Blood Stasis Syndrome Research Articles

DNA Methylation Expression Profile of Blood Heat Syndrome and Blood Stasis Syndrome in TCM Psoriasis.

Objective Traditional Chinese medicine (TCM) emphasizes treatment based on syndrome differentiation. This study aimed to clarify the characteristics of DNA methylation expression profiles in peripheral blood mononuclear cells (PBMCs) in patients with psoriasis and analyze the differences in these profiles among different TCM syndromes of psoriasis in order to provide a material basis for the diversity of these syndromes. Methods Blood samples were collected from 32 participants, including 14 patients with psoriatic blood heat syndrome (BHS), 12 patients with psoriatic blood stasis syndrome (BSS), and 6 healthy controls. PBMCs were extracted and subjected to DNA quality inspection. An Illumina Human Methylation 850k chip was used to sequence each group of samples. According to gene annotation classification together with CpG island annotation classification, the differentially methylated regions between sample groups were screened, while Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were applied to perform functional analyses of DMGs. Finally, the DMGs closely correlating with psoriatic severity were screened using Spearman's correlation analysis. Results Compared with normal controls, patients with psoriasis showed an overall trend of hypermethylation. In psoriasis, the differential methylation probes were mainly distributed on gene body region on the genome, while those in CpG regions were mainly distributed in CpG islands. Compared with healthy controls, the overall trends in methylation were similar in psoriatic BHS and BSS patients compared to healthy controls. However, bioinformatic analysis revealed different functions of DMGs. We also found that the methylation levels of TRIM14 and PRDM16 were closely correlated with PASI scores and could serve as potential biomarkers to assess the severity of psoriasis. Conclusions Our study, for the first time, indicated the possible involvement of DNA methylation in regulating the characteristics of TCM syndromes of psoriasis, providing a new direction for research into TCM psoriatic syndromes.

Integrating pharmacokinetics and network analysis to investigate the mechanism of Moutan Cortex in blood-heat and blood stasis syndrome

BackgroundRaw Moutan Cortex (RMC) has been used in China and other Asian countries for thousands of years. Its medical application is the treatment of cooling blood and promoting blood circulation. However, its therapeutic mechanism is still undefined.MethodsIn this study, the pharmacokinetics strategy that integrated network analysis was employed to explore the mechanism of RMC in blood-heat and blood stasis syndrome (BHS) model rats. Firstly, Ultra-High performance Liquid Chromatography coupled with Diode Array Detector (UHPLC-DAD) method was developed to determine nine absorbed compounds in rat serum in BHS and normal rats after oral administration of RMC extract respectively. Then the pharmacology network was established based on the relationship between nine compounds absorbed into the blood and BHS targets. Finally, the predicted hub targets were validated experimentally in human umbilical vein endothelial cells (HUVECs).ResultsPharmacokinetic study showed that the pharmacokinetic parameters of nine absorbed compounds had significant differences between BHS and normal groups (p < 0.05). Network analysis showed that 8 target genes, namely, F2, F10, F7, PLAU, MAPK14, MAPK10, AKT1, and NOS3 may be the primary targets regulated by RMC for the treatment of BHS. Among them, targets (F2, F10, F7 and MAPK14, MAPK10, AKT) and 4 active ingredients (paeonol, paeoniflorin, quercetin and oxypaeoniflorin) were selected for evaluating the reliability in vitro experiments, which revealed that the mechanism of RMC against BHS syndrome may inhibit inflammatory pathways and regulate coagulation cascades pathway for cooling and promoting blood circulation.ConclusionThe proposed pharmacokinetics study integrated network analysis strategy provides a combination method to explore the therapeutic mechanism of RMC on BHS.Graphical

The Inspiration of Tang Zonghai’s Syndrome of Blood Stasis Treatment Method for the Treatment of Malignant Tumors

Tang Zonghai has its unique treatment idea for treating syndrome of blood stasis. Combined with the relationship between syndrome of blood stasis and tumors, it discusses the ideas and methods of clinical treatment of malignant tumors. Treating syndrome of blood stasis should take dispelling stasis as the first essence. It uses syndrome differentiation to treat syndrome of blood stasis, location differentiation and select drugs and treatments. Comprehensive syndrome differentiation and location differentiation therapy, and flexible applications of activating blood circulation and resolving stasis method are used to treat syndrome of blood stasis. The treatment method has apparent regularity and open-mindedness and is informative. It has its adaptability and practicality in clinical application to treat malignant tumors.

Revealing the mechanism of raw and vinegar-processed Curcuma aromatica Salisb. [Zingiberaceae] regulates primary dysmenorrhea in rats via integrated metabolomics.

Primary dysmenorrhea (PDM) is a common disorder among women around the world. Two processed products of Curcuma aromatica Salisb. [Zingiberaceae] (CAS) are traditional Chinese medicine (TCM) that have long been used to treat gynecological blood stasis syndrome such as primary dysmenorrhea. The mechanisms and active substances of CAS are still largely unknown. The study aimed to establish a rat model of primary dysmenorrhea which investigates the differences between the pharmacodynamics and mechanisms of raw CAS (RCAS) and vinegar-processed CAS (VCAS). Histopathology, cytokinetics, and metabolomics were adopted to evaluate the anti-blood stasis effect of RCAS and VCAS. In metabolomics, endogenous differential metabolites in plasma, urine, and feces are the essential steps to evaluate the effect of RCAS and VCAS. In this study, the rat model of primary dysmenorrhea was successfully established. After RCAS and VCAS intervention, the uterine tissue morphology of dysmenorrhea model rats was improved, and gland hypertrophy and myometrial hyperplasia were reduced as well as neutrophil content. Compared with the RCAS group, the VCAS group had better uterine morphology, few inflammatory factors, and significantly improved amino acid and lipid metabolism. The aforementioned results support the conclusion that VCAS performed better than RCAS in primary dysmenorrhea and that vinegar processing increases the efficacy of CAS.

Experience of He's three-clear method by stages for herpes zoster on the head and face

The clinical experience of He's three-clear method by stages for herpes zoster on the head and face is summarized. The strong-clear method (blood-letting therapy) combined with mild-clear method (acupuncture with filiform needle) are applied for the acute pain period and subacute pain period of herpes zoster on the head and face. For acute pain period, the bleeding volume should be large (more than 10 mL), and treatment is given once every other day; for the subacute pain period, the bleeding volume should be 5-10 mL, and treatment is given 2-3 times a week. In the chronic pain period, the fire needle of the warm-clear method combined with mild-clear method (acupuncture with filiform needle) are applied for the syndrome of qi-stagnation and blood-stasis, while the warm acupuncture of the warm-clear method combined with mild-clear method (acupuncture with filiform needle) ware applied for the syndrome of qi-deficiency yin-injury blood-stasis.

Mechanism of Shaofu Zhuyu Decoction in treatment of endometriosis-associated dysmenorrhea with syndrome of cold coagulation and blood stasis based on MSK1/2

This study aims to decipher the mechanism underlying the effect of Shaofu Zhuyu Decoction on endometriosis(EMT)-associated dysmenorrhea in rats with the syndrome of cold coagulation and blood stasis based on mitogen-and stress-activated protein kinase 1/2(MSK1/2).We employed a random number table to randomly assign SPF female non-pregnant rats into the sham group, and treated the rest rats with autologous transplantation+refrigerator freezing for the modeling of the syndrome of cold coagulation and blood stasis.The modeled rats were then randomly assigned into the control group and high-, medium-and low-dose Shaofu Zhuyu Decoction groups.The rats in the low-, medium-, and high-dose decoction groups were respectively administrated with 9, 4.5, and 2.3 g·kg~(-1) decoction through gavage once a day for 2 consecutive weeks, and those in the control group were administrated with 0.24 mg·kg~(-1) gestrinone through gavage once every 3 days for 2 weeks.After that, the size of ectopic focus in each rat was measured via laparotomy.Enzyme-linked immunosorbent assay(ELISA) was adopted to determine the expression of interleukin(IL)-6, IL-10, prostaglandin E2(PGE2), tumor necrosis factor-α(TNF-α).Western blot was employed to determine the protein levels of MSK1/2 and dual-specificity phosphatase 1(DUSP1) and real-time quantitative polymerase chain reaction(RT-PCR) to determine the mRNA levels of the two genes in rat eutopic endometrial tissue.Compared with the sham group, the model group showed increased levels of IL-6, PGE2, and TNF-α while decrease level of IL-10 in the serum(P&lt;0.01).Compared with the model group, the high-and medium-dose decoction groups and the gestrinone group had declined levels of IL-6, PGE2, and TNF-α while risen level of IL-10 in the serum(P&lt;0.01).The model group had lower protein levels and mRNA levels of MSK1/2 and DUSP1 in the eutopic endometrial tissue than the sham group(P&lt;0.01). The high-and medium-dose decoction groups and the gestrinone group had higher protein and mRNA levels of MSK1/2 and DUSP1 in the eutopic endometrial tissue than the model group(P&lt;0.01).The results indicated that Shaofu Zhuyu Decoction can regulate the abnormal expression of pro-inflammatory cytokines TNF-α, IL-6, and PGE2 and anti-inflammatory cytokines IL-10 and DUSP1 via MSK1/2 to alleviate EMT-associated dysmenorrhea in rats with the syndrome of cold coagulation and blood stasis.

Efficacy and Safety of Modified Yupingfeng Nasal Spray in Controlling the Recurrence of Persistent and Moderate-Severe Allergic Rhinitis: Study Protocol for a Multicenter, Open-Label, Randomized, and Parallel-Arm Trial.

Background Recurrent episode of allergic rhinitis (AR) is one of the leading illnesses that affects patients. However, there is little research evidence to support pharmacotherapy for AR recurrence. Therefore, this study was designed to explore the efficacy of pharmacotherapy in the control of the recurrence of AR. Methods In this study, a multicenter, open-label, randomized, and parallel-arm trial will be conducted at three study centers. A total of 190 subjects aged 18–65 with persistent and moderate-severe AR (Qi deficiency and blood stasis syndrome) will be randomly assigned to receive the modified Yupingfeng nasal spray or mometasone furoate aqueous nasal spray. When subjects' rhinitis control assessment test (RCAT) score is >21 for two weeks, they will stop taking the medication and enter the follow-up. Once a relapse occurs, the time point will be recorded, and the follow-up stops. The primary outcome is the six-month recurrence rate of AR after intervention withdrawal. The secondary outcomes are the one-month recurrence rate of AR, the RCAT score, the duration of follow-up, the duration of medication, the nasal endoscopic results, and questionnaires to evaluate symptoms, signs, and quality of life. The mechanism outcomes include some indicators that may be associated with AR recurrence. In addition, electrocardiograms and other safety indicators will be applied to evaluate the drug's safety. Discussion. This is the first study to explore the efficacy of traditional Chinese medicine nasal spray on AR from the perspective of controlling recurrence. The results of this trial may provide valuable clinical evidence for controlling the recurrence of this disease by pharmacotherapy. Trial Registration. This study was registered with registration number ChiCTR2100047053 (Chinese Clinical Trial Registry, https://www.chictr.org.cn/showproj.aspx?proj=127432 on June 7, 2021).

Therapeutic mechanism of Curcuma aromatica Salisb. rhizome against coronary heart disease based on integrated network pharmacology, pharmacological evaluation and lipidomics.

Curcuma aromatica Salisb. rhizome (CASR) has multifunctional characteristics worldwide and a long history of use as a botanical drug with. Currently, it is often used clinically to treat coronary heart disease (CHD) caused by blood stasis syndrome. However, the therapeutic mechanism of CASR in the treatment of CHD remains poorly understood. In study, the main chemical constituents of CASR were analyzed using UPLC-Q-TOF-MS/MS. Then, its potential therapeutic mechanism against CHD was predicted. Subsequently, pharmacological evaluation was performed using CHD rat model. Finally, a lipidomics approach was applied to explore the different lipid metabolites to verify the regulation of CASR on lipid metabolism disorders in CHD. A total of 35 compounds was identified from CASR. Seventeen active components and 51 potential targets related to CHD were screened by network pharmacology, involving 13 key pathways. In vivo experiments showed that CASR could significantly improve myocardial infarction, blood stasis, and blood lipid levels and regulate the PI3K/AKT/mTOR signaling pathway in CHD rats. Lipidomics further showed that CASR could regulate abnormal sphingolipid, glycerophospholipid, and glycerolipid metabolism in CHD rats. The therapeutic mechanism of CASR against CHD was initially elucidated and included the regulation of lipid metabolism. Its effects may be attributed to active ingredients, such as curzerene, isoprocurcumenol, and (+)-curcumenol. This study reveals the characteristics of multi-component and multi-pathway of CASR in the treatment of CHD, which provides a basis for the follow-up development and utilization of CASR.

Effect of diabetes blood-stasis syndrome and Xuefu Zhuyu decoction on ERK1/2-VEGF signal pathway in rat retina Müller cells.

This research was aimed to investigate whether diabetic blood-stasis syndrome had a relationship with ERK1/2-VEGF signaling pathway in rat retina Müller cells and Traditional Chinese Drugs designed for promoting blood circulation to remove blood stasis had effectiveness for diabetic retinopathy (DR) treatment. Immunofluorescence was applied to determine purity of Müller cells. Müller cells were stimulated by blood serum obtained from rats with blood-stasis syndrome and then treated by Xuefu Zhuyu decoction. Western blot analysis, RT-PCR and ELISA were used to measure the expression of VEGF. Western blot analysis was used to determine the phosphorylation of ERK1/2. The status of AP-1 DNA binding activity was monitored by electrophoretic mobility shift assay (EMSA). Stimulation of Müller cells by blood serum of rat with diabetic blood stasis increased the secretion of VEGF, activated ERK1/2 and AP-1 DNA-binding activity. And treatment of Xuefu Zhuyu decoction could weaken this phenomenon. What's more, ERK1/2 signaling pathway inhibitor U0126 also could inhibit the expression of VEGF. Diabetic blood-stasis syndrome in theory of traditional Chinese Medicine has positive role in regulating ERK1/2-VEGF signaling pathway. Traditional Chinese drugs for promoting blood circulation to remove blood stasis would be an effective therapy to treat DR.

A UPLC-Q-TOF-MS-Based Metabolomics Approach to Screen out Active Components in Prepared Rhubarb for Its Activity on Noxious Heat Blood Stasis Syndrome.

Background: Prepared rhubarb was obtained by steaming raw rhubarb with wine. Different from raw rhubarb with a purgative effect, prepared rhubarb shows effects of promoting blood circulation and removing blood stasis. However, the mechanisms of its action through regulating endogenous metabolites remain unclear. Purpose: The purpose of this study was to explore active chemical components in prepared rhubarb for its activity on noxious heat blood stasis syndrome (NHBS) by comprehensive metabolomics profiling. Study design: Plant extracts usually show their activities in a synergistic way; therefore, integrated omics was developed as a rational way for a better understanding of their biological effects and potential active compounds. Methods: The activities of prepared rhubarb were evaluated by biochemical and metabolomic analysis; meanwhile, serum chemical profiles were sought using UHPLC-Q-TOF-MS. Gray correlation analysis (GCA) was used for calculating the underlying correlations between them. Results: The metabolomics profiles of rat plasma from model and control groups were significantly different, with 31 endogenous metabolites changed by NHBS. Then, after the administration of prepared rhubarb, 18 of them were regulated. Multiple metabolic pathways were disturbed after NHBS modeling and restored by prepared rhubarb, among which had a greater impact on sphingolipid metabolism. A total of 28 compounds from prepared rhubarb absorbed into the plasma were identified, including nine prototypes and 19 metabolites. Statistical results suggested that rhein and its metabolites accounted for half of the top 10 active compounds in prepared rhubarb for its biomedical activities. Conclusion: This study presented evidence for the therapeutic effects and active chemicals of prepared rhubarb on NHBS in the way of metabolomics.

The Correlation between the Level of Skin Advanced Glycation End Products in Type 2 Diabetes Mellitus and the Stages of Diabetic Retinopathy and the Types of Traditional Chinese Medicine Syndrome.

Objective We aimed to analyze the correlation between the level of skin advanced glycation end products (AGEs) in type 2 diabetes mellitus (T2DM) patients and the diabetic retinopathy (DR) staging in different traditional Chinese medicine (TCM) syndromes. Methods 416 T2DM patients were divided into normal group, nonproliferative diabetic retinopathy (NPDR) group (mild, moderate, and severe), and proliferative diabetic retinopathy (PDR) group according to the DR grade. Patients' height, weight, fasting blood glucose (FBG), hemoglobin A1C (HbA1c), blood lipid, renal function, and skin AGEs were measured. According to TCM syndrome differentiation criteria, 230 patients with T2DM and DR were divided into I. qi and yin deficiency, collateral stasis group; II. liver and kidney deficiency, eye collaterals loss group; and III. yin and yang deficiency, blood stasis, and phlegm coagulation group. Results The skin AGEs levels of different DR staging groups were statistically significant (P < 0.05), and the skin AGEs levels in the mild and moderate NPDR groups were significantly higher (P < 0.05) than those of the normal group. It was significantly higher (P < 0.05) in the severe NPDR group than in the normal group, mild and moderate NPDR groups. The skin AGEs levels of the PDR group were significantly higher (P < 0.05) than the normal group, mild and moderate NPDR groups. It was positively correlated with DR stage, HbA1c, total cholesterol (TC), low-density lipoprotein (LDL), and urine metal analysis (UMA) (r = 0.467, 0.411, 0.413, 0.503, 0.424, P < 0.05). The skin AGEs levels of the qi and yin deficiency and collaterals stasis syndrome group were significantly higher (P < 0.05) than in the liver and kidney deficiency and eye collaterals loss groups. It was also significantly higher (P < 0.05) in yin and yang deficiency, blood stasis, and phlegm coagulation syndrome groups than in qi and yin deficiency and collaterals stasis syndrome groups. Conclusion There is a positive correlation between skin AGEs and DR staging in T2DM patients. Skin AGEs level is predictive for the risk of DR complications in T2DM patients and is vital in assessing DR degree per TCM syndrome type.

Integrating network pharmacology and in vivo experimental validation to reveal the alleviation of mailuoning oral liquid on non-alcoholic fatty liver disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) especially the later stage non-alcoholic steatohepatitis (NASH) seriously endangers human's health and has become a global public health issue in recent years. Mailuoning Oral Liquid (MLN) is a modern traditional Chinese medicine prescription composed by Lonicerae japonicae flos, Achyranthis bidentatae radix, Scrophulariae radix and Dendrobium Caulis. MLN is generally used to treat the syndrome of blood stasis in clinical practice. PurposeTo observe the alleviation of MLN on NASH in vivo, and explore the possible underlying mechanism. Furthermore, this study also aims to find which Chinese medicinal drug contained in MLN exerts the main pharmacological activity. MethodsNASH model was induced in mice by feeding with methionine and choline deficient (MCD) diet. The effects of MLN on hepatic lipids accumulation, liver inflammation, hepatic fibrosis, and the expression of some molecules were investigated by histological observation, biochemical index analysis, quantitative real-time PCR and western blot. Network pharmacology was applied to predict those involved molecular targets and potential mechanisms, which was further validated in vivo. BODIPY fluorescence staining assay was used to detect cellular lipids accumulation. ResultsMLN (7.8, 23.4 ml/kg) improved NASH in MCD-fed mice. Network pharmacology results demonstrated that peroxisome proliferator-activated receptor α (PPARα) signaling pathway was crucially involved in the MLN-provided alleviation on NASH. Further experimental validation results showed that MLN increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and restored the decreased expression of nuclear PPARα in MCD-fed mice. Further results displayed that Achyranthis bidentatae radix and Lonicerae japonicae flos contributed greatly to the MLN-provided alleviation on NASH in vivo. BODIPY fluorescence staining assay showed that 25R-inokosterone and cynaroside, two compounds from Achyranthis bidentatae radix and Lonicerae japonicae flos, obviously reduced intracellular lipids accumulation in hepatocytes stimulated by non-esterified fatty acid (NEFA). ConclusionMLN improved NASH in MCD-fed mice, and the PGC-1α-PPARα signaling pathway was involved in this process. Moreover, Lonicerae japonicae flos and Achyranthis bidentatae radix contained in MLN contributed greatly to the MLN-provided improvement on NASH.

Antifungal effects of Paeonia lactiflora seed extracts

Paeonia lactiflora is a plant resources widely distributed in Asia. The root of Paeonia lactiflora have been used to traditional herbal medicine for blood stasis syndrome in Korea. Until now, many studies have been conducted on the root of Paeonia lactiflora, but studies on seed are insufficient. This study was carried out to determine the inhibitory effect of Paeonia lactiflora seed extract against the phytopathogenic fungi Alternaria panax, Botrytis cinerea, Colletotrichum acutatum, Cylindrocarpon destructans, Colletotrichum gloseosporiades, Phytophthora cactorum, and Pythium ultimum. The results demonstrated that the seed extract showed potent antifungal effects against Alternaria panax, Colletotrichum acutatum, Cylindrocarpon destructans, Colletotrichum gloseosporiades, Phytophthora cactorum, and Pythium ultimum. Especially, the Paeonia lactiflora seed extract showed the highest antifungal activity against Pythium ultimum and Phytophthora cactorum, and the antifungal activity was not affected by heat treatment. Therefore, the antifungal component of the Paeonia lactiflora seed extract was concluded thermostable and it is suggested that the Paeonia lacflora seed extract has stability for antifungal activity maintaining. These results suggested that Paeonia lacflora seed extract may be useful as a natural antifungal agent to prevent plant diseases.

Study on the Correlation between Chinese Medicine Syndrome and Cognitive Dysfunction in Mild Cognitive Impairment.

Objective To investigate the correlation between Chinese medicine syndrome and cognitive dysfunction in patients with mild cognitive impairment (MCI). Methods 121 MCI patients were included for syndrome differentiation and syndrome scoring according to the Chinese medicine syndrome classification standard of senile dementia. The cognitive function and cognitive subitems (including visual space and executive function, naming, attention, language, abstraction, delayed recall, and orientation) of patients with different Chinese medicine syndromes were scored with the Montreal Cognitive Assessment (MoCA). Correlation analysis was made on Chinese medicine syndromes and cognitive domain damage. Results Chinese medicine syndromes from most to least were kidney deficiency and marrow reduction syndrome, turbid phlegm obstructing orifices syndrome, deficiency of heart and spleen syndrome, qi stagnation and blood stasis syndrome, and yin deficiency of heart and liver syndrome. There were no significant differences in MoCA scores among different Chinese medicine syndromes (P > 0.05).In the kidney deficiency and marrow reduction syndrome, the delayed recall score was 1.74 ± 1.23 and the difference was statistically significant when compared with deficiency of heart and spleen syndrome or the yin deficiency of heart and liver syndrome (P < 0.05). In the turbid phlegm obstructing orifices syndrome, the delayed recall score was 1.81 ± 1.33 and the difference was statistically significant when compared with the yin deficiency of heart and liver syndrome (P < 0.05). There was a significant negative correlation between the kidney deficiency and marrow reduction syndrome's Chinese medicine syndrome scores and MoCA scores (P < 0.01), and there was a negative correlation between the turbid phlegm obstructing orifices syndrome's Chinese medicine syndrome scores and MoCA scores (P < 0.05). Correlation analysis showed that the kidney deficiency and marrow reduction syndrome was significantly negatively correlated with delayed recall scores (P < 0.01), and it was also negatively correlated with visual space and executive function scores (P < 0.05). The turbid phlegm obstructing orifices syndrome was significantly negatively correlated with delayed recall scores (P < 0.01). Conclusion The kidney deficiency and marrow reduction syndrome and the turbid phlegm obstructing orifices syndrome were the most common syndromes in MCI. Patients with kidney deficiency and marrow reduction syndrome might have obvious damage in delayed recall function and have damage in visual space and executive function. Patients with turbid phlegm obstructing orifices syndrome might have obvious damage in delayed recall function.

Combining ultra-high-performance liquid chromatography quadruple exactive orbitrap mass spectrometry with chemometrics to identify and verify the blood-activating components of hawthorn.

Hawthorn, one of the widely-used Chinese herbal medicines, has been used to treat blood stasis syndrome in the clinic, but its blood-activating components are unclear. This study combined the ultra-high-performance liquid chromatography-quadruple exactive-orbitrap mass spectrometry with chemometrics to identify the blood-activating components of hawthorn. Different polar fractions of hawthorn aqueous extracts were extracted and mixed to prepare 14 samples. The contents of 25 chemical components for 14 samples were determined by the proposed quantitative method which was validated in terms of linearity, precision, stability, repeatability, and recovery, while the blood-activating effect was evaluated by measuring the whole blood viscosity, plasma viscosity, and plasma fibrinogen levels. Then the partial least squares model was established on the spectrum-effect relationship. The result showed that vitexin-2″-O-rhamnoside, rutin, citric acid, malic acid, gallic acid, and fumaric acid could reduce the whole blood viscosity, plasma viscosity, and plasma fibrinogen levels in blood stasis model rats, and these components were the blood-activating components of hawthorn. This study provided a scientific basis for clarifying the blood-activating components of hawthorn, and the spectrum-effect approach proved to be an effective approach to discovering the bioactive components of Chinese herbal medicines.

A Randomized Controlled Trial on the Efficacy of Xinnaoning Capsule in the Treatment of CSAP Complicated With Qi Stagnation and Blood Stasis Syndrome.

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.

Clinical effectiveness of Qilong capsule in patients with ischemic stroke: A prospective, multicenter, non-randomized controlled trial

BackgroundThe Qilong capsule (QLC) is a Chinese patented medicine characterized by an equal emphasis on replenishing Qi and activating blood circulation. In 2000, China's FDA approved the use of QLC for ischemic stroke (IS). However, there is not yet much high-quality evidence of the clinical effectiveness of QLC combined with conventional treatment (CT) for IS with Qi deficiency and blood stasis syndrome. PurposeIn this study, we conducted a prospective, multicenter, non-randomized controlled trial at 7 hospitals in China to investigate the clinical effectiveness of QLC combined with CT for IS with Qi deficiency and blood stasis syndrome. MethodsParticipants aged 35 to 80 years old diagnosed as IS with Qi deficiency and blood stasis syndrome in TCM were recruited. Participants were treated with QLC (intervention group) or non-QLC (control group). The intervention course of QLC was 12 weeks. All participants in two groups received standard treatment. All participants returned for in-person follow-up visits at the 12th week and 24th week. Primary outcome measures included a modified Rankin Scale (mRS), the National Institute of Health Stroke Scale (NIHSS), and the Barthel Index (BI). Secondary outcome measures included TCM syndromes (Qi deficiency syndrome score, blood stasis syndrome score), psychological index (self-rating depression scale, SDS; self-rating anxiety scale, SAS), blood lipid index, blood coagulation index, homocysteine, and favorable functional outcome (mRS 0 – 3). Multiple imputations were used for any missing data. Propensity score matching (PSM) was used to deal with any confounding factors (age, gender, scale score, etc.). Rank alignment transformation variance analysis (ART ANOVA) and generalized linear mixed model (GLMM) were introduced to improve the scientific and accuracy of repeated measurement data. All statistical calculations were carried out with R 3.6.1 statistical analysis software. ResultsA total of 2468 participants were screened from November 2016 to January 2019. Finally, 2302 eligible participants were included in the analysis. There were 1260 participants in the intervention group (QLC group) and 1042 participants in the control group (non-QLC group). After PSM matching, sub-samples of 300 participants in the QLC group and 300 participants in the non-QLC group were finally formed. The final results of clinical effectiveness are the same results shared by the total samples and sub-samples after PSM. In the 24th week after treatment, QLC combined with CT proved to be significantly better than CT alone in reducing the scores of mRS (p < 0.05), NIHSS (p < 0.001), Qi deficiency syndrome (p < 0.01), and blood stasis syndrome (p < 0.001), SAS (p < 0.05), as well as in improving BI score (p < 0.05). The favourable functional outcome (mRS score of 0 to 3 at week 12) was statistically different between QLC and non-QLC group in the sub-samples (p < 0.01, 97% vs 91.7%). The results of the ART ANOVA showed that the improvement of mRS (p < 0.01), BI (p < 0.05) and NIHSS (p < 0.001) in QLC group was better than non-QLC group when the interaction effect was considered. The results of GLMM showed that the reduction of mRS and NIHSS scores of patients in the QLC group were better than those of the non-QLC group (p < 0.001). The BI score of the QLC group in the sub-samples after PSM increased more than the non-QLC group (p < 0.001). There was no evidence showing that QLC can cause serious adverse reactions (ADRs) in treating patients with IS. ConclusionQLC combined with CT was better than CT alone in reducing mRS score, NIHSS score, Qi deficiency syndrome score, blood stasis syndrome score, and SAS score, as well as improving BI score after treatment. Further high-quality RCTs are needed to confirm the positive results. The study protocol was embedded in a registry study that registered in the Clinical Trials USA Registry (registration No. NCT03174535).

YANG Jun's clinical experience of acupuncture for oculomotor paralysis

Professor YANG Jun's clinical experience of acupuncture and moxibustion for oculomotor paralysis is summarized. Professor YANG Jun pays attention to disease differentiation and syndrome differentiation in the treatment of this disease. According to the characteristics of oculomotor paralysis, "early diagnosis and seeking treatment from the source" is advocated. According to the etiology and pathogenesis, professor YANG divides oculomotor paralysis into three types: the syndrome of wind-evil attacking collaterals, the syndrome of spleen-stomach weakness and the syndrome of qi-deficiency and blood-stasis. As such, the acupoints are selected according to syndrome differentiation, and several different acupuncture methods (pricking needling at eyelids, penetrating needling and lifting eyelids and contralateral- balance needling on the healthy side) are adopted to improve the symptoms of oculomotor paralysis. It is also suggested to use the combination of scalp acupuncture and electroacupuncture to achieve the best dose-effect state. Moreover, local stimulation around the eyes is important to achieve the effects of "qi reaching affected area".

Blood Stasis Syndrome Accelerates the Growth and Metastasis of Breast Cancer by Promoting Hypoxia and Immunosuppressive Microenvironment in Mice.

Blood stasis syndromes (BSSs) are closely related to the occurrence and development of tumors, although the mechanism is still unclear. This study was aimed at exploring the effect and mechanism underlying different BSSs on tumor growth and metastasis. We established four BSS mouse models bred with breast cancer: qi deficiency and blood stasis (QDBS), cold coagulation blood stasis (CCBS), heat toxin and blood stasis (HTBS), and qi stagnation and blood stasis (QSBS). The results showed that microcirculation in the lower limb, abdominal wall, and tumor in situ decreased by varying degrees in the BSS groups. In addition, BSS promoted tumor growth and lung metastasis. The ratio of regulatory T cells in the tumor microenvironment was downregulated. Moreover, hypoxia-inducible factor 1-α, Wnt1, β-catenin, vascular endothelial growth factor, and Cyclin D1 levels increased in the tumors of BSS mice. In conclusion, BSS not only promoted the formation of a hypoxic and immunosuppressive microenvironment but also promoted the neovascularization.

Triterpenoid saponins from Ilex pubescens promote blood circulation in blood stasis syndrome by regulating sphingolipid metabolism and the PI3K/AKT/eNOS signaling pathway

BackgroundBlood stasis syndrome (BSS) is a severe disorder involving disturbances in glycerophosphocholine metabolism. Ilex pubescens (IP) can regulate the levels of lipids, such as lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE); however, the main active constituent of IP and its corresponding mechanism in BSS treatment are still unclear. PurposeTo explore the mechanisms by which triterpenoid saponins of IP (IPTS) promote blood circulation using system pharmacology-based approaches. MethodsSprague-Dawley (SD) rat BSS model was prepared by oral administration of IPTS for 7 days followed by adrenaline hydrochloride injection before immersion in ice water. Coagulation parameters in plasma and thromboxane B2 (TXB2), endothelin (ET) and 6-keto-PGF1α in serum were measured. The possible influence on abdominal aortas was evaluated by histopathology assessment. Human vein endothelial cells (HUVECs) were incubated with ox-LDL, and the effects of IPTS on cell viability and LDH release were investigated. UPLC-QTOF-MS/MS was used for metabolic profile analysis of lipid-soluble components in rat plasma and intracellular metabolites in HUVECs. Network pharmacology was used to predict the relevant targets and model pathways of BSS and the main components of IPTS. Molecular docking, molecular dynamics (MD) simulation and biochemical assays were used to predict molecular interactions between the active components of IPTS and target proteins. RT-PCR was used to detect the mRNA level of target proteins. Western blotting and immunohistochemistry (IHC) were used to verify the mechanisms by which IPTS promotes blood circulation in BSS. ResultsIPTS improved blood biochemical function in the process of BSS and played a role in vascular protection and maintenance of the normal morphology of blood vessels. Furthermore, metabolite pathways involved in steroid biosynthesis and sphingolipid metabolism were significantly perturbed. Both metabolomics analysis and network pharmacology results showed that IPTS ameliorates vascular injury and that lipid accumulation may be mediated by PI3K/AKT signaling pathway activation. MD simulation and enzyme inhibitory activity results suggested that the main components of IPTS can form stable complexes with PI3K, AKT and eNOS and that the complexes have significant binding affinity. PI3K, AKT, p-AKT, and eNOS mRNA and protein levels were considerably elevated in the IPTS-treated group. Thus, IPTS protects the vasculature by regulating the PI3K/AKT signaling pathway, activating eNOS and increasing the release of NO. ConclusionA possible mechanism by which IPTS prevents BSS is proposed: IPTS can promote blood circulation by modulating sphingolipid metabolism and activating the PI3K/AKT/eNOS signaling pathways.