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Refractory angina is characterized by recurrent and persistent angina with a duration of not less than three months， which is related to reversible ischemia and hypoxia caused by coronary stenosis and obstruction. It mainly involves obstructive coronary artery disease and non-obstructive coronary artery disease with coronary artery spasm and coronary microvascular dysfunction. “Stasis and toxin” play an important role in the pathogenesis of cardiovascular diseases. The pathogenesis of stasis and toxin is stubborn filthy turbidity featured by slow accumulation and sudden onset，and rapid changes，which coincides with the characteristics of refractory angina which is complex and changeable，prolonged and difficult to cure. The pathogenesis of refractory angina involves a combination of underlying deficiency and excessive manifestation， with "stasis and toxin" playing a crucial role as an important pathological factor in the whole process of refractory angina. Traditional Chinese medicine （TCM） employs a holistic approach known as "activating blood circulation and removing toxins"， which is supplemented by various methods to tonify Qi and warm Yang， nourish the kidneys and invigorate the spleen， clear heat and transform phlegm. This approach applies anti-inflammatory measures， regulates lipid metabolism， inhibits oxidative stress and thrombus formation， protects endothelial function in blood vessels， as well as establishes collateral circulation for the prevention and treatment of refractory angina. Therefore，based on the theory of "stasis and toxin"，combined with TCM theory and modern medical research，this paper discusses the pathogenesis of refractory angina and the prevention and treatment strategy of TCM，and elucidates the reasons for the difficulty in curing refractory angina and the relationship between refractory angina and common angina pectoris，coronary microvascular dysfunction，coronary artery spasm and obstructive coronary artery disease，hoping to provide certain theoretical basis and clinical ideas for the prevention and treatment of refractory angina with TCM.
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Diabetic retinopathy（DR） and coronary heart disease（CHD） are both major chronic vascular complications that seriously jeopardize the health of the population and often occur together in clinical practice， it is of great clinical value to actively explore the association between the two in the process of disease development and methods of prevention and treatment of modern medicine and traditional Chinese medicine（TCM）. According to TCM， the heart and eyes physiologically communicate with each other by taking Qi， blood and veins as bridges， blood stasis obstructing collaterals is the common TCM etiology of DR and CHD， whose mechanism involves inflammation， oxidative stress and endothelial dysfunction. Promoting blood circulation and removing blood stasis plays an important role in the same treatment for different diseases and prevention and treatment of comorbidities， possibly by inhibiting the expression of interleukin-1β（IL-1β）， endothelin-1（ET-1） and hypoxia inducible factor-1α/vascular endothelial growth factor（HIF-1α/VEGF）， regulating phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR） pathway， initiating adenosine monophosphate（AMP）-activated protein kinase/silent information regulator 1（AMPK/SIRT1） and nuclear transcription factor erythroid 2-related factor 2/heme oxygenase-1（Nrf2/HO-1） signaling pathways， inhibiting Hippo/Yes-associated protein（Hippo/YAP） signaling pathway， inhibiting mitochondrial permeability transition pore and anti-platelet agglutination for treating DR and CHD， which provides a multi-component， multi-pathway and multi-target selection strategies and ideas for the prevention and treatment of DR and CHD by TCM from a biological perspective. Based on this， subsequent studies should focus on constructing clinically relevant comorbidity models， conducting multicenter prospective studies， and fully utilizing artificial intelligence technology to gain a deeper understanding of the relationship between the two diseases， so as to elucidate the mechanism of promoting blood circulation and removing blood stasis in preventing and treating panvascular diseases.
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ObjectiveTo explore the application effect of Jianpi Huoxue prescription combined with acupuncture in patients with chronic atrophic gastritis （CAG） of gastric blood stasis type. MethodA total of 86 patients with CAG admitted to Wuhan First Hospital from November 2021 to March 2023 were selected and randomly divided into two groups. The control group was treated with conventional Western medicine， while the observation group was treated with Jianpi Huoxue prescription combined with acupuncture. The clinical efficacy， traditional Chinese medicine （TCM） syndrome score， pathological score， negative conversion rate of Helicobacter pylori （Hp）， inflammatory indicators ［neutrophils/lymphocytes （NLR） and interleukin （IL）-1β］， changes in levels of gastric protease （PG） Ⅰ， PG Ⅰ/PG Ⅱ， and gastrin-17 （G-17）， and drug safety during treatment were observed after treatment in both groups. ResultAfter treatment， the total effective rate of the observation group ［95.35% （41/43）］ was significantly better than that of the control group ［79.07% （34/43）］， and the difference was statistically significant （χ2=5.108， P<0.05）. After treatment， the scores of the primary and secondary TCM syndromes in the observation group and the control group were significantly decreased （P<0.05）. After treatment， the scores of primary and secondary TCM syndromes in the observation group were significantly lower than those in the control group （P<0.05）. After treatment， the pathological scores of gastric mucosa atrophy， activity， chronic inflammation， intestinal metaplasia， and dysplasia were significantly lower in the observation group and control group （P<0.05）. After treatment， the pathological scores of gastric mucosa atrophy， activity， chronic inflammation， intestinal metaplasia， and dysplasia in the observation group were significantly lower than those in the control group （P<0.05）. After treatment， the Hp conversion rate in the observation group was significantly increased compared with the control group （P<0.05）. After treatment， the levels of inflammatory indicators NLR and IL-1β in the observation group and control group were significantly lower （P<0.05）， and the levels of inflammatory indicators NLR and IL-1β in the observation group were significantly lower than those in the control group （P<0.05）. After treatment， the levels of PGI and PGⅠ/PGⅡ in the observation group and control group were significantly higher （P<0.05）， and the levels of PGI and PGⅠ/PGⅡ in the observation group were significantly higher than those in the control group （P<0.05）. After treatment， the G-17 level of the observation group and the control group was different at different time points （P<0.05）， and the G-17 level of the observation group was higher at different time points than that of the control group （P<0.05）. The G-17 level of the observation group had an increasing trend compared with the control group （P<0.05）. There was no significant difference in the risk of adverse reactions between the two groups. ConclusionThe combination of Jianpi Huoxue prescription and acupuncture can effectively alleviate symptoms， increase Hp negative conversion rate， inhibit inflammation， and regulate PG and G-17 levels in CAG patients， thus controlling or even reversing gastric mucosal atrophy and reducing the probability of its progression to gastric cancer.
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The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.
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ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.
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ObjectiveTo explore the mechanism of Bushen Huoxue enema in treating the rat model of kidney deficiency and blood stasis-thin endometrium （KDBS-TE） by transcriptome sequencing. MethodThe rat model of KDBS-TE was established by administration of tripterygium polyglycosides tablets combined with subcutaneous injection of adrenaline. The pathological changes of rat endometrium in each group were then observed. Three uterine tissue specimens from each of the blank group， model group， and Bushen Huoxue enema group were randomly selected for transcriptome sequencing. The differentially expressed circRNAs， lncRNAs， and miRNAs were screened， and the disease-related specific competitive endogenous RNA （ceRNA） regulatory network was constructed. Furthermore， the gene ontology （GO） functional annotation and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed for the mRNAs in the network. ResultCompared with the blank group， the model group showed endometrial dysplasia， decreased endometrial thickness and endometrial/total uterine wall thickness ratio （P<0.01）， and differential expression of 18 circRNAs， 410 lncRNAs， and 7 miRNAs. Compared with the model group， the enema and estradiol valerate groups showed improved endometrial morphology and increased endometrial thickness and ratio of endometrial to total uterine wall thickness （P<0.05）. In addition， 21 circRNAs， 518 lncRNAs， and 17 miRNAs were differentially expressed in the enema group. The disease-related specific circRNA-miRNA-mRNA regulatory network composed of 629 nodes and 664 edges contained 2 circRNAs， 34 miRNAs， and 593 mRNAs. The lncRNA-miRNA-mRNA regulatory network composed of 180 nodes and 212 edges contained 5 lncRNAs， 10 miRNAs， and 164 mRNAs. The mNRAs were mainly enriched in Hippo signaling pathway， autophagy-animal， axon guidance， etc. ConclusionBushen Huoxue enema can treat KDBS-TE in rats by regulating specific circRNAs， lncRNAs， and miRNAs in the uterus and the ceRNA network.
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ObjectiveTo objectively evaluate the clinical efficacy of multiple therapies of traditional Chinese medicine （TCM） in low-prognosis patients who received antagonist protocol for in vitro fertilization and embryo transfer （IVF-ET） again. MethodA total of 128 patients with kidney Yin deficiency， liver depression， and blood stasis who planned to receive antagonist protocol for IVF-ET in the West China Second Hospital of Sichuan University were enrolled and assigned into two groups by random number table method. The observation group （64 casces） was treated by oral administration of Chinese medicine decoction + enema of kidney-tonifying and blood-activating method + auricular point sticking + oral administration of dehydroepiandrosterone （DHEA）， while the control group （64 casces） was treated by only oral administration of DHEA. After treatment for three menstrual cycles， both groups received the antagonist protocol for IVF-ET. The TCM syndrome scores， basic sex hormone levels， antral follicle count （AFC）， the usage of gonadotropin （Gn）， endometrial receptivity indicators， embryo quality indicators， and pregnancy outcomes were compared between the two groups. ResultAfter treatment， the observation group showed decreased follicle-stimulating hormone （FSH）/luteinizing hormone （LH） ratio， lowered level of estradiol （E2）， increased AFC， decreased amount and days of Gn usage， improved endometrial receptivity indicators （endometrial thickness on trigger and ET days， proportion of endometrial type A in endometrial types and the level of E2 on trigger day） and embryo quality indicators （the rates of mature follicles， fertilization， normal fertilization， and premium embryos）， and decreased TCM syndrome scores （P<0.05， P<0.01）. Moreover， the observation group had lower FSH/LH ratio， E2 level， and amount of Gn usage， higher AFC， poorer endometrial receptivity and embryo quality indicators， and lower TCM syndrome scores than the control group after treatment （P<0.05， P<0.01）. In addition， except for 3 cases of natural pregnancy， the observation group outperformed the control group in terms of improving the clinical pregnancy rates during initiation cycle and transplantation cycle and clinical pregnancy rate and decreasing biochemical pregnancy rate and early abortion rate （P<0.05）. ConclusionCombined therapies of TCM can alleviate the clinical symptoms， reduce TCM syndrome scores， reduce the Gn usage amount， improve the number and quality of embryos and endometrial receptivity， and coordinate the synchronous development of endometrium and embryo. In this way， they can increase the clinical pregnancy rate and reduce biochemical pregnancy rate and early abortion rate in the low prognosis patients with kidney yin deficiency， liver depression， and blood stasis who are undergoing IVF-ET again.
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ObjectiveTo observe and compare the electrocardiogram index， myocardial morphology， and connexin 43 （Cx43） expression of two rat models of acute cerebral infarction （ACI） due to stasis combined with toxin complicated with cerebral-cardiac syndrome （CCS）， and to provide experimental evidence for the research on the occurrence mechanism of cardiac diseases induced by ACI and the clinical diagnosis and treatment of CCS. MethodSixty SPF-grade male SD rats were randomized into six groups （n=10）： normal ， syndrome of stasis combined with toxin induced by carrageenin combined with dry yeast （CA/Y）， multi-infarct induced by micro-embolism （ME）， middle cerebral artery occlusion （MCAO）， CA/Y+ME， and CA/Y+MCAO groups. The model of syndrome of stasis combined with toxin was established by intraperitoneal injection with carrageenan （CA） at 10 mg·kg-1 on the first day and subcutaneous injection with dry yeast （Y） suspension （2 mg·kg-1） on the second day of modeling. Twenty-four hours after the modeling of ACI， the electrocardiograms （ECGs） of rats in each group were collected and the number/percentage （%） of abnormal ECG was calculated. The infarct area of the brain was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and myocardial injury was assessed by hematoxylin-eosin （HE） staining. Immumohistochemical staining and Western blot were employed to determine the expression of Cx43 in the myocardium. ResultA certain number of rats in each model group presented abnormal ECG. Compared with the normal group and CA/Y group， CA/Y+MCAO group had the highest rate of abnormal ECG （P<0.01）. Compared with the normal， CA/Y， ME， and CA/Y+ME groups， the CA/Y+ME and CA/Y+MCAO groups showed decreased amplitudes of P-wave and T-wave， shortened P-R interval， and extended Q-T interval， which were particularly obvious in the CA/Y+MCAO group （P<0.05， P<0.01） and in accordance with the cerebral infarction area and pathological changes. The expression of Cx43 was up-regulated in both CA/Y+ME and CA/Y+MCAO groups， especially in the CA/Y+MCAO group （P<0.01）. ConclusionThe two rat models of ACI due to stasis combined with toxin complicated with CCS can be used to study the mechanism of heart diseases caused by cerebrovascular diseases and the therapeutic effects of Chinese medicines with the functions of resolving stasis and detoxifying. Moreover， the CA/Y+MCAO method has higher abnormal electrocardiogram rate， severer myocardial pathological injury， and higher expression of Cx43 protein. The models can be chosen according to specific experimental purpose.
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ObjectiveTo explore the clinical efficacy and safety of Fuzheng Huaji Longbi decoction in treating benign prostatic hyperplasia （BPH） in the patients with the syndrome of healthy Qi deficiency and blood stasis. MethodA total of 94 BPH patients were randomized into control and observation groups， with 47 patients in each group. The control group was treated with doxazosin mesylate sustained-release tablets， and the observation group with Fuzheng Huaji Longbi decoction on the basis of the therapy in the control group. After eight weeks， the international prostate symptom score （IPSS）， quality of life （QOL） score， residual urine volume （RUV）， maximum urinary flow rate （Qmax）， TCM syndrome score， TCM symptom score， electrocardiogram， and liver and kidney function were determined to evaluate the clinical efficacy and safety of the two groups. ResultAfter 8 weeks of treatment， the total response rate in the control group was 63.64% （28/44）， which was lower than that （84.44%， 38/45） in the observation group （χ2=5.026， P<0.05）. The clinical efficacy in the observation group was higher than that in the control group （Z=-2.17， P=0.030）. The treatment in both groups decreased the IPSS， QOL score， RUV， and TCM syndrome scores and increased the Qmax （P<0.05）. Moreover， the observation group had lower IPSS， QOL score， RUV， and TCM syndrome score （P<0.05） and higher Qmax than the control group after treatment （P<0.05）. The treatment in the observation group decreased all the TCM symptom scores （P<0.05）， while that in the control group only decreased the frequency of urination at night and the scores of dysuria， weak urine stream， and post-urinary drainage （P<0.05）. After treatment， the observation group had lower frequency of urination at night and lower scores of mental fatigue， cold limbs， lower abdominal discomfort， and loose stool than the control group （P<0.05）. No adverse events associated with the administration of Fuzheng Huaji Longbi decoction were observed during the treatment period. ConclusionFuzheng Huaji Longbi decoction is effective in treating BPH in the patients with the syndrome of healthy qi deficiency and blood stasis. It can relieve the clinical symptoms and improve the quality of life， being a safe and reliable choice for clinical application.
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ObjectiveTo decipher the mechanism of Danshenyin in regulating platelet activation in the rat model of hyperlipidemia by means of proteomics and molecular biology. MethodWistar rats were randomized into blank， model， and Danshenyin groups （n=10） according to the blood lipid level. The rats in the blank group were fed with a basic diet， and those in the model and Danshenyin groups with a high-fat diet. All the rats had free access to water and food. The treatment began at the 9th week. The rats in the Danshenyin group were administrated with Danshenyin by gavage at a crude drug dose of 3.6 g·kg-1. The rats in the model and blank groups were administrated with an equal volume of normal saline according to body weight. At the 12th week， the tissue samples were collected for the measurement of related indicators， and the blood lipid level was measured by an automatic biochemical analyzer. The whole blood viscosity and plasma viscosity were measured by an automatic hemorheometer. The platelet proteome was determined by liquid chromatography-mass spectrometry. Western blotting was employed to determine the protein levels of platelet membrane glycoprotein 4 （CD36）， focal adhesion kinase （FAK）， phosphatidylinositol 4-phosphate 5-kinase （PIP5K）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， protein kinase B （Akt）， and phosphorylated protein kinase B （p-Akt）. ResultCompared with the model group， Danshenyin lowered the levels of total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） in the plasma （P<0.05）， elevated the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）， and reduced the platelet aggregation rate （P<0.05）. Compared with the blank group， the modeling up-regulated the expression of 44 proteins and down-regulated the expression of 12 proteins. Compared with the model group， Danshenyin up-regulated the expression of 21 proteins and down-regulated the expression of 22 proteins. Compared with the blank group， Danshenyin up-regulated the expression of 31 proteins and down-regulated the expression of 49 proteins. The gene ontology （GO） functional enrichment showed that the differentially expressed proteins were mainly involved in cholesterol transport and efflux， production of cytokines， dyslipidemia， and platelet activation. The Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment showed that the differentially expressed proteins were mainly involved in ECM-receptor interaction， peroxisome proliferators-activated receptors （PPAR）， focal adhesion， and PI3K/Akt signaling pathways. Danshenyin can significantly down-regulate the expression of CD36， FAK， PIP5K， PI3K， p-Akt （Ser473）， and p-Akt1/2/3 （Thr308）. ConclusionDanshenyin can restore the blood lipid level of hyperlipidemia rats and inhibit the platelet activation caused by abnormal lipid levels by down-regulating the CD36/PI3K/Akt signal cascade.
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Depression syndromes(anxiety and depression), as typical psychological disorders, often coexist with and mutually influence coronary heart disease(CHD). They constitute a psycho-cardiology disease involving both the blood vessels of the heart and the spirit of the heart. Based on the theory of "coexistence of diseases and depression syndromes", it was proposed that CHD and depression syndromes coexisted independently and were causally related. The factors of depression syndromes go through the entire course of CHD and have different causal relationships at different stages, leading to a pathogenic process of "depression causing disease" or "disease causing depression". In the chronic latent period, phlegm predominates, with depression leading to the production of phlegm. Phlegm accumulation and Qi stagnation initiate a mutual damage process of psycho-cardiology, marking the onset of the disease. In the pathological development period, blood stasis becomes predominant. Depression leads to blood stasis, which further obstructs Qi circulation, accelerating disease progression. In the acute attack period, toxicity becomes crucial. Depression transforms into toxicity, damaging Qi and blood, disturbing the balance of the mind, and inducing a sudden and severe exacerbation of the disease. Based on this, the approach of treating phlegm and depression together, treating blood stasis and depression together, and treating toxicity and depression together by stages was established. Research has found that this approach can simultaneously improve organic damage and emotional disorders, and also has a regulating effect on micro-level syndrome indicators, achieving harmonization of psycho-cardiology in the treatment.
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Humans , Medicine, Chinese Traditional , Depression/diagnosis , Coronary Disease/diagnosis , Mucus , Syndrome , AnxietyABSTRACT
This study investigated the effects of Xuefu Zhuyu Decoction on myocardial metabolites in a rat model of coronary heart disease with heart blood stasis syndrome and explored the therapeutic mechanism of blood circulation-promoting and blood stasis-removing therapy. SD rats were randomly divided into a sham operation group, a model group, a Xuefu Zhuyu Decoction group(14.04 g·kg~(-1)), and a trimetazidine group(5.4 mg·kg~(-1)). The sham operation group underwent thread insertion without ligation, while the other groups underwent coronary artery left anterior descending branch ligation to induce a model of coronary heart disease with heart blood stasis syndrome. Three days after modeling, drug intervention was performed, and samples were taken after 14 days of intervention. General conditions were observed, and electrocardiogram and cardiac ultrasound indices were measured. Hematoxylin-eosin(HE) staining and Masson staining were used to observe tissue pathological morphology. The enzyme linked immunosorbent assay(ELISA) was used to measure the levels of triglyceride(TG) and total cholesterol(TC) in the serum. Ultra high performance liquid chromatography-quantitative exactive-mass spectrometry(UHPLC-QE-MS) technology was used to screen differential metabolites in myocardial tissue and conduct metabolic pathway enrichment analysis. The results showed that Xuefu Zhuyu Decoction significantly improved the general condition of the model rats, reduced heart rate and ST segment elevation in the electrocardiogram, increased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), and decreased left ventricular internal diameter in diastole(LVIDd) and left ventricular internal diameter in systole(LVIDs). HE staining and Masson staining showed that Xuefu Zhuyu Decoction effectively alleviated myocardial tissue structural disorders, inflammatory cell infiltration, and collagen fiber deposition in the model rats. ELISA results showed that Xuefu Zhuyu Decoction effectively regulated serum TG and TC levels in the model rats. There were significant differences in the metabolic phenotypes of myocardial samples in each group. Fourteen differential metabolites were identified in the Xuefu Zhuyu Decoction group, involving five metabolic pathways, including arginine and proline metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, ether lipid metabolism, and alanine, aspartate, and glutamate metabolism. Xuefu Zhuyu Decoction improved cardiac function and myocardial structural damage in the rat model of coronary heart disease with heart blood stasis syndrome, and its biological mechanism involved the regulation of lipid metabolism, choline metabolism, amino acid metabolism, energy metabolism, and protein synthesis pathways.
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Rats , Animals , Stroke Volume , Rats, Sprague-Dawley , Ventricular Function, Left , Coronary Disease/drug therapy , MetabolomicsABSTRACT
Objective:To evaluate the efficacy of Qinggan Huashi Huoxue Decoction combined with conventional Western medicine in the treatment of alcoholic cirrhosis with spleen deficiency and phlegm stasis syndrome.Methods:Randomized controlled trial. A total of 110 patients from Tangshan Fengrun District Hospital of Traditional Chinese Medicine from March 2020 to March 2022 were selected as observation objects and divided into 2 groups with 55 patients in each group by computer random drawing method. The control group was treated with conventional Western medicine, while the observation group was treated with Qinggan Huashi Huoxue Decoction on the basis of the control group treatment. Both groups were treated for 3 months. The traditional Chinese medicine syndrome score was performed before and after treatment, and the levels of proline peptidase (PLD), type Ⅳ collagen (Ⅳ-C) and type Ⅰ procollagen aminopeptidase (PINP) were detected by phthalaldehyde contrast colorimetry, and the levels of pentamylin 3 (PTX3), protein kinase B (Akt) and B cell activating factor receptor (BAFF-R) were determined by ELISA. Adverse events were recorded and clinical efficacy was evaluated.Results:The total effective rate in the observation group was 92.73% (51/55), while that in the control group was 76.36% (42/55), the difference between the two groups was statistically significant ( χ2=5.64, P=0.018). After treatment, the score and total score of costal pain and fullness, swelling and firmness, anorexia, white and greasy tongue coating in the observation group were significantly lower than those in the control group ( t values were 11.02, 7.36, 7.47, 6.38, 9.37, respectively, P<0.01). After treatment, the levels of serum PLD[(143.28±16.38)U/L vs. (160.69±18.35)U/L, t=5.25], Ⅳ-C[(71.93±8.33)μg/L vs. (83.12±9.91)μg/L, t=6.41], and PINP[(32.36±5.32)ng/L vs. (39.02±5.61)ng/L, t=6.39] in the observation group were significantly lower than those in the control group ( P<0.01); The levels of PTX3[(36.82±4.96)ng/L vs. (42.14±5.83)ng/L, t=5.15], Akt[(69.22±7.94)ng/L vs. (77.24±8.63)ng/L, t=5.07], and BAFF-R[(15.29±3.64)ng/L vs. (19.92±4.15)ng/L, t=6.22] in the observation group were significantly lower than those in the control group ( P<0.01). During the treatment period, the incidence of adverse reactions was 12.73% (7/55) in the observation group and 9.09% (5/55) in the control group, with no statistically significant difference between the two groups ( χ2=0.37, P=0.541). Conclusion:Qinggan Huashi Huoxue Decoction combined with conventional Western medicine therapy can improve the Traditional Chinese Medicine syndrome and the degree of liver fibrosis damage in patients with alcoholic cirrhosis with spleen deficiency and phlegm stasis syndrome, inhibit the expression of serum inflammatory factors, and improve clinical efficacy.
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Objective:To explore the medication law and core Traditional Chinese Medicine (TCM) compounds in the treatment of blood stasis vascular dementia (VD) based on data mining.Methods:The literature about TCM treatment for blood stasis VD was retrieved from the databases of CNKI, Wanfang, VIP, and CBM from January 2000 to November 2021. Microsoft Office Excel 2019, SPSS Modeler 18.0, SPSS Statistics 25.0, R X64 4.1.2, and Origin 2021 were used to perform medication frequency analysis, frequency analysis of four properties and five tastes of TCM, association rules, clustering analysis, factor analysis and data visualization.Results:A total of 196 articles were included, with 196 TCM prescriptions, involving 200 kinds of Chinese materia medica. High-frequency drugs were for Acori Tatarinowii Rhizoma, Chuanxiong Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Polygalae Radix, Carthami Flos. The medicinal properties were mainly warm, mild and cold, the tastes were mainly sweet, bitter and pungent, and the meridians were mainly liver meridian, spleen meridian and heart meridian. A total of 19 association rules were obtained from the analysis of association rules for 2 kinds of Chinese materia medica, and the rules of the representative were Acori Tatarinowii Rhizoma- Polygalae Radix, Chuanxiong Rhizoma- Carthami Flos, Acori Tatarinowii Rhizoma- Curcumae Radix. A total of 4 categories were extracted through clustering analysis. Factor analysis extracted a total of 8 common factors. Conclusion:The core pathogenesis of blood stasis VD is blood stasis blocking brain collaterals, and there were also pathological factors such as qi deficiency, yin deficiency, phlegm turbidity and so on. The basic treatment is promoting blood circulation and removing stasis, and different methods of promoting blood circulation and drugs are selected. The methods of strengthening spleen and reducing phlegm, nourishing yin and blood, inducing resuscitation, tonifying the kidney and spleen, regulating qi, promoting collaterals and so on can also be used based on syndromes and symptoms of the patients.
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Objective:To reveal the regular pattern characteristics of different diseases with the same treatment in the most common diseases with blood stasis syndrome; To provide reference for the clinical treatment of blood stasis syndrome and the development of new drugs.Methods:RCTs of blood stasis syndrome were retrieved from CNKI, Chongqing VIP, Wanfang Data, SinoMed, and China Medical Journal Full-text Database from the establishment of the databases to December 31, 2022. Diseases, accompanied symptoms, prescriptions and medicines were extracted. The diseases with the highest frequency among the three disease systems with the highest frequency were collected, and their medication characteristics and prescription rules were analyzed using frequency statistics and association rules Apriori algorithm. The core prescriptions of blood stasis syndrome of three kinds of diseases were excavated and their network similarity was analyzed.Results:A total of 2 052 articles were included. Stable coronary heart disease, ischemic stroke and DN were more common diseases with blood stasis syndrome. The common drugs for the three diseases were Chuanxiong Rhizoma, Carthami Flos, Persicae Semen, Angelicae Sinensis Radix. The core prescription of stable coronary heart disease was Persicae Semen- Carthami Flos- Chuanxiong Rhizoma- Angelicae Sinensis Radix- Paeoniae Radix Rubra; the core prescription of ischemic stroke is Buyang Huanwu Decoction; the core prescription of DN was Persicae Semen- Carthami Flos- Chuanxiong Rhizoma- Angelicae Sinensis Radix- Cornus Officinalis- Dioscoreae Rhizoma- Astragali Radix. The similarity between stable coronary heart disease and ischemic stroke core prescription network was 0.35, the similarity between ischemic stroke and DN core prescription network was 0.29, and the similarity between stable coronary heart disease and DN core prescription network was 0.26. Conclusions:The theory of "different diseases with the same treatment" can profoundly guide clinical practice. The core medicines of blood stasis syndrome are Persicae Semen, Carthami Flos, Angelicae Sinensis Radix, and Chuanxiong Rhizoma. On this basis, combined with different diseases and syndromes to make changes of adding and subtracting.
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Objective:To evaluate the efficacy of Peiyuan Kangai Decoction combined with acupuncture in the treatment of advanced liver cancer with qi deficiency and blood stasis syndrome.Methods:Randomized controlled trial. From May 2019 to May 2021, 162 advanced liver cancer patients with qi deficiency and blood stasis syndrome in Shizhong District Cancer Hospital of Leshan were randomly divided into three groups by random drawing method, with 54 in each group. All patients were given FOLFOX4 chemotherapy regimen. Based on the chemotherapy, the 1st control group was given Peiyuan Kangai Decoction, and the 2nd control group was given acupuncture therapy, and the combined group was given decoction and acupuncture therapy. All three groups were treated for 6 weeks. Traditional Chinese Medicine syndrome score was performed before and after treatment, Piper fatigue scale was used to evaluate the fatigue degree of patients. Vimentin (VIM), Golgi transmembrane glycoprotein 73 (GP73) and chemokine ligand 1 (CXCL1) were determined by ELISA. The adverse reactions during treatment were observed and the clinical efficacy was evaluated.Results:The combined group showed the response rate was 61.11% (33/54), the disease control rate was 72.22% (39/54), the 1st control group showed the response rate was 40.74% (22/54), the disease control rate was 53.70% (29/54), and the 2nd control group showed the response rate was 38.89% (21/54), and the disease control rate was 51.85% (28/54). The response rate and disease control rate of the combined group were significantly higher than either the control group 1 and 2 ( χ2 values were 6.59, 5.68, respectively, and P values were 0.037, 0.043, respectively). After treatment, the scores of liver swelling and pain, fatigue and shortness of breath, anorexia, sallow and emaciation in the combined group were significantly lower than those in the control group 1 and the control group 2 ( F values were 13.90, 15.69, 13.20, 10.55, respectively, P<0.01); the scores of emotions, feeling, behavior and cognition were significantly lower than those in the control group 1 and control group 2 ( F values were 49.55, 27.42, 19.69, 20.55, respectively, P<0.01). After treatment, the levels of serum VIM [(52.54±6.69) ng/L vs. (61.29±7.89) ng/L, (65.11±7.92) ng/L, F=39.63], GP73 [(19.72±3.90) ng/L vs. (24.42±4.23) ng/L, (25.12±4.76) ng/L, F=25.05], CXCL1 [(3.12±0.72) ng/L vs. (4.85±0.95) ng/L, (4.98±0.91) ng/L, F=77.67] in the combined group were significantly lower than those in the control group 1 and the control group 2 ( P<0.01). During the treatment, the incidence of toxic and side effects in the combined group was 18.52% (10/54), the control group 1 was 27.78% (15/54), and the control group 2 was 24.07% (13/54). There was no statistically significant difference in the incidence of toxic and side effects among the three groups ( χ2=1.31, P=0.520). Conclusion:On the basis of FOLFOX4 chemotherapy, combined therapy with Peiyuan Kangai Decoction and acupuncture treatment can improve the symptoms and fatigue of patients with advanced liver cancer, reduce the levels of serum VIM, GP-73, CXCL1, improve the efficacy safely.
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Objective:To evaluate the clinical effect of treatment of activating blood and removing blood stasis, invigorating the spleen and soothing the liver for the patients with gastric collateral stasis syndrome and chronic atrophic gastritis (CAG).Methods:Randomized controlled trial. A total of 68 CAG patients admitted to the Huairou Hospital of Traditional Chinese Medicine from January 2018 to January 2021 who met the selection criteria were divided into 2 groups according to the random number table method, with 34 in each group. The control group received conventional western medicine treatment, such as inhibition of acid, protecting the gastric mucosa, and the observation group was treated with Traditional Chinese Medicine (TCM) herbal prescription of activating blood and removing blood stasis, invigorating the spleen and soothing the liver. Both groups were treated for 12 weeks. TCM symptom scores were performed before and after treatment. The serum level of pepsinogen Ⅰ(PG Ⅰ), pepsinogen Ⅱ (PGⅡ) were detected by ELISA, and the PG Ⅰ/PG Ⅱ ratio was calculated. Gastroscopic biopsy was performed to observe the changes of intestinal metaplasia of gastric mucosa and glandular atrophy, and to evaluate the clinical efficacy.Results:The total responsive rate was 85.3% (29/34) in the study group and 58.8% (20/34) in the control group. There was significant difference between the two groups ( χ2=9.35, P=0.030). After treatment, the scores of stomachache, fullness of feeling in the observation group were significantly lower than those in the control group ( t=2.97, 3.80, P<0.05). After treatment, the level of serum PG Ⅰ[(76.21 ± 17.35) mg/L vs. (66.8 ± 18.77) mg/L, t=2.15] and PG Ⅰ/PG Ⅱ [(4.67 ± 0.99) vs. (3.90± 1.25), t=2.81] in the study group were significantly higher than those in the control group ( P<0.05), and PG Ⅱ [(16.36 ± 1.85) mg/L vs. (17.42 ± 2.05) mg/L, t=2.24] was significantly lower than that of the control group ( P<0.05). After treatment, intestinal metaplasia and glandular atrophy was significantly more improved or reversed than those in the control group ( χ2=20.67,9.33, P<0.05). Conclusion:The methods of activating blood and removing blood stasis, invigorating the spleen and soothing the liver can reverse the precancerous lesions of patients with gastric collateral stasis syndrome of chronic atrophic gastritis and have a good prognosis.
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Objective:To observe the intervention mechanism of phlegm-stasis co-treatment for the JNK signaling pathway in the myocardium of diabetes rats.Methods:Totally 50 male SD rats of SPF grade were selected. Diabetes model was established by single intraperitoneal injection of 55 mg/kg streptozotocin (STZ) solution. After continued feeding for 3 weeks, the rats were divided into normal group, model group, alachloramine group, blood stasis removing group, phlegm removing group and phlegm-blood stasis co-treatment group according to random number table method, with 6 rats in each group. Xiaoxianxiong Decoction (4.05 g/kg), Xuefu Zhuyu Decoction (7.02 g/kg), Didang Xianxiong Decoction (8.10 g/kg) were administered to the stomach respectively in the phlegm removing group, the blood stasis removing group and the phlegm-blood stasis co-treatment group. Alachloramine (3 mg/kg) was administered to the stomach by gavage in the alachloramine group. After 8 weeks, HE staining was used to observe the morphological changes of myocardial tissue in diabetic rats. Masson staining was used to observe the deposition of collagen fibers in the myocardial interstitium in rats. The expression of JNK1 protein was determined by immunohistochemistry. JNK1 mRNA, IRS1 mRNA and NLRP3 expression levels were detected by Real-time PCR. Western blot was used to detect the protein expressions of IRS-1, p-Akt and NLRP3.Results:The myocardial cells in the model group were disorganized, with hypertrophy, blurred texture, inflammatory infiltration of interstitium, increased collagen fibers, and focal necrosis. All treatment groups could improve fibrosis, inflammatory infiltration and reduce myocardial collagen deposition in different degrees. Compared with the model group, the mRNA and protein expressions of JNK1 and NLRP3 bodies decreased ( P<0.01), the IRS-1 mRNA and protein increased ( P<0.01), and p-Akt protein expression increased ( P<0.01). Conclusions:The phlegm and stasis co-treatment can effectively improve the cardiomyopathy of diabetes rats, and the effect is better than the phlegm-resolving method or the stasis resolving method alone. The mechanism may be related to the inhibition of JNK signaling pathway activation, reduce the expressions of JNK1 and NLRP3, and increase the IRS-1 and Akt.
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Objective:To observe the clinical efficacy of Qigui Tangtongning Granules in the treatment of diabetic peripheral neuropathy (DPN) with qi deficiency and blood stasis.Methods:Prospective cohort study. A total of 80 DPN patients with Qi deficiency and blood stasis in Endocrinology Department of the First Affiliated Hospital of Anhui University of Chinese Medicine from May 2021 to May 2022 who met the inclusion criteria were divided into 2 groups by random number table method, with 40 cases in each group. The control group was treated with epalrestat on the basis of routine hypoglycemia, and the treatment group was treated with Qigui Tangtongning Granules on the basis of control group. Both groups were treated for 8 weeks. TCM syndromes were scored before and after treatment. Disease severity was assessed using the Toronto Clinical Scoring System (TCSS). The motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of median nerve and common peroneal nerve were detected by electromyography/induced potentiometer. Serum CRP, TNF-α and IL-6 were detected by ELISA, fasting blood glucose (FPG) and two hours post-meal blood glucose (2 hPG) were detected by automatic biochemical analyzer, and glycosylated hemoglobin (HbA1c) was detected by automatic HBA1C analyzer. Adverse reactions were recorded and clinical efficacy was evaluated.Results:The total effective rate was 95.0% (38/40) in the treatment group and 77.5% (31/40) in the control group, the difference between the two groups was statistically significant ( χ2=5.17, P=0.023). After treatment, the TCM syndrome score and TCSS score of the treatment group were significantly lower than those in the control group ( t=-3.19 and -7.63, P<0.01); Median nerve SNCV [(47.90±4.51) m/s vs. (44.76±3.72) m/s, t=3.40], MNCV [(53.79±3.65) m/s vs. (51.32±4.25) m/s, t=2.79] and common peroneal nerve SNCV [(44.21±2.08) m/s vs. (40.51±2.49) m/s, t=7.23], MNCV [(44.63±4.72) m/s vs. (41.36±4.87) m/s, t=3.05] were significantly higher than those in the control group ( P<0.01); FPG [(5.05±0.63) mmol/L vs. (7.05±1.23) mmol/L, t=-9.17], 2 hPG [(9.10±1.64) mmol/L vs. (12.19±2.61) mmol/L, t=-6.35], HbA1c [(6.79±0.90) % vs. (7.22±1.02) %, t=-2.02] were significantly lower than those in the control group ( P<0.01 or P<0.05); TNF-α [(15.75±5.44) ng/L vs. (32.01±5.33) ng/L, t=-13.51], hs-CRP [(2.58±0.80) mg/L vs. (3.79±1.04) mg/L, t=-5.83], IL-6 [(18.20±4.92) ng/L vs. (29.97±5.18) ng/L, t=-10.41] were significantly lower than those in the control group ( P<0.01). No obvious adverse reactions were observed in 2 groups during treatment. Conclusion:Qigui Tangtongning Granules combined with conventional Western medicine can improve nerve conduction velocity, reduce inflammation and improve clinical efficacy in DPN patients with Qi-deficiency and blood-stasis syndrome.
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Objective:To observe the effects of TCM compounds for eliminating phlegm and removing blood stasis on the ultrastructure of atrial myocardium in atrial fibrillation (AF) rats; To explore its possible mechanism.Methods:Totally 60 male SD rats were divided into blank group (10 rats) and model group (50 rats) according to random number table method. The atrial fibrillation model was established by tail vein injection of ACh-CaCl 2 mixture for 7 consecutive days, and then the rats with successful modeling were divided into model group, verapamil group, TCM compounds high-, medium- and low-dosage groups according to random number table method, with 10 rats in each group. TCM compounds high-, medium- and low-dosage groups were given Chinese herbal decoction 41.25, 20.63, 10.31 g/(kg?d) by gavage, respectively, and the verapamil group was given verapamil solution 25 g/(kg?d). The blank group and the model group were given an equal volume of normal saline by gavage for consecutive 14 days. After 14 consecutive days, electrophysiological recorder was used to measure the duration of atrial fibrillation in each group of rats; the changes of ultrastructure of atrial myocytes in each group were observed under transmission electron microscope; serum ROS, SOD and GSH-Px levels of rats were detected by ELISA. Results:Compared with the model group, the duration of atrial fibrillation in TCM compounds high-, medium- and low-dosage groups and verapamil group decreased ( P<0.05); the ultrastructural damage of atrial myocytes was improved; the content of ROS [(139.20±3.34) ng/ml,(139.00±3.28) ng/ml, (139.25±3.82) ng/ml vs. (155.60±7.32) ng/ml] in TCM compounds high- and medium-dosage groups and verapamil group decreased; the contents of SOD [(2.41±0.26) ng/ml, (2.40±0.12) ng/ml, (2.37±0.06) ng/ml vs.(2.12±0.21) ng/ml] increased ( P<0.05); the content of GSH-Px [(3.61±0.06) ng/ml, (3.60±0.08) ng/ml, (3.47±0.15) ng/ml, (3.51±0.19) ng/ml vs.(3.27±0.12) ng/ml] in TCM compounds high-, medium- and low-dosage groups and verapamil group increased ( P<0.05). Conclusion:TCM compounds for eliminating phlegm and removing blood stasis can shorten the duration of atrial fibrillation in rats, reduce the damage of ultrastructure of atrial myocytes in AF rats, regulate the expressions of serum ROS, SOD and GSH-Px in AF rats, and inhibit oxidative stress, which may be one of its mechanisms of action in the treatment of atrial fibrillation.