower than the scores of patients received measures in control group （P<0.01）. Levels of OLGA （Z=2.037， P<0.05） and OLGIM （Z=2.014， P<0.05） of patients treated in observation group were better than the levels of patients received measures in control group. And levels of PGⅠ， G-17 and PG Ⅰ/PGⅡ of patients treated in observation group were higher than the dates of patients received measures in control group （P<0.01）. Positive rates of CagA and VacA were all lower than the dates in control group （P<0.05）. And gastroscopic mucosal signs and dyspepsia symptoms and scores of PRO were all lower than dates of patients received measures in control group （P<0.01）.ConclusionOn the basis of eradicating Hp， treatment of Shaoyao Gancaotang with Yiguanjian modified can relieve the clinical symptoms， improve the quality of life of patients， promote mucosal repair， improve the pathological changes， reduce the degree and scope of gastric mucosal atrophy， which is conducive to delay the progression of lesions and reduce the risk of canceration when it used on CAG. It has good clinical efficacy and was worthy of further study
Keywords：chronic atrophic gastritis;deficiency of stomach yin;Shaoyao Gancaotang;Yiguanjian;atrophic degree;intestinal metaplasia degree
Abstract：ObjectiveTo investigate the influence of particle size on density of binary powder mixture of traditional Chinese medicine （TCM）， and to provide reference for formulation design of TCM preparations.MethodThree groups of binary powder mixtures with different particle size ratio （α） were constructed， namely Oroxyli Semen-microcrystalline cellulose PH102 （MCC PH102） （α=0.071 7）， Stellariae Radix-MCC PH200 （α=0.158 7） and Angelicae Sinensis Radix-MCC KG802 （α=0.840 6）. Binary powder mixtures with nine mass ratios （90∶10， 80∶20， 70∶30， 60∶40， 50∶50， 40∶60， 30∶70， 20∶80 and 10∶90） were prepared for each group， and 27 binary powder mixtures containing TCM were obtained. The particle size distribution， density and other parameters of six single materials and 27 binary powder mixtures were characterized. Based on the packing theory and multivariate analysis， the effects of particle size related parameters on the filling structure and density of the binary powder mixtures were elucidated.ResultThe α of Angelicae Sinensis Radix-MCC KG802 binary mixture system was larger than the replacement rate （αr=0.741 0）， and its density had a good linear relationship with the mass ratio， which conformed to the replacement mechanism. The α of Oroxyli Semen-MCC PH102 binary mixture system was smaller than the critical ratio （αc=0.154 0）， and its density was nonlinear with the mass ratio of components， which conformed to the filling mechanism. The α of Stellariae Radix-MCC PH200 binary mixture system was between αc and αr， its density was affected by both of replacement mechanism and filling mechanism. Based on the partial least squares （PLS） model， the variable importance in the projection （VIP） analysis further proved that the mixing mass ratio （VIP value=1.62）， α （VIP value=1.13） and D10 （the corresponding particle size when the particle size distribution accumulated to 10%， VIP value=1.06） were the key factors affecting the density of binary powder mixtures of TCM.ConclusionIn the binary powder mixtures of TCM， the linearity relationship between density and mass ratio is largely depended on particle size difference of components.
Abstract：ObjectiveTo study the effects of different processing methods on the anti-gouty arthritis and cardiotoxicity of Aconiti Radix， and to explore the possible attenuation and synergism mechanism of these different processing methods.MethodThe swelling degree of knee joint， levels of inflammatory factors ［interleukin （IL） -1β， IL-18， tumor necrosis factor （TNF）-α］ and the activities of liver energy metabolism-related enzymes ［Ca2+-Mg2+-adenosine triphosphatase （ATPase）， Na+-K+-ATPase， succinate dehydrogenase （SDH）］ in rats with gouty arthritis were used as indicators to evaluate the effects of pharmacopoeia steaming Aconiti Radix， pharmacopoeia boiling Aconiti Radix， Jianchang faction processed Aconiti Radix， Zhang faction processed Aconiti Radix and raw Aconiti Radix. The activity of creatine kinase （CK）， lactate dehydrogenase （LDH） and the content of B-type natriuretic peptide （BNP） were used as indexes to evaluate the cardiotoxicity of Aconiti Radix and its different processed products.ResultIn the anti-gouty arthritis test， compared with the blank group， the knee joint of the model group was significantly swollen （P<0.01）， the levels of IL-1β， IL-18， and TNF-α in serum were significantly increased （P<0.01）， and the Ca2+-Mg2+-ATPase activity was significantly decreased （P<0.01）. Compared with the model group， raw Aconiti Radix and the four processed products could reduce knee joint swelling and decrease IL-1β， IL-18， and TNF-α levels in serum of rats. The activity of Ca2+-Mg2+-ATPase in the liver of rats from the pharmacopoeia steaming Aconiti Radix group was significantly higher than that in the model group （P<0.01）， and there was no statistical difference in other groups. In the cardiotoxicity test， compared with the blank group， the activities of CK and LDH were significantly increased and the level of BNP was significantly increased in the raw Aconiti Radix group and the pharmacopoeia steaming/boiling Aconiti Radix groups （P<0.01）. In terms of LDH activity and BNP content， the Zhang faction and Jianchang faction processed Aconiti Radix groups were significantly lower than those in the raw Aconiti Radix group （P<0.01）. In the CK activity， the Zhang faction processed Aconiti Radix group was significantly lower than that in the raw Aconiti Radix group （P<0.01）.ConclusionRaw Aconiti Radix and the four processed products have certain anti-inflammatory effects， but there are some differences among different indicators. There are significant differences in cardiotoxicity between the raw products and processed products of Aconiti Radix， and the cardiotoxicity of Jianchang faction and Zhang faction processed products was the weakest.
Keywords：Aconiti Radix Cocta;attenuation and synergism;gouty arthritis;cardiotoxicity;energy metabolism;processing;inflammatory cytokines
Abstract：ObjectiveTo explore the effect of different proportions of organic fertilizer and chemical fertilizer on the agronomic traits， yield and quality of Artemisiae Argyi Folium in Qichun county， and provide a theoretical basis for scientific fertilization of its planting.MethodField plot experiment was carried out to set up 5 treatment methods with different proportions of organic fertilizers and chemical fertilizers［OM0 （no combined application of biological organic fertilizer）， OM17 （combined application of 17% biological organic fertilizer）， OM33 （combined application of 33% biological organic fertilizer）， OM67 （combined application of 67% biological organic fertilizer）， OM100 （combined application of 100% biological organic fertilizer）］. The effects of different treatment methods on the agronomic characters， leaf yield， output rate of moxa， volatile oil content， flavonoid and phenolic acid contents and mineral element contents of Artemisiae Argyi Folium in Qichun county were determined.ResultWith the increase of the proportion of organic fertilizer in application， the seedling number per unit area， plant height， stem diameter， leaf number， leaf width， leaf length， height of dead leaves and leaf yield of Artemisiae Argyi Folium were increased at first and then decreased. Among them， the yield of Artemisiae Argyi Folium in OM33 treatment was 61.37% higher than that in OM0 treatment. With the increase of the proportion of organic fertilizer， the output rate of moxa of Artemisiae Argyi Folium showed continuously increasing trend， contents of volatile oil and volatile components （eucalyptol， α-thujone， borneol， camphor and caryophyllene oxide） increased at first and then decreased， while the contents of α-caryophyllene and β-syringene decreased gradually， the contents of phenolic acids （neochlorogenic acid， chlorogenic acid， isochlorogenic acid B， A and C） increased at first and then decreased， while the contents of flavonoids （jaceosidin and eupatilin） increased continuously， and the contents of mineral elements （Ca， Cu and Zn） continued to increase， but the content of K decreased significantly at the high proportion of organic fertilizer. After treated with principal component analysis （PCA）， it was found that OM17 treatment had the highest quality， while OM100 and OM0 treatment had low quality.ConclusionBased on comprehensive analysis of agronomic traits， yield and quality indexes of Artemisiae Argyi Folium in Qichun county， it is suggested that 17%-33% proportion of organic fertilizer should be used in its production， in order to improve the quality and efficiency of Artemisiae Argyi Folium industry in Qichun county.
Keywords：Artemisiae Argyi Folium;organic fertilizer;chemical fertilizer;output rate of moxa;volatile oil;flavonoids;phenolic acids
Abstract：ObjectiveTo explore the genetic diversity and population structure of Erigeron breviscapus， so as to provide a scientific basis for its resource protection and rational utilization.MethodTwelve pairs of simple sequence repeat（SSR） primers were screened out from 243 individuals in 16 natural populations to calculate the genetic diversity parameters of E. breviscapus， which were then subjected to principal coordinate analysis and cluster analysis.ResultTwelve SSR markers generated 209 alleles， with an average of 17.417 alleles per locus. Based on 12 SSR markers and 16 populations of E. breviscapus， the observed heterozygosity （H0） values were determined to be 0.603 and 0.613， the expected heterozygosity （He）to be 0.658 and 0.659， and the Shannon's information index （I） to be 1.443 and 1.446， respectively. The Wright's fixation index （Fst） was 0.123 and gene flow （Nm） was 2.077. Analysis of molecular variance （AMOVA） and genetic differentiation revealed that genetic variation within populations was the main source of total variation. The Nei's genetic distance and genetic identity coefficients were within the ranges of 0.107 （YA and XY）-0.713 （SZ and XZD） and 0.490 （SZ and XZD）-0.899 （YA and XY）， respectively. As demonstrated by the principal coordinate analysis and cluster analysis， the 16 populations of breviscapus were divided into two clusters.ConclusionThe genetic diversity of E. breviscapus was relatively high and there existed certain genetic differentiation and gene flow within and among populations. The genetic variation was mainly present within populations. All these have provided reference for subsequent study on good germplasm selection of E. breviscapus.
Abstract：Gecko and Skink have a long history of medicinal use and they are often confused. The modern research mainly focuses on their clinical efficacy， effective ingredients， and anti-cancer mechanisms， and there are few literature-based studies. The paper summarized the names， origins， efficacy， indications， processing methods and contraindications of Gecko and Skink in ancient and modern literature. It was found that Gecko and Skink were regarded as the same animal in the pre-Qin period but two different animals during the Han dynasty. However， they were confused again in the Three Kingdoms period. It was not until the Ming dynasty that they were distinguished from each other in Bencao Gangmu（《本草纲目》）. The origins of Skink included Eremias argus Peters， E.brenchleyi Günther and Eumeces chinensis （Gray）， while those of Gecko mainly included G. japonicus （Dumeril et Bibron）， G. hokouensis Pope， G. swinhonis Güenther and G. subpalmatus Güenther. In terms of efficacy and indications， Skink was mostly responsible for promoting urination，and Gecko for expelling wind and resolving stasis. Among multiple processing methods for Gecko and Skink， the traditional "fire method" was most preferred. As for contraindications， Skink shall not be used together with sulfur， fructus ulmi and mylabris， and it was not applicable to pregnant patients. Gecko should be used with caution for people with blood and qi deficiency. This paper has sorted out the historical evolutions of Gecko and Skink in their names， efficacy， indications， and processing methods， all of which will serve as the basis for further development and clinical utilization of Gecko and Skink.
Keywords：Gecko;Skink;textual research;origin;efficacy and indications
Abstract：ObjectiveTo investigate the expression of the cell cycle mitotic spindle checkpoint serinel/threonine kinase （BUB1） gene in breast cancer and its relationship with the prognosis，and further explore the intervention effect of japonicone A on BUB1 gene in breast cancer cells.MethodThrough Oncomine，GEPIA，GEO database，bc-GenExMiner v4.5 and Kaplan-Meier Plotter database， in-depth mining was conducted for BUB1 gene expression-related data，in order to explore the difference in the expression of BUB1 gene in breast cancer tissues and normal breast tissues and its relationship with patient prognosis. Encyclopedia of Cancer Cell Lines （CCLE） was used to analyze the expression of BUB1 in T cells and B cells of breast cancer tissues，STRING database was used to draw BUB1-related protein network diagram and gene ontology（GO） function annotation and analyze relevant pathways in Kyoto Encyclopedia of Genes and Genomes （KEGG）. The tumor immune assessment resource（TIMER） database was used to analyze the expression of BUB1 in immune infiltrates and its impact on the survival and prognosis of patients with gastric cancer. Finally， the effect of japonicone A on the expression level of BUB1 gene in breast cancer cells was further analyzed.Result①The mRNA level of BUB1 in breast cancer tissues was significantly higher than that of normal tissue samples， but the expression levels of BUB1 in breast cancer patients with different molecular subtypes varied. ② Increased expression of BUB1 could lead to longer distant metastasis-free survival（DMFS），overall survival（OS），and recurrence free survival（RFS） in luminal A subtypes. ③ BUB1 was positively correlated with structural maintenance of chro-mosome 4（SMC4） mRNA expression level， and might be interacted with 10 proteins， such as NUF2， with the strongest interaction relationship. ④ The high expression of BUB1 mRNA in CD8+ T cells and neutrophils in breast invasive carcinoma（BRCA） and BRCA-basal had a better two-year survival prognosis than the low expression group；the low expression of BUB1 mRNA in B cells in BRCA-Her2 had a better two-year survival prognosis than the high expression group. ⑤ GEO database analysis data set GSE85871 found that japonicone A could down-regulate the expression of BUB1 gene in breast cancer MCF7 cells.ConclusionBUB1 gene is highly expressed in breast cancer tissues and related to the prognosis of breast cancer and immune cell infiltration. This may be a new potential therapeutic target for japonicone A to intervene breast cancer cells.
Abstract：ObjectiveTo explore the potential mechanism of Qingke Pingchuan granule in treating acute and chronic bronchitis complicated with chronic obstructive pulmonary disease （COPD） by network pharmacology.MethodThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） was retrieved to collect the active components of Qingke Pingchuan granule and predict the action targets， followed by the construction of component-target network using Cytoscape 3.8. GeneCards， Online Mendelian Inheritance in Man（OMIM）， and DrugBank were used to harvest disease targets， whose names were put into UniProt for standardization. The treatment targets of Qingke Pingchuan Granule against the two diseases were obtained based on Venn diagram， which were then imported into the STRING platform for constructing the protein-protein interaction （PPI） network. Following the gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis based on MetaScape， the active component-common target-signaling pathway network of Qingke Pingchuan granule against acute and chronic bronchitis complicated with COPD was finally constructed. The accuracy of the target was confirmed by literature.ResultA total of 165 active components， 374 related targets， 512 disease-related targets， and 130 common targets were obtained. Among them， the 14 core therapeutic targets were further subjected to GO enrichment analysis， which yielded 390 biological processes， nine cell components， and 23 molecular functions. The KEGG pathway analysis revealed 22 signaling pathways.ConclusionQingke Pingchuan granule alleviates the diseases possibly by regulating such targets as vascular endothelial growth factor receptor 2（KDR）， transforming growth factor beta-1 （TGF-β1）， caveolin 1（CAV1）， hypoxia-inducible factor-1alpha（HIF-1α）， and interleukin-2（IL-2）， affecting the synthesis and transport of regulatory factors in cytoplasm， and controlling the cell proliferation and apoptosis.
Abstract：［Abstract］ObjectiveTo evaluate the efficacy and safety of fermented cordyceps powder combined with angiotensin-converting enzyme inhibitors （ACEI）/angiotensin Ⅱ receptor blocker （ARB） in the treatment of diabetic kidney disease （DKD）.MethodThe randomized controlled trials （RCTs） concerning the treatment of DKD with fermented cordyceps powder plus ACEI/ARB were retrieved from Pubmed， Embase， Cochrane library， China National Knowledge Infrastructure （CNKI）， Chinese BioMedical Literature Database on disc （CBMdisc）， Wanfang Data Knowledge Service Platform， and Chongqing Weipu Database for Chinese Technical Periodicals （VIP）. The quality of the included articles was evaluated by the Cochrane Collaboration's tool， followed by data analysis using RevMan 5.3.ResultA total of 48 RCTs were included， involving 4 562 cases. As revealed by Meta-analysis， the effective rate of fermented cordyceps powder combined with ACEI/ARB was higher than that of ACEI/ARB ［risk ratio （RR）=1.20， 95% confidence interval （CI） （1.15，1.24）， P<0.000 01］. Moreover， such combination effectively reduced urinary albumin excretion rate ［standardized mean difference （SMD）=-2.61，95%CI （-3.17，-2.05），P<0.000 01］，24-h proteinuria［SMD=-1.75，95%CI （-2.15，-1.35），P<0.000 01］， serum creatinine（Scr）［mean difference （MD）=-14.57，95%CI （-17.94，-11.21），P<0.000 01］， blood urea nitrogen（BUN）［MD=-1.05，95%CI （-1.29，-0.81），P<0.000 01］， cystatin C （Cys-C） ［MD=-0.52，95%CI （-0.68，-0.36），P<0.000 01］， fasting blood glucose（FBG）［MD=-0.59，95%CI （-0.93，-0.25），P=0.000 6］， hemoglobin A1c（HbA1c）［MD=-0.50，95%CI（-0.75，-0.24），P=0.000 1］， tumor necrosis factor-α（TNF）-α ［SMD=-1.68，95%CI （-2.21，-1.15），P<0.000 01］， C-reactive protein（CRP） ［SMD=-1.35，95%CI （-1.77，-0.93），P<0.000 01］， and interleukin-6 （IL-6） ［SMD=-1.52，95%CI （-1.98，-1.07），P<0.000 01］. There was no significant difference in the incidence of adverse events between the two groups ［RR=0.77，95%CI （0.49，1.21），P=0.25］.ConclusionFermented cordyceps powder combined with ACEI/ARB is more effective than ACEI/ARB in the treatment of DKD， which is worthy of clinical promotion and use. More multi-center RCTs with a large sample size are needed for verification.
Abstract：With the emerging cases of tumor is about to exceed 4 million per year in China， tumor prevention and control is also a formidable barrier hitting the world. Overall， an increasing trend of incidence and mortality of tumor in China has been observed in recent years， and the high mortality and low cure rate of tumor have seriously threaten the health of Chinese people， greatly affected the quality of life of patients， greatly reduced the living standard of patients and endangered the physical and mental health of patients. Traditional Chinese medicine（TCM） believes that the etiology of tumor is complex and pathogenesis is variable， which is the result of interaction between internal and external factors. If the treatment is carried out based on syndrome differentiation in time at the beginning when exogenous pathogens act on the human body， so as to prevent the spread of latent pathogen in human body， the occurrence and development of tumor diseases will be significantly reduced. Therefore， the theory of exogenous pathogenic factors and the pathogenesis of tumor need to be further explored. A total of 67 Chinese and English literatures were searched out with key words like external contraction， pathogenic Qi， TCM， tumor and pathogenesis in China National Knowledge Infrastructure （CNKI） and Public Medline （PubMed） databases for reference， so as to discuss the theory of exogenous pathogens and the pathogenesis of tumor comprehensively. The important role of exogenous pathogens in tumor pathogenesis and the significance of TCM in the early prevention and treatment of tumors were emphasized. Exogenous pathogenic factors such as wind， cold， dampness， fire， natural and social factors， diet and living conditions lead to the complexity of the occurrence of tumors. TCM can effectively prevent and intervene in the early stage of tumor onset， contribute to disease prevention and tumor resistance， reduce the occurrence， development and transformation of tumors， and make the clinical medication more effective， more accurate and more targeted， so as not to miss the opportunity for treating tumor， and provide a more clear guidance for clinical treatment of tumors.
Keywords：tumor;traditional Chinese medicine;external;pathogenic Qi;pathogenesis
Abstract：Huangliantang has been included in Catalogue of Ancient Classical Prescriptions（the First Batch）. However， opinions on the function of Cinnamomi Ramulus in Huangliantang vary significantly among doctors of all dynasties， which can be summarized as releasing exterior， expelling cold pathogen out of the stomach， and communicating Yin and Yang of the upper body with those in the lower body. Considering the limitations of each opinion， this paper compared Huangliantang with Banxia Xiexintang and Xiao Chaihutang that are composed of similar Chinese medicinals based on the stated symptoms， herbal indications， and prescription indications to expound the function of Cinnamomi Ramulus in Huangliantang. The findings demonstrated that Cinnamomi Ramulus in Huangliantang was mainly responsible for alleviating the abdominal pain. Nevertheless， the abdominal pain treated by Huangliantang was not the indication of Cinnamomi Ramulus but the indication of Paeonia lactiflora. Hence， it was believed that Cinnamomi Ramulus in Huangliantang should be P. lactiflora. The replacement of Cinnamomi Ramulus with P. lactiflora allowed the correspondence between herbs and indications as well as between prescription and indications. Cinnamomi Ramulus and P. lactiflora have often been used in combination since the era when medical books were written on bamboo and silk. When used alone， they might be confused. Therefore， the efficacy of Cinnamomi Ramulus and P. lactiflora in Shanghanlun（《伤寒论》） should be further analyzed.
Abstract：As the body ages， the immune system will undergo a series of changes， which are termed "immunosenescence" and are embodied in immune cells. Previous studies have shown that the immune cells involved in the regulation of immunosenescence include intrinsic immune cells and adaptive immune cells. Intrinsic immune cells are neutrophils， monocytes/macrophages， myeloid-derived suppressor cells， dendritic cells， natural killer cells， etc.， and the underlying mechanisms involve the regulation of cell number， phagocytosis， chemotaxis， adhesion， the function of toll-like receptor （TLR）， antigen presentation， macrophage polarization， cytotoxicity， migration， etc. The adaptive immune cells include T-lymphocytes and B-lymphocytes， and the underlying mechanisms involve the regulation of cell development， proliferation， differentiation， cell number， telomerase activity， self-reactive antibodies， etc. Immunosenescence is the manifestation of aging in the human body and is also an important target for delaying aging by Chinese medicine and western medicine. In recent years， scholars have found some classical prescriptions and their active components （such as Dushentang and total saponins in Panax ginseng leaves， and Shengmaiyin and anwulignan and total saponins in P. ginseng stems and leaves） can regulate immunosenescence by targeting the immune cells and interfering with their molecular regulatory mechanisms. In addition， the mechanisms of the classical prescriptions in regulating immunosenescence are closely related to autophagy. The representative prescription embodying the therapeutic principles of resolving blood stasis and promoting regeneration， Dahuang Zhechongwan， can delay D-galactose-induced renal aging in mice， and its underlying mechanisms are related to the regulation of the number and activity of thymic immune cells and improvement of the protein expression of autophagy-related markers and inflammatory cytokines in the kidney. Therefore， exploring the effects of the classical prescriptions and their active components by targeting the mechanisms of immunosenescence will become a new direction for investigating and developing anti-aging drugs.
Abstract：Paeoniae Radix Rubra is a traditional Chinese medicine commonly used in clinical practice， it is mostly wild and widely distributed in different areas of China. In addition， the plant of Paeoniae Radix Rubra also has ornamental value. Modern phytochemical researches showed that the chemical constituents of Paeoniae Radix Rubra were complex. Up to now， more than 300 chemical constituents have been found， mainly including monoterpene glycosides， triterpenoids， flavonoids， tannins， phenolic acids， saccharides， steroids， volatile oils and so on. Among them， the content of monoterpene glycosides was the highest， and the types of volatile oil were the most. Paeoniae Radix Rubra has a wide range of pharmacological effects， exerting different curative effects in multiple systems such as blood， cardiovascular， nervous and digestive system. It can protect myocardial cells and nerve cells， stabilize microcirculation， anti-endotoxin， anti-atherosclerosis， reduce pulmonary hypertension， anti-depression， protect liver， anti-gastric ulcer， anti-tumor， slow down aging， treat Parkinson's syndrome and diabetes and its complications， anti-radiation， anti-inflammatory， anti-virus and so on. Through reviewing the literature on chemical constituents and pharmacological effects of Paeoniae Radix Rubra， it was found that total glycosides and monomers such as paeoniflorin， albiflorin， benzoylpaeoniflorin and gallic acid may be the main active components of Paeoniae Radix Rubra. At present， the research on Paeoniae Radix Rubra mainly focused on monoterpene glycosides， while the research on flavonoids and volatile oil in Paeoniae Radix Rubra was less. It is suggested that research on these two components should be strengthened in the future.
Abstract：Epilepsy is a common nervous system disorder characterized by repeated attacks and a protracted course， which can cause great harms to the physical and mental health of patients. Antiepileptic drugs have been proved effective， but the resulting toxic and side effects cannot be ignored. Traditional Chinese medicine （TCM） has a long history of dealing with epilepsy. At present， in addition to enriching the cognitive theory of epilepsy treatment with TCM， we have also focused on the role of TCM in regulating the epilepsy-related signaling pathways from the perspective of molecular biology. The review of literature in China and abroad has uncovered that epilepsy is closely related to such pathophysiological processes as cell proliferation， apoptosis， autophagy， inflammatory response， and immune response. At the same time， the modern research of Chinese and western medicines shows that the efficacy of Chinese herbal monomers， single Chinese herbs or Chinese herbal compounds in treating epilepsy is directly or indirectly related to their regulation of signaling pathways. To be specific， they control epileptic seizures and alleviate epileptic brain injury by regulating the expression of key molecules in corresponding signaling pathways. This paper summarized the research progress in China and abroad as follows： ①Tangeretin and ginkgolide B inhibit apoptosis and oxidative stress by activating the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. ②Baicalin and osthol suppress autophagy by inhibiting the mammalian target of rapamycin （mTOR） signaling pathway. ③Ganoderan and astragaloside reduce apoptosis by inhibiting the mitogen-activated protein kinase （MAPK） signaling pathway. ④Salidroside and resveratrol reverse oxidative stress and apoptosis by activating the nuclear factor E2-related factor 2/antioxidant reaction element/heme oxygenase 1 （Nrf2/ARE/HO-1） signaling pathway. ⑤Curcumin and baicalin diminish inflammatory response and apoptosis by inhibiting the nuclear transcriptional factor-κB （NF-κB） signaling pathway. The above summary is expected to provide reference for the in-depth study and clinical application of TCM for the treatment of epilepsy.
Keywords：epilepsy;traditional Chinese medicine;signaling pathway;research progress
Abstract：As a new technology with unique drug delivery advantages， nanoemulsion has been widely used in the field of traditional Chinese medicine （TCM） preparations. By searching， classifying and sorting out the literature reports at home and abroad in recent years， this paper systematically expounded the application advantages and production mechanism of nanoemulsion in delivering effective components of TCM from three aspects of improving oral bioavailability， enhancing targeting effect and delaying drug release. The current formulation optimization strategies， preparation processes and quality evaluation indicators commonly used in TCM nanoemulsion were summarized. Based on the research status of TCM nanoemulsion with different active components， the common problems and possible solutions in the development of TCM nanoemulsion were discussed， and the future research hotspots and directions of TCM nanoemulsion were prospected. This article clarifies the feasibility of nanoemulsion for enriching the selection of TCM dosage forms， which can provide reference for the subsequent rational design and improvement of TCM preparations. At the same time， it is revealed that the research focus of TCM nanoemulsion in the future lies in the integrated research of TCM compounds， and shows a trend of multi-disciplinary joint and targeted research.
Keywords：nanoemulsion;traditional Chinese medicine preparations;active ingredients;bioavailability;targeting technology;processing technology;quality evaluation
Abstract：Osteoporosis （OP） is one of the most common diseases in the aged population worldwide. Due to the rapid change in world population structure， the effective prevention and treatment of OP is increasingly becoming the health problem of global concern and also the hot spot of clinical research. OP can be affected by many factors such as heredity， endocrine dyscrasia， nutritional deficiency， and bad living habits. The breakdown of coupling of osteoclast-mediated bone resorption to osteoblast-mediated bone formation leads to stronger bone resorption than bone formation， which is currently recognized as the main pathogenesis of OP. The exploration of OP in modern medicine based on molecular immunology has revealed that related cytokines play an important role in the pathogenesis of OP，and regulating the osteoclast-mediated bone resorption and osteoblast-mediated bone formation is essential for controlling the occurrence and development of OP. Tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） are able to stimulate bone formation and inhibit osteoblast function， thus playing a key role in bone destruction. By contrast， such cytokines as vascular endothelial growth factor （VEGF）， transforming growth factor-β （TGF-β）， bone morphogenetic protein （BMP）， and osteoprotegerin （OPG） strengthen osteoblast differentiation and promote bone formation. At present， western medicine like calcitonin， estrogen， and bisphosphonate are mostly used for clinical treatment of OP， but a long-term use of these drugs will result in poor compliance and obvious gastrointestinal adverse reactions. Traditional Chinese medicine （TCM） occupies an important position in the treatment of OP due to its advantages of overall regulation， low price， and few side effects. In addition， with the deepening of research on network pharmacology and molecular biology， it has been found that TCM exerts the therapeutic effect against OP by interfering with the expression of various cytokines and adjusting bone homeostasis. This paper has elaborated the role of related cytokines in the pathogenesis of OP and reviewed the research results concerning the regulation of related cytokines by TCM， in order to provide reference for the prevention and treatment of OP with TCM.
Keywords：osteoporosis （OP）;cytokines;traditional Chinese medicine;regulation;bone homeostasis
Abstract：Cells in the arterial wall are constantly subjected to the shear stress generated by the blood flow. Shear stress plays a pivotal role in the formation of atherosclerosis. The endothelial cells located between the blood and the vessel wall have a unique response to the shear stress of the blood flow， which can convert mechanical stimulation into intracellular signals， thereby affecting the pathological process of atherosclerosis. Endothelial function is not only regulated by hormones， growth factors and other biochemical substances， but also affected by mechanical forces such as blood flow shear stress. Physiologically， shear stress can play an anti-atherosclerotic role in maintaining the homeostasis of endothelial cells. Pathological shear stress will lead to endothelial dysfunction and promote the progression of atherosclerosis. Under the mediation of different shear stress， the endothelial function can be regulated through epigenetic pathways or mechanically sensitive cation channels. Therefore， it is necessary to understand how various signal transduction pathways are affected by pathological shear stress， so as to cause endothelial dysfunction and atherosclerosis. Traditional Chinese medicine（TCM） has been increasingly recognized for its curative effect in treating atherosclerosis， with the advantages of few side effects， multiple targets and multiple mechanisms. In recent years， the understanding of the anti-atherosclerosis mechanism of TCM mediated by shear stress has gradually deepened. This review will take endothelial function as the breakthrough point， systematically sort out the influence of shear stress on the pathological process of atherosclerosis and the related molecular mechanisms. Meanwhile， it is the first time to summarize the latest research progress of Chinese medicine against shear stress damage by sorting out the existing literature. This article mainly clarify the relationship between shear stress， endothelial function， atherosclerosis and TCM， in order to provide a theoretical basis for the clinical treatment and pathological mechanism of atherosclerosis.
Keywords：atherosclerosis（AS）;shear stress;endothelial function;traditional Chinese medicine
Abstract：In order to explore the pathological mechanism of perimenopausal syndrome and seek prevention and treatment measures， it is necessary to establish animal models that similar to human perimenopausal syndrome， so as to provide reference for drug research， new drug development and clinical application. In this paper， the keywords of "perimenopausal period" "perimenopausal syndrome" "menopause" "menopausal syndrome""menopausal period" "menopausal syndrome" and "animal" were searched in China National Knowledge Infrastructure （CNKI）， Chongqing Weipu， China Biomedical Literature Database （CBM） and Pubmed. In addition， the selection of domestic peripheral menopausal syndrome model animals in recent years and the advantages and disadvantages of corresponding models were summarized. A total of 673 studies were identified， of which 61 were included in the analysis. The most common animal model of perimenopausal syndrome is castration model， while the immunodeficiency model is less used. With the aging of the population and the rapid increase of psychosocial stress， the incidence of perimenopausal syndrome is high. Therefore， it is particularly important to explore the mechanism of perimenopausal syndrome. According to the experimental purpose， experimental period， experimental technology and other factors， the selection of appropriate model animals and modeling methods is the key of the success of the experiment of perimenopausal syndrome.
Keywords：pre-menopause;climacteric syndrome;menopausal syndrome;post-menopause;animal model