Combined Therapies of Traditional Chinese Medicine Treat Low-prognosis Patients Undergoing IVF-ET Again / 中国实验方剂学杂志

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.

Comparison on Rat Models of Acute Cerebral Infarction Due to Stasis Combined with Toxin Complicated with Cerebral-cardiac Syndrome / 中国实验方剂学杂志

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.

Clinical Efficacy of Fuzheng Huaji Longbi Decoction in Treating Benign Prostatic Hyperplasia with Syndrome of Healthy Qi Deficiency and Blood Stasis / 中国实验方剂学杂志

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.

Mechanism of Danshenyin in Inhibiting Platelet Activation in Rat Model of Hyperlipidemia Based on Proteomics / 中国实验方剂学杂志

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.

Pathogenesis and Traditional Chinese Medicine Prevention and Treatment Strategy of Refractory Angina Based on Theory of Stasis and Toxin / 中国实验方剂学杂志

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.

Exploring Modern Mechanism of Treating Diabetic Retinopathy and Coronary Heart Disease from Perspective of Blood Stasis Under Viewpoint of Treating Different Diseases with the Same Method / 中国实验方剂学杂志

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.

Clinical Effect of Jianpi Huoxue Prescription Combined with Acupuncture on Chronic Atrophic Gastritis with Gastric Blood Stasis and Its Impact on Inflammatory Indicators and Gastric Mucosal Function / 中国实验方剂学杂志

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.

Discussion on the Scientific Connotation of Fortifying Spleen， Resolving Phlegm and Dispelling Stasis in the Treatment of Coronary Heart Disease under the Guidance of Dysfunctional High-Density Lipoprotein / 中医杂志

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.

Cinobufagin Combined with Thalidomide/Dexamethasone Regimen in the Treatment of Patients with Newly Diagnosed Multiple Myeloma of Phlegm and Stasis Obstruction： A Retrospective Study / 中医杂志

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.

Transcriptome Sequencing on Treatment of Kidney Deficiency and Blood Stasis-thin Endometrium in Rats with Bushen Huoxue Prescription Through Enema / 中国实验方剂学杂志

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.

Mechanism of Danggui Sini Decoction in improving kidney injury caused by blood stasis syndrome based on metabolomics and network pharmacology / 中国中药杂志

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

Characteristic changes of blood stasis syndrome in rat model of steroid-induced femoral head necrosis based on the combination of disease, syndrome, and symptom / 中国中药杂志

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

Syndrome differentiation and treatment of coronary heart disease combined with anxiety and depression from stages of phlegm, blood stasis, and toxic pathogen based on theory of "coexistence of diseases and depression syndromes" / 中国中药杂志

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.

Efficacy and mechanism of Xuefu Zhuyu Decoction on model rats of coronary heart disease with heart blood stasis syndrome based on metabolomics / 中国中药杂志

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.

Therapy of Dispelling Stasis， Removing Toxin， and Promoting Urination （Xuebijing Injection Combined with Modified Linggui Zhugantang） Affects Prognosis of Sepsis-induced Cardiomyopathy / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of the therapy of dispelling stasis， removing toxin， and promoting urination （modified Linggui Zhugantang combined with Xuebijing injection） on the prognosis of sepsis-induced cardiomyopathy （SICM）. MethodA total of 96 patients were randomly assigned into an observation group and a control group， with 48 patients in each group. The patients in the control group received sepsis bundle， and those in the observation group additionally received the therapy of dispelling stasis， removing toxin， and promoting urination （intravenous drip of Xuebijing injection and oral administration of modified Linggui Zhugantang）. The course of treatment in both groups was 7 days. The disease and prognosis indicators ［28-day mortality， intensive care unit （ICU） length of stay， major adverse cardiac events （MACE）， acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ）， sequential organ failure assessment （SOFA） score， and mortality in emergency department sepsis （MEDS） score］， cardiac function indicators ［left ventricular ejection fraction （LVEF）， E/A ratio of peak velocity blood flow from left ventricular relaxation in early diastole （the E wave） to peak velocity flow in late diastole caused by atrial contraction （the A wave）， E/e′ ratio of mitral peak velocity of early filling （E） to early diastolic mitral annular velocity （e′）， and afterload-corrected cardiac performance （ACP）］， myocardial injury markers ［high-sensitivity cardiac troponin T （hs-cTnT）， N-terminal pro-brain natriuretic peptide （NT-proBNP）， heart-type fatty acid-binding protein （H-FABP）， and high mobility group box-1 （HMGB-1）］， hemodynamic indicators ［extravascular lung water index （EVLWI）， global end-diastolic volume index （GEDVI）， cardiac index （CI）， and systemic vascular resistance index （SVRI）］， and TCM syndrome scores were assessed and compared between the two groups. ResultThe 28-day mortality and the incidence of MACE in the observation group were slightly lower than those in the control group. The ICU length of stay in the observation group was shorter than that in the control group （P<0.05）. After treatment， APACHE Ⅱ， SOFA， MEDS， syndrome score of stasis-caused internal obstruction， E/e′ ratio， hs-cTnT， NT-proBNP， H-FABP， and HMGB1 decreased compared with those before treatment （P<0.05）， while LVEF， E/A ratio， and ACP increased （P<0.05）. Moreover， the changes were more significant in the observation group （P<0.05）. On days 3， 5， and 7 after treatment， the EVLWI and SVRI in the observation group were lower than those in the control group （P<0.05）， while CI showed an opposite trend （P<0.05）. The observation group had higher GEDVI than the control group on days 3 and 5 after treatment （P<0.05）. ConclusionOn the basis of conventional bundle therapy， modified Linggui Zhugantang combined with Xuebijing injection with the effect of dispelling stasis， removing toxin， and promoting urination can inhibit the generation of myocardial injury markers and improve hemodynamics to shorten the length of ICU stay， mitigate the TCM syndrome， and reduce the risk of death， thereby improving the prognosis of SICM.

Syndrome Distribution and Characteristics of Endometriosis in 1 895 Cases / 中国实验方剂学杂志

ObjectiveTo explore the distribution and characteristics of traditional Chinese medicine （TCM） syndromes in patients with endometriosis （EMS）. MethodA cross-sectional survey was conducted to analyze the characteristics of TCM syndromes in 1 895 cases of EMS in hospitals of 19 provinces， autonomous regions， and municipalities. ResultAmong the 1 895 patients， Qistagnation and blood stasis syndrome accounted for the highest proportion， followed by Qi deficiency and blood stasis syndrome， cold coagulation and blood stasis syndrome， and kidney deficiency and blood stasis syndrome. The distribution of TCM syndrome types of patients with EMS in different regions， different treatment stages， and different disease types and with different therapeutic goals was different， and the differences were statistically significant. However， under different conditions， the Qi stagnation and blood stasis syndrome accounted for the highest proportion. Under the stratification of different regions， the cold coagulation and blood stasis syndrome in north China was relatively high， the kidney deficiency and blood stasis syndrome in south China was relatively high， and the combined phlegm and stasis syndrome was relatively high in southwest China. Different diagnosis and treatment goals corresponded to different clinical syndromes. With pelvic pain as the main manifestation， the proportion of cold coagulation and blood stasis syndrome was higher. The proportion of kidney deficiency and blood stasis syndrome was higher in married patients with infertility. Patients with the main diagnosis and treatment goals of controlling mass and inhibiting recurrence had a higher proportion of Qi deficiency and blood stasis syndrome. In different treatment stages， the proportion of Qi deficiency and blood stasis syndrome in postoperative patients and those with recurrent EMS was higher. Among different disease types， the Qi deficiency and blood stasis syndrome accounted for a higher proportion in patients with ovarian endometriosis （OEM）. The cold coagulation and blood stasis syndrome accounted for a higher proportion in patients with deep invasive endometriosis （DIE）. The kidney deficiency and blood stasis syndrome accounted for a higher proportion in patients with peritoneal EMS. There were significant differences in age， body mass index （BMI）， and course of disease among patients with different syndromes. Patients with Qi deficiency and blood stasis syndrome was relatively older， and their course of the disease was relatively long. Patients with combined phlegm and stasis syndrome had relatively high BMI. There was no significant difference in CA125 and CA199 levels among all syndrome types. ConclusionThe distribution of TCM syndromes of EMS has a certain regularity， and there are differences in regional distribution， therapeutic goals， treatment stages， and disease types（P<0.05）. However， the Qi stagnation and blood stasis syndrome accounts for a large proportion under different conditions， suggesting that Qi stagnation is the key link of EMS. In the early stage， the team took relieving depression and activating blood as the primary treatment， and created Huoxue Xiaoyi prescription， which was the core prescription for the treatment of EMS with Qi stagnation and blood stasis syndrome， achieving good clinical effect. At the same time， it is emphasized that EMS treatment should be integrated into the concept of chronic disease management and combined with health management. Through psychological counseling， cognitive behavior intervention， popular science lectures， and other methods， it is advised to adjust the emotion of patients with EMS， thereby increasing the curative effect. This study is expected to provide references for the clinical treatment of EMS.

Heterogeneity of Outcomes Reporting in Trials Evaluating Traditional Chinese Medicine Breast Massage for Stasis Acute Mastitis: A Methodological Review / 中国医学科学杂志(英文版)

Objective To systematically analyze the current status of outcomes reporting in clinical trials on treating stasis acute mastitis with Traditional Chinese Medicine breast massage.Methods We searched CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Embase, Cochrane library, JBI, CINAHL, PsycINFO, Clinical Trials Registry Platform portal, Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, Center Watch Registry from inception to May 15, 2022 to find randomized controlled trials, non-randomized controlled trials, case series and cohort studies which reported the outcomes of stasis acute mastitis managed with Traditional Chinese Medicine breast massage, with search terms of mastitis, acute mastitis, lactation mastitis, puerperal mastitis, breast problem, breast engorgement, milk stasis, blocked ducked, breast pain, breast massage, and acupoint massage. Outcomes and the measurement schemes (measurement methods, timing of assessing outcome, frequency of assessing outcome, measurers) were extracted from the included studies. We used the Management of Otitis Media with Effusion in Children with Cleft Palate (MOMENT) to assess the quality of each study, then categorized outcomes derived from the included studies into different domains according to the Outcome Measures in Rheumatology Arthritis Clinic Trials (OMERACT) Filter 2.1 framework.Results We identified 85 clinical trials, in which 54 different outcomes were reported. A total of 81.2% (69/85) of studies were assessed as medium quality with a mean score of 2.6, and 18.8% (16/85) as low quality with a mean score of 0.9. These outcomes were organized in three core areas. Lump size (89.4%, 76/85) was the most frequently reported outcome, followed by breast pain (69.4%, 59/85) and milk excretion (68.2%, 58/85). Five methods were used to assess lump size and four methods to assess breast pain.Conclusions The outcomes reported in clinical trials regarding stasis acute mastitis treated by Traditional Chinese Medicine breast massage are heterogeneous. Developing a core outcome set to achieve consistent standards for reporting outcomes and modalities for validation of the outcomes is clearly warranted.

Effect of Liangfang Wenjing Decoction on expression of key glycolytic enzymes in uterus and ovaries of rats with coagulating cold and blood stasis syndrome / 中国中药杂志

This study aimed to investigate the relationship between coagulating cold and blood stasis syndrome and glycolysis, and observe the intervention effect of Liangfang Wenjing Decoction(LFWJD) on the expression of key glycolytic enzymes in the uterus and ovaries of rats with coagulating cold and blood stasis. The rat model of coagulating cold and blood stasis syndrome was established by ice-water bath. After modeling, the quantitative scoring of symptoms were performed, and according to the scoring results, the rats were randomly divided into a model group and LFWJD low-, medium-and high-dose groups(4.7, 9.4, 18.8 g·kg~(-1)·d~(-1)), with 10 in each group. Another 10 rats were selected as the blank group. After 4 weeks of continuous administration by gavage, the quantitative scoring of symptoms was repeated. Laser speckle flowgraphy was used to detect the changes of microcirculation in the ears and uterus of rats in each group. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of uterus and ovaries of rats in each group. The mRNA and protein expressions of pyruvate dehydrogenase kinase 1(PDK1), hexokinase 2(HK2) and lactate dehydrogenase A(LDHA) in the uterus and ovaries of rats were examined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. The rats in the model group showed signs of coagulating cold and blood stasis syndrome, such as curl-up, less movement, thickened veins under the tongue, and reduced blood perfusion in the microcirculation of the ears and uterus, and HE staining revealed a thinning of the endometrium with disorganized arrangement of epithelial cells and a decrease in the number of ovarian follicles. Compared with the model group, the treatment groups had alleviated coagulating cold and blood stasis, which was manifested as red tongue, reduced nail swelling, no blood stasis at the tail end as well as increased blood perfusion of the microcirculation in the ears and uterus(P<0.05 or P<0.01). Among the groups, the LFWJD medium-and high-dose groups had the most significant improvement in coagulating cold and blood stasis, with neatly arranged columnar epithelial cells in uterus, and the number of ovarian follicles was higher than that in the model group, especially mature follicles. The mRNA and protein expressions of PDK1, HK2, LDHA in uterus and ovaries were up-regulated in the model group(P<0.05 or P<0.01), while down-regulated in LFWJD medium-and high-dose groups(P<0.05 or P<0.01). The LFWJD low-dose group presented a decrease in the mRNA expressions of PDK1, HK2 and LDHA in uterus and ovaries as well as in the protein expressions of HK2 and LDHA in uterus and HK2 and PDK1 in ovaries(P<0.05 or P<0.01). The therapeutic mechanism of LFWJD against coagulating cold and blood stasis syndrome is related to the down-regulation of key glycolytic enzymes PDK1, HK2 and LDHA, and the inhibition of glycolytic activities in uterus and ovaries.

Integrated strategy for biomarkers of stable coronary heart disease with phlegm and blood stasis syndrome based on RNA-seq and network pharmacology / 中国中药杂志

This study aimed to analyze the biological foundation and biomarkers of stable coronary heart disease(CHD) with phlegm and blood stasis(PBS) syndrome based on RNA-seq and network pharmacology. Peripheral blood nucleated cells from five CHD patients with PBS syndrome, five CHD patients with non-PBS syndrome, and five healthy adults were collected for RNA-seq. The specific targets of CHD with PBS syndrome were determined by differential gene expression analysis and Venn diagram analysis. The active ingredients of Danlou Tablets were screened out from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the "component-target" prediction was completed through PubChem and SwissTargetPrediction. The "drug-ingredient-target-signaling pathway" network of Danlou Tablets against CHD with PBS syndrome was optimized by Cytoscape software. After the target biomarkers were identified, 90 participants were enrolled for diagnostic tests, and 30 CHD patients with PBS syndrome were included in before-and-after experiment to determine the therapeutic effect of Danlou Tablets on those targets. As revealed by RNA-seq and Venn diagram analysis, 200 specific genes were identified for CHD with PBS syndrome. A total of 1 118 potential therapeutic targets of Danlou Tablets were predicted through network pharmacology. Through integrated analysis of the two gene sets, 13 key targets of Danlou Tablets in the treatment of CHD with PBS syndrome were screened out, including CSF1, AKR1C2, PDGFRB, ARG1, CNR2, ALOX15B, ALDH1A1, CTSL, PLA2G7, LAP3, AKR1C3, IGFBP3, and CA1. They were presumably the biomarkers of CHD with PBS syndrome. The ELISA test further showed that CSF1 was significantly up-regulated in the peripheral blood of CHD patients with PBS syndrome, and was significantly down-regulated after Danlou Tablets intervention. CSF1 may be a biomarker for CHD with PBS syndrome, and it is positively correlated with the severity of the disease. The diagnostic cut-off of CSF1 for CHD with PBS syndrome was 286 pg·mL~(-1).

Mechanism of tonifying kidney and activating blood therapy for premature ovarian failure:a review / 中国中药杂志

Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-β/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.