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Jin-yu Shi,1,* Ting-ting Li,1,2,* Hui-ting Yang,1 Shi Zhang,2 Ran An,2 Liang Mao,2 Yang Li,2 Qian Li,2 Guang-yi Luan,2 Yan Shen,2 En-long Wang,2 Guang-hui Liu1,2 1First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang-hui Liu, First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China; Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, No. 33, Beiling Street, Huanggu District, Shenyang, Liaoning, 110032, People’s Republic of China, Email guanghui04-09@163.comObjective: This study aimed to investigate the features and underlying principles of acupuncture points used in the treatment of headaches associated with blood stasis syndrome.Methods: Literature on the treatment of blood stasis headache with acupuncture and moxibustion was searched across three Chinese databases and one English database from January 1st, 2000, to January 1st, 2024. Relevant data including titles, journals, authors, keywords, interventions, main acupoints, and outcomes were extracted for further analysis.Results: A total of 112 papers with 102 complete prescriptions were analyzed. Of the 77 acupoints examined, 72 were meridian points, and 5 were extraordinary points, used 699 times in total. The top ten acupoints by frequency were Fengchi (GB20), Taiyang (EX-HN5), Baihui (GV20), Hegu (LI4), Shuaigu (GB8), Taichong (LR3), Xuehai (SP10), Touwei (ST8), Geshu (BL17), and Waiguan (TE5). Yang meridian points were used more frequently than Yin meridian points (82.8% vs 17.2%), with the Gallbladder Meridian of Foot Shaoyang being the most common. Nearly half of the acupoints (49.9%) were on the head and neck, and 23.1% on the lower limbs. Specific acupoints accounted for 53.5% of the total frequency. Fengchi (GB20) and Taiyang (EX-HN5) showed the highest correlation. Association rule mining highlighted combinations like Fengchi (GB20) with Taiyang (EX-HN5) and Baihui (GV20). Cluster analysis yielded five clusters.Conclusion: The study provides insights into selecting effective acupoints and combinations for clinical acupuncture practice and experimental studies in treating blood stasis headaches. Acupoints like Fengchi (GB20), Taiyang (EX-HN5), and Baihui (GV20) may be effective for clinical treatment, but further studies are needed to validate their efficacy.Keywords: headache, blood stasis syndrome, acupuncture, treatment rule, data mining

Paeonia lactiflora Pall. (PLP) is thought to promote blood circulation and remove blood stasis. This study used blood component analysis, network pharmacology, and molecular docking to predict the mechanism of PLP in the treatment of blood stasis syndrome (BSS). PLP was processed into Paeoniae Radix Alba (PRA) and Paeoniae Radix Rubra (PRR). PRA and PRR could significantly reduce whole blood viscosity (WBV) at 1/s shear rates and could increase the erythrocyte aggregation index (EAI), plasma viscosity (PV), and erythrocyte sedimentation rate (ESR) of rats with acute blood stasis. They prolonged the prothrombin time (PT), and PRR prolonged the activated partial thromboplastin time (APTT). PRA and PRR increased the thrombin time (TT) and decreased the fibrinogen (FBG) content. All the results were significant (p < 0.05). Ten components of Paeoniflorin, Albiflorin, Paeonin C, and others were identified in the plasma of rats using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A protein–protein interaction network (PPI) analysis showed that AKT1, EGFR, SRC, MAPK14, NOS3, and KDR were key targets of PLP in the treatment of BSS, and the molecular docking results further verified this. This study indicated that PLP improves BSS in multiple ways and that the potential pharmacological mechanisms may be related to angiogenesis, vasoconstriction and relaxation, coagulation, and the migration and proliferation of vascular cells. [ABSTRACT FROM AUTHOR]

Blood stasis syndrome (BSS) has persistent health risks; however, its pathogenesis remains elusive. This obscurity may result in missed opportunities for early intervention, increased susceptibility to chronic diseases, and reduced accuracy and efficacy of treatments. Metabolomics, employing the matrix-assisted laser desorption/ionization (MALDI) strategy, presents distinct advantages in biomarker discovery and unraveling molecular mechanisms. Nonetheless, the challenge is to develop efficient matrices for high-sensitivity and high-throughput analysis of diverse potential biomarkers in complex biosamples. This work utilized nitrogen-doped porous transition metal carbides and nitrides (NP-MXene) as a MALDI matrix to delve into the molecular mechanisms underlying BSS pathogenesis. Structural optimization yielded heightened peak sensitivity (by 1.49-fold) and increased peak numbers (by 1.16-fold) in clinical biosamples. Validation with animal models and clinical serum biosamples revealed significant differences in metabolic fingerprints between BSS and control groups, achieving an overall diagnostic efficacy of 0.905 (95% CI, 0.76–0.979). Prostaglandin F2α was identified as a potential biomarker (diagnostics efficiency of 0.711, specificity = 0.7, sensitivity = 0.6), and pathway enrichment analysis disclosed disruptions in arachidonic acid metabolism in BSS. This innovative approach not only advances comprehension of BSS pathogenesis, but also provides valuable insights for personalized treatment and diagnostic precision. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the efficacy and cost-effectiveness of Xueshuantong injection ( lyophilized) (XIL) combined with conventional therapy in the treatment of unstable angina pectoris ( UAP ), so as to provide therapeutic and economic reference for the rational allocation of healthcare medical resources. METHODS: From the perspective of health system, a decision tree model for the treatment of UAP was constructed based on the evaluation results of one Meta-analysis, the intrinsic advantages and economic value of XIL were identified by cost-effectiveness analysis, with the intervention cycle for 14 days, and the sensitivity analysis was conducted on the results of this study. RESULTS: Meta-analysis showed that compared with the control group (conventional therapy), the efficacy of angina pectoris symptoms in the observation group (XIL+conventional therapy) was significantly better, and the results were more homogenous. The basic analysis results of pharmacoeconomic evaluation showed that the incremental costeffectiveness ratio of the two groups was 3 289. 11 yuan, indicated that compared with the control group, the observation group needed to spend 3 289. 11 yuan more for each additional case of effectively treated UAP patient. When the individual willingness-to-pay price was greater than 3 289. 11 yuan, the intervention regimen of observation group had more economical efficiency. The sensitivity analysis showed that the efficacy of angina pectoris symptoms and the conventional therapy cost of UAP in the control group had a certain effect on the study results. When the individual willingness-to-pay price was greater than 3 000 yuan, the intervention regimen of observation group had a higher economic probability, which is the same as the result of basic analysis. CONCLUSIONS: In terms of improving the angina pectoris symptoms in UAP patients, the choice of XIL combined with conventional therapy was more economical than conventional therapy alone when the individual willingness-to-pay price was greater than 3 000 yuan. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlations between intestinal flora, plasma metabolites, and blood stasis syndrome in coronary heart disease (CHD), and the mechanisms of Yangxin Tongmai Formula (养心通脉方, YXTMF) for blood stasis syndrome in CHD rats. Methods: A total of 18 specific pathogen free (SPF) male Sqrague-Dawley (SD) rats were used to establish CHD rat models with blood stasis syndrome, which were then randomized into model, YXTMF, and atorvastatin calcium (AVT) groups, with six rats in each group, and were intervened through gavage for two weeks. Subsequently, additional six rats that received normal diet were included as normal group. The pathological changes in the CHD rat models were identified by hematoxylin-eosin (HE) staining. The electrocardiogram, hemodynamics, and lipid profiles of the rats were detected as well. The untargeted plasma metabolomics of rats were analyzed by liquid chromotography-tandem mass spectrometry (LC-MS/MS), their ileal mucosal flora by 16S rRNA sequencing, and the correlation between the two results were also analyzed. Results: The whole blood viscosity, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) of rats in the model group increased compared with those in the control group (P < 0.05). In the model group, the proliferation of endothelial cells in the coronary artery of rats was damaged, with quite a few vacuolated pathological changes observed. However, the endothelial lesions in the coronary artery of rats were alleviated in the intervention groups (YXTMF and AVT groups). With the use of LC-MS/MS, a total of 33 potential endogenous metabolites were identified in plasma, among which 1-methylhistidine, N-acetylhistamine, progesterone, and deoxycorticosterone were expected to be the differential metabolites in CHD rats with blood stasis syndrome. The 16S rRNA sequencing results showed that improved diversity and abundance of intestinal flora were observed in the YXTMF group. The correlation analysis suggested that Hydrogenophaga, Limnohabitans, and Polaromonas, which were highly related to the formation of blood stasis syndrome in CHD patients, were positively correlated with plasma metabolites such as 5-hydroxyindole, N-acetylhistamine, and progesterone (P < 0.01), but were negatively correlated with plasma metabolites such as L-arginine, homoarginine, and Boc-beta-cyano-L-alanine (P < 0.01). After YXTMF intervention, Lactobacillus, Corynebacterium, and Candidatus Nitrososphaera were positively correlated with plasma metabolites such as Boc-β-cyano-L-alanine, stachydrine, and naringenin (P < 0.05), while negatively correlated with 5-hydroxyindole, N-acetylhistamine, and oleoylethanolamide (P < 0.05). Conclusion: YXTMF could alleviate blood stasis syndrome in CHD rats through improving their plasma metabolisms achieved by regulating the intestinal flora.

Objective To explore the clinical practice effect and optimization method of optimizing the Traditional Chinese Medicine (TCM)nursing plan for chest obstruction and heart pain (coronary heart disease) based on Feng Yunhua's academic viewpoint of blood stasis syndrome and nursing for promoting blood circulation and resolving stasis. Methods The clinical data of 793 patients with chest obstruction and heart pain admitted to the hospital from June 2021 to May 2022 were retrospectively analyzed. Totally 390 patients with hospital admission between June 2021 and November 2021 were recruited as the control group, receiving routine nursing plan of promoting blood circulation and resolving blood stasis. Another 403 patients with hospital admission between December 2021 and May 2022 were included as the observation group, received modified nursing plan. Effect of nursing interventions on main symptoms and syndrome integral of blood stasis syndrome were measured, and patient satisfaction and evaluation of nursing program by nurses were investigated. Results The effect of nursing interventions on chest tightness/chest pain and Palpitations/shortness of breath were higher in the observation group than those in the control group(P

Background Coronary heart disease (CHD) belongs to the category of "pectoral stuffiness and pains" in traditional Chinese medicine (TCM) . Blood stasis syndrome is the most common syndrome distribution and the incidence of that in middle-aged and young adults is higher than old adults. Expending on the previous team study, the artery stiffness, vascular endothelial function and apolipoprotein ration were combined for the diagnosis of CHD with blood stasis syndrome in middle-aged and young adults for the first time in the study, in order to provide new approaches for the early detection and reference for optimising diagnostic criteria of CHD with blood stasis syndrome in middle-aged and young adults. Objective To investigate the correlation between ankle brachial index (ABI) , brachial-ankle pulse wave velocity (baPWV) , flow-mediated dilation (FMD) , apolipoprotein B to apolipoprotein A-1 ratio (apoB/apoA-1) and CHD with blood stasis syndrome in middle-aged and young adults (

Danggui Sini decoction is a traditional Chinese medicine preparation commonly used in the treatment of blood stasis syn)drome through a mechanism yet to be defined. Therefore, we have explored its mechanism of action by combining phar)macology and gut microbiota analysis. To this end, female Sprague-Dawley rats were divided into 5 groups, including the control group, the acute blood stasis group, the Danshen tablet-treated group, the low-dose Danggui Sini decoction group, and the high-dose Danggui Sini decoction group. Danggui Sini decoction led to a significant reduction in the changes in the whole blood viscosity and plasma viscosity of rats with acute blood stasis syndrome, improved the coagulation func)tion and cardiopulmonary pathological injury, upregulated the plasma 6-keto prostaglandin F1α and endothelial nitric oxide synthase, and downregulated thromboxane B2 and endothelin-1. The high throughput 16S rRNA gene sequencing results showed that Danggui Sini decoction reduced the number of pathogenic proteobacteria, significantly reduced erysipelas and suzericella, and increased the beneficial bacteria Roche, effectively improving the status of intestinal flora disorder in acute blood stasis rats. The Spearman correlation analyses showed that there was a close correlation between intestinal flora distribution and changes in blood stasis-related biochemical indices. In addition, network pharmacological analysis showed that the epidermal growth factor receptor, tumor protein p53, signal transducer and activator of transcription 3, vascular endothelial growth factor A, and hypoxia-inducible factor 1-alpha were the core targets of Danggui Sini decoction in alleviation of blood stasis. Further genetic ontological and pathway enrichment analyses suggested that the therapeu)tic effect of Danggui Sini decoction on blood stasis involved the lipid and atherosclerosis pathways, advanced glycation end-product-receptor for advanced glycation end-product signaling pathways in diabetic complications, fluid shear stress and atherosclerosis pathways, and hypoxia-inducible factors, 1-alpha signaling pathway, phosphatidylinositol 3-kinase)protein kinase B signaling, and other pathways. These results are helpful in understanding the mechanism by which Danggui Sini decoction improves blood stasis and provide a reference for further research. [ABSTRACT FROM AUTHOR]

Objective To investigate the therapeutic effect of Yangxin Tongmai formula（YTF）on myocardial injury in rats with myocardial ischemia-reperfusion injury (MIRI) and blood stasis syndrome, and to analyze its related mechanism. Methods Wistar rats were divided into the normal control group, model control group, negative control group, positive control group, low-dose YTF group, medium-dose YTF group and high-dose YTF group, with 10 rats in each group. The rats in the low-dose, medium-dose, and high-dose YTF groups were given 4. 725, 9. 450, and 18. 900 g/kg of YTF by gavage, respectively. Rats in the positive control group were given Guanxin Suhe pill suspension at a dose of 10. 710 g/kg. Rats in the negative control group were given equal volume of normal saline by gavage, twice a day, for 14 days. Rats in the normal control group were fed routinely without gavage. The apoptosis of cardiomyocytes was observed by TUNEL fluorescence staining. The swelling degree of mitochondrial membrane（OD540） and the content of mitochondrial superoxide anion were detected by microplate labeling instrument. Results The results of transmission electron microscopy showed that in the normal control group, the myocardial myofilaments were arranged neatly, the sarcomere was regu-lar, the structure was clear, the mitochondrial outer membrane was intact, and the cricrists were normal and densely ar-ranged. In the model control group and the negative control group, the myocardial sarcomere was ruptured, the perinuclear space was widened, the mitochondria were arranged disorderly, some outer membrane was blurred or even ruptured and de-formed, the mitochondrial crest structure was partially missing, a small number of autophagosomes-wrapped mitochondria and cytoplasm, and a small number of lysosomes appeared. In the positive control group and the medium-dose and highdose YTF groups, the mitochondria were densely arranged, the breakage of myofilaments was light, the sarcomere was neat, the outer membrane and cristulation structure of mitochondria were clear, and the number of small autophagosomes, lysosomes and mitochondria wrapped by autophagosomes increased in the early stage. In the low-dose YTF group, the mitochondrial myofilament was relatively intact but the sarcomere was unclear, the mitochondrial outer membrane and cristulation structure were unclear, and the number of small autophagosomes increased in the early stage. The apoptosis rates of cardiomyocytes in the model control group and the negative control group were higher than that in the normal control group, and the apoptosis rates of cardiomyocytes in the positive control group and the medium-dose YTF group were lower than that in the negative control group (all P＜0. 05）. OD540 values in the model control group and the negative control group were lower than that in the normal control group. The OD540 values of the positive control group, low-dose YTF group, medium-dose YTF group and high-dose YTF group were higher than that of the negative control group, and the OD540 value of the low-dose YTF group increased more significantly than that of the medium-dose YTF group (all P＜0. 05). The content of superoxide anion in myocardial tissue of the model control group and negative control group was higher than that of the normal control group, and the content of superoxide anion in myocardial tissue of the high-dose YTF group was lower than that of the negative control group (all P＜0. 05). Conclusion YTF can alleviate myocardial injury in rats with MIRI and blood stasis syndrome, and its mechanism may be related to promoting mitochondrial selective autophagy, reducing super-oxide anion content, and reducing mitochondrial membrane swelling, so as to slow down the myocardial apoptosis. [ABSTRACT FROM AUTHOR]

Objective: The incidence of headaches with blood stasis syndrome has increased. Herein, we used scientific, statistical methods to explore the medication rules of Chinese herbal medicines (CHMs) to treat headaches with blood stasis syndrome and provide a scientific and reliable theoretical basis for clinical treatment. Methods: First, we retrieved studies related to CHMs used to treat headaches with blood stasis syndrome from the VIP, CNKI, Wanfang, and PubMed databases. We used Excel 2013 to establish a database and SPSS Modeler 18.0 and SPSS 25.0 to conduct frequency, association rule, and cluster analyses. Results: Based on the screening criteria, we retrieved 126 CHM prescriptions for headaches with blood stasis syndrome involving 149 herbs. The top three high-frequency herbs were Chuanxiong Rhizoma (Chuanxiong), Angelica Sinensis Radix (Danggui), and Carthami Flos (Honghua). Blood-activating and stasis-eliminating herbs were the most frequently used herb efficacy categories. The liver meridian represented the most frequently used herb meridian tropism. The properties and taste of herbs were mainly warm and bitter, respectively. We obtained 21 association rules and five new clusters. The Chuanxiong Rhizoma (Chuanxiong) and Angelica Sinensis Radix (Danggui) herb pair had the strongest correlation. Conclusion: We analyzed published CHM prescriptions for headaches with blood stasis syndrome and eliminated factors that did not reach an agreement, such as herb dosage. We used different data mining and analysis methods to ensure that the method and process were scientific and the conclusion was reliable, comprising a valuable reference for selecting herbs for the clinical treatment of headaches with blood stasis syndrome. The Xuefu Zhuyu Decoction (XFZYD) was the primary CHM prescription for headaches with blood stasis syndrome. Xiaoyao San (XYS) and Buyang Huanwu Decoction (BYHWD) might also be clinical references for treatment selection. Meridian-inducing and insect herbs might be used according to syndromes.

Ethnopharmacological Relevance: Traditional Chinese Medicine (TCM) formula Wenjing Decoction (WJD) longstanding efficacy in enhancing blood circulation, resolving blood stasis, and mitigating dysmenorrhea symptoms. Despite its prevalent application, the specific mechanism underlying effect of WJD remains elusive., Objective: The purpose of this study is to examine the material basis of Wenjing Decoction and explore the effect of WJD on rat models of dysmenorrhea with blood stasis syndrome and elucidate its mechanism., Methods: In this study, we initially identified the chemical constituents of WJD using liquid chromatography-mass spectrometry (LC-MS). Subsequently, we employed network pharmacology to predict the mechanism of WJD in treating acute blood stasis dysmenorrhea. To further investigate the role of WJD, we established a rat model of acute blood stasis. We monitored changes in blood coagulation indexes, IL-6, TNF-α, NO, and COX-2 in rats before and after administration to confirm the successful establishment of the rat model and evaluate the therapeutic effect of WJD on dysmenorrhea and acute blood stasis. Finally, real-time fluorescence quantitative PCR (qPCR) and Western blot (WB) were utilized to investigate its mechanism., Results: Through LC-MS analysis, 69 chemical substances were identified in WJD. Network pharmacology study revealed that the mechanism of WJD in treating BSS may be associated with the PI3K/AKT/NF-κB pathway. Following administration, the WJD group showed gradual recovery of physical signs and coagulation index to a healthy level. Additionally, the levels of IL-6, TNF-α, and COX-2 decreased in a dose-dependent manner, whereas NO levels increased. Results from QPCR and WB detection indicated increased expression levels of p-PI3K, p-AKT, Bcl-2, and eNOS, and decreased expression levels of Bax, NFκBp65, ICAM1, and VCAM1., Conclusion: The results show that WJD significantly improves the characterization, dysmenorrhea index, and coagulation-related factors in BSS rats. Through network pharmacological prediction, real-time fluorescence quantitative PCR, and Western blot analysis, it is postulated that the beneficial effects of WJD on dysmenorrhea may be linked to the PI3K/AKT/NF-κB signaling pathway. These findings offer a theoretical foundation for the advancement and utilization of WJD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Szechwan lovage rhizome ( SLR , the rhizome of Ligusticum chuanxiong Hort., Chuanxiong in Chinese transliteration) is one Chinese materia medica (CMM) commonly used to activate blood circulation and remove blood stasis. SLR is applicable to most blood stasis syndromes. It has significant clinical efficacy in relation to human diseases of the cardiocerebrovascular system, nervous system, respiratory system, digestive system, urinary system, etc. Apart from China, SLR is also used in Singapore, Malaysia, the European Union, and the United States of America. However, the current chemical markers in pharmacopeia or monography for the quality assessment of SLR are not well characterized or specifically characterized, nor do they fully reflect the medicinal efficacy of SLR, resulting in the quality of SLR not being effectively controlled. CMM can only have medicinal efficacy when they are applied in vivo to an organism. The intensity of their pharmaceutical activities can more directly represent the quality of CMM. Therefore, the chemical constituents and pharmacological actions of SLR are reviewed in this paper. In order to demonstrate the medicinal efficacy of SLR in promoting blood circulation and removing blood stasis, bioassay methods are put forward to evaluate the pharmaceutical activities of SLR to improve hemorheology, hemodynamics, and vascular microcirculation, as well as its anti-platelet aggregation and anticoagulation properties. Through comprehensive analyses of these pharmaceutical properties, the quality and therapeutic value of SLR are ascertained.

ObjectiveThis study was designed to explore the efficacy and safety of Xinnaoning Capsule (XNNC) in the treatment of patients with chronic stable angina pectoris (CSAP) complicated with Qi stagnation and blood stasis syndrome.MethodsA total of 240 patients with CSAP complicated with Qi stagnation and blood stasis syndrome who met the inclusion criteria were enrolled from 8 medical centers across China. The trial treatment lasted 14 weeks, including a 2-week lead-in period and a 12-week double-blind treatment period. Patients in the experimental group were treated with XNNC, while patients in the control group were treated with placebos. Thereafter, examinations were conducted on the efficacy of angina pectoris before and after treatment and the relief of symptoms, followed by the recording of grading changes in angina severity, changes in the number of angina pectoris, and the amount of taken nitroglycerin. Finally, adverse events were assessed.ResultsCompared with the control group, the total score and the effective rate of angina pectoris were significantly increased in the experimental group, accompanied by the statistically significant improvement in the severity of angina pectoris (all p < 0.05). Furthermore, there was no statistically significant difference in the adverse events and serious adverse events between the experimental group and the control group (p = 1.0000) before and after treatment.ConclusionXNNC is a safe and effective medicine for patients with CSAP complicated with Qi stagnation and blood stasis syndrome.

The abnormality of platelet function plays an important role in the pathogenesis and evolution of blood stasis syndrome (BSS). The explanation of its mechanism is a key scientific issue in the study of cardiovascular and cerebrovascular diseases and treatment. System biology technology provides a good technical platform for further development of platelet multi-omics, which is conducive to the scientific interpretation of the biological mechanism of BSS. The article summarized the pathogenesis of platelets in BSS, the mechanism of action of blood activating and stasis resolving drugs, and the application of genomics, proteomics, and metabonomics in platelet research, and put forward the concept of "plateletomics in BSS". Through the combination and cross-validation of multi-omics technology, it mainly focuses on the clinical and basic research of cardiovascular and cerebrovascular diseases; through the interactive verification of multi-omics technology and system biology, it mainly focuses on the platelet function and secretion system. The article systematically explains the molecular biological mechanism of platelet activation, aggregation, release, and other stages in the formation and development of BSS, and provides a new research idea and method for clarifying the pathogenesis of BSS and the mechanism of action of blood activating and stasis resolving drugs. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the mechanism of Huangqi Guizhi Wuwu decoction in rats with blood stasis syndrome. METHODS: The rats were divided into blank group, model group and administration group. The blood stasis model of rats was induced by subcutaneous injection of adrenaline combined with ice water bath（ model group and administration group）. The rats in the administration group were given Huangqi Guizhi Wuwu Decoction 8 g/kg by gavage once a day for 7 days, and the rats in the blank group and the model group were given the same amount of0. 9% sodium chloride solution by gavage once a day for 7 days. The blood coagulation index levels of the three groups were measured. A large amount of endogenous metabolite data were collected and processed by liquid chroma to graphy quadrupole time of flight-mass spectrometry. Non-parametric univariate analysis and multivariate statistical analysis were used for the screening and identification of potential biomarkers. Metabolic pathways based on blood biomarkers were constructed to explore the pathogenesis of blood stasis syndrome and the mechanism of Huangqi Guizhi Wuwu decoction. RESULTS: Compared with the blank group, the TT,PT and APTT of the model group was shortened significantly, and the FIB content increased significantly, the difference was statistically significant（ P < 0. 01）.Compared with the model group, the TT,PT and APTT of the rats in the administration group was prolonged significantly, and the FIB content decreased significantly, the difference was statistically significant（ P < 0. 05）. The results of metabonomics showed that the intervention of Huangqi Guizhi Wuwu decoction on rats with blood stasis syndrome could cause substantial and characteristic changes of metabolic profile. Totally 10 metabolites were screened out, such as L-glutamic acid,L-phenylalanine and L-tryptophan; these metabolites returned to the normal levels after administration of Huangqi Guizhi Wuwu decoction. CONCLUSIONS: Huangqi Guizhi Wuwu decoction has a certain therapeutic effect on blood stasis syndrome. Regulation of metabolic pathways such as glutamic acid acid phenylalanine and tryptophan may be the mechanism of the treatment of blood stasis syndrome. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation of platelet and coagulation function with blood stasis syndrome (BSS) in coronary heart disease (CHD). Methods: The protocol for this meta-analysis was registered on PROSPERO (CRD42019129452). PubMed, Excerpta Medica Database (Embase), the Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to 1st June, 2020. Trials were considered eligible if they enrolled BSS and non-BSS (NBSS) patients with CHD and provided information on platelet and coagulation function. The platelet function, coagulation function, and fibrinolytic activity were compared between the BSS and NBSS groups. Forest plots were generated to show the SMDs or ESs with corresponding 95% CIs for each study. Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity. Results: The systematic search identified 1,583 articles. Thirty trials involving 10,323 patients were included in the meta-analysis. The results showed that mean platelet volume, platelet distribution width, platelet aggregation rate, platelet P selectin, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), thromboxane B2 (TXB2), 6-keto-prostaglandin F1alpha (6-keto-PGF1 α), and TXB2/6-keto-PGF1 α were higher in the BSS group than in the NBSS group (P<0.05 or P<0.01). Activated partial thromboplastin time was lower in the BSS group than in the NBSS group in the acute phase of CHD (P<0.01). The R and K values in thromboelastography and tissue plasminogen activator (t-PA) and t-PA/PAI-1 were lower in the BSS group than in the NBSS group (all P<0.01). No difference was found in the results of platelet count, plateletcrit, maximum amplitude, von Willebrand factor, prothrombin time, thrombin time, international normalized ratio, etc. between groups. Conclusions: Increased platelet function, hypercoagulability, and decreased fibrinolytic activity were found among CHD patients with BSS. [ABSTRACT FROM AUTHOR]

Abstract Background Fire needle therapy is a characteristic treatment in traditional Chinese medicine (TCM). An increasing number of studies have indicated that fire needle treatment for psoriasis provides satisfactory results with few side effects and a low recurrence rate. We herein describe the protocol for a multicenter, randomized, single-blind, placebo-controlled trial that will provide high-quality evidence on the efficacy and safety of fire needle therapy for plaque psoriasis. Methods Ninety-two patients with blood stasis syndrome (BSS) of plaque psoriasis will be enrolled and randomly assigned to receive fire needle therapy (intervention group) or fire needle control therapy (control group) once a week for 4 weeks. The Psoriasis Area and Severity Index (PASI) score will serve as the major efficacy index, while the body surface area (BSA), Physician Global Assessment (PGA) score, Dermatology Life Quality Index (DLQI) score, patient-reported quality of life (PRQoL), visual analog scale (VAS) score for itching, TCM symptom score, and relapse rate will be assessed as secondary outcomes. The PASI score, BSA, PGA score, and VAS score for itching will be evaluated at baseline and during the 4-week treatment and follow-up periods. DLQI score, PRQoL, and TCM symptom score will be assessed at baseline and during the treatment period. Recurrence will be evaluated during the follow-up period. Safety assessments include vital sign monitoring, routine blood tests, blood biochemistry, routine urine tests, pregnancy tests, physical examinations, and adverse-event recording. SAS software will be used for data analysis. The data network platform will be designed by the data management center of Nanjing Ningqi Medical Technology Co., Ltd. Discussion It is believed that fire needle therapy can activate the meridians, promote blood circulation, and regulate skin immunity. BSS of plaque psoriasis is related to not only immune dysfunction but also poor or stagnant blood flow. We anticipate that the results of the trial described in this protocol will provide strong evidence for the safety and efficacy of fire needle therapy for BSS of plaque psoriasis. Trial registration Clinicaltrials.gov NCT03953885 . Registered on May 15, 2019. Name: Fire Needle Therapy on Plaque Psoriasis with Blood Stasis Syndrome

Paeonia lactiflora Pall. (PLP) is thought to promote blood circulation and remove blood stasis. This study used blood component analysis, network pharmacology, and molecular docking to predict the mechanism of PLP in the treatment of blood stasis syndrome (BSS). PLP was processed into Paeoniae Radix Alba (PRA) and Paeoniae Radix Rubra (PRR). PRA and PRR could significantly reduce whole blood viscosity (WBV) at 1/s shear rates and could increase the erythrocyte aggregation index (EAI), plasma viscosity (PV), and erythrocyte sedimentation rate (ESR) of rats with acute blood stasis. They prolonged the prothrombin time (PT), and PRR prolonged the activated partial thromboplastin time (APTT). PRA and PRR increased the thrombin time (TT) and decreased the fibrinogen (FBG) content. All the results were significant ( p < 0.05). Ten components of Paeoniflorin, Albiflorin, Paeonin C, and others were identified in the plasma of rats using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A protein-protein interaction network (PPI) analysis showed that AKT1, EGFR, SRC, MAPK14, NOS3, and KDR were key targets of PLP in the treatment of BSS, and the molecular docking results further verified this. This study indicated that PLP improves BSS in multiple ways and that the potential pharmacological mechanisms may be related to angiogenesis, vasoconstriction and relaxation, coagulation, and the migration and proliferation of vascular cells.

Objective: To explore Professor Yang Suqing's experience in treating blood stasis syndrome of psoriasis vulgaris and analyze the characteristics of its prescription; Methods: Outpatient prescriptions for the treatment of psoriasis vulgaris with blood stasis syndrome were selected and extracted traditional Chinese medicine for standardized processing. Then analyze the data by using set visualization analysis and Apriori algorithm. Results: A total of 149 traditional Chinese herbs were extracted. Among them, and the top 12 commonly used herbs with frequency > 30 were Licorice, Saposhnikovia, Schizonepeta tenuifolia, Angelica sinensis, Paeonia lactiflora, Ligusticum chuanxiong, Rehmannia glutinosa, Cicada slough, Oyster and Keel through the set visualization analysis, herbs association rules analysis, and herbs combination analysis. Saposhnikovia, Liquorice, Schizonepeta tenuifolia, Angelica sinensis and Paeonia Alba are the most commonly used combination of herbs by Professor Yang Suqing in the treatment of blood stasis syndrome of psoriasis vulgaris. Conclusion: In addition to invigorating blood circulation and removing blood stasis herbs, which are preferred for the treatment of blood stasis syndromes, Saposhnikovia and Schizonepeta tenuifolia, etc., are used to synergistically exert the functions of invigorating blood circulation and removing blood stasis and eliminating wind expression, with remarkable efficacy. [ABSTRACT FROM AUTHOR]

Background: Blood stasis syndrome (BSS) is considered as the cause of several chronic disease including metabolic diseases in traditional East Asian medicine. In this study, we investigated the levels of serum resistin and other proteins related to metabolic syndrome (MS) and several other diseases categories to identify the association with BSS. Methods: This was a cross-sectional, multicenter study of patients recruited from seven traditional Korean Medicine (TKM) hospitals. To identify whether there was an association with BSS in specific disease conditions, including MS, serum protein levels were evaluated using the multiplex method. Results: A total of 885 patients (419 patients with BSS, 376 patients without BSS, and 90 healthy controls) participated in the study, and 139 patients had MS. The resistin and insulin levels were significantly higher in patients with BSS than in patients without BSS and normal subjects (P = 0.002 and P = 0.046, respectively). Patients with BSS who had MS exhibited significantly higher resistin levels than those in patients without BSS and normal subjects (P = 0.049). In addition, the levels of serum resistin were significantly correlated with symptoms of the BSS, especially dark red gums, dark facial complexion, and nocturnal pain. Conclusions: Despite several limitations, these results demonstrated that resistin levels are potentially associated with the pathogenesis of BSS in MS. Trial registration number: Clinical Research Information Service (CRIS): KCT0000916.

OBJECTIVE: Traditional Chinese medicine (TCM), acupuncture, and massage have irreplaceable effects in the treatment of lumbar disc herniation. Currently, although pairwise comparisons are mostly conducted due to the diversity of treatment measures, there is still a lack of comparing the therapeutic efficacy among various measures. In this study, we conducted a Bayesian network Meta-analysis to evaluate the therapeutic efficacy of TCM therapies in patients with lumbar disc herniation of blood stasis type as well as pain relief after treatment. METHODS: CNKI, VIP, WanFang, PubMed, and the Cochrane Library were searched for randomized controlled trials regarding TCM treatment of blood stasis type lumbar disc herniation. The retrieval date was from inception until February 2020. Two researchers independently selected literature, extracted data and evaluated quality and risk deviation according to the set criteria. Stata 14.2 was used to draw a network structure chart, prediction interval chart and comparison-correction funnel chart of publication bias. Ge MTC version 0.14.3 was used to carry out a network Meta-analysis. RESULTS: In total, 28 randomized controlled trials were included in this study, with a total of 2 508 patients with lumbar disc herniation. These trials involved 11 treatment measures, including TCM, acupuncture, moxibustion, massage, western medicine, acupuncture and moxibustion, TCM + moxibustion, massage + moxibustion, TCM + acupuncture, acupuncture + massage, acupuncture + massage + TCM. According to the results of Cochrane’s biased risk tool evaluation, 21 of the 28 articles included were evaluated as high risk, and 7 articles were evaluated as unclear. The results of network meta-analysis showed that: in terms of efficiency, other treatment measures are superior to western medicine, moxibustion, acupuncture, TCM + moxibustion, massage + moxibustion, TCM + acupuncture, acupuncture + massage, acupuncture + massage + TCM are superior to traditional Chinese medicine, moxibustion, acupuncture, massage + moxibustion, TCM + acupuncture are superior to acupuncture, and massage + moxibustion is superior to massage. In terms of Visual Analogue Scale score, other treatments are better than western medicine, TCM + moxibustion, massage + moxibustion, TCM + acupuncture, acupuncture + massage + TCM are better than TCM. Efficiency in descending order is as follows: massage + moxibustion > TCM + moxibustion > acupuncture > acupuncture + massage + TCM > TCM + acupuncture > moxibustion > acupuncture + massage > massage > acupuncture > TCM > western medicine. The score of Visual Analogue Scale from the best to the worst is as follows: massage + moxibustion > acupuncture + massage + TCM > TCM + moxibustion > TCM + acupuncture > acupuncture > acupuncture + massage > moxibustion > massage > acupuncture > TCM > western medicine. CONCLUSION: Existing evidence indicates massage + moxibustion is superior to the other 10 kinds of interventions; therefore, the combination therapy is mostly superior to the single therapy. Exact results should certainly be confirmed by a large amount of randomized controlled trials. [ABSTRACT FROM AUTHOR]

Blood stasis syndrome (BSS) is the pathological basis of many cardiovascular diseases. Ginger is often used as herbal medicine, condiment, and health food in China and Southeast Asia to improve some symptoms of cardiovascular disease, but its mechanism of efficacy and metabolic processes is not clear enough. In this study, a rat model of BSS was successfully established and treated with different doses of dried ginger extract. After the end of the administration period, the blood and urine of 5 groups of rats were collected for metabonomic analysis. Multivariate statistical analysis was used to explore metabolites and metabolic pathways, and the correlation between metabolites and pharmacodynamic indicators was further explored. The experimental results show that the pharmacodynamic indicators of dried ginger group (DG) extracts of different doses have different degrees of changes than model group (MG), and the high dose of dried ginger group (GJH) changes is the most significant (p <.05 or p <.01). Besides, 22 different metabolites were identified in the experiment. These metabolites mainly involve seven metabolism pathways in different impact value. DG has therapeutic effects on BSS rats by regulating multiple metabolic pathways. This study provides an effective method for understanding the metabolic mechanism of DG extracts on BSS. [ABSTRACT FROM AUTHOR]

The drug preparations from dried flower of Carthamus tinctorius L. (CTL) are widely used as an adjuvant medication in cardiovascular diseases in China. In this research, Safflower yellow extract (SYE), a CTL drug in market, was studied through components analysis and two animal experiments with different dosages to assess its pharmacodynamic effects. The whole constituents of SYE were characterized through ultra-fast liquid chromatography–diode array detector–quadrupole time-of-flight tandem mass spectrometry. Cerebral arteriole thrombus was induced in C57BL/6J mouse by laser irradiation in vivo using two-photon laser-scanning microscopy. The time of thrombus formation and vessel diameter were calculated to evaluate the antithrombotic effect. In the model of blood stasis syndrome, rats were injected with adrenaline injection before and after ice-bath to induce hemorheology disorders. The results identified 29 constituents in SYE and hydroxysafflor yellow A was the main component (19.8%). In the mouse model, SYE inhibited thrombus formation in a dose-dependent manner and postponed the occlusion time in brain arteriole at dosages of 26.0 and 52.0 mg/kg. In the rat model of blood stasis syndrome, SYE significantly decreased the whole blood viscosity, suppressed red blood cell aggregation and platelet aggregation in high-dose (p < 0.01). The activated partial thromboplast in time was prolonged at a dosage of 7.0 mg/kg (p < 0.05) as well. In conclusion, SYE administration could inhibit the thrombus formation and beneficially influence the blood rheologyin blood stasis syndromes at relevant low dosages.

Objective: To investigate the pathological features of blood stasis syndrome (BSS) in non-diabetic peripheral neuropathy. Methods: Clinical data of 31 patients with non-diabetic peripheral neuropathy who had undergone nerve biopsy during December 2004 and December 2010 in Xuanwu Hospital Capital Medical University were retrospectively analyzed. According to Chinese medicine (CM) syndrome differentiation and signs, 26 patients were blood stasis type and 5 patients were non-blood stasis type. Clinical and pathological data were compared in detail. Results: Clinically, although both groups shared similar symptoms of limb numbness, weakness and sensory disturbances, the prevalence of neuralgia was much grievous in BSS group (73.1%, 26/31) compared with the non-BSS group (0%, 0/5). As for signs, dermal nutrients disturbance (84.6%, 22/26), dark or purple tongue (100.0%, 26/26), and sublingual varices (80.7%, 21/26) were more common in the BSS group than the non-BSS group (0%, 60%, 20%, respectively). The prevalence of qi deficiency cases (19/26) in the BSS group was significantly higher compared with the non-BSS group (1/5). The unique histological manifestations of BSS were axonal degeneration (16/26 vs 2/5 in non-BSS group), which was the hallmark of ischemia. Cases with BSS had prominent microangiopathy (61.5%, 16/26), manifested as epineurium vasculitis (inflammatory cell infiltrated to the vessel wall, obliteration and recanalization, vascular proliferation, extravascular hemosiderin deposition), angiotelectasis, proliferation and hyaline degeneration of endoneurium capillary. In the BSS group, impaired blood-nerve barrier was indicated by sub-perineurial edema (46.2%, 11/26) and endoneurial edema (15.4%, 4/26). The Renaut body (15.4%, 4/26) and amyloid deposition (3.8%, 1/26) found in the BSS group were absent in the non-BSS group. Conclusions: BBS was common in non-diabetic peripheral neuropathies. The nerves exhibited ischemic alteration of primary axon degeneration and secondary demyelination. The interstitial tissue revealed microcirculation impairment, blood-nerve barrier disturbance, amyloid deposition and proliferation changes. The high prevalence of qi deficiency also highlights the therapy of promotion of blood circulation and removal of blood stasis. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect and safety of Hydroxysafflor Yellow A for Injection (HSYAI) in treating patients with acute ischemic stroke (AIS) and blood stasis syndrome (BSS). Methods: A multicenter, randomized, double-blind, multiple-dose, active-controlled phase II trial was conducted at 9 centers in China from July 2013 to September 2015. Patients with moderate or severe AIS and BSS were randomly assigned to low-, medium-, high-dose HSYAI groups (25, 50 and 70 mg/d HSYAI by intravenous infusion, respectively), and a control group (Dengzhan Xixin Injection (灯盏细辛注射液, DZXXI) 30 mL/d by intravenous infusion), for 14 consecutive days. The primary outcome was the Modified Rankin Scale (mRS) score ⩽1 at days 90 after treatment. The secondary outcomes included the National Institute of Health Stroke Scale (NIHSS) score ⩽1, Barthel Index (BI) score ⩾95, and BSS score reduced ⩾30% from baseline at days 14, 30, 60, and 90 after treatment. The safety outcomes included any adverse events during 90 days after treatment. Results: Of the 266 patients included in the effectiveness analysis, 66, 67, 65 and 68 cases were in the low-, medium-, and high-dose HSYAI and control groups, respectively. The proportions of patients in the medium- and high-dose HSYAI groups with mRS score ⩽1 at days 90 after treatment were significantly larger than the control group (P<0.05). The incidences of favorable outcomes of NIHSS and BI at days 90 after treatment as well as satisfactory improvement of BSS at days 30 and 60 after treatment in the medium- and high-dose HSYAI groups were all significantly higher than the control group (P<0.05). No significant difference was reported among the 4 groups in any specific adverse events (P>0.05). Conclusions: HSYAI was safe and well-tolerated at all doses for treating AIS patients with BSS. The medium (50 mg/d) or high dose (75 mg/d) might be the optimal dose for a phase III trial. (Registration No. ChiCTR-2000029608) [ABSTRACT FROM AUTHOR]

Blood stasis syndrome (BSS) is characterized by blood retardation and is the major cause of some deadly diseases. Some factors that affect BSS have been identified. However, the small molecule that related to BSS is still largely unknown. Traditional Chinese Medicine (TCM), such as Sanleng and Ezhu, has been used for a long time in treating BSS and promising outcomes have been achieved. However, the mechanism of how they work is unclear. Thus, we constructed the Rat BSS model and treated them with Sanleng and Ezhu. Then, the liver dialysis of those rats was collected and the small molecule metabolites were analyzed by GC-MS based metabolomics approach. Our results showed after Sanleng and Ezhu treatment, several small molecule metabolites were significantly changed metabolites (VIP>1 and P<0.05). Pathway enrichment analysis also showed that Sanleng and Ezhu share the similar mechanism in treating BSS, such as regulating Glyoxylate and dicarboxylate metabolism pathway and energy metabolism. Besides, we also identified some key metabolites that were significantly correlated with BSS. In conclusion, those findings uncover the mechanism of Sanleng and Ezhu in treating BSS. [ABSTRACT FROM AUTHOR]

Abstract Background Blood stasis syndrome (BSS) is a general pattern identification and refers to pathological stagnation of blood circulation, dysfunction of endothelial cells or metabolic disorder in traditional Korean medicine (TKM). Dohongsamul-Tang (DHSMT) is a well-known traditional herbal formula which used for treatment and prevention of BSS by promoting blood circulation in TKM. Methods Cytotoxicity of DHSMT was examined by cell counting kit-8 (CCK-8). We also investigated the anti-adipogenesis effect of DHSMT by using Oil Red O staining, intracellular triglyceride assay leptin ELISA and western blot analysis in 3T3-L1 adipocytes. In addition, the accumulation of adiponectin, resistin and plasminogen activator inhibitor-1 (PAI-1) were measured by magnetic bead panel kit. Results Oil Red O staining showed that DHSMT markedly reduced fat accumulation without affecting cell cytotoxicity. DHSMT also significantly decreased accumulation of triglyceride and adipokines such as leptin, adiponectin, resistin and PAI-1 compared with fully differentiated adipocytes. Furthermore, our results found that DHSMT significantly suppressed the adipocyte differentiation by downregulating adipogenic-specific transcriptional factors such as peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding proteins alpha (C/EBPα) and fatty acid binding protein 4 (FABP4) in adipocytes. Conclusions Taken together, our findings provide that DHSMT has potential for treatment and prevention of obesity or MS related to BSS.

BackgroundCoronary heart disease (CHD) remains highly prevalent and is one of the largest causes of death worldwide. Blood stasis syndrome (BSS) is the main syndrome associated with CHD. However, the underlying biological basis of BSS with CHD is not yet been fully understood.Materials and MethodsWe proposed a metabolomics method based on 1H-NMR and random forest (RF) models to elucidate the underlying biological basis of BSS with CHD. Firstly, 58 cases of CHD patients, including 27 BSS and 31 phlegm syndrome (PS), and 26 volunteers were recruited from Xiangya Hospital affiliated to Central South University. A 1 mL venous blood sample was collected for NMR analysis. Secondly, principal component analysis (PCA), partial least squares discrimination analysis (PLS-DA) and RF was applied to observe the classification of each group, respectively. Finally, RF and multidimensional scaling (MDS) were utilized to discover the plasma potential biomarkers in CHD patients and CHD–BSS patients.ResultsThe models constructed by RF could visually discriminate BSS from PS in CHD patients. Simultaneously, we obtained 12 characteristic metabolites, including lysine, glutamine, taurine, tyrosine, phenylalanine, histidine, lipid, citrate, choline, lactate, α-glucose, β-glucose related to the CHD patients, and Choline, β-glucose, α-glucose and tyrosine were considered as potential biomarkers of CHD–BSS.ConclusionThe combining of 1H-NMR profiling with RF models was a useful approach to analyze complex metabolomics data (should be deleted). Choline, β-glucose, α-glucose and tyrosine were considered as potential biomarkers of CHD–BSS.

Objective: Stable angina pectoris (SAP) in patients with coronary heart disease (CHD) and blood stasis syndrome (BSS) is a potentially serious threat to public health. NF-κB signaling is associated with angina pectoris. 1-Deoxynojirimycin (DNJ), which is a unique polyhydroxy alkaloid, is the main active component in mulberry (Morus indica L.) leaves and may exhibit protective properties in the prevention of SAP in patients with CHD by affecting the NF-κB pathway.Methods: DNJ was purified from mulberry leaves by using a pretreated cation exchange chromatography column. A total of 144 SAP patients were randomly and evenly divided into experimental (DNJ treatment) and control (conventional treatment) groups. Echocardiography and ascending aortic elasticity were evaluated. The changes in inflammatory, oxidative, and antioxidant factors, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and malondialdehyde (MDA), were measured before and after a 4-week treatment. Self-Rating Anxiety Scale (SAS) and Hamilton Depression Scale (HAMD) scores were compared between the two groups. The improvement in SAP score, associated symptoms, and BSS was also investigated. The levels of IkB kinase (IKK), nuclear factor-kappa B (NF-κB), and inhibitor of kappa B α (IkBα) were measured by Western blot.Results: After the 4-week treatment, DNJ increased left ventricular ejection fraction and reduced left ventricular mass index, aortic distensibility, and atherosclerosis index (p < 0.05). DNJ intervention increased angina-free walking distance (p < 0.05). DNJ significantly reduced the levels of hs-CRP, IL-6, TNF-a, MDA, SAS, HAMD, AP, and BSS scores and increased SOD level (p < 0.05). The total effective rate was significantly increased (p < 0.05). The symptoms of angina attack frequency, nitroglycerin use, chest pain and tightness, shortness of breath, and emotional upset were also improved. DNJ reduced IKK and NF-κB levels and increased IkBα level (p < 0.05).Conclusion: The DNJ in mulberry leaves improved the SAP of patients with CHD and BSS by increasing their antioxidant and anti-inflammatory capacities.

Objectives: Blood stasis is the slowing or stagnation of blood and can cause metabolic, musculoskeletal, and gynecological diseases. This study developed the Blood Stasis Questionnaire for gynecological disease (BSQ-GD) by extracting clinical indicators related to gynecological diseases using the Blood Stasis Questionnaires I and II (BSQ-I and II, respectively) and analyzed the clinical data of a cross-sectional study., Patients and Methods: In total, 103 women aged between 25 and 65 years who met gynecological disease criteria were enrolled in this study. Blood stasis scores (BSS) were evaluated using the BSQ-II and categorized into BSS and non-BSS groups. To assess the reliability of BSQ-GD, the internal consistency coefficient was employed using Cronbach's α. Furthermore, correlation analyses were conducted for the clinical symptoms related to gynecological diseases, and the discriminant validity was confirmed by comparing the two groups. The prediction accuracy was determined using logistic regression and the cut-off value of the BSQ-GD was established via the sensitivity and specificity calculations., Results: The BSQ-GD showed satisfactory internal consistency (Cronbach's α coefficient = 0.71) and validity, with significant differences in mean scores between blood stasis (22.30 ± 3.34) and non-blood stasis (14.93 ± 3.49) groups. The cut-off value of the BSQ-GD score was 19 points when the Youden index (73.45) and the concordance probability (0.75) were at their maximum. The area under the receiver operating characteristic curve was approximately 96%, and the sensitivity and specificity of the diagnostic accuracy according to the cut-off value are 80.95% and 92.50%, respectively., Conclusion: The BSQ-GD can be an appropriate instrument to estimate blood stasis in patients with gynecological diseases; its diagnostic sensitivity according to the cut-off value is high., (© 2024 S. Karger AG, Basel.)

This article analyzed the mechanism of Danggui Sini Decoction(DSD) in improving kidney injury caused by blood stasis syndrome(BSS) in rats. Firstly, 32 female SD rats were randomly divided into the following four groups: a normal group and a BSS group, both receiving an equal amount of distilled water by gavage; a normal+DSD group and a BSS+DSD group, both receiving 5.103 g·kg~(-1) DSD orally for a total of 14 days. Daily cold water bath was given to establish the BSS model, and on the 14th day, BSS rats were subcutaneously injected with 0.8 mg·kg~(-1) adrenaline. Normal rats were subjected to the water bath at 37 ℃ and injected with an equal volume of distilled water. After the experiment, 24-hour urine, serum, and kidney samples were collected for metabolomic analysis, biochemical measurements, and hematoxylin-eosin(HE) staining. The study then employed ~1H-NMR metabolomic technology to reveal the metabolic network regulated by DSD in improving BSS-induced kidney injury and used network pharmacology to preliminarily elucidate the key targets of the effectiveness of DSD. Pathological and biochemical analysis showed that DSD intervention significantly reduced inflammation and abnormal levels of blood creatinine, blood urea nitrogen, and urine protein in the kidneys. Metabolomic analysis indicated that DSD attenuated BSS-induced kidney injury primarily by regulating 10 differential metabolites and three major metabolic pathways(taurine and hypotaurine metabolism, citrate cycle, and acetaldehyde and dicarboxylic acid metabolism). Network pharmacology analysis suggested that the protective effect of DSD against BSS-induced kidney injury might be related to two key genes, ATP citrate lyase(ACLY) and nitric oxide synthase 2(NOS2), and two main metabolic pathways, i.e., arginine biosynthesis, and arginine and proline metabolism. This study, from the perspective of network regulation, provides initial insights and evidence into the mechanism of DSD in improving kidney injury induced by BSS, offering a basis for further investigation into the molecular mechanisms underlying its efficacy.

The approach combining disease, syndrome, and symptom was employed to investigate the characteristic changes of blood stasis syndrome in a rat model of steroid-induced osteonecrosis of the femoral head(SONFH) during disease onset and progression. Seventy-two male SD rats were randomized into a healthy control group and a model group. The rat model of SONFH was established by injection of lipopolysaccharide(LPS) in the tail vein at a dose of 20 μg·kg~(-1)·d~(-1) on days 1 and 2 and gluteal intramuscular injection of methylprednisolone sodium succinate(MPS) at a dose of 40 mg·kg~(-1)·d~(-1) on days 3-5, while the healthy control group received an equal volume of saline. The mechanical pain test, tongue color RGB technique, gait detection, open field test, and inclined plane test were employed to assess hip pain, tongue color, limping, joint activity, and lower limb strength, respectively, at different time points within 21 weeks of modeling. At weeks 2, 4, 8, 12, 16, and 21 after modeling, histopathological changes of the femoral head were observed by hematoxylin-eosin(HE) staining and micro-CT scanning; four coagulation items were measured by rotational thromboelastometry; and enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of six blood lipids, vascular endothelial growth factor(VEGF), endothelin-1(ET-1), nitric oxide(NO), tissue-type plasminogen activator(t-PA), plasminogen activator inhibitor factor-1(PAI-1), bone gla protein(BGP), alkaline phosphatase(ALP), receptor activator of nuclear factor-κB(RANKL), osteoprotegerin(OPG), and tartrate-resistant acid phosphatase 5b(TRAP5b) in the serum, as well as the levels of 6-keto-prostaglandin 1α(6-keto-PGF1α) and thromboxane B2(TXB2) in the plasma. The results demonstrated that the pathological alterations in the SONFH rats were severer over time. The bone trabecular area ratio, adipocyte number, empty lacuna rate, bone mineral density(BMD), bone volume/tissue volume(BV/TV), trabecular thickness(Tb.Th), trabecular number(Tb.N), bone surface area/bone volume(BS/BV), and trabecular separation(Tb.Sp) all significantly increased or decreased over the modeling time after week 4. Compared with the healthy control group, the mechanical pain threshold, gait swing speed, stride, standing time, and walking cycle of SONFH rats changed significantly within 21 weeks after modeling, with the greatest difference observed 12 weeks after modeling. The time spent in the central zone, rearing score, and maximum tilt angle in the open field test of SONFH rats also changed significantly over the modeling time. Compared with the healthy control group, the R, G, and B values of the tongue color of the model rats decreased significantly, with the greatest difference observed 11 weeks after modeling. The levels of total cholesterol(TC), total triglycerides(TG), low-density lipoprotein-cholesterol(LDL-C), and apoprotein B(ApoB) in the SONFH rats changed significantly 4 and 8 weeks after modeling. The levels of VEGF, ET-1, NO, t-PA, PAI-1, 6-keto-PGF1α, TXB2, four coagulation items, and TXB2/6-keto-PGF1α ratio in the serum of SONFH rats changed significantly 4-16 weeks after modeling, with the greatest differences observed 12 weeks after modeling. The levels of BGP, TRAP5b, RANKL, OPG, and RANKL/OPG ratio in the serum of SONFH rats changed significantly 8-21 weeks after modeling. During the entire onset and progression of SONFH in rats, the blood stasis syndrome characteristics such as hyperalgesia, tongue color darkening, gait abnormalities, platelet, vascular, and coagulation dysfunctions were observed, which gradually worsened and then gradually alleviated in the disease course(2-21 weeks), with the most notable differences occurred around 12 weeks after modeling.

Background: Coronary heart disease (CHD) remains highly prevalent and is one of the largest causes of death worldwide. Blood stasis syndrome (BSS) is the main syndrome associated with CHD. However, the underlying biological basis of BSS with CHD is not yet been fully understood. Materials and Methods: We proposed a metabolomics method based on 1H-NMR and random forest (RF) models to elucidate the underlying biological basis of BSS with CHD. Firstly, 58 cases of CHD patients, including 27 BSS and 31 phlegm syndrome (PS), and 26 volunteers were recruited from Xiangya Hospital affiliated to Central South University. A 1 mL venous blood sample was collected for NMR analysis. Secondly, principal component analysis (PCA), partial least squares discrimination analysis (PLS-DA) and RF was applied to observe the classification of each group, respectively. Finally, RF and multidimensional scaling (MDS) were utilized to discover the plasma potential biomarkers in CHD patients and CHD–BSS patients. Results: The models constructed by RF could visually discriminate BSS from PS in CHD patients. Simultaneously, we obtained 12 characteristic metabolites, including lysine, glutamine, taurine, tyrosine, phenylalanine, histidine, lipid, citrate, choline, lactate, α-glucose, β-glucose related to the CHD patients, and Choline, β-glucose, α-glucose and tyrosine were considered as potential biomarkers of CHD–BSS. Conclusion: The combining of 1H-NMR profiling with RF models was a useful approach to analyze complex metabolomics data (should be deleted). Choline, β-glucose, α-glucose and tyrosine were considered as potential biomarkers of CHD–BSS. [ABSTRACT FROM AUTHOR]

Xuefu Zhuyu Tang (XFZY), a famous formula in traditional Chinese medicine, has been demonstrated to show good therapeutic effects on diseases caused by blood stasis syndrome. Two of its eleven herbs, Radix Platycodonis and Radix Cyathulae, have been considered as Shi ingredients in the hierarchy of traditional formula compatibility and proven possessing synergistic properties that strengthen the formula's potency of activating blood circulation and resolving blood stagnation. However, its mechanism is still not clearly elucidated. In our previous study, we observed their effects on paeoniflorin pharmacokinetics of XFZY in rats. In this study, we continued by detecting and comparing their effect on the tissue distribution of paeoniflorin after oral administration of XFZY and its three variants (XFZY without Radix Platycodonis or/and Radix Cyathulae) in blood-stasis mice via HPLC assay. The results indicated that combining usage of Radix Platycodonis and Radix Cyathula increased the distribution of paeoniflorin in the lung and kidney and introduced the paeoniflorin into the liver, spleen and heart. It might explain their synergistic properties that strengthen the formula's effect of invigorating blood and dissolving stasis and provide experimental evidence to understand the pharmacological effects of Shi herbs in the hierarchy of traditional formula compatibility. [ABSTRACT FROM AUTHOR]

Objective: Stable angina pectoris (SAP) in patients with coronary heart disease (CHD) and blood stasis syndrome (BSS) is a potentially serious threat to public health. NF-κB signaling is associated with angina pectoris. 1-Deoxynojirimycin (DNJ), which is a unique polyhydroxy alkaloid, is the main active component in mulberry (Morus indica L.) leaves and may exhibit protective properties in the prevention of SAP in patients with CHD by affecting the NF-κB pathway. Methods: DNJ was purified from mulberry leaves by using a pretreated cation exchange chromatography column. A total of 144 SAP patients were randomly and evenly divided into experimental (DNJ treatment) and control (conventional treatment) groups. Echocardiography and ascending aortic elasticity were evaluated. The changes in inflammatory, oxidative, and antioxidant factors, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and malondialdehyde (MDA), were measured before and after a 4-week treatment. Self-Rating Anxiety Scale (SAS) and Hamilton Depression Scale (HAMD) scores were compared between the two groups. The improvement in SAP score, associated symptoms, and BSS was also investigated. The levels of IkB kinase (IKK), nuclear factor-kappa B (NF-κB), and inhibitor of kappa B α (IkBα) were measured by Western blot. Results: After the 4-week treatment, DNJ increased left ventricular ejection fraction and reduced left ventricular mass index, aortic distensibility, and atherosclerosis index (p < 0.05). DNJ intervention increased angina-free walking distance (p < 0.05). DNJ significantly reduced the levels of hs-CRP, IL-6, TNF-a, MDA, SAS, HAMD, AP, and BSS scores and increased SOD level (p < 0.05). The total effective rate was significantly increased (p < 0.05). The symptoms of angina attack frequency, nitroglycerin use, chest pain and tightness, shortness of breath, and emotional upset were also improved. DNJ reduced IKK and NF-κB levels and increased IkBα level (p < 0.05). Conclusion: The DNJ in mulberry leaves improved the SAP of patients with CHD and BSS by increasing their antioxidant and anti-inflammatory capacities. [ABSTRACT FROM AUTHOR]

Abstract Danggui-Sini Decoction (DSD) is one of the most widely used traditional Chinese medicine formulae (TCMF) for treating various diseases caused by cold coagulation and blood stasis due to its effect of nourishing blood to warm meridians in clinical use. However, studies of the mechanism of how it dispels blood stasis and its compatible regularity are challenging because of the complex pathophysiology of blood stasis syndrome (BSS) and the complexity of DSD, with multiple active ingredients acting on different targets. Observing variations of endogenous metabolites in rats with BSS after administering DSD may further our understanding of the mechanism of BSS and the compatible regularity of DSD. In this study, to understand the pathogenesis of BSS and assess the compatibility effects of DSD, an ultra-performance liquid chromatography quadrupole-time of flight mass spectrometry-based untargeted metabolomics approach was used. Serum metabolic profiles in rats with BSS that was induced by an ice water bath associated with subcutaneous injection of epinephrine hydrochloride were compared with the intervention groups which were administered with DSD or its compatibility. Using pattern recognition analysis, a clear separation between the BSS model and control group was observed; DSD and its compatibility intervention groups were clustered closer toward the control than the model group, which corroborates results of hemorheology studies. In addition, 20 metabolites were considered as potential biomarkers associated with the development of BSS. Nine metabolites were regulated by DSD in intervening blood stasis, they were considered to be correlated with the effect of nourishing blood to warm meridians. Additionally, the results suggested that the intervention effect of DSD on BSS may involve regulating four pathways, namely, arachidonic acid metabolism, glycerophospholipid metabolism, bile acid biosynthesis, and pyruvate metabolism. Moreover, each functional unit (monarch, minister, and assistant) in DSD regulates different metabolites and metabolic pathways to achieve different effects on dispelling blood stasis; however, their intervention efficacies are inferior to the holistic formula, which may be due to the synergism of the bioactive ingredients in seven herbs of DSD. This study demonstrated that metabolomics is a powerful tool for evaluating the efficacy and compatibility effects of traditional Chinese medicine (TCM). Graphical abstract Unlabelled Image Highlights • The efficacy of Danggui-Sini Decoction (DSD) and its compatibility groups on rats with blood stasis syndrome (BSS) were characterized by a metabolomics approach. • DSD and its compatibility groups significantly regulated the disorder indexes of hemorheology. • Twenty metabolites were considered as potential biomarkers concerning BSS, with arachidonic acid and glycerophospholipid metabolism being mainly involved. • The efficacy of DSD was better, maybe attribute to the synergism of bioactive ingredients in the seven herbs of DSD. [ABSTRACT FROM AUTHOR]

Objective: To investigate the innate characters of 3 endometriosis (EMT) syndromes, blood stasis (BS), qi stagnation and blood stasis (QSBS) as well as Shen (Kidney) deficiency and blood stasis (KDBS) in terms of proteomics, lay a molecular biological basis for the differentiation of various blood stasis syndromes of EMT, establish a EMT microscopic syndrome differentiation and diagnosis system in terms of proteomics, discover the evolution principles and therapeutic targets of these EMT syndromes, and search their signifificant molecular markers and genetic intervention targets.Methods: Six specimens from the ectopic and entopic endometrium tissues of patients with EMT in each syndrome, BS, QSBS as well as KDBS, in the early proliferative phase of the menstrual cycle, and 6 specimens from normal endometrium tissues in the early proliferative phase of the menstrual cycle were obtained. Three groups were formed in each syndrome by mixing two random specimens in equal amount, and then their respective two-dimensional electrophoresis graphs were obtained after total protein extraction. Finally, the detected differences in protein expression were identifified through matrix-assisted laser desorption Ionization-time of flflight mass spectrometry (MALDI-TOF/MS) and protein database.Results: The results of differential proteins expressed in each syndrome were shown as follows: BS syndrome had 2 differential proteins in entopic endometrium and 1 differential protein in ectopic endometrium; KDBS syndrome had 3 in entopic endometrium and 3 in ectopic endometrium; and QSBS syndrome had 3 in entopic endometrium and 4 in ectopic endometrium. It was found out that annexin was highly expressed in both entopic and ectopic endometrium of KDBS syndrome; and myosin light chain 3 was highly expressed in both entopic and ectopic endometrium of QSBS syndrome.Conclusion: There are differential protein expressions among the 3 EMT syndromes, which might be the inner origin of syndrome characters, and these differential proteins might be the candidate biomarkers for the pathogenesis of various EMT syndromes. [ABSTRACT FROM AUTHOR]

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Objective To observe and evaluate the regulating effect of Xuefuzhuyu capsule combined with clopidogrel on clopidogrel resistance. Methods After PCI operation, 80 patients with clopidogrel resistance were randomly divided into three different treatments, A :clopidogrel (Tai Jia) combined with Xuefuzhuyu capsule; B :clopidogrel (Plavix ); C :clopidogrel (Tai Jia) combined with cilostazol.) After three months of continuous medication . and the inhibition rate of platelet aggregation was detected by thromboekrstogram (TEG). The patients were followed up for half a year to observe the incidence of adverse events. Results After three months of treatment, the inhibition rates of the three groups were improved (P<0.05). The effective rate of platelet inhibition in group A was 40% (10/25 ), which was higher to group C (33.33%), and which was equivalent to group B (40.74%). The effect of platelet agg rogation inhibition was better in patients who were not sensitive to aspirin and clopidogrel and then with imported Plavix . And the treatment group of clopidogrel combined with Xuefuzhuyu capsule had a synergistic effect on platelet aggregation inhibition for clopidogrel insensitive patients. After six months' followup, it was found that the platelet inhibition was enhanced but the bleeding risk and abnormal coagulation function was not increased after prolonged using of Xuefuzhuyu capsule. Conclusion Xuefuzhuyu capsule had a certain effect on improving the inhibition rate of platelet aggregation, which had little effect on the risk of bleeding. [ABSTRACT FROM AUTHOR]

Objective: To investigate the important diagnostic indicators for blood stasis syndrome (BSS) in patients of childbearing age with gynaecological diseases.Methods: A partial least squared-discriminant analysis (PLS-DA) were applied to BSS symptoms data of patients with gynaecological diseases, and the diagnostic indicators used by doctors of Korean medicine (DKMs) among BSS patients with gynaecological diseases were also investigated.Results: A total of 103 patients of childbearing age with gynaecological diseases and 40 healthy controls were enrolled. Among the 103 patients, 63 (61.7%) and 40 (38.8%) were diagnosed with BSS and non-BSS, respectively, and BSS patients exhibited a more severe extent of disease. A score plot of PLS-DA showed clearly different patterns among the 3 groups. Based on the variable importance on projection of PLS-DA model, menstrual pains, dark lumps in the menstrual blood, ileocoecal tenderness and resistance, sharp pains, and sublingual varicosities were selected as the top five most important indicators. Moreover, more than 75% of DKMs chose dark lumps in menstrual blood, menstrual pain, and dark menstrual blood as the diagnostic indicators of BSS in patients with gynaecological diseases, and more than 49% of them also considered sharp pains, dark red tongue, sublingual varicosities, and tendency to bruise easily as diagnostic indicators of BSS.Conclusion: DKMs focused on menstrual symptoms and certain gynaecological symptoms to diagnose BSS patients of childbearing age with female diseases. [ABSTRACT FROM AUTHOR]

Blood stasis syndrome (BSS) is one of the most common Chinese medicine patterns in coronary heart disease. Our previous work proved that Xueshuan Xinmaining Tablet (XXT) could treat blood stasis through regulating the expression of F13a1, Car1 and Tbxa2r. In the current study, the effect and mechanism of XXT on BSS was comprehensively and holistically investigated based on a metabolomics approach. Urine and plasma samples of 10 BBS rats treated with XXT (XT), 9 BSS model rats (BM) and 11 normal control (NC) rats were collected and then determined by UPLC-Q/TOP-MS. Multivariate analyses were applied to distinguish differentiate urinary and plasma metabolite patterns between three groups. Results showed that a clear separation of three groups was achieved. XT group was located between BM group and NC group, and showing a tendency of recovering to NC group, which was consistent with the results of hemorheological studies. Some significantly changed metabolites like cortexolone, 3α,21-dihydroxy-5β-pregnane-11,20-dione and 19S-hete and leukotriene A4, chiefly involved in steroid hormone biosynthesis, arachidonic acid metabolism and lipid metabolism, were found and identified to explain the mechanism. These potential markers and their corresponding pathways will help explain the mechanism of BSS and XXT treatment. This work also proves that metabolomics is effective in traditional Chinese medicinal research. [ABSTRACT FROM AUTHOR]

The drug preparations from dried flower of Carthamus tinctorius L. (CTL) are widely used as an adjuvant medication in cardiovascular diseases in China. In this research, Safflower yellow extract (SYE), a CTL drug in market, was studied through components analysis and two animal experiments with different dosages to assess its pharmacodynamic effects. The whole constituents of SYE were characterized through ultra-fast liquid chromatography-diode array detector-quadrupole time-of-flight tandem mass spectrometry. Cerebral arteriole thrombus was induced in C57BL/6J mouse by laser irradiation in vivo using two-photon laser-scanning microscopy. The time of thrombus formation and vessel diameter were calculated to evaluate the antithrombotic effect. In the model of blood stasis syndrome, rats were injected with adrenaline injection before and after ice-bath to induce hemorheology disorders. The results identified 29 constituents in SYE and hydroxysafflor yellow A was the main component (19.8%). In the mouse model, SYE inhibited thrombus formation in a dose-dependent manner and postponed the occlusion time in brain arteriole at dosages of 26.0 and 52.0 mg/kg. In the rat model of blood stasis syndrome, SYE significantly decreased the whole blood viscosity, suppressed red blood cell aggregation and platelet aggregation in high-dose (p < 0.01). The activated partial thromboplast in time was prolonged at a dosage of 7.0 mg/kg (p < 0.05) as well. In conclusion, SYE administration could inhibit the thrombus formation and beneficially influence the blood rheologyin blood stasis syndromes at relevant low dosages. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic indicators and herbal treatments for blood stasis syndrome (BSS) patients with traumatic injuries and to identify the association between BSS and traumatic injury in Korea.Methods: Two-hundred and four patients with traumatic injury were recruited from the Gangnam and Daejeon branches of Jaseng Hospital of Oriental Medicine between June 2014 and December 2014. Two independent doctors of Korean medicine (DKMs) determined the diagnosis of BSS or non-BSS based on the subjects signs and symptoms. The scores assigned to BSS symptoms and DKMs' reasons for diagnosing BSS in patients with traumatic injury were investigated. Both medication and herbal prescription records from a 3-month period were collected for all patients diagnosed with BSS by both DKMs.Results: A total of 169 of 204 (82.8%) patients received consistent diagnosis related to BSS by two DKMs. Among them, 54.4% (92 cases) were diagnosed with BSS, and 45.6% (77 cases) were not diagnosed with BSS. DKMs most frequently cited symptoms of recent traumatic injury as justifications for BSS diagnoses, and also selected pain-related indicators such as abdominal pain, sharp pain and nocturnal pain as important reasons in diagnosing BSS. In addition, an inconsistency in the pattern identification theory with respect to traumatic injury was observed. Although only 92 cases (54.4%) of patients were diagnosed with BSS, 77.6% of them were prescribed decoctions for BSS.Conclusions: DKMs considered traumatic injury could cause BSS, and utilized decoction for BSS in patients with traumatic injury without confirming a diagnosis of BSS because they assumed the main symptoms or pathologies of traumatic injury to be closely related to BSS. [ABSTRACT FROM AUTHOR]

ZHENG of traditional Chinese medicine (TCM) theory is the unique way to understand diseases through observing morbid phenomena in the holistic view, and is the basis of diagnosis and treatment for TCM. ZHENG is dynamic in the process of diseases' production, development and transformation. To understand ZHENG's essence systematicly is a possibility by the continuous development of genomics. The therapy thought and method for blood stasis syndrome (BSS), a major classification of ZHENG, is widely used in treatment of cardiovascular diseases in clinic, and reflects the unique advantage of TCM therapy. Ambiguous differentiation of syndrome has long restricted the recognition and treatment of BSS. The latest genomics theory, especially the application of high-throughput gene chip technology make it possible to objectively define and accurately diagnose or cure BSS by screening BSS related key genetic group and establishing differential gene expression profile. This text systematically review the recent literatures on the study of differential gene expression profile of BSS. [ABSTRACT FROM AUTHOR]

Objective: To explore the association of the platelet-activating factor receptor (PAFR) gene rs5938, rs313152 and rs76744145 polymorphisms with coronary heart disease (CHD) and blood stasis syndrome (BSS) of CHD in Chinese Han population. Methods: A total of 570 CHD patients (299 with BSS and 271 with non-BSS) and 317 controls were enrolled. The PAFR gene rs5938, rs313152 and rs76744145 polymorphisms were genotyped using the multiplex SNaPshot technology. The statistical analysis was conducted using a multiple variable logistic regression model. Results: Significant differences were detected in the genotypes frequency distributions of the rs5938 ( P<0.01), but not the rs313152 ( P>0.05), between the controls and CHD patients. Individuals with an rs5938 or rs313152 mutated allele had a low risk for CHD [adjusted odds ratio (aOR)=0.35, 95% confidence interval (CI): 0.23 to 0.56, P<0.01; aOR=0.65, 95% CI: 0.46 to 0.91, P<0.05, respectively]. After the CHD patients were stratified as BSS or non-BSS according to their Chinese medicine patterns, the rs5938 polymorphism mutated alleles had a significant association with a low risk for BSS of CHD (aOR=0.32, 95% CI: 0.18 to 0.57, P<0.01) and non-BSS of CHD (aOR=0.31, 95% CI: 0.17 to 0.55, P<0.01). The rs313152 polymorphism was associated with a low risk for BSS (aOR=0.51, 95% CI: 0.33 to 0.79, P<0.01), but not for non-BSS (aOR=1.22, 95% CI: 0.81 to 1.85, P<0.05). Furthermore, the interaction effect of the rs5938 and rs313152 polymorphisms for BSS of CHD was significantly based on an aOR value associated with the combination of the rs5938 GT genotype with the rs313152 TC genotype of 0.27 (95% CI: 0.1 to 0.7, P<0.01). Conclusion: The PAFR gene rs5938 or rs313152 polymorphisms might be a potential biomarker for susceptibility to CHD, especially to BSS of CHD in Chinese Han population. [ABSTRACT FROM AUTHOR]