Novel technologies and models for studying pharmacological activities of traditional Chinese medicine for promoting blood circulation and removing blood stasis

OBJECTIVE Our previous studies demonstrated that various ingredients from the traditional Chinese medicine(TCM)for promoting blood circulation and removing blood stasis,as exemplified by cryptotanshinone and salvianolic acid B,exerted striking effects on modulating angiogenesis and vascular permeability,which suggests that they may be effective in treating vascular leak-driven diseases(e.g.tumor,cerebral cavernous malformation and diabetic retinopathy).However,the lack of reliable and advanced technologies and models sets up difficult hurdles for better understanding the role of TCM for promoting blood circulation and removing blood stasis.To this end,this study is to outline numerous cutting-edge platforms that can be utilized for exploring the function of TCM for promoting blood circulation and removing blood stasis in vascular leak-driven diseases.METHODS Two-photon laser scanning fluorescence microscopy was used to observe the interactions between neutrophils and blood vessels in a real-time manner.Dynamic flow system was employed to mimic the in vivo behaviors of neutrophils.RIP1-Tag5 spontaneous pancreatic cancer model was used to study the function of tumor blood vessels.CCM2ECKO(deletion of CCM2 in endothelial cells)mice were employed to establish the cerebral cavernous malformation(CCM)animal model.Micro-computed tomography(micro-CT)was utilized to assess the CCM lesion.Müller cell-knockout mouse model was used to study the progression of diabetic retinopathy.Vascular permeability in this model was assessed by fluorescein angiography.RESULTS The interactions between neutrophils and endothelial cells involve a series of complicated processes,including rolling,adhesion,intraluminal crawling and transmigration,which were all monitored in vivo by two-photon laser scanning fluorescence microscopy in a real-time manner.Dynamic flow system was capable of recapitulating the biological behaviors of neutrophils in vitro.Tumor vascular function in particular vascular perfusion could be assessed in the RIP1-Tag5 spontaneous pancreatic cancer model.In terms of CCM studies,specific deletion of CCM2 in endothelial cells resulted in the initiation of CCM lesion.The size and number of CCM lesions could be visualized and quantified by micro-CT.Furthermore,the Müller cell-knockout mouse model was able to precisely reflect the clinical symptoms of diabetic retinopathy.Vascular leak could be monitored at different time points using fluorescein angiography.CONCLUSION An array of high technologies and animal models can be used in investigating the occurrence and progression of multiple vascular leak-driven diseases.The pre-clinical and clinical studies of TCM for promoting blood circulation and removing blood stasis provide fundamental support for the application of the above-mentioned platforms,with the purpose of uncovering the scientific basis of TCM for promoting blood circulation and removing blood stasis.

Research Progress and Research Ideas on Anti-hepatic Fibrosis and Promoting Blood Circulation and Removing Blood Stasis of the National Drug Plumbapin Based on TLR4 Signal Pathway

Hepatic fibrosis is a reversible pathological phenomenon in the early and middle stages,but but no satisfactory intervention drugs have been available so far.Recent studies have suggested that microcirculation disturbance of liver is one of the important pathogenesis of chronic liver disease,the improvement of microcirculation is beneficial to the recovery of liver function and the delay of liver fibrosis.Hepatic stellate cells are the core cells of hepatic fibrosis,and also the most critical cells that affect the microcirculation of the liver.While TLR4/MyD88/NF-κB and TLR4/MyD88/MAPKs which are based on the action of hepatic stellate cells are two pathways that have very important influence on the inflammatory response of liver,the proliferation and apoptosis of hepatic stellate cells,and the secretion of fibrogenic cytokines.It was found that Plumbapin,the active ingredient of Guangxi specialty ethnic medicine,has the definite effect of promoting blood circulation and removing blood stasis and anti-hepatic fibrosis,but its mechanism is not clear.In this study,the research progress of the above problems was reviewed,and further research ideas were derived as follows:the pharmacological effect of Plumbapin on anti-hepatic fibrosis,promoting blood circulation and removing stasis was based on the influence of TLR4/MyD88/NF-κB and MAPKs signal pathway.

Research Progress and Research Ideas on Anti-hepatic Fibrosis and Promoting Blood Circulation and Removing Blood Stasis of the National Drug Plumbapin Based on W-P Body

Hepatic sinusoidal endothelial cells(HSEC)are the most important cells that constitute the microcirculation barrier of liver.Clinically,W-P bodies have been detected in the HSEC cells of most patients with liver fibrosis,and these bodies have become the synthesis and storage sites of vW factor,ET-1 and other factors of liver fibrosis;during pathological stimulation,W-P bodies will excrete the above factors into the cytoplasm,which can make the structure and function of HSEC maladjusted,cause the disturbance of liver microcirculation,and aggravate the process of liver fibrosis.However,previous studies have found that Plumbagin,the active ingredient of Guangxi specialty ethnic medicine,has the definite function of promoting blood circulation and removing blood stasis and anti-liver fibrosis,but its mechanism is not clear.In this study,the research progress of the above problems was reviewed,and further research ideas were derived from it as follows:the role of Plumbagin in promoting blood circulation and removing blood stasis and anti-liver fibrosis is produced by affecting the formation quantity of W-P bodies,affecting the synthesis and storage of the contents of W-P bodies,and interfering with their exocytosis ability.

Observation on Therapeutic Effect of Lotus Needle Cupping Therapy for Removing Blood Stasis in Zhuang Medicine on PHN and Its Influ-ence on Inflammatory Mediators

[Objectives]To observe the clinical effect of the lotus needle cupping therapy for removing blood stasis in Zhuang medicine in treating PHNand its influence on inflammatory factors.[Methods]96 patients with PHN were randomly divided into three groups:lotus nee-dle cupping therapy group,TCM surrounding acupuncture group and gabapentin group.Venous blood and acupoint blood were collected at 0,21 and 42 d of treatment,and the expression levels of 5-HT,SP and CGRPinflammatory mediators were detected before and after treatment.The changes of VAS scores before,during and after treatment and the clinical efficacy were observed.[Results]The total effective rate of the lotus needle cupping group was 87.50%,which was better than that of the TCM acupuncture group(81.25%)and the gabapentin group(62.50%);after treatment,the VAS scores and the expression of inflammatory mediators in the three groups of patients were lower than those before treatment,and the decrease was more significant in the treatment group(P<0.05).[Conclusions]The lotus needle cupping therapy for removing blood stasis in Zhuang medicine is effective in treating PHN,and its mechanism is to reduce the release of inflammatory media-tors,reduce hyperalgesia,relieve pain and improve the quality of life of patients.

Clinical Observation on Influence of Chinese Medicines for Promoting Blood Circulation to Remove Blood Stasis on FIB and DD in Plasma of Patients with Cerebral Thrombosis

to study the influence of Chinese medicines for promoting blood circulation to remove blood stasis on fibrinogen(FIB)and D-dimer(DD)in plasma of patients with cerebral thrombosis. Method:73 inpatients with acute cerebral thrombosis were randomly divided into a control group of 34 cases and a treatment group of 39 cases.The content of FIB and DD in plasma was detected before treatment and on the 7th and 14th days after treatment.Result:FIB content in plasma after treatment was lower than that before treatment in the control group(P<0.01)and more remarkable in the treatment group(P<0.001).There was an obvious difference in DD content before and after treatment in both groups.DD content on the 7th and 14th days after treatment in the treatment group was obviously higher than that in the control group(P<0.01 and P<0.05 respectively). Conclusion:Chinese medicines for promoting blood circulation to remove blood stasis can reduce the FIB content in plasma of patients with cerebral thrombosis,raise the DD content in plasma, cause the peak of DD content appear earlier and obviously improve hypercoagulability of blood in patients with cerebral thrombosis.

Comparison of mechanisms and efficacies of five formulas for improving blood circulation and removing blood stasis

Objective This study aimed to compare the mechanisms and efficacies of five formulas that improve blood circulation and remove blood stasis.Methods(1)A network pharmacology method was used to determine the targets of five formulas that promote circulation and remove blood stasis.Compounds of the five formulas,namely Danshen Yin(丹参饮,DSY),Huoluo Xiaoling Dan(活络效灵丹,HLXLD),Shixiao San(失笑散,SXS),Taohong Siwu Tang(桃红四物汤,THSWT),and Xuefu Zhuyu Tang(血府逐瘀汤,XFZYT),were retrieved from the Traditonal Chinese Medicine System Pharmacology Database(TCMSP),the Shanghai Institute of Organic Chemistry of CAS,and the TCM Integrated Database.Drug target network was constructed by searching the Swiss Target Prediction database and the STITCH database.The target network of stasis was extracted from the PharmGKB database,the Online Mendelian Inheritance in Man(OMIM)database,the Genetic Association Database(GAD),and the Therapeutic Target Database(TTD).Candidate targets were determined using protein-protein interaction(PPI)network extension and topology selection.Thereafter,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was used to determine the differentiation of the mechanism of the five formulas.(2)Animal experiments were conducted to explore the efficacies of the five formulas in treating blood stasis.Seventy New Zealand rabbits were exposed to high-fat feeding+epinephrine injection to construct a blood stasis syndrome model.The rabbits were evenly divided into control,model,DSY,HLXLD,SXS,THSWT,and XFZYT groups.The latter five groups were orally administered the corresponding formulas[DSY:3.92 g/(kg·d),XFZYT:7.10 g/(kg·d),SXS:1.12 g/(kg·d),HLXLD:5.60 g/(kg·d),THSWT:4.48 g/(kg·d)].Serum lipid and blood rheology were analyzed,and pathology slices were observed.Results(1)A total of 269,358,288,370,and 376 candidate targets of DSY,HLXLD,SXS,THSWT,and XFZYT were obtained among which were 232 shared candidate targets.Fluid shear stress and atherosclerosis were the biological processes common to the five formulas.HLXLD,SXS,DSY,and THSWT regulated lipolysis in adipocytes,and XFZYT,HLXLD,SXS,and THSWT regulated the AGE-RAGE signaling pathway and complement and coagulation cascades.HLXLD,SXS,and XFZYT regulated the HIF-1 signaling pathway,DSY regulated the cGMP-PKG signaling pathway,HLXLD reduced platelet activation,SXS regulated the calcium signaling pathway,and XFZYT regulated the PPAR signaling pathway.(2)In the animal experiments,the values of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL),high density lipoprotein cholesterol(HDL),TC/HDL,and TG/HDL in each group decreased,among which the ones seen in XFZYT,HLXLD,and SXS groups were statistically significant(P<0.05).XFZYT presented the best effect,followed by HLXLD and SXS.XFZYT and HLXLD decreased apolipoprotein B100(apoB100)and increased apolipoprotein A1/apoB100(P<0.05).XFZYT decreased all the values of hematocrit(HCT),plasma viscosity,whole blood viscosity(WBV);HLXLD and SXS affected HCT;and DSY and THSWT regulated WBV(P<0.05).All the five formulas decreased the values of optical density and area of plaque,among which XFZYT and HLXLD showed statistical significance(P<0.05).Conclusion Adjusting fluid shear stress and alleviating the injury of endothelial cells might be the common mechanisms by which the five formulas promote blood circulation and remove blood stasis.Different formulas also have unique targets,which may provide guidance for clinical drug selection.By regulating different indices,the five formulas can regulate blood lipid and hemorheology,improve the state of blood stasis,and decrease the degree of aortic plaque in the blood stasis model rabbits.XFZYT and HLXLD had higher efficacies than DSY,THSWT,and SXS.

Treatment of Hypertensive Cerebral Hemorrhage by Activating Blood Circulation to Remove Stasis

The treatment of hy-pertensive cerebral hemorrhage(HCH)by activatingblood circulation to removestasis(ABCRS)is a newtherapeutic approach,which is initiated by clinical specialists of TCM andintegrative Chinese andwestern medicine.Al-though it is not a flawless

Effect of Chinese Herbs for Activating Blood Circulation,Removing Stasis and Supplementing Qi on the Circulating Endothelial Cells in Patients with Unstable Angina Pectoris

Objective: To observe the effect and clinical significance of circulating endothelial cells (CEC) in the pathogenesis of coronary heart disease with unstable angina pectoris (CHD-UAP), and to explore the protective effect of Chinese herbs for activating blood circulation, removing stasis and supplementing Qi (CH) on CHD-UAP patient's CEC. Methods: Sixty patients with diagnosis of CHD-UAP confirmed and differentiated to be Qi-deficiency and blood stasis by TCM were randomly divided into two groups and treated, on the basis of Western drug-therapy, with Tongxinluo capsule (通心络胶囊, TXL) and Huoxue Tongmai capsule (活血通脉胶囊, HXTM) respectively by way of oral taking three times a day, 3 capsules every time, with 1 month as one therapeutic course. The number of CEC in patients' blood circulation was counted before and after treatment. Besides, the number of CEC in 30 healthy persons was also counted for control. Results: The number of CEC in CHD-UAP patients was significantly higher than that in the healthy persons (P<0.01). After the patients were treated with CH, either TXL or HXTM, it significantly decreased (P<0.01)with insignificant difference between the two treated groups. Conclusion: CEC in CHD-UAP patients is severely damaged and endothelial function in disorder, Chinese herbs have protective effect on patients' CEC.

Research Progress and Prospects on the Anti-liver Fibrosis,Blood Circulation-promoting and Stasis-resolving Effects of Curcuma kwangsiensis Based on W-P Bodies

Liver fibrosis is a necessary stage in the progression of chronic liver disease to cirrhosis.So far,no satisfactory drugs have been found to intervene in liver fibrosis.Liver microcirculation disorders are one of the important pathogenesis of chronic liver disease,and hepatic sinusoidal endothelial cells(HSECs)are the main cells that constitute the liver microcirculation barrier.In clinical practice,W-P bodies have been detected in HSECs of most patients with liver fibrosis.W-P bodies serve as a site for the synthesis and storage of vW factors,ET-1 and other cytokines that promote liver fibrosis.They can disrupt the structure and function of HSECs,cause liver microcirculation disorders,and exacerbate the progression of liver fibrosis.Previous studies have found that the Guangxi specialty ethnic medicine,C.kwangsiensis S.G.Lee et C.F.Liang,has definite effects in promoting blood circulation,resolving blood stasis,and resisting liver fibrosis.Based on this,a further research idea has been derived,stating that the blood circulation-promoting,blood stasis-resolving,and anti-liver fibrosis effects of C.kwangsiensis are produced by affecting the formation of W-P bodies,the synthesis and storage of contents in W-P bodies,and intervening in their exocytosis capacity.

Clinical Experience in the Treatment of Vitiligo by the Method of Invigorating Qi,Promoting Blood Circulation and Detoxification

Studies have shown that traditional Chinese medicines have clear curative effects in the treatment of vitiligo with few side effects.Through literature research and clinical observation,the study summarized the etiology and pathogenesis of vitiligo in traditional Chinese medicine as"deficiency,toxin,and stasis",formulated the method of invigorating qi,promoting blood circulation and detoxification,and prescribed Fuse Hexue Jiawei Decoction for the treatment of vitiligo.

Treating Ulcerative Colitis by Activating Blood Circulation to Dissipate Blood Stasis

Ulcerative colitis(UC)is a worldwide refractory bowel disease with unclear pathogenesis.Its lesions can lead to colorectal cancer over time・UC is classified as"diarrhea,""dysentery,"and other categories in traditional Chinese medicine.Its etiology and pathogenesis in traditional Chinese medicine are complex,but it has been found that blood stasis plays an important role in its occurrence and development.Combined with modem research,the relationship between blood stasis and ulcerative colitis is analyzed in this article along with a discussion on the therapeutic effect of activating blood and removing blood stasis on the disease,aiming to provide new ideas for the treatment of UC.

Effect of the Principle of Activating Blood Circulation to Break Stasis on GMP-140 and D_2 Dimer in Patients with Acute Cerebral Infarction

Objective: To explore the clinical efficacy of the principle of activating blood circulation to break stasis (ABCBS) and its influence on platelet membranous protein particle (GMP-140) and D 2 dimer (D-dimer) before and after treatment. Methods: Eighty-eight patients with blood stasis syndrome (BSS) of acute cerebral infarction (ACI) were randomly divided into two groups, both of which were treated with conventional treatment, i.e. with western medicine (WM), with Salvia injection added through intravenously dripping.One of the two groups was used as the control and the other group as the treated group who had ABCBS herbs orally taken in addition. The duration of treatment course for both groups was 3 weeks. Results: There were changes in both groups over clinical symptoms, nerve function deficit scoring and GMP-140, D-dimer, but the treated group showed significantly better than that of the control group, ( P <0.05). Conclusion: ABCBS principle could serve as an important auxiliary treating method for BSS of ACI, as it can effectively alter the blood of ACI patients which was viscous, condense, coagulant and aggregating.

Effects of Activating Blood Circulation to Resolve Blood Stasis and Glucosamine Capsules Therapy on the Expression of Matrix Metalloproteinase in Post-traumatic Knee Osteoarthritis

[Objectives] To observe the clinical effects of activating blood circulation to resolve blood stasis and glucosamine hydrochloride capsules therapy on post-traumatic knee osteoarthritis treatment,to measure the expression of matrix metalloproteinase in post-traumatic knee osteoarthritis patients before and after treatment,and to explore its relevant molecular mechanisms. [Methods]A total of 60 patients with posttraumatic knee osteoarthritis in early stage in Affiliated Hospital of Shannxi University of Chinese Medicine from January 2015 to December2017 were selected and randomly divided into the control group( n = 30) and the observation group( n = 30). The control group was given oral administration of glucosamine hydrochloride capsules for 6 courses of the treatment. The observation group was using the activating blood circulation to resolve blood stasis therapy for 6 courses of treatment. The recovery of traumatic knee osteoarthritis and the symptom of traditional Chinese medicine( TCM) in 2 groups was compared before and after treatment. The symptoms and the quantitative assessment rating scale of knee osteoarthritis,the pain index of knee and the TCM symptom scores were recorded in both groups. And the synovial fluid and serum of patients were collected to detect the expression of matrix metalloproteinase. [Results]The symptoms and the quantitative assessment rating scale of knee osteoarthritis,the pain index of knee and TCM symptom scores of the 2 groups in the 1 st week,the 12 th week and the 24 th week after the treatment were significantly lower than those before the treatment,and the difference was statistically significant( P < 0. 05). Two therapeutic methods had certain therapeutic effects on the recovery from traumatic knee osteoarthritis,and could significantly improve the TCM syndrome. There were better therapeutic effects on oral decoction of traditional Chinese medicine than oral glycosaminoglycans hydrochloride capsules on treating traumatic knee osteogenesis( P < 0. 05). The expression level of MMP3 was decreased significantly in both groups( P <0. 001),while the expression level of MMP13 had no significant change in both groups( P >0. 05). The expression level of MMP1 was decreased significantly in the observation group( P < 0. 001),but there was no significant change in the control group after treatment( P >0. 05). [Conclusions]Two treatment methods have been effective in this clinical study. We found that the expression level of MMP3 was decreased significantly after treatment in 2 therapies,which can be clinically applied.

Revealing the material basis of MMP9-mediated activating blood and removing blood stasis drugs on Danshen-Ligusticum chuanxiong anti- vascular effect

Objective:Reveal the material basis and mechanism of angiogenesis effect of Danshen-chuanxiong herb-partners.Methods:The effective components of Danshen and chuanxiong were searched in the TCM System Pharmacology Database(TCMSP),and the drug targets were searched in the Swiss Target Prediction database;in the Disease-Gene Database(DisGeNET))Search for angiogenesis-promoting and inhibiting angiogenesis targets;use the protein interaction database(STRING)database and Cytoscape software to analyze the network core targets;use the DAVID database to enrich the drug-disease target intersection for GO and KEGG;RT-qPCR experiments verified the effect of luteolin on MMP9 gene expression;in vitro tube formation experiments analyzed the effect of luteolin on endothelial cell neovascularization.Results:After analysis,it is concluded that Danshen has 10 active ingredients and 50 angiogenesis targets;Chuanxiong has 2 active ingredients and 4 angiogenesis targets.The intersection of drug-taking targets yielded 9 targets,including AR,PARP1,MMP9,MMP2,MMP12,AKR1B10,ABCC1,CDK6,and STAT3.After analyzing the active ingredient-target network graph of Danshen/Chuanxiong,it was concluded that luteolin is the key chemical ingredient.After protein interaction(PPI)analysis,the results showed that MMP9 is the core target.The KEGG pathway is mainly enriched in 5 signaling pathways,the most important pathway is cancer-related pathways.There are 22 main biological processes of GO,which mainly involve collagen catabolism,protein extracellular matrix,metal endopeptidase activity,etc.The preliminary analysis of tubule formation experiment shows that luteolin inhibits angiogenesis and down-regulates the expression of MMP9 gene.Conclusion:Luteolin,the key chemical component of the Danshen-Ligusticum chuanxiong drug pair,inhibits angiogenesis by regulating the MMP9 target,and develops the reverse regulation of angiogenesis for the traditional Chinese medicine for promoting blood circulation and removing blood stasis on the basis of the known treatment of ischemic diseases.Provide a new perspective and theoretical basis for the use of Danshen and Chuanxiong medicine in clinical cancer patients.Reveal the material basis and mechanism of angiogenesis effect of Danshen-chuanxiong herb-partners.

Research Progress in Chinese Medicine Preparations for Promoting Blood Circulation and Removing Blood Stasis for Cirrhotic Patients with Portal Vein Thrombosis Following Splenectomy

This article presented an overview of the therapeutic effects of Chinese medicine(CM)preparations for promoting blood circulation and removing blood stasis for patients with portal vein thrombosis(PVT)after splenectomy.Based on published clinical researches of CM preparations for PVT after splenectomy in patients with cirrhotic portal hypertension(CPH),this paper evaluated the incidence of PVT,and explored potential active components and mechanisms of CM preparations.Safflower Yellow Injection,Danshen Injection,Danhong Injection,and Compound Danshen Dropping Pill achieved good curative effect alone or combined with anticoagulant therapy.In addition,Compound Biejia Ruangan Tablet and Anluo Huaxian Pill can also significantly improve the hemodynamic disorders of portal vein system in patients with cirrhosis.Considering the role of CM preparations in ameliorating the incidence of PVT after splenectomy in patients with CPH,we suggested that future research should provide more attention to CM alone or CM combined with anticoagulant for cirrhosis with PVT.

Summary of 32 Patients with Cardiac Syndrome X Treated by TCM Therapy of Regulating Qi Relieving Chest Stuffiness and Promoting Blood Circulation

Objective： To evaluate the clinical effect of Liqi Kuanxiong Huoxue method （宽胸活血,LKH, traditional Chinese medicine, TCM therapeutic method for regulating qi, relieving chest stuffiness and promoting blood circulation） in treating patients with cardiac syndrome X （CSX）. Methods： The prospective, non-randomized controlled study was conducted on 51 selected patients with CSX, who were non-randomly assigned to 2 groups, the treated group treated with LKH in addition to the conventional treatment （32 patients）, and the control group treated with conventional treatment （19 patients） like nitrate, diltiazem hydrochloride, etc. The treatment course was 14 days. The changes of such symptoms as angina pectoris, TCM syndrome and indexes of treadmill exercise test before and after treatment were observed. Results： After treatment, such symptoms as chest pain and stuffy feeling and palpitation in the treated group were improved more than those in the control group （P〈0.05）; the total effective rate on angina pectoris and TCM syndrome in the treated group was better than that in the control group （P〈0.05）. The treadmill exercise test showed that the maximal metabolic equivalent （Max MET）, the time of angina onset and ST segment depression by 0.1 mV were obviously improved after treatment in both groups, but the improvement in the treated group was better than that in the control group respectively （P〈0.05）. Conclusion： The LKH method could reduce the frequency of angina attacks and improve the clinical condition of patients with CSX.

Exploration of the Effect and Mechanism of Activating Blood Circulation and Stasis-Removing Therapy on Tumor Metastasis

Metastasis is one of the specificities of late stage tumor and also a lethal factor often encountered. The study of tumor metastasis has important meaning for prolonging patients＇ survival and elevating their quality of life, but no really ideal prevention and treatment method has been found so far. Recent researches showed that tumor metastasis is correlated with platelet aggregation and blood hyperviscosity manner. Therefore, the early application of surgery, radiotherapy, chemotherapy and biological therapies, in combination with Chinese medicine therapy for activating blood circulation and removing stasis （ABCRS） may be, after all, an effective approach. ABCRS therapy is an important therapy of Chinese medicine, which, composed of several methods like smoothening blood flow in vessels, promoting blood circulation and dispersing stagnant blood, could influence tumor metastasis to different extents, and could coordinate with some other Chinese medicine therapeutic methods like supplementing qi, promoting qi, clearing heat, removing toxic substances, warming meridian, dispelling wind, eliminating dampness, nourishing yin, dissolving sputum, relieving stagnancy, emptying viscerals, etc. The effect and acting mechanism of ABCRS on tumor metastasis is summarized in this paper and its bi-directional regulatory effects discussed as well.

Traditional Chinese Medicines alleviated myocardial ischemia by regulating Qi and promoting blood circulation

OBJECTIVE:To investigate the efficacy of Chinese medicines on Qi stagnation and blood stasis in rats with myocardial ischemia.METHODS:Fifty male Wistar rats were randomly divided into five groups(n=10)as follows:(a)sham operation(Sham),(b)myocardial ischemia(Model),(c)treatment that regulates Qi(Qi),(d)treatment that promotes blood circulation(Blood),(e)treatment that both regulates Qi and promotes blood circulation(QB).The rat model was established via activities restriction for 6 h followed by tail clamp stimulation for 5 mins every day for 7 d and occlusion left coronary anterior descending artery.Afterwards rats were treated with medicines that regulate Qi and/or promote blood circulation via gavage for 14 d.Behavioral parameters were evaluated using open field and elevated plus-maze tests.The tongue color and sublingual vein were visually examined.Blood flow perfusion of tongue and auricle were detected using PIMⅡ.The mesenteric microcirculation was examined via capillaroscopy,and hemodynamics was assessed using a polygraph system.Serum homocysteine(Hcy),creatine kinase isoenzyme(CKMB)levels and endothelin-1(ET-1)were measured.Hematoxylin and eosin staining and transmission electron microscopy were employed to detect the myocardial morphology and ultrastructure,respectively.RESULTS:Compared with findings in Sham group,rats in model group had coarse hair,dark mucosa of the lips and claw,low activity,and increased anxiety.Compared with findings in Model group,rats in the three treatment groups exhibited a lighter tongue color without an extended and varicose sublingual vein.There were significant increases of auricle blood flow perfusion in the Qi group and tongue bottom blood flow perfusion in the QB group.Compared with findings in Model rats,rats in Blood group exhibited improved mesenteric microcirculation associated with increased mesenteric blood flow and a larger arteriole diameter.Moreover,compared with findings in Model rats,Qi and QB rats exhibited increased left ventricular±dp/dtmax,decreased serum CKMB,Hcy,ET-1 levels,and reduced myocardial ultrastructural damage.CONCLUSION:Myocardial ischemia damage was suppressed by Traditional Chinese Medicines that regulate Qi and promote blood circulation.

Effect of warming Yang and removing blood stasis method on matrix metalloproteinases/tissue inhibitor metalloproteinases levels secreted by cultured endometrial cells from patients with endometriosis

OBJECTIVE:To investigate the effect of Chinese medicines using the warming Yang and removing blood stasis method on levels of matrix metalloproteinases(MMPs)/tissue inhibitor metalloproteinases(TIMPs) secreted by cultured endometrial cells from patients with endometriosis.METHODS:Ectopic and eutopic endometrial cells obtaind from 15 endometriosis patients were cultured in vitro,and divided randomly into five groups:high dose;moderate dose;low dose;nemestran;blank control.The three dose groups were treated with a decoction prepared according to the principle of warming Yang and removing blood stasis;nemestran and 0.9%NaCI were administered to the nemestran group and balnk control group,respectively.Eutopic endometrial cells obtaind from 10 hysteromyoma patients were cultured in vitro,as the normal control group,0.9%NaCI were administered to the normal control group.Cell culture supernatants were collected and levels of matrix metalloproteinase-1(MMP-1),matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9),tissue inhibitor metalloproteinase-1(TIMP-1) and tissue inhibitor metalloproteinase-2(TIMP-2) detected by enzyme-linked immuno sorbent assay(ELISA).RESULTS:Compared with the normal control group,levels of MMP-1,MMP-2,and MMP-9 in eutopic and ectopic endometrium cell supernatants in the blank control group were increased,whereas levels of TIMP-1 and TIMP-2 were decreased(P <0.05).Compared with the blank control group,levels of MMP-1 and MMP-2 in ectopic and eutopic endometrium cell supernatants cultured in low-dose,middle-dose,and high-dose groups were decreased,whereas levels of TIMP-1 and TIMP-2 were increased significantly(P < 0.05).CONCLUSION:The warming Yang and removing blood stasis method affects expression of MMPs andTIMPs.

The Proteomic Research of the Cure of Experimental Diabetes Deafness by Granules of Eliminating Phlegm and Removing Blood Stasis

Objective: Observing the expression changes of serum proteome in model rats after intervention of the Granules of Eliminating Phlegm and Removing Blood Stasis (豁痰祛瘀颗粒 also known as GEPRB), screening out and identifying the differentially expressed proteins by mass spectrometry and bioinformatics analysis, discussing the molecular mechanism of control the Diabetes deafness by GEPRB. Methods: By use of proteomics technology, the serum protein serum proteome of the control group, model control group, Duxil and each observation group were observed for 2-DE gel pattern matching, and the difference in the relative content of 2 times was chosen for the differentially expressed proteins. Identification of differentially expressed proteins by MALDI-TOF MS/MS, the authors further analysis the phosphorylation, subcellular localization, interaction, direct regulation, and transmembrane of the differences proteins by the way of bioinformatics analysis. Sixty SPF level SD rats elected in diabetic rats model group (abbreviated as DM group) were be randomly divided into 5 groups based on random number sheet, namely model control group, positive drug control group (Du-ke-xi group) and Mai-tong-fang high, medium and low dose group respectively. In addition, set of normal control group. 10 rats in each group. Results: By Coomassie brilliant blue staining, identified 51 differential protein spots dug from 2-D gel by mass spectrometry, successfully identified 13 non-redundant proteins. Most of the identified proteins were secreted protein and belong to different protein families. There were about 12 proteins have the transmembrane region from the authors’ result, ten of them were plasma membrane proteins. Conclusion: It’s suggesting that 13 differential proteins is most likely the protein response to GEPRB in vivo, these proteins may play key role for the treatment of GEPRB to Diabetes deafness. The two highly differentially expressed proteins Apolipoprotein E (apoE) and C3 may be a potential drug target of GEPRB.