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ObjectiveTo investigate the menstrual conditions of women infected with COVID-19 in Shanghai and analyze the influencing factors.MethodsFrom December 2022 to March 2023， menstrual data from 281 women infected with COVID-19 in Shanghai were collected with a questionnaire survey， including usual menstrual characteristics， the most recent menstrual period post-infection， symptoms of infection， and medication usage. According to the crossover period between the menstrual period and the infection period of the respondents， the samples were divided into two groups for comparative analysis： those whose menstrual and infection periods overlapped （positive group） and those whose menstruation started after conversion to virus-negative （negative conversion group）.ResultsAmong the 281 respondents， 196 （65.8%） experienced menstrual changes. Among them， 145 （51.6%） had changes in menstrual volume， color and texture， and 109 （38.8%） had changes in menstrual duration or cycle. Decreased menstrual volume （22.1%）， darker color （23.49%）， thicker texture （21.0%）， increased blood clots （16.7%）， and prolonged duration （21.8%） were observed in both groups. The rate of changes in menstrual volume， color， and texture was higher in the positive group （56.8%， 69/110） than that in negative group （37.3%， 76/171） （P

Cardioembolic stroke is one of the most devastating complications of nonischemic dilated cardiomyopathy (NIDCM). However, in clinical trials of primary prevention, the benefits of anticoagulation are hampered by the risk of bleeding. Indices of cardiac blood stasis may account for the risk of stroke and be useful to individualize primary prevention treatments. We performed a cross-sectional study in patients with NIDCM and no history of atrial fibrillation (AF) from two sources: 1) a prospective enrollment of unselected patients with left ventricular (LV) ejection fraction <45% and 2) a retrospective identification of patients with a history of previous cardioembolic neurological event. The primary end point integrated a history of ischemic stroke or the presence intraventricular thrombus, or a silent brain infarction (SBI) by imaging. From echocardiography, we calculated blood flow inside the LV, its residence time (TR) maps, and its derived stasis indices. Of the 89 recruited patients, 18 showed a positive end point, 9 had a history of stroke or transient ischemic attack (TIA) and 9 were diagnosed with SBIs in the brain imaging. Averaged TR, T R ¯ ,   performed well to identify the primary end point [AUC (95% CI) = 0.75 (0.61–0.89), P = 0.001]. When accounting only for identifying a history of stroke or TIA, AUC for T R ¯ was 0.92 (0.85–1.00) with odds ratio = 7.2 (2.3–22.3) per cycle, P < 0.001. These results suggest that in patients with NIDCM in sinus rhythm, stasis imaging derived from echocardiography may account for the burden of stroke. NEW & NOTEWORTHY: Patients with nonischemic dilated cardiomyopathy (NIDCM) are at higher risk of stroke than their age-matched population. However, the risk of bleeding neutralizes the benefit of preventive oral anticoagulation. In this work, we show that in patients in sinus rhythm, the burden of stroke is related to intraventricular stasis metrics derived from echocardiography. Therefore, stasis metrics may be useful to personalize primary prevention anticoagulation in these patients. [ABSTRACT FROM AUTHOR]

This study investigated the primary pathogenesis and syndrome evolution of different heart failure with preserved ejection fraction (HFpEF) stages based on the classical and clinical experience of traditional Chinese medicine (TCM), combined with the clinical characteristics of pre-heart failure, symptomatic heart failure, and advanced heart failure. This study summarizes and refines the three core syndrome factors: water, deficiency and blood stasis. Water-fluid retention was observed throughout these three stages, from the beginning to the end. With the advancement of the disease, the heart yang changes from stagnation to deficiency, water-fluid retention gradually increases, blood stasis becomes increasingly prominent, and the disease location develops dynamically from the upper to the middle and lower jiao. This study proposes three methods of treating HFpEF. The main pathogenesis of pre-heart failure is lung qi dysfunction-induced water retention, which can be treated by dispersing lung qi and transforming water retention using Fuling Xingren Gancao Decoction. The primary pathogenesis of symptomatic heart failure is yang and qi deficiency-induced water retention, which can be treated with tonifying yang, supplementing qi, and transforming water retention using Shengxian Decoction combined with Linggui Zhugan Decoction. The primary pathogenesis of advanced heart failure is yang deficiency with blood stasis and water retention affecting the heart, which can be treated with tonifying yang, circulating blood, and expelling water retention using Zhenwu Tingli Decoction. Chinese medicine can be flexibly added or subtracted according to the patients' concurrent patterns. However, the daily care of patients should be considered. This study explores the staging treatment of HFpEF from water, deficiency and blood stasis to provide a TCM clinical reference for treating HFpEF. [ABSTRACT FROM AUTHOR]

Abstract Background Blood stasis constitution in traditional Chinese medicine (TCM) is believed to render individuals more susceptible to metabolic diseases. However, the biological underpinnings of this constitutional imbalance remain unclear. Methods This study explored the association between blood stasis constitution, serum metabolic markers including uric acid (UA), high-density lipoprotein cholesterol (HDLC), their ratio (UHR), serum metabolites, and gut microbiota. Clinical data, fecal and serum samples were acquired from 24 individuals with a blood stasis constitution and 80 individuals with a balanced constitution among healthy individuals from Guangdong. Gut microbiota composition analysis and serum metabolomics analysis were performed. Results Females with a blood stasis constitution had higher UA levels, lower HDLC levels, and higher UHR in serum, suggesting a higher risk of metabolic abnormalities. Analysis of the gut microbiome revealed two distinct enterotypes dominated by Bacteroides or Prevotella. Intriguingly, blood stasis subjects were disproportionately clustered within the Bacteroides-rich enterotype. Metabolomic analysis identified subtle differences between the groups, including lower phenylalanine and higher trimethylaminoacetone levels in the blood stasis. Several differential metabolites displayed correlations with HDLC, UA, or UHR, unveiling potential new markers of metabolic dysregulation. Conclusions These findings elucidate the intricate interplay between host constitution, gut microbiota, and serum metabolites. The concept of blood stasis offers a unique perspective to identify subtle alterations in microbiome composition and metabolic pathways, potentially signaling underlying metabolic vulnerability, even in the presence of ostensibly healthy profiles. Continued investigation of this TCM principle may reveal critical insights into the early biological processes that foreshadow metabolic deterioration.

BACKGROUND: Knee osteoarthritis is a common disease in middle-aged and elderly people. It is a kind of disease that seriously affects the quality of life of patients and even has the risk of disability. Therefore, the pathogenesis and treatment of knee osteoarthritis have become the focus of research. In Chinese medicine, knee osteoarthritis is often treated as “biness,” which is closely related to “biness” caused by blood stasis and blood vessels blocking collaterals in the theory of “blood stasis” in traditional Chinese medicine. Iron overload is a kind of pathological state caused by iron metabolism disorder, which highly coincides with the pathogenic characteristics and clinical manifestations of the “blood stasis” theory of traditional Chinese medicine, and is a risk factor that promotes the development of knee osteoarthritis. OBJECTIVE: Based on the “blood stasis” theory, to summarize the effects of iron overload on cartilage metabolism and subchondral bone reconstruction, to lay a new theoretical foundation for the treatment of knee osteoarthritis with traditional Chinese medicine, and to explore the therapeutic effect of traditional Chinese medicine for promoting blood circulation after interfering with bone tissue. METHODS: CNKI, WanFang database, PubMed and Web of Science databases were searched for relevant literature. The Chinese search terms were “ferroptosis, iron, iron overload, osteoarthritis, blood stasis” and the English search terms were “ferroptosis, iron, iron overload, osteoarthritis, TCM.” In the end, 76 articles were included for further review. RESULTS AND CONCLUSION: First of all, we explored the potential of the “blood stasis” theory in treating knee osteoarthritis, and found that “blood stasis” is a crucial part in the progress of knee osteoarthritis, indicating that the “blood stasis” theory is the key to the treatment of knee osteoarthritis in traditional Chinese medicine. Secondly, “blood stasis” and iron overload have a high degree of similarity in pathogenic factors, clinical manifestations, and pathogenic characteristics, suggesting the possibility of “blood stasis” theory in treating iron overload. This finding reminds us that iron overload may be an important mechanistic basis for the “blood stasis” theory in the treatment of knee osteoarthritis. The extracts of blood-activating drugs can relieve iron overload and treat knee osteoarthritis, but the specific mechanism is still unclear. Therefore, we believe that the relationship between “blood stasis” theory and iron overload and related mechanisms are important research directions for knee osteoarthritis in the future. The related mechanism of “blood stasis” theory to alleviate iron overload and then treat knee osteoarthritis also provides a theoretical basis for the modernization of traditional Chinese medicine, such as the development of new drugs and innovative usage, and has certain guiding significance for clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: According to traditional Chinese veterinary medicine, endometritis is caused by a combination of Qi deficiency, blood stasis, and external evil invasion. Salvia miltiorrhiza is a traditional Chinese medicine that counteracts blood stasis and has additional demonstrated effects in boosting energy and restraining inflammation. Salvia miltiorrhiza has been employed in many traditional Chinese prescriptions that have proven effective in healing clinical dairy cow endometritis. Methods: the in vivo effect of Salvia miltiorrhiza in treating endometritis was evaluated in dairy cows. In addition, bovine endometrial epithelium cell inflammation and rat blood stasis models were employed to demonstrate the crosstalk between energy, blood circulation and inflammation. Network analysis, western blotting, qRT-PCR and ELISA were performed to investigate the molecular mechanism of Salvia miltiorrhiza in endometritis treatment. Results: The results demonstrate that treatment with Salvia miltiorrhiza relieves uterine inflammation, increases blood ATP concentrations, and prolongs blood clotting times. Four of the six Salvia miltiorrhiza main components (SMMCs) (tanshinone IIA, cryptotanshinone, salvianolic acid A and salvianolic acid B) were effective in reversing decreased ATP and increased IL-1ß, IL-6, and IL-8 levels in an in vitro endometritis model, indicating their abilities to ameliorate the negative energy balance and external evil invasion effects of endometritis. Furthermore, in a blood stasis rat model, inflammatory responses were induced in the absence of external infection; and all six SMMCs inhibited thrombin-induced platelet aggregation. Network analysis of SMMC targets predicted that Salvia miltiorrhiza may mediate anti-inflammation via the Toll-like receptor signaling pathway; anti-aggregation via the Platelet activation pathway; and energy balance via the Thermogenesis and AMPK signaling pathways. Multiple molecular targets within these pathways were verified to be inhibited by SMMCs, including P38/ERK-AP1, a key molecular signal that may mediate the crosstalk between inflammation, energy deficiency and blood stasis. Conclusion: These results provide mechanistic understanding of the therapeutic effect of Salvia miltiorrhiza for endometritis achieved through Qi deficiency, blood stasis, and external evil invasion. [ABSTRACT FROM AUTHOR]

Background: To systematically evaluate the efficacy and safety of activating blood and resolving stasis in patients with IgA nephropathy. Methods: From inception to May 2022, databases including PubMed, Embase, the Cochrane Library, Web of Science, WanFang database, Chinese Biomedical Database, VIP, and China National Knowledge Infrastructure were searched for randomized controlled trials about enhancing blood circulation and removing stasis for IgA nephropathy. For the articles that satisfied the requirements, quality assessment and meta-analysis were done. Results: Seventeen randomized controlled trials with a total of 1653 patients were included. Meta-analysis showed that activating blood and resolving stasis could increase therapeutic effectiveness (risk ratio (RR) = -0.47, 95% confidence interval (CI) (-0.37, -0.2), P = 0.0006) and decrease levels of serum creatinine (RR = -0.47, 95% CI (-0.37, -0.2), P = 0.0006), urea nitrogen (RR = 0.85, 95% CI (1.44, 0.26), P = 0.005), 24-hour urinary protein quantification (RR = 1.6, 95% CI (2.44, 0.95). P = 0.00001), and urine red blood cell count (RR = 1.7, 95% CI (2.57, 0.82), P = 0.0001). There was no significant difference between the two groups in terms of security (RR = 0.6, 95% CI (0.36, 1.01), P = 0.05). Conclusion: Western medicine combined activating blood and resolving stasis is more efficient than Western medicine therapy alone in treating IgA nephropathy, but it still needs to be supported by additional large-scale, multi-center randomized controlled clinical trials due to the poor quality of the included trials. [ABSTRACT FROM AUTHOR]

Background: Blood stasis constitution in traditional Chinese medicine (TCM) is believed to render individuals more susceptible to metabolic diseases. However, the biological underpinnings of this constitutional imbalance remain unclear. Methods: This study explored the association between blood stasis constitution, serum metabolic markers including uric acid (UA), high-density lipoprotein cholesterol (HDLC), their ratio (UHR), serum metabolites, and gut microbiota. Clinical data, fecal and serum samples were acquired from 24 individuals with a blood stasis constitution and 80 individuals with a balanced constitution among healthy individuals from Guangdong. Gut microbiota composition analysis and serum metabolomics analysis were performed. Results: Females with a blood stasis constitution had higher UA levels, lower HDLC levels, and higher UHR in serum, suggesting a higher risk of metabolic abnormalities. Analysis of the gut microbiome revealed two distinct enterotypes dominated by Bacteroides or Prevotella. Intriguingly, blood stasis subjects were disproportionately clustered within the Bacteroides-rich enterotype. Metabolomic analysis identified subtle differences between the groups, including lower phenylalanine and higher trimethylaminoacetone levels in the blood stasis. Several differential metabolites displayed correlations with HDLC, UA, or UHR, unveiling potential new markers of metabolic dysregulation. Conclusions: These findings elucidate the intricate interplay between host constitution, gut microbiota, and serum metabolites. The concept of blood stasis offers a unique perspective to identify subtle alterations in microbiome composition and metabolic pathways, potentially signaling underlying metabolic vulnerability, even in the presence of ostensibly healthy profiles. Continued investigation of this TCM principle may reveal critical insights into the early biological processes that foreshadow metabolic deterioration. [ABSTRACT FROM AUTHOR]

BackgroundCoronary heart disease (CHD) is representative of cardiovascular disease and the leading cause of death in humans. Previous studies have shown that kidney disease is associated with CHD, and current treatment options that can improve both cardiac and renal functions still have some limitations. The traditional Chinese medicine Bu-Shen-Huo-Xue granule (BSHXG) can promote blood rheology, inhibit platelet agglutination, and improve heart and kidney functions.MethodsThis is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 210 participants will be randomized to the intervention group and the placebo group. The Guang’anmen Hospital of China Academy of Chinese Medical Sciences is the leading center, and the Affiliated Hospital of Shandong University of Chinese Medicine and the First Affiliated Hospital of Guangzhou University of Chinese Medicine are the participating units. In addition to conventional pharmacotherapy for angina, the intervention group will receive BSHXG while the placebo group will receive BSHXG placebo. All participants will receive 2 months of treatment with 6 months of follow-up. The primary outcome is the efficacy of angina pectoris symptoms in CHD. Secondary outcomes are nitroglycerin arrest, ECG efficacy, Seattle Angina Questionnaire score, serology indicators, assessment of safety, and cardiovascular endpoint events. The transcriptome and metabolome will be used to screen biomarkers for diagnosis and efficacy evaluation.DiscussionThis study aimed to evaluate the efficacy and safety of Bu-Shen-Huo-Xue granule in the treatment of coronary heart disease, and to evaluate the benefits to patients with coronary heart disease from both cardiac and renal indicators.Trial registrationThis trial is approved by the Ethical Review Committee of the Guang’anmen Hospital China Academy of Chinese Medical Sciences with the number 2022-224-KY-01, and has been registered on the Chinese Clinical Trials Registry with the number ChiCTR2300070977 on 27 April 2023.

Objective: Our study aims to assess Ardisia japonica (AJ)'s anti-blood-stasis effect and its underlying action mechanisms. Methods: The primary components of AJ were determined using liquid chromatography–mass spectrometry (LC-MS). The blood stasis model was used to investigate the anti-blood-stasis effect of AJ extract. The underlying mechanisms of AJ against blood stasis were investigated via network pharmacology, molecular docking, and plasma non-targeted metabolomics. Results: In total, 94 compounds were identified from an aqueous extract of AJ, including terpenoids, phenylpropanoids, alkaloids, and fatty acyl compounds. In rats with blood stasis, AJ reduced the area of stasis, decreased the inflammatory reaction in the liver and lungs of rats, lowered the plasma viscosity, increased the index of erythrocyte deformability, and decreased the index of erythrocyte aggregation, suggesting that AJ has an anti-blood-stasis effect. Different metabolites were identified via plasma untargeted metabolomics, and it was found that AJ exerts its anti-blood-stasis effect by reducing inflammatory responses through the cysteine and methionine metabolism, linolenic acid metabolism, and sphingolipid metabolism. For the effect of AJ on blood stasis syndrome, the main active ingredients predicted via network pharmacology include sinensetin, galanin, isorhamnetin, kaempferol, wogonin, quercetin, and bergenin, and their targets were TP53, HSP90AA1, VEGFA, AKT1, EGFR, and PIK3CA that were mainly enriched in the PI3K/AKT and MAPK signaling pathways, which modulate the inflammatory response. Molecular docking was also performed, and the binding energies of these seven compounds to six proteins were less than −5, indicating that the chemical components bind to the target proteins. Conclusions: This study suggests AJ effectively prevents blood stasis by reducing inflammation. [ABSTRACT FROM AUTHOR]

Introduction: The CK1 family is involved in a variety of physiological processes by regulating different signaling pathways, including the Wnt/β-catenin, the Hedgehog and the p53 signaling pathways. Mutations or dysregulation of kinases in general and of CK1 in particular are known to promote the development of cancer, neurodegenerative diseases and inflammation. There is increasing evidence that CK1 isoform specific small molecule inhibitors, including CK1δ- and CK1ε-specific inhibitors of Wnt production (IWP)-based small molecules with structural similarity to benzimidazole compounds, have promising therapeutic potential. Methods: In this study, we investigated the suitability of the zebrafish model system for the evaluation of such CK1 inhibitors. To this end, the kinetic parameters of human CK1 isoforms were compared with those of zebrafish orthologues. Furthermore, the effects of selective CK1δ inhibition during zebrafish embryonic development were analyzed in vivo. Results: The results revealed that zebrafish CK1δA and CK1δB were inhibited as effectively as human CK1δ by compounds G2-2 with IC50 values of 345 and 270 nM for CK1δA and CK1δB versus 503 nM for human CK1δ and G2-3 exhibiting IC50 values of 514 and 561 nM for zebrafish CK1δA and B, and 562 nM for human CK1δ. Furthermore, the effects of selective CK1δ inhibition on zebrafish embryonic development in vivo revealed phenotypic abnormalities indicative of downregulation of CK1δ. Treatment of zebrafish embryos with selected inhibitors resulted in marked phenotypic changes including blood stasis, heart failure, and tail malformations. Conclusion: The results suggest that the zebrafish is a suitable in vivo assay model system for initial studies of the biological relevance of CK1δ inhibition. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effect of activating blood circulation and removing blood stasis on the recurrence of alcoholic acute pancreatitis (AAP), and its possible mechanism. Methods: Sixty healthy rats were selected and assigned to control, model and treatment groups (n =20/group). Treatment group was given Taohong Siwu decoction, while control and model groups were given abdominal injection of 0.9 % normal saline. Serum levels of amylase, pancreatic histopathological score, col - content, mRNA expression levels of TGF-ß 1, TßRII, and Smad3, as well as sPLA2 activity, were determined. Results: Serum amylase, pancreatic histopathological score and col - content were significantly reduced in treatment group, relative to model group, while relative mRNA expressions of TGF-ß 1, TßRII and Smad3 at each time point were significantly lower than those in the model group (p < 0.05). Serum PLA2 activity and sPLA2 - p a mRNA expression were significantly lower than those in the model group (p < 0.05). Conclusion: Activation of blood circulation and removal of blood stasis significantly prevents the relapse of AAP in rats through regulation of PLA2 activity and TGF-ß1/TßRII/Smad3 signaling pathway. Cohort studies in humans would be required to confirm the application of Taohong Siwu decoction to prevent recurrence of AAP. [ABSTRACT FROM AUTHOR]

Introduction: The CK1 family is involved in a variety of physiological processes by regulating different signaling pathways, including the Wnt/β-catenin, the Hedgehog and the p53 signaling pathways. Mutations or dysregulation of kinases in general and of CK1 in particular are known to promote the development of cancer, neurodegenerative diseases and inflammation. There is increasing evidence that CK1 isoform specific small molecule inhibitors, including CK1δ- and CK1ε-specific inhibitors of Wnt production (IWP)-based small molecules with structural similarity to benzimidazole compounds, have promising therapeutic potential.Methods: In this study, we investigated the suitability of the zebrafish model system for the evaluation of such CK1 inhibitors. To this end, the kinetic parameters of human CK1 isoforms were compared with those of zebrafish orthologues. Furthermore, the effects of selective CK1δ inhibition during zebrafish embryonic development were analyzed in vivo.Results: The results revealed that zebrafish CK1δA and CK1δB were inhibited as effectively as human CK1δ by compounds G2-2 with IC50 values of 345 and 270 nM for CK1δA and CK1δB versus 503 nM for human CK1δ and G2-3 exhibiting IC50 values of 514 and 561 nM for zebrafish CK1δA and B, and 562 nM for human CK1δ. Furthermore, the effects of selective CK1δ inhibition on zebrafish embryonic development in vivo revealed phenotypic abnormalities indicative of downregulation of CK1δ. Treatment of zebrafish embryos with selected inhibitors resulted in marked phenotypic changes including blood stasis, heart failure, and tail malformations.Conclusion: The results suggest that the zebrafish is a suitable in vivo assay model system for initial studies of the biological relevance of CK1δ inhibition.

Image thinking in traditional Chinese medicine ( TCM) is a way of thinking to establish connections with corresponding “images” and to explore the links between the essential laws of TCM and the material attributes, laws, and properties known in nature. Based on traditional image thinking, we compare hair to trees and combine TCM with the modern understanding of androgenetic alopecia to describe its pathogenesis. It is believed that plants and trees wither in dry conditions. This is similar to a lack of kidney essence; when blood can’t be transformed into essence,resulting in damage to emptiness of hair follicles, hair shrivels and falls off. Similarly, plants and trees can die due to excessive water over a long period of time, which is analogous to steaming on the parietal bone due to dampness-heat; the hair root is soaked, becomes soft, and dies. In other cases, because of soil hardening and poor permeability, the root cannot grow, which is analogous to blood stasis in the hair follicle; the flow of qi in the meridians is not smooth and the hair roots are not moistened, resulting in hair loss. The treatment of androgenic alopecia is therefore analogous to the treatment of natural plants and trees. Plants and trees need to be fertilized and irrigated; in analogy, the kidney should be nourished to secure the root so as to replenish yin and grow hair. Plants and trees need water drainage; similarly, turbidity and the fat should be transformed and reduced to strengthen the roots. Plants and trees need loose soil; in analogy, in the scalp, blood stasis should be removed to improve the blood supply of hair follicles. Furthermore, new hairs are like seedlings; therefore, we should pay attention to disease aftercare. This article discusses the treatment of androgenic alopecia based on image thinking in order to provide a new perspective for the clinical treatment of androgenic alopecia. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to investigate the efficacy of Traditional Chinese Herbs (TCH) combined with bioelectrical stimulation (BES) on patients with kidney deficiency and blood stasis type thin endometrium. PATIENTS AND METHODS: A retrospective observational study was conducted on 83 patients diagnosed with thin endometrium, treated in our hospital from August 2019 to August 2021. The clinical data of the patients were reviewed, and 60 eligible patients were categorized into two groups based on the treatment they received: the TCH-BES group (n=30, patients received Femoston, TCH and BES treatment) and the control group (n=30, patients received Femoston only). The endometrial thickness (EMT), uterine artery resistance index (RI) and pulsatility index (PI), serum reproductive hormone levels, traditional Chinese medicine (TCM) syndrome scores, and clinical pregnancy outcomes between the two groups were compared. Continuous data were described as mean ± standard deviation (X-± S). Student's t-test was used for comparison between the two groups and paired-sample t-test was used for comparison within the same group before and after the treatment. RESULTS: A total of 60 patients with thin endometrium, aged 20-35 years (average, 31.67±3.19 years), were included in this study. After the treatment, the EMT, E2 and progesterone (P) levels of the TCH-BES group were higher than that of the control group (p<0.001, p<0.05 and p<0.001, respectively), the PI, RI level and TCM syndrome scores of the TCH-BES group were lower than those of the control group (p<0.001). The clinical efficacy and pregnancy rate in the TCH-BES group were significantly higher than those in the control group (p<0.05). CONCLUSIONS: TCH combined with EBS has a satisfactory efficacy on patients with kidney deficiency and blood stasis type thin endometrium, and improves EMT, E2 and P levels, reduces PI, RI and TCM syndrome, and eventually leads to a favorable clinical pregnancy outcome. [ABSTRACT FROM AUTHOR]

Coronary no-reflow phenomenon belongs to a type of coronary microcirculation disturbance, and its main pathogenic factors are vascular endothelial cell injury, microembolism and inflammatory reaction, which are corresponding to the pathogenesis of choroid injury, blood stasis and heat toxin in traditional Chinese medicine, such as NO, ET-1, chemokine, IL and other cytokines. The degree of improvement of patients' symptoms and laboratory examination data provide a basis for traditional Chinese medicine compound prescription, monomer and traditional Chinese medicine characteristic therapy for the treatment of no-reflow phenomena (NRP). Combined with related factors, the author summarizes the research progress of traditional Chinese medicine treatment of NRP in recent years, in order to provide clinical reference. [ABSTRACT FROM AUTHOR]

This article offers a model of ageing based not on deficiency but on stasis and blockage. Supported by findings from modern research and based on the ageing and blood stasis theory of Yan Dexin, this paper argues that ageing is due to different types of constraint and blockage hindering the free flow of qi, blood and fluids. Deficiency only ensues thereafter. Thus, resolution of stasis and freeing of qi are key aspects in the treatment of disease. An approach to the treatment of stasis based on the modern classic Yi Lin Gai Cuo (Corrections of the Errors in Medicine) by Wang Qingren is presented, as well as other exemplary stasis-resolving formulas such as Yue Ju Wan (Escape Restraint Pill) and the author's own anti-ageing tea, Chang Sheng Cha (Tea for Long Life). [ABSTRACT FROM AUTHOR]

This study analyzed a lipidomic profile of platelets from blood stasis rats by liquid chromatography‐tandem mass spectrometry. The blood stasis rat was established by low‐dose continuous subcutaneous injection of adrenaline, and the evaluation indexes included hemorheology and platelet aggregation. Principal component analysis and partial least‐squares discriminant analysis were used to analyze platelet lipidomics, and p‐value < 0.05, fold change > 1.5, and variable importance plot > 2 were used to screen potential biomarkers. Then, the biomarkers were optimized by the receiver operating characteristic curve. Compared with the normal rat, the blood stasis model group's whole blood viscosity and platelet aggregation rate were also significantly increased at different shear rates (p < 0.05). Twenty‐four potential lipid biomarkers showed significant changes in platelets between the two groups. Among them, six long‐chain acylcarnitine components and three sphingosine components showed a consistent downward trend, suggesting that these two kinds of components may play an essential role in the process of platelet aggregation. Liquid chromatography‐tandem mass spectrometry‐based lipidomics studies provide much information to understand the pathology of platelets in blood stasis. [ABSTRACT FROM AUTHOR]

Postmenopausal osteoporosis (PMOP) is mainly due to the gradual decline of ovarian function and estrogen levels in postmenopausal women, so that the rate of bone resorption by osteoclasts is faster than that of osteoblasts, thereby causing progressive bone loss. The kidney governs bone and marrow, serving as the congenital foundation. The spleen controls muscle, which is the foundation of the acquired constitution and transports water and grain essence. Therefore, the kidney and the spleen play an important role in promoting the growth of the bone. PMOP is mostly based on the gradual deficiency of the spleen and kidney, blood stasis caused by Qi deficiency, liver stagnation, and chronic disease entering the collaterals, which cause syndromes of deficiency and excess. Therefore, this article discusses the etiology and pathogenesis of PMOP based on the thought of invigorating the spleen and kidney accompanied by removing blood stasis. Hence, this generalizes the treatment principle of tonifying the kidney strengthening the spleen-promoting blood circulation and removing blood stasis. This paper discusses the rationality of the treatment principle and discusses the three stages of prevention and treatment of the disease under the guidance of the treatment principle. Finally, we summarize the prevention and treatment of PMOP with traditional Chinese medicine and acupuncture, thus expanding clinical thinking. [ABSTRACT FROM AUTHOR]

Objective: Our study aims to assess Ardisia japonica (AJ)’s anti-blood-stasis effect and its underlying action mechanisms. Methods: The primary components of AJ were determined using liquid chromatography–mass spectrometry (LC-MS). The blood stasis model was used to investigate the anti-blood-stasis effect of AJ extract. The underlying mechanisms of AJ against blood stasis were investigated via network pharmacology, molecular docking, and plasma non-targeted metabolomics. Results: In total, 94 compounds were identified from an aqueous extract of AJ, including terpenoids, phenylpropanoids, alkaloids, and fatty acyl compounds. In rats with blood stasis, AJ reduced the area of stasis, decreased the inflammatory reaction in the liver and lungs of rats, lowered the plasma viscosity, increased the index of erythrocyte deformability, and decreased the index of erythrocyte aggregation, suggesting that AJ has an anti-blood-stasis effect. Different metabolites were identified via plasma untargeted metabolomics, and it was found that AJ exerts its anti-blood-stasis effect by reducing inflammatory responses through the cysteine and methionine metabolism, linolenic acid metabolism, and sphingolipid metabolism. For the effect of AJ on blood stasis syndrome, the main active ingredients predicted via network pharmacology include sinensetin, galanin, isorhamnetin, kaempferol, wogonin, quercetin, and bergenin, and their targets were TP53, HSP90AA1, VEGFA, AKT1, EGFR, and PIK3CA that were mainly enriched in the PI3K/AKT and MAPK signaling pathways, which modulate the inflammatory response. Molecular docking was also performed, and the binding energies of these seven compounds to six proteins were less than −5, indicating that the chemical components bind to the target proteins. Conclusions: This study suggests AJ effectively prevents blood stasis by reducing inflammation.

AIM: To observe the efficacy of addition and subtraction of Buyang Huanwu decoction in the adjuvant treatment of non-proliferative diabetic retinopathy of Qi-Yin deficiency and blood stasis and its effects on traditional Chinese medicine(TCM)syndromes and visual function level. METHODS: A total of 110 patients with non-proliferative diabetic retinopathy of Qi-Yin deficiency and blood stasis in our hospital between January 2017 and December 2019 were selected and divided into observation group(55 cases, 110 eyes)and control group(55 cases, 110 eyes). Patients in control group received conventional treatment according to the condition of patients with reference to relevant guidelines, and patients in observation group were combined with addition and subtraction of Buyang Huanwu decoction adjuvant therapy on this basis. The clinical efficacy after 3mo of treatment, and TCM syndromes scores, clinical indicators(macular edema score, macular retinal volume, macular foveal retinal thickness), visual function(best corrected visual acuity, average visual field sensitivity)and serum biochemical indicators [vascular endothelial growth factor(VEGF), hypoxia-inducible factor-1(HIF-1)] before treatment and 3mo after treatment were compared between the two groups.RESULTS: After 3mo of treatment, the total effective rate of treatment in observation group was significantly higher than that in control group(P

Background: The aim of this study was to perform hemodynamic simulations of a three-dimension ideal inferior vena cava-iliac vein model with artificial stenosis to determine the degree of stenosis that requires clinical intervention. Methods: Four three-dimension stenosis models (30%, 50%, 70%, and 90% stenosis) were constructed using commercial software (Solidworks). The inlet flow rates were acquired from previous literatures to perform the hemodynamic simulations. Changes in the old blood volume fraction, as well conventional hemodynamic parameters including pressure, differential pressure, wall shear stress, and flow patterns, over time were recorded. The pressure at the telecentric region of the stenosis increased with increasing degree of stenosis. Results: For the 70% stenosis model, the pressure at the telecentric region of the stenosis reached 341 Pa, and the differential pressure between the two ends of the stenosis was 363 Pa (approximately 2.7 mmHg). Moreover, in the 70% and 90% stenosis models, there was a marked change in wall shear stress in the stenosis and the proximal end region, and the flow patterns began to show the phenomenon of flow separation. Blood stasis analysis showed that the 70% stenosis model had the slowest decrease in old blood volume fraction, while the proximal end region had the largest blood residue (15%). Conclusion: Iliac vein stenosis of approximately 70% is associated with clinically relevant hemodynamic changes, and is more closely related to DVT than other degrees of stenosis.

The formation of thrombosis is a major concern in the false lumen (FL) for post-TEVAR (thoracic endovascular aortic repair) patients. Blood stasis is one of the key factors which lead to the formation of thrombosis in the arterial systems. This study proposed a computational model for blood stasis, using a two-fluid principle to track the locations of blood residual over time. The current study applied this novel model to evaluate blood stasis and thrombosis potential in four patient-specific post-TEVAR FLs of type B aortic dissection, with their follow-up in-vivo observations two years after TEVAR. The locations and topologies of residual blood in the FL predicted by the model agreed well with the in-vivo observations of thrombus. In addition, the results corresponded better with clinical observations in terms of interpatient comparison of degree of thrombosis, compared with conventional hemodynamic parameters. The blood stasis model serves as a valuable addition to conventional metrics to better predict thrombosis potential. Collectively, these metrics can provide an efficient non-invasive method for evaluating blood stasis and thrombosis potential in arterial system, and useful guidance for clinicians' operative planning and postoperative evaluation. [ABSTRACT FROM AUTHOR]

Background: Although blood-activating Chinese medicine (BACM) has been reported as adjuvant therapy for intracranial hemorrhage (ICH) in China, high-quality evidence is still lacking. Our study aimed to collect the latest high-quality randomized controlled trials (RCTs) and to evaluate the efficacy and safety of BACM for ICH.Methods: RCTs published between January 2015 and March 2022 were searched in databases, including China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Sino-Med, Wanfang, PubMed, Web of Science, Cochrane Library, and Embase without language restrictions. Eligible RCTs were included and both primary (clinical efficacy evidenced by decreased neurological deficit scores) and secondary outcomes (increased Barthel index, decreased NIHSS, hematoma volume, the volume of cerebral edema, the incidence of side effects, and mortality) were analyzed. The quality of included RCTs was assessed using the Cochrane risk of bias tool. In the meta-analysis, the pooled results were analyzed using Review Manager 5.3 and STATA14.0. Finally, The GRADEpro GDT software (Guideline Development Tool) was used to summarize the results. Sensitivity and subgroup analyses were conducted based on the follow-up time.Results: Fifteen RCTs, involving 1,579 participants, were included for analysis in our study. The pooled outcomes indicated that BACM combined with western medicine treatment (WMT) was superior to WMT alone for patients with ICH, demonstrated by the improvements in efficacy (RR = 1.22 (95% CI, [1.13 to 1.32], p < 0.001), neurological functions (MDNIHSS = −2.75, 95% CI [−3.74 to −1.76], p < 0.001), and activities of daily living (MDBarthel index = 5.95, 95% CI [3.92 to 7.98], p < 0.001), as well as decreased cerebral hematoma, cerebral edema (MD cerebral hematoma = −2.94, 95% CI [−3.50 to −2.37, p < 0.001 and MDcerebral edema = −2.66, 95% CI [−2.95 to −2.37], p < 0.001), side effects and mortality (RR = 0.84 (95% CI [0.60 to 1.19], p = 0.330 and RR = 0.51 (95% CI, [0.16 to 1.65], p = 0.260). In addition, Conioselinum anthriscoides “Chuanxiong” [Apiaceae], Camellia reticulata Lindl. [Theaceae], and Bupleurum sibiricum var. jeholense (Nakai) C.D.Chu [Apiaceae]) were the most frequently used herbs in the treatment of ICH. Recently, there was a trend toward the extensive use of another two herbs, including Rheum palmatum L. [Polygonaceae], Astragalus mongholicus Bunge [Fabaceae]) for ICH.Conclusion: BACM combined with WMT seems to be superior to WMT alone for patients with ICH. Further high-quality RCTs are warranted to confirm the efficacy and safety of BACM.

The aim of this study is to perform patient-specific hemodynamic simulations of patients with iliac vein compression syndrome (IVCS) and evaluate the deep venous thrombosis (DVT) potential, with clinical observations as reference. 15 patient-specific IVCS models were reconstructed from computed tomography venography (CTV) data, and divided into three groups, i.e. two groups with thrombosis: Group A (complete obstruction) and Group B (incomplete obstruction), and a third group without DVT, Group C. Hemodynamic simulations were conducted with patient-specific inlet flow rates. The blood residue was predicted using the blood stasis model. Time histories of old blood volume fraction (OBVF) was obtained, in addition to conventional hemodynamic parameters such as wall shear stress (WSS). The mean area-averaged WSS of the stenosis region for Group A and Group B were 3.68 Pa and 1.78 Pa, respectively. For the telecentric end region, the WSS were 0.76 Pa and 0.58 Pa, respectively. For Group C, the WSS at these two regions were 4.61 Pa and 1.57 Pa, respectively. The OBVF was 74.0% at the stenosis region and 76.2% at the telecentric end region for Group A, much higher than 4.8% and 43.1% of Group B. For Group C, the OBVF at the two regions were close to 0. This corresponded well with clinical observations. The potential of DVT can be predicted through patient-specific hemodynamic simulations in combination of blood stasis model. The findings of this study are of great significance for the preoperative evaluation and treatment prognosis of IVCS patients with DVT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cerebrovascular accidents (CVAs) can complicate the follow-up of patients with acute myocardial infarction (AMI). Intracavitary blood stasis evaluation can be useful to stratify cardioembolic risk and optimize medical therapy. Cardiac magnetic resonance (CMR) imaging is increasingly used in AMI patients for prognostic purposes. Slow-flow artefact is common on T2-weighted images in presence of left ventricular (LV) blood stasis. In this observational retrospective study, all patients with AMI undergoing CMR in our hospital were included. T2-weighted images were used to assess the presence of LV blood stasis. Among the 209 patients enrolled (males 72%, mean age 61 ± 12 years), LV blood stasis was detected in 48 (23%) and was significantly more prevalent in patients with extensive anterior or antero-apical AMI, lower LV ejection fraction, greater infarct size and microvascular obstruction. During follow-up (54 months, IQR 41–70), 8 CVAs and 6 cardiovascular deaths occurred. LV blood stasis emerged as a significant risk factor for both endpoints (logRank p < 0.001 and p = 0.008, respectively) and remained independent predictor of CVAs (HR 9.819, 95% CI 1.733–55.617, p = 0.010). LV blood stasis identified with CMR predicts the occurrence of CVAs in patients with AMI. These results may be helpful to personalize antithrombotic therapy for prevention strategies. • Cerebrovascular accidents can complicate the follow-up of patients with acute myocardial infarction. • CMR imaging is increasingly used in patients suffering from acute myocardial infarction for prognostic purposes. • LV blood stasis identified with CMR predicts the occurrence of CVAs in patients with acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to numerically evaluate thrombosis risk within occluded coronary arterial fistulas (CAF) with terminal aneurysms, and provide guidance in choosing occlusion positions, with clinical observations as reference. Method: Four patients with CAF were studied, with different occlusion positions in actual treatments. Hemodynamics simulations were conducted, with blood residue predicted using the blood stasis model. Three types of models (untreated model, aneurysm-reserved model and aneurysm-removed model) were studeid for each patient. Four metrics, i.e., proportion of high oscillatory shear index (OSI), area of high OSI, old blood volume fraction (OBVF)) and old blood volume (OBV) was obtained to distinguish the thrombosis risk of different treatments (proximal or distal occlusion), comparing with the follow-up CTA. Results: For all the postopertive models, the high OBVF, high OSI(>0.3) and low time-averaged wall shear stress (TAWSS) regions were mainly at the distal fistula, indicating these regions were prone to thrombosis. The regions where blood residue remains are roughly regions of high OSI, corresponding well with clinical observations. In contrast, TAWSS failed to distinguish the difference in thrombosis risk. Absolute values (area of high OSI, OBV) can better reflect the degree of thrombosis risk between treatment types compared with percentage values (proportion of high OSI, OBVF). By comparing with the actual clinical treatments and observations, the OBV is superior to the area of high OSI in determining treatment type. Conclusion: The OBV, a volumetric parameter for blood stasis, can better account for the CAF thrombosis and reflect the degree of blood stasis compared with OSI or TAWSS, is a more appropriate metric for thrombosis in the fistula. Together with morphological parameters, the OBV could guide clinicians to formulate more appropriate surgical plans, which is of great significance for the preoperative evaluation and treatment prognosis of CAF patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to numerically evaluate thrombosis risk within occluded coronary arterial fistulas (CAF) with terminal aneurysms, and provide guidance in choosing occlusion positions, with clinical observations as reference.Method: Four patients with CAF were studied, with different occlusion positions in actual treatments. Hemodynamics simulations were conducted, with blood residue predicted using the blood stasis model. Three types of models (untreated model, aneurysm-reserved model and aneurysm-removed model) were studeid for each patient. Four metrics, i.e., proportion of high oscillatory shear index (OSI), area of high OSI, old blood volume fraction (OBVF)) and old blood volume (OBV) was obtained to distinguish the thrombosis risk of different treatments (proximal or distal occlusion), comparing with the follow-up CTA.Results: For all the postopertive models, the high OBVF, high OSI(>0.3) and low time-averaged wall shear stress (TAWSS) regions were mainly at the distal fistula, indicating these regions were prone to thrombosis. The regions where blood residue remains are roughly regions of high OSI, corresponding well with clinical observations. In contrast, TAWSS failed to distinguish the difference in thrombosis risk. Absolute values (area of high OSI, OBV) can better reflect the degree of thrombosis risk between treatment types compared with percentage values (proportion of high OSI, OBVF). By comparing with the actual clinical treatments and observations, the OBV is superior to the area of high OSI in determining treatment type.Conclusion: The OBV, a volumetric parameter for blood stasis, can better account for the CAF thrombosis and reflect the degree of blood stasis compared with OSI or TAWSS, is a more appropriate metric for thrombosis in the fistula. Together with morphological parameters, the OBV could guide clinicians to formulate more appropriate surgical plans, which is of great significance for the preoperative evaluation and treatment prognosis of CAF patients.

Background Blood stasis (BS) is commonly used for pattern identification in traumatic injuries, including traffic accidents (TAs). Various studies have identified the efficacy of Korean medicine treatments for TA patients, but studies focusing on the BS-based herbal medicine (BSHM), including Tongdo-san (TDS), are rare. Methods This was a single-center, prospective observational study, conducted from August 24th, 2018 to December 27th, 2018, which included 40 TA patients. Participants underwent routine Korean medicine treatments including acupuncture, electronic moxibustion, cupping, physical therapy, and herbal medicine. In the herbal medicine treatment, participants took BSHM with more than 3 days including taking TDS. The primary outcome measures were the scores from a 100 mm visual analogue scale (VAS) and numerical rating scale (NRS). Secondary outcome measures included scores from EuroQol-5 dimension (EQ-5D) and EQ-VAS questionnaires, the BS and cold/heat indices, and safety assessments. Results There were significant improvements in the VAS, NRS, EQ-5D, EQ-VAS scores, and BS index after treatment. In the sub-analysis, VAS, NRS, EQ-5D, and EQ-VAS scores were higher in groups with a higher BS index. The moderate and severe BS index groups showed more improvement than the minor BS index group, and there was a significant difference in the EQ-5D scores. There was no significant differences observed in cold/heat index groups scores. Conclusion BS is associated with TA-related symptoms. BSHM, including TDS, may significantly reduce BS, pain, and discomfort.

Abstract Background Shoulder pain is an uncomfortable feeling in the muscle around the shoulder. The cause of myalgia is the accumulation of lactic acid in muscles and impaired blood circulation, which is called blood stasis in traditional East Asian medicine. This study aimed to explore the therapeutic effect of Gyejibongnyeong-Hwan (GBH) for shoulder discomfort related to blood stasis before and after treatment. Methods/design This study will be a double-centre, randomised, wait-list controlled pilot trial. Participants with shoulder pain and with a visual analogue scale score of 4 or higher out of 10, blood stasis score of 9 or higher, and triglyceride level of ≥150 mg/dl or total cholesterol level of ≥200 mg/dl will be recruited from two university hospitals. A total of 40 participants will be assigned to the immediate and waiting treatment groups. The immediate treatment group will receive GBH for 8 weeks on enrolment while the waiting treatment group will receive GBH for 8–16 weeks after 8 weeks of controlled waiting. The primary outcome is shoulder pain, and the secondary outcomes are the blood stasis score, blood pressure, ankle–brachial pressure index, brachial–ankle pulse wave velocity, body mass index, waist circumference, indexes of oximetry, and levels of blood lipid, blood sugar, resistin, C-reactive protein, serum amyloid P, and D-dimer. Discussion The results of this pilot trial will be the bases for a full-scale clinical trial of GBH. Trial registration Clinical Research Information Service, KCT0003837. Registered on 23 April 2019. https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=14258

The concept of “blood stasis” – called yū xiě in Chinese, Oketsu in Japanese – is one of the unique pathophysiology of traditional medicine that originated in China and inherited in Korea and Japan. This concept is related to the multiple aspects of hemodynamic disorders brought on by quantitative and qualitative changes. It theorizes that the quantitative changes of “blood stasis” are related to peripheral circulatory insufficiency. When chronic qualitative changes of “blood stasis” produce stagnant blood that turns into a pathological product, it could cause inflammation and lead to organic changes. Trauma induced hematomas, that are considered to be a quantitative change of blood, are also a form of blood stasis. The basic medicine research on Keishibukuryogan (KBG)–a Japanese name in Traditional Japanese Medicine (Kampo) for one of the most common anti- “blood stasis” prescriptions, also known as gui-zhi-fu-ling-wan (GFW) in Chinese in Traditional Chinese Medicine (TCM)–indicated that the initiation of quantitative changes was closely related to loss of redox balances on endothelial function induced by oxidative stress. The following qualitative changes were related to coagulopathy, hyper viscosity; anti-platelet aggregation, lipid metabolism; a regulation of systemic leptin level and/or lipid metabolism, inflammatory factor; cyclooxygenase-1,2 (COX-1, 2), interleukin-6, 8 tumor necrosis factor-α, macrophage infiltration, hyperplasia, tissue fibrosis and sclerosis caused by transforming growth factor-β1 and fibronectin, the dysfunction of regulated cell deaths, such as, apoptosis, autophagy, ferroptosis and ovarian hormone imbalance. Clinically, KBG was often used for diseases related to Obstetrics and Gynecology, Endocrine Metabolism, Rheumatology and Dermatology. In this review, we give an overview of the mechanism and its current clinical application of KBG through a summary of the basic and clinical research and discuss future perspective.

Background: Despite the recent advances in computational fluid dynamics (CFD) techniques applied to blood flow within the left atrium (LA), the relationship between atrial geometry, flow patterns, and blood stasis within the left atrial appendage (LAA) remains unclear. A better understanding of this relationship would have important clinical implications, as thrombi originating in the LAA are a common cause of stroke in patients with atrial fibrillation (AF)., Aim: To identify the most representative atrial flow patterns on a patient-specific basis and study their influence on LAA blood stasis by varying the flow split ratio and some common atrial modeling assumptions., Methods: Three recent techniques were applied to nine patient-specific computational fluid dynamics (CFD) models of patients with AF: a kinematic atrial model to isolate the influence of wall motion because of AF, projection on a universal LAA coordinate system, and quantification of stagnant blood volume (SBV)., Results: We identified three different atrial flow patterns based on the position of the center of the main circulatory flow. The results also illustrate how atrial flow patterns are highly affected by the flow split ratio, increasing the SBV within the LAA. As the flow split ratio is determined by the patient's lying position, the results suggest that the most frequent position adopted while sleeping may have implications for the medium- and long-term risks of stroke., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Premenstrual syndrome(PMS) lacks a highly consistent and feasible animal model that aligns with diagnostic and therapeutic standards in both traditional Chinese medicine(TCM) and western medicine, resulting in a lack of reliable experimental carriers for studying its pathogenesis and pharmacological effects. This study aims to systematically analyze the biological implications of PMS from the perspective of the &quot;disease-syndrome-symptom&quot; correlation and establish preparation and evaluation methods for an improved animal model of this disease. Firstly, clinical symptom gene sets related to the Qi stagnation syndromes due to liver depression and blood stasis in PMS in both modern medicine and TCM diagnostic standards were collected through GeneCards, DisGeNET, Mala-Cards, and the System of Foundational Diagnostic Association(SoFDA) database, as well as published literature. Based on the interaction information between genes, a &quot;disease-syndrome-symptom&quot; correlation network of PMS was established. Based on data mining results, an improved rat model of PMS was prepared by combining chronic restraint stress with the classical progesterone-withdrawal mo-del to simulate emotional depression caused by external environmental stimuli during the clinical onset process, inducing pathological damage from both physiological and emotional dimensions. The evaluation of the improved model before and after modification included open field experiment scores, organ indices, ovarian pathological changes, serum levels of estradiol(E&#95;2), follicle-stimulating hormone/luteinizing hormone(FSH/LH), 5-hydroxytryptamine(5-HT), dopamine(DA), norepinephrine(NE), as well as coagulation parameters and hemorheology indexes. By calculating the degree, betweenness, and closeness centrality of nodes in the &quot;disease-syndrome-symptom&quot; correlation network, 163 core genes with topological importance were identified. Further biological function mining results indicated that core genes in PMS mainly participated in the regulation of the &quot;nervous-endocrine-immune&quot; system and pathways related to circulatory disorders. Mapping analysis of clinical phenotype symptom gene sets suggested significant correlations between core genes in PMS and depressive symptoms and pain symptoms caused by blood stasis. Compared with the simple progesterone withdrawal model, rats subjected to combined injections and restraint stress showed more significant abnormalities in open field experiment scores, ovarian tissue pathology, serum neurotransmitter levels of 5-HT and DA, as well as serum hormone levels of E&#95;2 and FSH/LH. The modified modeling conditions exacerbated the pathological changes in blood rheology, coagulation function, and red blood cell morphology in model rats, confirming that the improved rat model could characterize the &quot;nervous-endocrine-immune&quot; system disorder and circulatory system disorders in the occurrence and progression of PMS, consistent with the clinical diagnostic and therapeutic standards of both TCM and western medicine. The establishment of the improved rat model of PMS can provide a reliable experimental carrier for elucidating the pathogenesis of PMS and discovering and evaluating therapeutic drugs. It also provides references for objectively reflecting the clinical characteristics of PMS in TCM and western medicine and precision treatment.

Background: Coronary heart disease (CHD) is representative of cardiovascular disease and the leading cause of death in humans. Previous studies have shown that kidney disease is associated with CHD, and current treatment options that can improve both cardiac and renal functions still have some limitations. The traditional Chinese medicine Bu-Shen-Huo-Xue granule (BSHXG) can promote blood rheology, inhibit platelet agglutination, and improve heart and kidney functions., Methods: This is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 210 participants will be randomized to the intervention group and the placebo group. The Guang'anmen Hospital of China Academy of Chinese Medical Sciences is the leading center, and the Affiliated Hospital of Shandong University of Chinese Medicine and the First Affiliated Hospital of Guangzhou University of Chinese Medicine are the participating units. In addition to conventional pharmacotherapy for angina, the intervention group will receive BSHXG while the placebo group will receive BSHXG placebo. All participants will receive 2 months of treatment with 6 months of follow-up. The primary outcome is the efficacy of angina pectoris symptoms in CHD. Secondary outcomes are nitroglycerin arrest, ECG efficacy, Seattle Angina Questionnaire score, serology indicators, assessment of safety, and cardiovascular endpoint events. The transcriptome and metabolome will be used to screen biomarkers for diagnosis and efficacy evaluation., Discussion: This study aimed to evaluate the efficacy and safety of Bu-Shen-Huo-Xue granule in the treatment of coronary heart disease, and to evaluate the benefits to patients with coronary heart disease from both cardiac and renal indicators., Trial Registration: This trial is approved by the Ethical Review Committee of the Guang'anmen Hospital China Academy of Chinese Medical Sciences with the number 2022-224-KY-01, and has been registered on the Chinese Clinical Trials Registry with the number ChiCTR2300070977 on 27 April 2023., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Liu, Wang, Li, Li, Li, Liu, Yang, Mao, Wang, Yao, Wang, Zong and Liu.)

Hawthorn, a commonly used traditional Chinese medicine, has been suggested to have therapeutic effects on cardiovascular disease. However, effective fractions of hawthorn extract in the treatment of cardiovascular disease, together with possible therapeutic mechanisms, remain unclear. This study aimed to investigate the effects of four different polar fractions of hawthorn extract on blood stasis model rats, and explore the possible metabolic mechanisms by using a liquid chromatography–mass spectrometry metabolomics approach. Evaluation of hemorheology and fibrinogen showed that n‐butanol and ethyl acetate fractions of hawthorn extract had significant therapeutic effects on blood stasis model rats. Furthermore, metabolomics analysis showed that n‐butanol and ethyl acetate fractions of hawthorn extract could reverse imbalanced biomarkers in plasma and urine of blood stasis model rats. Additionally, metabolic pathway analysis revealed that plasma biomarkers were responsible for several important pathways, including d‐glutamine and d‐glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, alanine, aspartate, and glutamate metabolism, sphingolipid metabolism, and arginine biosynthesis. Meanwhile, urine biomarkers were responsible for some important pathways, including phenylalanine metabolism, tyrosine metabolism, and lysine degradation. This study demonstrated that n‐butanol and ethyl acetate fractions of hawthorn extract had significant therapeutic effects on blood stasis model rats, and the underlying mechanisms involved multiple metabolic pathways. [ABSTRACT FROM AUTHOR]

Objective To study the clinical effect of Danhong injection combined with conventional treatment in chronic kidney disease (CKD) with hypoxemia chronic obstructive pulmonary disease (COPD). Methods Clinical data of CKD patients with hypoxemian COPD were retrospectively analyzed. There were 50 cases in the conventional treatment group and 50 cases in the Danhong injection group. The conventional treatment group was given the treatment of diuresis, detumescence, anti-inflammation, cough and phlegm, anti-spasmodic and anti-asthma. The Danhong injection group was given intravenous Danhong injection for 14 days on the basis of conventional treatment. Before and after the treatment, the change of indexes including arterial blood gas analysis, renal function and liver function were compared between the two groups. The total score of traditional Chinese medicine (TCM) syndromes, the effective rate of treatment, the improvement of hypoxemia and the safety of treatment were evaluated before and after treatment. Results After treatment, compared with the conventional treatment group, p(O2) was increased in Danhong injection group, while p(CO2), blood β2, CYS-C and the total score of TCM syndromes were decreased in Danhong injection group (P＜0.05). In the Danhong injection group, blood urea nitrogen (BUN), β2-MG, CYS-C and the total score of TCM syndromes were decreased after treatment (P＜0.05). The therapeutic effect of Danhong injection group was superior than that of conventional treatment group (Z=2.268, P＜0.05). The improvement rate of hypoxemia was significantly higher in the Danhong injection group (56.00%) than that in the conventional treatment group (30.00%, χ² =4.889, P＜0.05). There were no significant differences in related indexed of liver function before and after treatment between the two groups (P＞0.05). Conclusion Danhong injection can improve renal function, hypoxic environment and clinical symptoms in CKD patients with hypoxemia COPD. [ABSTRACT FROM AUTHOR]

The combined use of Panax notoginseng saponins (PNS)–based drugs and aspirin (ASA) to combat vascular diseases has achieved good clinical results. In this study, the superior efficacy was observed via the combined use of PNS and ASA on acute blood stasis rats, and untargeted metabolomics was performed to holistically investigate the therapeutic effects of coupling application and its regulatory mechanisms. The combined use of PNS and ASA exhibited better improvement effects when reducing the evaluated hemorheological indicators (whole blood viscosity, plasma viscosity, platelet aggregation, and fibrinogen content) in the blood stasis rats vs. single use of PNS or ASA at the same dose. The combined use of both drugs was the most effective application method, as shown by the relative distance in partial least-squares discriminant analysis score plots. Twelve metabolites associated with blood stasis were screened as potential biomarkers and were mainly involved in amino acid metabolism, lipid metabolism, and energy metabolism. After coherently treated with PNS and ASA, the altered metabolites could be partially adjusted to be closer to normal levels than single use. The collective results revealed that PNS could cooperate with ASA to treat blood stasis and provided a scientific explanation for the superior efficacy of their combined use.

Case: Eosinophilic sinusitis is a pathological condition, different from conventional chronic sinusitis. A treatment method has not been established other than oral steroids. Surgical treatment is performed, but it recurs easily and is intractable. We report a case of eosinophilic sinusitis controlled by Kampo medicine. The patient was a 70‐year‐old man and had an olfactory disorder since he was in his 50s. He was diagnosed with chronic sinusitis and was treated at another hospital, but after moving, was transferred to our department. Outcome: We diagnosed our patient with severe eosinophilic sinusitis, which temporarily improved with oral steroid administration, but relapsed after about one month. We diagnosed him with phlegm‐rheum and blood stasis, and administered heiisan and keishibukuryogan. His symptoms gradually improved, and remission was maintained without the use of steroids. Conclusion: Heiisan and keishibukuryogan was a beneficial alternative treatment for the case. [ABSTRACT FROM AUTHOR]

Lagopsis supina (Steph.) IK. -Gal. ex Knorr. has been used for centuries as an empiric treatment for blood stasis syndrome in China without scientific validation. The aim of this study was to evaluate for the first time the chemical profiling, efficacy and mechanism of L. supina ethanol extract (LS) and its four fractions (LSA∼D) in Dextran 500-induced acute blood stasis model rats. Oral administration of LS (229.0∼916.0 mg/kg) and LSC (17.6∼70.4 mg/kg) once daily for seven consecutive days significantly improved microcirculation hemodynamics function (blood flow, blood concentration and blood flow velocity), hemorheological parameters (whole blood viscosity, whole blood reduced viscosity, plasma viscosity, platelet aggregation rate, hematokrit, erythrocyte assembling index and erythrocyte deformation index), and coagulation parameters (thrombin time, prothrombin time, activated partial thromboplastin time, fibrinogen and antithrombin III). Furthermore, their markedly down-regulated thromboxane B2 and 6-keto-prostaglandin F1α levels. In addition, it significantly decreased tissue-type plasminogen activator (t-PA), urokinasetype plasminogen activator (u-PA) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as PAI-1/t-PA and PAI-1/u-PA rations. In parallel, 51 chemical constituents were identified from LS based on ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-qTOF-MS/MS), and quantitative analysis showed that the two major constituents of stachysoside A and acteoside were present in 0.90 ± 0.01 and 1.36 ± 0.01 mg/g of the L. supina whole plant, respectively. These findings suggest that LS and LSC possess prominent anti-blood stasis effect on rats by modulating the anti-coagulation, anti-platelet activation and anti-fibrinolysis, and supports the traditional folk use of this plant.

Introduction and Objectives: In the setting of ST-segment elevation myocardial infarction (STEMI), imaging-based biomarkers could be useful for guiding oral anticoagulation to prevent cardioembolism. Our objective was to test the efficacy of intraventricular blood stasis imaging for predicting a composite primary endpoint of cardioembolic risk during the first 6 months after STEMI., Methods: We designed a prospective clinical study, Imaging Silent Brain Infarct in Acute Myocardial Infarction (ISBITAMI), including patients with a first STEMI, an ejection fraction ≤ 45% and without atrial fibrillation to assess the performance of stasis metrics to predict cardioembolism. Patients underwent ultrasound-based stasis imaging at enrollment followed by heart and brain magnetic resonance at 1-week and 6-month visits. From the stasis maps, we calculated the average residence time, R T , of blood inside the left ventricle and assessed its performance to predict the primary endpoint. The longitudinal strain of the 4 apical segments was quantified by speckle tracking., Results: A total of 66 patients were assigned to the primary endpoint. Of them, 17 patients had 1 or more events: 3 strokes, 5 silent brain infarctions, and 13 mural thromboses. No systemic embolisms were observed. R T (OR, 3.73; 95%CI, 1.75-7.9; P<.001) and apical strain (OR, 1.47; 95%CI, 1.13-1.92; P=.004) showed complementary prognostic value. The bivariate model showed a c-index=0.86 (95%CI, 0.73-0.95), a negative predictive value of 1.00 (95%CI, 0.94-1.00), and positive predictive value of 0.45 (95%CI, 0.37-0.77). The results were confirmed in a multiple imputation sensitivity analysis. Conventional ultrasound-based metrics were of limited predictive value., Conclusions: In patients with STEMI and left ventricular systolic dysfunction in sinus rhythm, the risk of cardioembolism may be assessed by echocardiography by combining stasis and strain imaging. Registered at ClinicalTrials.gov (NCT02917213)., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: According to traditional Chinese veterinary medicine, endometritis is caused by a combination of Qi deficiency, blood stasis, and external evil invasion. Salvia miltiorrhiza is a traditional Chinese medicine that counteracts blood stasis and has additional demonstrated effects in boosting energy and restraining inflammation. Salvia miltiorrhiza has been employed in many traditional Chinese prescriptions that have proven effective in healing clinical dairy cow endometritis. Methods: the in vivo effect of Salvia miltiorrhiza in treating endometritis was evaluated in dairy cows. In addition, bovine endometrial epithelium cell inflammation and rat blood stasis models were employed to demonstrate the crosstalk between energy, blood circulation and inflammation. Network analysis, western blotting, qRT-PCR and ELISA were performed to investigate the molecular mechanism of Salvia miltiorrhiza in endometritis treatment. Results: The results demonstrate that treatment with Salvia miltiorrhiza relieves uterine inflammation, increases blood ATP concentrations, and prolongs blood clotting times. Four of the six Salvia miltiorrhiza main components (SMMCs) (tanshinone IIA, cryptotanshinone, salvianolic acid A and salvianolic acid B) were effective in reversing decreased ATP and increased IL-1β, IL-6, and IL-8 levels in an in vitro endometritis model, indicating their abilities to ameliorate the negative energy balance and external evil invasion effects of endometritis. Furthermore, in a blood stasis rat model, inflammatory responses were induced in the absence of external infection; and all six SMMCs inhibited thrombin-induced platelet aggregation. Network analysis of SMMC targets predicted that Salvia miltiorrhiza may mediate anti-inflammation via the Toll-like receptor signaling pathway; anti-aggregation via the Platelet activation pathway; and energy balance via the Thermogenesis and AMPK signaling pathways. Multiple molecular targets within these pathways were verified to be inhibited by SMMCs, including P38/ERK-AP1, a key molecular signal that may mediate the crosstalk between inflammation, energy deficiency and blood stasis. Conclusion: These results provide mechanistic understanding of the therapeutic effect of Salvia miltiorrhiza for endometritis achieved through Qi deficiency, blood stasis, and external evil invasion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Liu, Jiang, Zhao, Fan, Zhang, Ma, Guo, Wang and Liu.)

This study observed the effects of Notoginseng Radix et Rhizoma on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin complex 1(mTORC1) signaling pathway and mitochondrial energy metabolism in the rat model of adriamycin-induced renal fibrosis with blood stasis syndrome to explore the mechanism of Notoginseng Radix et Rhizoma in protecting the kidney. Thirty male rats with adriamycin-induced renal fibrosis were randomized into model, low-, medium-, and high-dose Notoginseng Radix et Rhizoma, and positive control groups(n=6). Six clean SD male rats were selected into the normal group. The normal group and model group were administrated with normal saline, and other groups with corresponding drugs. After 8 weeks of treatment, the renal function, renal pathology, adenosine triphosphate(ATP) levels, Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities, and the protein levels of ATP5B, mTORC1, 70 kDa ribosomal protein S6 kinase(P70S6K), P85, Akt, p-Akt, and SH2-containing inositol phosphatase(SHIP2) in the renal tissue were determined. Compared with the normal group, the model group showed elevated levels of blood urea nitrogen(BUN) and serum creatinine(SCr)(P&lt;0.01). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control lowered the levels of BUN and SCr, which were significant in the medium-and high-dose Noto-ginseng Radix et Rhizoma groups and the positive control group(P&lt;0.05). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control alleviated the pathological changes in the renal tissue, such as vacuolar and fibroid changes, glomerulus atrophy, cystic expansion of renal tubules, and massive infiltration of inflammatory cells. Compared with the normal group, the model group showed decreased mitochondrial ATP content and Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities in the renal tissue(P&lt;0.05), and medium-and high-dose Notoginseng Radix et Rhizoma and positive control mitigated such decreases(P&lt;0.05). Compared with the model group, medium-and high-dose Notoginseng Radix et Rhizoma and the positive control up-regulated the protein levels of ATP5B and SHIP2 and down-regulated the protein levels of mTORC1, P70S6K, P85, Akt, and p-Akt(P&lt;0.05 or P&lt;0.01 or P&lt;0.001). Notoginseng Radix et Rhizoma may exert an anti-fibrosis effect by inhibiting the activation of the PI3K/Akt/mTORC1 pathway to restore mitochondrial energy metabolism, thus protecting the kidney.

Objective: Our aim was to investigate the correlation between free fatty acid (FFA) spectrum, blood stasis (BS) score, and macroangiopathy in type 2 diabetic patients with or without BS, as well as the possible relationship between BS and lipotoxicity. Methods: A total of 50 type 2 diabetes (T2D) patients with or without BS were enrolled from June to December 2014 in Shenzhen Traditional Chinese Medicine (TCM) Hospital, with 25 patients allocated to each of two groups. Basic information, BS score, blood glucose, blood lipids, etc., were measured for each patient. In addition, we tested the levels of interleukin (IL)-6, tumor necrosis factor α (TNF-α), and IL-18 with enzyme-linked immunosorbent assay. The macroangiopathy status of patients in the two groups was examined by color ultrasound and all factors related to BS scores were analyzed. Gas chromatography-mass spectrometry was used to explore the difference in the serum FFA spectra between the two different groups. In addition, the relationship between FFA spectra, BS scores, and macroangiopathy was analyzed. Results: BS scores, total cholesterol (TC), total triglyceride (TG), low-density lipoprotein cholesterol, IL-6, TNF-α, IL-18, carotid and femoral artery plaque, carotid intima-media thickness, carotid plaque area, and femoral artery plaque area were all significantly increased in T2D patients with BS syndrome (P < 0.05). A positive correlation was observed between age, duration of diabetes, carotid intima-media thickness, carotid plaque area, femoral artery plaque area, and BS score (P < 0.05). A total of 21 fatty acids were found in the serum, and total FFA (TFFA), saturated fatty acid (SFA), lauric acid (C12:0), palmitic acid (16:0), stearic acid (C18:0), arachidonic acid (C20:4n6), behenic acid (C22:0), and lignoceric acid (C24:0) scores were all found to contribute to the difference between FFA spectrums of the two groups; of the fatty acids, C12:0, C16:0, C18:0, C22:0, TFFA, and SFA positively correlated with BS scores as evaluated by Pearson's or Spearman's correlation analysis (P < 0.05). Only SFA entered the regression equation in the multiple linear regression analysis. C12:0, C16:0, C18:0, C20:4n6, TFFA, and SFA were positively correlated with carotid plaque area, whereas linoleic acid (C18:3n3), Cis-5, 8, 11, 14, and 17-eicosapentaenoic acids (C20:5n3) were negatively correlated (P < 0.05). C16:0 was positively correlated with the femoral artery plaque area and C18:3n3, cis-4, 7, 10, 13, 16, and 19-docosahexaenoic acids (C22:6) and nervonic acid were negatively correlated (P < 0.05). Conclusion: Serum FFA spectra were significantly different between T2D patients with BS and those without, and long-chain SFA made the greatest contribution. Serum FFA spectra were correlated with BS scores and diabetic macroangiopathy, which means that lipotoxicity and BS are correlated in T2D.

Qi deficiency and blood stasis is one of the key pathogeneses of atherosclerosis in the stable period. In the acute episode，atherosclerosis is often characterized by abrupt onset? rapid progress and multiple changes in clinical manifestations. It is similar to the wind pattern in TCM，which is difficult to be fully interpreted from the perspective of qi deficiency and blood stasis. Therefore，in this article the pathogenesis of atherosclerosis of u qi deficiency and blood stasis as the basis, and being further induced by wind" is put forward, which would possibly be the key pathogenesis affecting the progression and outcome of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Shoulder pain is an uncomfortable feeling in the muscle around the shoulder. The cause of myalgia is the accumulation of lactic acid in muscles and impaired blood circulation, which is called blood stasis in traditional East Asian medicine. This study aimed to explore the therapeutic effect of Gyejibongnyeong-Hwan (GBH) for shoulder discomfort related to blood stasis before and after treatment.Methods/design: This study will be a double-centre, randomised, wait-list controlled pilot trial. Participants with shoulder pain and with a visual analogue scale score of 4 or higher out of 10, blood stasis score of 9 or higher, and triglyceride level of ≥150 mg/dl or total cholesterol level of ≥200 mg/dl will be recruited from two university hospitals. A total of 40 participants will be assigned to the immediate and waiting treatment groups. The immediate treatment group will receive GBH for 8 weeks on enrolment while the waiting treatment group will receive GBH for 8-16 weeks after 8 weeks of controlled waiting. The primary outcome is shoulder pain, and the secondary outcomes are the blood stasis score, blood pressure, ankle-brachial pressure index, brachial-ankle pulse wave velocity, body mass index, waist circumference, indexes of oximetry, and levels of blood lipid, blood sugar, resistin, C-reactive protein, serum amyloid P, and D-dimer.Discussion: The results of this pilot trial will be the bases for a full-scale clinical trial of GBH.Trial Registration: Clinical Research Information Service, KCT0003837. Registered on 23 April 2019. https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=14258. [ABSTRACT FROM AUTHOR]