Treatment of diabetic retinopathy with herbs for tonifying kidney and activating blood circulation: A review of pharmacological studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes. Chinese medicine believes that kidney deficiency and blood stasis are significant pathogenesis of DR. A characteristic therapeutic approach for this pathogenesis is the kidney-tonifying and blood-activating method. By literature retrieval from several databases, we methodically summarized the commonly used kidney-tonifying and blood-activating herbs for treating DR, including Lycii Fructus, Rehmanniane Radix Praeparata, and Corni Fructus with the function of nourishing kidney; Salvia Miltiorrhizae Radix et Rhizoma with the function of enhancing blood circulation; Rehmanniae Radix with the function of nourishing kidney yin; and Astragali Radix with the function of tonifying qi. It has been demonstrated that these Chinese herbs described above, by tonifying the kidney and activating blood circulation, significantly improve the course of DR. AIM OF THE STUDY: Through literature research, to gain a thorough comprehension of the pathogenesis of DR. Simultaneously, through the traditional application analysis, modern pharmacology research and network pharmacology analysis of kidney-tonifying and blood-activating herbs, to review the effectiveness and advantages of kidney-tonifying and blood-activating herbs in treating DR comprehensively. MATERIALS AND METHODS: PubMed, the China National Knowledge Infrastructure (CNKI), and Wanfang Data were used to filter the most popular herbs for tonifying kidney and activating blood in the treatment of DR. The search terms were "diabetic retinopathy" and "tonifying kidney and activating blood". Mostly from 2000 to 2023. Network pharmacology was applied to examine the key active components and forecast the mechanisms of kidney-tonifying and blood-activating herbs in the treatment of DR. RESULTS: Kidney deficiency and blood stasis are the pathogenesis of DR, and the pathogenesis is linked to oxidative stress, inflammation, hypoxia, and hyperglycemia. Scientific data and network pharmacology analysis have demonstrated the benefit of tonifying kidney and activating blood herbs in treating DR through several channels, multiple components, and multiple targets. CONCLUSIONS: This review first presents useful information for subsequent research into the material foundation and pharmacodynamics of herbs for tonifying kidney and activating blood, and offers fresh insights into the treatment of DR.

Supplementingand activating blood circulation method to treat vertebrobasilar dolichoectasia with posterior circulatory watershed infarction: a case report of two patients.

Vertebrobasilar dolichoectasia (VBD), a rare posterior circulation vascular variant disease, is an important risk factor for many acute cerebrovascular diseases. An insufficient understanding of VBD often leads to misdiagnose. Two cases of VBD that were initially diagnosed as posterior circulation watershed infarction are reported here. Absence of common causes of stroke including hypoperfusion, blood system diseases, carotid and aortic dissection, and eosinophil elevation, the symptoms of the 2 patients met the diagnostic criteria of VBD. Both patients displayed symptoms that were in line with the Traditional Chinese Medicine (TCM) syndrome pattern of "deficiency and blood stasis". Accordingly, they were comprehensively treated with Supplementingand activating blood circulation method. The clinical manifestations of the 2 patients were remarkably improved and no recurrence of watershed infarction was found in a 1-year follow-up. A detailed medical history and laboratory examination are capable of improving diagnostic accuracy of VBD. TCM treatment based on syndrome identification might be a promising candidate for VBD management.

Efficacy and safety of activating blood circulation and removing blood stasis of Traditional Chinese Medicine for managing renal fibrosis in patients with chronic kidney disease: a systematic review and Meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of activating blood circulation and removing blood stasis in terms of Traditional Chinese Medicine (TCM) for managing renal fibrosis (RF) in patients with chronic kidney disease (CKD). METHODS: We searched randomized controlled trials (RCTs) from eight databases. RESULTS: Sixteen eligible studies with 1,356 participants were included in this study. Compared to treatment with Western Medicine (WM) alone, the combined treatment with activating blood circulation and removing blood stasis in terms of TCM (ARTCM) and WM to manage RF in patients with CKD significantly ameliorated type Ⅳ collagen (CⅣ) (: 2.17, 95% : 3.01 to 1.34), type Ⅲ procollagen (PCⅢ) (: 1.08, 95% : 1.64 to 0.53), laminin (LN) (: 1.28, 95% : 1.65 to 0.90), transforming growth factor ß 1 (TGFß1) (: 0.65, 95% : 1.18 to 0.12), serum creatinine (Scr) (: 1.36, 95% : 1.85 to 0.87), blood urea nitrogen (BUN) (: 1.51, 95% : 2.59 to 0.43), and 24 h urine protein (24hUpro) (: 1.23; 95% : 1.96 to 0.50). The level of hyaluronic acid (HA) was similar in both types of treatment (: 0.74, 95% : 1.91 to 0.44). The subgroup analysis showed that the duration of 8 weeks might affect the concentration of C-Ⅳ, PC-Ⅲ, and LN (<0.05). The effectiveness of the longer duration to C-Ⅳ, PC-Ⅲ, and LN was not certain. However, the result should be interpreted in care. The safety of the treatment using ARTCM and WM could not be evaluated because a few studies had reported adverse effects. The results of the Metaanalysis were not stable enough. There was publication bias for the reports on Scr ( 0.001), C-Ⅳ ( 0.001), PC-Ⅲ ( 0.026), and LN ( 0.030) and no publication bias for the reports on BUN ( 0.293). The quality of evidence varied from low to very low. CONCLUSIONS: The combined treatment using ARTCM and WM to manage RF in patients with CKD has some advantages over treatment with WM alone. Highquality RCTs need to be conducted for the strong support.

Activating Blood Circulation, Anti-Inflammatory and Diuretic Effects of Leonurus japonicus Extract on a Rat Model of Trauma Blood Stasis and Its Phytochemical Profiling.

Leonurus japonicus Houtt. has been traditionally used to treat many ailments. This study evaluated the activating blood circulation, anti-inflammatory, and diuretic effects of L. japonicus extract (LJ) and identified its phytochemicals. In this work, the phytochemicals in LJ were identified using liquid chromatography mass spectrometry. Rats were randomly assigned to three groups (n=8): Control group was treated with saline, while the Model group (saline) and LJ group (426 mg/kg) had induced traumatic injury. All rats were treated with once by daily oral gavage for one week. The biochemical indices and protein expression were measured. Herein, 79 constituents were identified in LJ, which were effective in elevating body weight, food consumption, water intake, and urinary excretion volume, as well as in ameliorating traumatic muscle tissues in model rats. In addition, LJ prominently decreased the contents of plasma viscosity, platelet aggregation rate, thrombin time, prothrombin time, activated partial thromboplastin time, fibrinogen, thromboxane B2 (TXB2), TXB2/6-keto-prostaglandin F1α (6-keto-PGF1α), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), PAI-1/tissue-type PA (t-PA), and PAI-1/u-PA, while significantly increasing antithrombin III, 6-keto-PGF1α, and t-PA contents. Furthermore, LJ notably inhibited tumor necrosis factor alpha, interleukin 6 (IL-6), IL-8, angiotensin II, antidiuretic hormone, aldosterone, aquaporin 1 (AQP1), AQP2, and AQP3 levels, and markedly elevating IL-10 and natriuretic peptide levels. Finally, LJ markedly reduced the protein expression of AQP1, AQP2, and AQP3 compared to the model group. Collectively, LJ possessed prominent activating blood circulation, anti-inflammatory, and diuretic effects, thus supporting the clinical application of L. japonicus.

Clinical study on the treatment of chronic atrophic gastritis with gastric collateral stasis syndrome by activating blood and removing blood stasis, invigorating the spleen and soothing the liver / 国际中医中药杂志

Objective:To evaluate the clinical effect of treatment of activating blood and removing blood stasis, invigorating the spleen and soothing the liver for the patients with gastric collateral stasis syndrome and chronic atrophic gastritis (CAG).Methods:Randomized controlled trial. A total of 68 CAG patients admitted to the Huairou Hospital of Traditional Chinese Medicine from January 2018 to January 2021 who met the selection criteria were divided into 2 groups according to the random number table method, with 34 in each group. The control group received conventional western medicine treatment, such as inhibition of acid, protecting the gastric mucosa, and the observation group was treated with Traditional Chinese Medicine (TCM) herbal prescription of activating blood and removing blood stasis, invigorating the spleen and soothing the liver. Both groups were treated for 12 weeks. TCM symptom scores were performed before and after treatment. The serum level of pepsinogen Ⅰ(PG Ⅰ), pepsinogen Ⅱ (PGⅡ) were detected by ELISA, and the PG Ⅰ/PG Ⅱ ratio was calculated. Gastroscopic biopsy was performed to observe the changes of intestinal metaplasia of gastric mucosa and glandular atrophy, and to evaluate the clinical efficacy.Results:The total responsive rate was 85.3% (29/34) in the study group and 58.8% (20/34) in the control group. There was significant difference between the two groups ( χ2=9.35, P=0.030). After treatment, the scores of stomachache, fullness of feeling in the observation group were significantly lower than those in the control group ( t=2.97, 3.80, P<0.05). After treatment, the level of serum PG Ⅰ[(76.21 ± 17.35) mg/L vs. (66.8 ± 18.77) mg/L, t=2.15] and PG Ⅰ/PG Ⅱ [(4.67 ± 0.99) vs. (3.90± 1.25), t=2.81] in the study group were significantly higher than those in the control group ( P<0.05), and PG Ⅱ [(16.36 ± 1.85) mg/L vs. (17.42 ± 2.05) mg/L, t=2.24] was significantly lower than that of the control group ( P<0.05). After treatment, intestinal metaplasia and glandular atrophy was significantly more improved or reversed than those in the control group ( χ2=20.67,9.33, P<0.05). Conclusion:The methods of activating blood and removing blood stasis, invigorating the spleen and soothing the liver can reverse the precancerous lesions of patients with gastric collateral stasis syndrome of chronic atrophic gastritis and have a good prognosis.

Research progress on using traditional Chinese medicine and extracts for activating blood circulation in prevention and treatment of silicosis / 中国职业医学

Occupational silicosis features as irreversible pulmonary fibrosis, which is caused by long-term inhalation of free silica dust. The pathogenesis of silicosis is complex and there is no cure at present. Traditional Chinese medicine classifies silicosis fibrosis into the category of diseases as "pulmonary paralysis" and "pulmonary arthralgia", and its treatment is based on promoting blood circulation and activating qi. Traditional Chinese medicine for activating blood circulation is one of the commonly used medications, which has the effects of anti-oxidation, anti-inflammation, anti-fibrosis and immunomodulation, and has broad application prospect in the prevention and treatment of silicosis. At present, animal experiments and clinical studies have been carried out using the single Chinese herbs extracts that could activate blood circulation such as Salvia miltiorrhiza, Ligusticum chuanxiong Hort., Panax notoginseng, Curcuma longa L., peach kernel and Carthamus tinctorius L. as well as their compound herbs for the prevention and treatment of silicosis. The mechanisms of anti-pulmonary fibrosis and the efficacy and safety of treating silicosis and its complications were explored. There are also scholars studying Salvia miltiorrhiza, Curcuma longa L. and Danhong injection, Taohong Siwu Decoction and others for prevention and treatment of pulmonary fibrosis. Additionally, network pharmacological research, analyzing potential targets and pathways, were carried out to provide scientific rationale for prevention and treatment of silicosis. However, the effectiveness of research is still uncertain, and it cannot meet the clinical needs. In the future, it is necessary to explore the application of more high-quality active components of traditional Chinese medicine monomer or mixture of activating blood circulation in the prevention and treatment of silicosis, to provide new ideas and scientific basis for the prevention and treatment of silicosis using traditional Chinese medicine.

[Pharmacological research progress of five classical prescriptions in treatment of chronic heart failure].

Chronic heart failure(CHF) is a comprehensive clinical syndrome caused by multiple factors that result in structural and/or functional abnormalities of the heart, leading to impaired ventricular contraction and/or relaxation functions. This medical condition represents the final stage of various cardiovascular diseases. In the treatment of CHF, multiple clinical studies have demonstrated the benefits of using traditional Chinese medicine(TCM) to control oxidative stress, inflammation, and apoptosis, thereby delaying ventricular remodeling and reducing myocardial fibrosis. In this study, common TCM syndromes in the diagnosis and treatment of CHF in recent years were reviewed and summarized. Five common treatment methods including benefiting Qi and activating blood circulation, enhancing Qi and nourishing Yin, warming Yang for diuresis, eliminating phlegm and dampness, rescuing from collapse by restoring Yang, and corresponding classic prescriptions in prevention and treatment of CHF were concluded under the guidance of TCM syndrome differentiation thinking. Meanwhile, research progress on the modern pharmacological effects of these classic prescriptions was systematically discussed, so as to establish a unique treatment system for CHF by classic prescriptions under the guidance of TCM syndrome differentiation theory and provide innovative diagnosis and treatment strategies for clinical CHF.

Efficacy and safety of a sequential treatment with clearing heat and eliminating phlegm and tonifying and activating blood circulation in treating acute ischemic stroke: study protocol for a randomized controlled trial.

OBJECTIVE: To investigate the short-term efficacy and safety outcomes following a sequential treatment with clearing heat and eliminating phlegm (CHEP) formula and tonifying Qi and activating blood circulation (TQABC) formula in patients with acute ischemic stroke (AIS) within a 72 h time window. METHODS: In this randomized, multicenter, double-blinded, placebo-controlled trial, 500 participants will be randomly assigned in a ratio of 1∶1 to the CHEP+ TQABC group or control group. In addition to guideline-based standard medical care, participants in the treatment group will receive the CHEP formula for the first 5 consecutive days followed by the TQABC formula for another 10 consecutive days, while those in the control group will receive CHEP formula placebo and TQABC formula placebo consecutively. The primary outcome measure will be the comparison of the change in the National Institutes of Health Stroke Scale score from baseline to 15 days after randomization. The secondary outcome measures will include the scores on the modified Rankin Scale, Barthel Index, Patient-Reported Outcomes, TCM symptom pattern (Zheng-hou) evaluation Scale, and the incidence of in-hospital complications. Safety assessment will include the physical examination, laboratory detection, any adverse events or serious adverse events, and the proportion of any complications during hospitalization. DISCUSSION: The results of this study will provide objective and scientific data with which to assess the efficacy and safety of a sequential treatment based on "integrating disease and symptom pattern" for patients with AIS.

Stasis Caused by Depression and Coronary Heart Disease / 中国实验方剂学杂志

Anxiety and depression are common comorbidities of coronary heart disease and are considered as independent risk factors in addition to traditional cardiovascular risk factors. Anxiety，depression and other mental abnormalities belong to the category of "depressive syndrome" of traditional Chinese medicine，which can lead to stasis of blood due to the lack of Qi flow. "Blood stasis" involves abnormal blood rheology， vascular endothelial dysfunction， chronic inflammatory response， abnormal lipid metabolism and other comprehensive pathological changes， and is the core pathogenesis of coronary heart disease in traditional Chinese medicine. "Depressive syndrome"can aggravate the development of coronary heart disease by promoting blood stasis in multiple ways. Prescriptions and herbs of promoting blood circulation and removing blood stasis can have a clinical effect by promoting blood circulation （improving physiological functions） and removing blood stasis （eliminating pathological changes）. In clinical practice， strengthening the screening of the mental and psychological status of patients with coronary heart disease and providing early and effective psychological interventions and combined Chinese and Western medicine drug treatment can significantly improve the clinical symptoms and prognosis of patients. This article was the first to put forward the academic view of "stasis caused by depression" for the first time，and discuss the modern biological research progress of "depression" in Chinese medicine that promotes blood stasis and aggravates coronary heart disease，in order to provide a basis for the subsequent development of Chinese medicine in the prevention and treatment of coronary heart disease. The aim is to provide a theoretical basis for the subsequent systematic research on the prevention and treatment of coronary heart disease with emotional abnormalities in Chinese medicine.

Experimental Research Progress of Replenishing Qi and Activating Blood Circulation Traditional Chinese Medicine on Mitochondrial Quality Control in Treatment of Chronic Heart Failure / 中国实验方剂学杂志

Heart failure is a complex clinical syndrome，which is the final result of compensatory failure of heart injury caused by various reasons. Long-term persistent cardiac stress leads to mitochondrial dysfunction，which in turn further damages cardiomyocytes and leads to disease progression. Timely removal of damaged mitochondria in cardiomyocytes and maintaining a good living environment of viable mitochondria is not only an effective means to protect cardiomyocytes，but also a new way to prevent and treat heart failure and ventricular remodeling. Mitochondrial quality control is a series of cellular activities for mitochondria to maintain their structural and functional stability，including oxidative stress response，regulation of mitochondrial dynamics，mitochondrial autophagy，intracellular calcium regulation and so on. Traditional Chinese medicine（TCM） mostly uses drugs of replenishing Qi and activating blood circulation in the treatment of chronic heart failure，and Qi and mitochondria are similar in function. According to TCM，the performance of the body as "static，descending and inhibitory" in the case of Qi deficiency can also be compared with the energy defect of mitochondria. The classical method of tonifying qi and activating blood circulation in TCM can be applied here. In recent years，TCM takes mitochondria as the target and carries out many related experimental studies from the point of view of myocardial energy supply. It is found that Chinese herbs for replenishing Qi and activating blood circulation can participate in regulating the quality control mechanism of intracellular mitochondria with multiple targets and links. It is proved by experiments that Chinese herbs for replenishing Qi and activating blood circulation can exert myocardial protective effect through this mechanism.

Exploration of the Two-Way Adjustment Mechanism of Rhei Radix et Rhizoma for Cardiovascular Diseases.

AIM AND OBJECTIVE: Myocardial infarction, cerebral infarction, and other diseases caused by vascular obstruction have always jeopardized human life and health. Several reports indicate that Rhei Radix et Rhizoma has a good clinical effect in the prevention and treatment of cardiovascular diseases. Owing to the complexity of herbal medicine, the pharmacodynamic mechanism of Rhei Radix et Rhizoma is still unclear. The objectives of this study were to explore the two-way adjustment mechanism of Rhei Radix et Rhizoma and provide a new solution for the prevention and treatment of cardiovascular disease. MATERIALS AND METHODS: This study used data mining, reverse pharmacophore matching, network construction, GO and KEGG Analysis, and molecular docking to investigate the two-way adjustment mechanism of Rhei Radix et Rhizoma. The methods used were based on systems pharmacology and big data analysis technology. RESULTS: The results suggest that Rhei Radix et Rhizoma uses a two-way adjustment of activating blood circulation, as well as blood coagulation in the prevention and treatment of cardiovascular diseases. The components involved in activating blood circulation are mainly anthraquinone components. The corresponding targets are NOS2, NOS3, CALM1, and the corresponding pathways are calcium signaling pathway, VEGF signaling pathway, platelet activation, and the PI3K-Akt signaling pathway. For blood coagulation, the components are mainly tannin components; the corresponding targets are F2, F10, ELANE, and the corresponding pathways are the neuroactive ligand-receptor interaction, complement and coagulation cascades. CONCLUSION: This study indicated that Rhei Radix et Rhizoma exerts the two-way adjustment of activating blood circulation and blood coagulation in the prevention and treatment of cardiovascular diseases. It can make up for the side effects of the existing blood circulation drugs for cardiovascular disease, only activating blood circulation, and the uncontrollable large-area bleeding due to the long-term use of the drugs. This study provides a material basis for the development of new blood-activating drugs based on natural medicine.

A network pharmacology approach to explore mechanisms of activating blood circulation and removing blood stasis herbs in the treatment of endometriosis / 药学实践杂志

Objective To explore the possible mechanism of activating blood circulation and removing blood stasis herbs in the treatment of endometriosis (EM) with network pharmacology approach. Methods Seven kinds of commonly used activating blood circulation and removing blood stasis herbs, such as: peach kernel, safflower, zeilan, salvia miltiorrhiza, leonuri, radix cyathulae, and wang buliuxing were selected as the research subjects. TCMSP platform, a database of traditional Chinese medicine chemical ingredients, was used to retrieve the effective ingredients of 7 herbs. The targets of the effective ingredients were obtained through the Targets information software. GeneCards database was used to collect EM related target genes. Venn diagram tool was used to obtain the target genes of active ingredients of activating blood circulation and removing blood stasis herbs. Cytoscape 3.6.0 software was used to construct the active ingredient-target-disease network. KEGG database was used to analyze the signal pathways of target gene enrichment. Results A total of 94 active ingredients and 119 targets of 7 herbs were screened. Quercetin, luteolin and kaempferol were the key active components. PTGS2, PTGS1, NCOA2 and NCOA1 were the key targets. The 7 herbs have 20 related KGEE pathways, involving sex hormones, inflammation, apoptosis and angiogenesis. PI3K-Akt signaling pathway, IL-17 signaling pathway, TNF signaling pathway were the main pathways. Conclusion The treatment of EM with activating blood circulation and removing blood stasis herbs has the characteristics of multiple components, multiple targets and multiple pathways, which can relieve the pain, inflammation and menstrual disorders symptoms of EM.

Detoxification and activating blood circulation decoction reduces restenosis involving the TLR4/NF-κB pathway after balloon injury.

Restenosis is a major problem after percutaneous coronary intervention (PCI) treatment. Inflammation is one of the major core mechanisms involved in the occurrence of restenosis, and plays an important role in intimal hyperplasia. Detoxification and activating blood circulation decoction (DABCD) is a traditional Chinese medicine that is used in the treatment and prevention of atherosclerotic and inflammatory diseases. Our previous studies demonstrated that DABCD-mediated cardioprotection involves anti-inflammatory mechanisms and could be developed as a novel drug for the treatment of vascular smooth muscle cell (VSMC) proliferation and aortic restenosis. A rat model of postoperative restenosis after PCI was generated by balloon injury to determine the protective effects and potential mechanisms of DABCD. The injured segments of aortae were collected on days 14 and 28 after the operation to observe the morphological changes in the vascular structure and measure the proportion of inflammatory factors in plasma and vascular tissues, as well as test the proliferative activity of VSMCs. The expression of related proteins, namely, Toll-like receptor (TLR) 4 and nuclear factor (NF)-κB, in the mechanistic study was clarified by western blot analysis. We tested the hypothesis that the cardioprotective effects of DABCD on aortic restenosis are associated with the inhibition of aortic intimal hyperplasia in this model. Our results showed that DABCD has protective effect on rat aortic restenosis and the anti-inflammatory mechanism of DABCD on balloon-induced restenosis in rat may be due to its ability to inhibit TLR4-mediated NF-κB signaling pathways. DABCD may be a potential therapeutic agent against restenosis.

Interventional Effect and Mechanism of Extract of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma on Vascular Endothelial Cellular Senescence Induced by High Glucose and High Fat / 中国实验方剂学杂志

Objective: To explore the mechanism of extract of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma in delaying the senescence of vascular endothelial cells induced by high glucose and high fat. Method: The 40 mmol·L-1 glucose and 100 μmol·L-1 palmitate were used to induce endothelial cell senescence. The experiment was divided into control group, model group and low, medium and high-dose traditional Chinese medicine groups (50,100,200 mg·L-1). The intervention lasted for 48 h. Cell proliferation was detected by cell counting kit-8(CCK-8); cell senescence was detected by senescence β-galactosidase staining; p16 and p21 protein expression levels were detected by Western blot; p-H2A. X(Ser139) expression, mitochondria ROS(mtROS) production and changes in mitochondrial membrane potential(MMP) were detected by immunofluorescence. Result: Compared with the control group, in model group, the cell proliferation ability and the number of SA-β-gal blue-stained cells decreased(PPPPβ-gal blue-stained cells, the mtROS production, and expression levels of p16, p21 and p-H2A. X(Ser139)(PPConclusion: The above results suggest that extract of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma delay of endothelial cellular senescence induced by high glucose and high fat, and its mechanism may be related to increasing mitochondrial membrane potential and reducing DNA damage accumulation caused by ROS production.

Effects of Zhizi Chuanxiong Capsule () on the Abnormal Methylation in Rabbits with Atherosclerosis.

OBJECTIVE: To investigate the effects of Zhizi Chuanxiong Capsule (ZCC, ) on abnormal DNA methylation in a rabbit model of atherosclerosis (AS). METHODS: After 1 week of adaptive feeding, 48 New Zealand white rabbits were randomly divided into 4 groups: a control group (n=12) fed with normal diet for 22 weeks; a model group (n=12) fed with high fat diet for 14 weeks followed by 8 weeks of normal diet feeding; a low-dose ZCC group (n=12) fed with high fat diet and low-dose ZCC for 14 weeks, followed by 8 weeks of normal diet and low-dose drug; a high-dose ZCC group (n=12) fed with high fat diet and high-dose drug for 14 weeks, followed by 8 weeks of normal diet and high-dose drug. After 22 weeks of feeding, blood samples were taken from the rabbit ear vein, and the genomic DNA was extracted for methylation immunoprecipitation sequencing (Medip-seq). The aorta tissues were collected for hematoxylin-eosin (HE) staining. RESULTS: Eight rabbits died during the feeding process. HE staining showed that the size of the lipid deposition on vessel wall and atherosclerotic plaque formation were reduced in both low- and high-dose group. The Medip-seq results showed that there were 146 abnormally methylated genes (including both hypermethylated gene and hypomethylated genes) in the model group, compared with the control group. Gene Ontology (GO) and Pathway analysis showed that these abnormally methylated genes were found to be involved in multiple AS-related functions and pathways, such as protein kinase C activity, cholesterol transport, mitogen-activated protein kinase (MAPK) signaling pathway, peroxisome proliferater-activated receptor signaling pathway, vascular smooth muscle contraction, inflammation and so on. The abnormal methylated genes in AS model group were altered in both low- and high-dose groups: low-dose ZCC could change 72 of the 146 abnormally methylated genes, high-dose ZCC could change 71. Through GO and Pathway analysis, these altered methylated genes were involved in protein kinase C activity, inflammatory pathway, MAPK signaling pathway, vascular endothelial growth factor signaling pathway, etc. CONCLUSION: ZCC could treat AS through regulating the abnormal hypermethylated and hypomethylated genes in AS rabbit model.

[Acupoint injection of BMSCs combined with Chinese herbs for capillary density in ischemic hind limb of diabetes mellitus rats].

OBJECTIVE: To observe the effect of acupoint injection of bone mesenchymal stem cells (BMSCs) combined with Chinese herbs of benefiting qi for activating blood circulation for capillary density and arterioles density in skeletal muscle in ischemic hind limb of diabetes mellitus (DM) rats. METHODS: A total of 80 rats were randomized into a normal sham operation group (10 rats) and a model group (70 rats). Disposable intraperitoneal injection of streptozotocin (STZ, 50.0 mg/kg) was used to establish DM model, and the rats in the model group were randomized into 7 subgroups, 10 rats in each one. The subgroups were the DM sham operation group, DM ischemic group, Chinese herb group (intragastric herbs of benefiting qi for activating blood circulation), local injection group (BMSCs local injection), local injection + Chinese herb group (BMSCs local injection combined with intragastric herbs of benefiting qi for activating blood circulation), acupoint injection group (BMSCs acupoint injection), acupoint injection + Chinese herb group (BMSCs acupoint injection combined with intragastric herbs of benefiting qi for activating blood circulation). The local injection was phosphate buffer (PBS) injection at the equidistant 5 points along the line between the ischemic tissue and the normal tissue a time. The acupoints were "Sanyinjiao" (SP 6), "Zhaohai" (KI 6), "Huantiao" (GB 30), "Housanli" (ST 36) and "Yanglingquan" (GB 34). 100 µL BMSCs with 1×107/mL was totally injected at the above acupoints for one rat, 20 µL an acupoint. 1.5 kg/L Chinese herbs were applied by intragastric administration, including 120 g Radix Astragali, 120 g Codonopsis, 48 g Radix Glycyrrhiza, 120 g Angelica sinensis, 120 g Blood Rattan, 48 g Achyranthes bidentata. Intragastric distilled water was used in the other non-Chinese herb groups. The expressions of α-smooth muscle actin (α-actin), latelet endothelial cell adhesion molecule (CD31) and von willebrand factor (vWF) in the skeletal muscle were detected with immunohistochemical SP two-step method. RESULTS: Twenty-one days after intervention, the expressions of α-actin and CD31 on the operation hind limb were higher than those on the healthy hind limb in all the groups, except the Chinese herb group (P<0.05，P<0.01). The vWF expressions on the operation side were lower than those on the healthy side in the Chinese herb group, the local injection group, the local injection + Chinese herb group and the acupoint injection + Chinese herb group (P<0.05, P<0.01). The α-actin expression on the operation side in the acupoint injection + Chinese herb group was higher than those in the normal sham operation group, DM sham operation group, the DM ischemic group and the local injection group (P<0.05, P<0.01). The CD31 expressions in the acupoint injection group, the acupoint injection + Chinese herb group, local injection + Chinese herb group were higher than those in the normal sham operation group, DM sham operation group and DM ischemic group (P<0.05, P<0.01). The CD31 expression in the acupoint injection + Chinese herb group was higher than those in the Chinese herb group and the local injection group (both P<0.05). The vWF expressions in the local injection + Chinese herb group, the acupoint injection group and the acupoint injection + Chinese herb group lower than those in the DM sham operation group and the DM ischemic group (P<0.05, P<0.01). CONCLUSION: schemia increases the expressions of the vascular density related factors of α-actin and CD31. It is more obvious for the increasing expressions of α-actin and CD31, and decreasing expression of vWF with the interventions of simple BMSCs injection and simple Chinese herbs of benefiting qi for activating blood circulation, especially with the combination of the above tow methods. It is indicated that acupoint injection of BMSCs combined with Chinese herbs of benefiting qi for activating blood circulation can improve the angiogenesis of ischemic tissue.

Tonifying Qi and activating blood circulation in terms of Traditional Chinese Medicine: their effects in patients with myocardial infarction.

OBJECTIVE: To investigate the effects of tonifying Qi and activating blood circulation (SQABC), a method in Traditional Chinese Medicine (TCM), on end-point events in patients with myocardial infarction (MI) in this retrospective cohort study. METHODS: Clinical data were obtained from the medical records of patients with acute MI (AMI), both during hospitalization and follow-up, and included general demographic information (age, gender, and contact information), TCM regimens used, and end-point events. RESULTS: A total of 1596 patients with AMI were enrolled to this study, but data of only 1210 cases are accessible till follow-up. We classified the patients based on the exposure levels of SQABC. When comparing the results between all exposure and non-exposure groups, significant differences were identified, both during hospitalization and follow-ups. During hospitalization, cardiac death (4.40% vs 21.55%, P < 0.05) and cardiac shock (3.04% vs 11.62%, P < 0.05) were significantly lower in the exposure group than the non-exposure group. Similarly, during the follow-up, cardiac death (12.04% vs 20.49%, P < 0.05), acute heart failure (7.27% vs 11.81%, P < 0.05), composite endpoint of reinfarction and stroke (9.11% vs 15.28%, P < 0.05), and rehospitalization due to angina (25.49% vs 34.38%, P < 0.05) were significantly lower in the exposure group than the non-exposure group. CONCLUSION: Our findings suggest that SQABC can significantly benefits the subjects in the management of high-risk AMI in them.

Acupoint injection of BMSCs combined with Chinese herbs for capillary density in ischemic hind limb of diabetes mellitus rats / 中国针灸

OBJECTIVE@#To observe the effect of acupoint injection of bone mesenchymal stem cells (BMSCs) combined with Chinese herbs of benefiting for activating blood circulation for capillary density and arterioles density in skeletal muscle in ischemic hind limb of diabetes mellitus (DM) rats.@*METHODS@#A total of 80 rats were randomized into a normal sham operation group (10 rats) and a model group (70 rats). Disposable intraperitoneal injection of streptozotocin (STZ, 50.0 mg/kg) was used to establish DM model, and the rats in the model group were randomized into 7 subgroups, 10 rats in each one. The subgroups were the DM sham operation group, DM ischemic group, Chinese herb group (intragastric herbs of benefiting for activating blood circulation), local injection group (BMSCs local injection), local injection + Chinese herb group (BMSCs local injection combined with intragastric herbs of benefiting for activating blood circulation), acupoint injection group (BMSCs acupoint injection), acupoint injection + Chinese herb group (BMSCs acupoint injection combined with intragastric herbs of benefiting for activating blood circulation). The local injection was phosphate buffer (PBS) injection at the equidistant 5 points along the line between the ischemic tissue and the normal tissue a time. The acupoints were "Sanyinjiao" (SP 6), "Zhaohai" (KI 6), "Huantiao" (GB 30), "Housanli" (ST 36) and "Yanglingquan" (GB 34). 100 μL BMSCs with 1×10/mL was totally injected at the above acupoints for one rat, 20 μL an acupoint. 1.5 kg/L Chinese herbs were applied by intragastric administration, including 120 g Radix Astragali, 120 g Codonopsis, 48 g Radix Glycyrrhiza, 120 g Angelica sinensis, 120 g Blood Rattan, 48 g Achyranthes bidentata. Intragastric distilled water was used in the other non-Chinese herb groups. The expressions of α-smooth muscle actin (α-actin), latelet endothelial cell adhesion molecule (CD31) and von willebrand factor (vWF) in the skeletal muscle were detected with immunohistochemical SP two-step method.@*RESULTS@#Twenty-one days after intervention, the expressions of α-actin and CD31 on the operation hind limb were higher than those on the healthy hind limb in all the groups, except the Chinese herb group (<0.05<0.01). The vWF expressions on the operation side were lower than those on the healthy side in the Chinese herb group, the local injection group, the local injection + Chinese herb group and the acupoint injection + Chinese herb group (<0.05, <0.01). The α-actin expression on the operation side in the acupoint injection + Chinese herb group was higher than those in the normal sham operation group, DM sham operation group, the DM ischemic group and the local injection group (<0.05, <0.01). The CD31 expressions in the acupoint injection group, the acupoint injection + Chinese herb group, local injection + Chinese herb group were higher than those in the normal sham operation group, DM sham operation group and DM ischemic group (<0.05, <0.01). The CD31 expression in the acupoint injection + Chinese herb group was higher than those in the Chinese herb group and the local injection group (both <0.05). The vWF expressions in the local injection + Chinese herb group, the acupoint injection group and the acupoint injection + Chinese herb group lower than those in the DM sham operation group and the DM ischemic group (<0.05, <0.01).@*CONCLUSION@#schemia increases the expressions of the vascular density related factors of α-actin and CD31. It is more obvious for the increasing expressions of α-actin and CD31, and decreasing expression of vWF with the interventions of simple BMSCs injection and simple Chinese herbs of benefiting for activating blood circulation, especially with the combination of the above tow methods. It is indicated that acupoint injection of BMSCs combined with Chinese herbs of benefiting for activating blood circulation can improve the angiogenesis of ischemic tissue.

Effects of Zhizi Chuanxiong Capsule () on the Abnormal Methylation in Rabbits with Atherosclerosis / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of Zhizi Chuanxiong Capsule (ZCC, ) on abnormal DNA methylation in a rabbit model of atherosclerosis (AS).@*METHODS@#After 1 week of adaptive feeding, 48 New Zealand white rabbits were randomly divided into 4 groups: a control group (n=12) fed with normal diet for 22 weeks; a model group (n=12) fed with high fat diet for 14 weeks followed by 8 weeks of normal diet feeding; a low-dose ZCC group (n=12) fed with high fat diet and low-dose ZCC for 14 weeks, followed by 8 weeks of normal diet and low-dose drug; a high-dose ZCC group (n=12) fed with high fat diet and high-dose drug for 14 weeks, followed by 8 weeks of normal diet and high-dose drug. After 22 weeks of feeding, blood samples were taken from the rabbit ear vein, and the genomic DNA was extracted for methylation immunoprecipitation sequencing (Medip-seq). The aorta tissues were collected for hematoxylin-eosin (HE) staining.@*RESULTS@#Eight rabbits died during the feeding process. HE staining showed that the size of the lipid deposition on vessel wall and atherosclerotic plaque formation were reduced in both low- and high-dose group. The Medip-seq results showed that there were 146 abnormally methylated genes (including both hypermethylated gene and hypomethylated genes) in the model group, compared with the control group. Gene Ontology (GO) and Pathway analysis showed that these abnormally methylated genes were found to be involved in multiple AS-related functions and pathways, such as protein kinase C activity, cholesterol transport, mitogen-activated protein kinase (MAPK) signaling pathway, peroxisome proliferater-activated receptor signaling pathway, vascular smooth muscle contraction, inflammation and so on. The abnormal methylated genes in AS model group were altered in both low- and high-dose groups: low-dose ZCC could change 72 of the 146 abnormally methylated genes, high-dose ZCC could change 71. Through GO and Pathway analysis, these altered methylated genes were involved in protein kinase C activity, inflammatory pathway, MAPK signaling pathway, vascular endothelial growth factor signaling pathway, etc. CONCLUSION: ZCC could treat AS through regulating the abnormal hypermethylated and hypomethylated genes in AS rabbit model.

Review and prospect of using traditional Chinese medicine drugs "supplementing Qi and nourishing Yin, activating blood circulation and detoxifying" for prevention and treatment of diabetes mellitus complicated with acute coronary syndrome / 中国中西医结合急救杂志

At present, the prevalence rate of diabetes presents a rising tendency. The cardiovascular disease is a major complication of diabetes mellitus and acute coronary syndrome (ACS) is a severe form of coronary heart disease. Compared with non-diabetic patients, the disease situation in diabetic ACS patients is more serious with more contradictory problems and difficulty in treatment. Although percutaneous coronary intervention (PCI) plays a certain role in re-canalization of coronary artery, after PCI the problems the patients with diabetic ACS will face are still serious. traditional Chinese medicine (TCM) recognizes that the etiology and pathogenesis of diabetic ACS are deficiency in Qi and Yin, and accumulation of blood stasis and toxin inside the body. Through clinical observation and retrospective analysis, it is found that using "supplementing Qi and nourishing Yin, activating blood circulation and detoxifying"can interfere with the patients' diabetic ACS and simplify the therapeutic regimen, which is an integrated regulatory treatment with multiple links, multiple pathways and multiple targets, and is a sufficient realization of unique superiority of traditional Chinese medicine by using holistic concept, syndrome differentiation and multiple-link interference for comprehensive prevention and treatment of diabetic ACS.