Exploring the medication pattern and mechanism of action of traditional Chinese medicine in treating polycystic ovary syndrome with kidney deficiency and blood stasis based on data mining and network pharmacology

Background:Using network pharmacology to explore the potential molecular mechanism of traditional Chinese medicine in treating polycystic ovary syndrome(PCOS)with kidney deficiency and blood stasis syndrome.Method:Collect the related literature materials of PCOS with kidney deficiency and blood stasis syndrome treated by traditional Chinese medicine in four databases in recent ten years,extract the information of prescriptions and complete the frequency analysis.Traditional Chinese Medicine Systems Pharmacology Database was used to screen out the effective components.Use Online Mendelian Inheritance in Man and other databases to screen PCOS disease targets.The intersection targets obtained by clustering prescription and PCOS disease targets were submitted to STRING database for protein-protein interaction network analysis,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes pathways were analysed by Metascape.Result:There are 155 kinds of traditional Chinese medicines used in the literature.The most commonly utilized ones are Cuscutae Semen,Angelicae Sinensis Radix,and Rehmanniae Radix Praeparata.The results of the cluster analysis indicated that the plants most commonly found throughout the prescription were Leonuri Herba,Lycopi Herba,Dipsaci Radix,etc.GO results show that biological processes include cell reaction to organic nitrogen compounds and cell reaction to nitrogen compounds.The functional display of GO molecule includes cytokine receptor binding,signal receptor regulator activity and so on.Kyoto Encyclopedia of Genes and Genomes results show that the possible mechanisms of action are cancer pathway,an endocrine resistance signal pathway.Conclusion:Through data mining,the cluster prescription for PCOS with kidney deficiency and blood stasis syndrome is Leonuri Herba,Lycopi Herba,Dipsaci Radix,etc.The network pharmacology research of cluster prescription shows that the main drug components for treating PCOS with kidney deficiency and blood stasis syndrome are quercetin,kaempferol,luteolin,tanshinone IIA,etc.,which act on PTGS2,NCOA2,and other targets,and treat PCOS with kidney deficiency and blood stasis syndrome through cancer and endocrine resistance.

Clinical Nursing Intervention of Moxibustion on Abdominal Distension Symptoms in Heart Failure (Heart and Kidney Yang Deficiency and Blood Stasis Blocking Collaterals Syndrome)

Objective:To investigate the clinical nursing intervention effect of moxibustion on abdominal distension symptoms in heart failure(heart and kidney yang deficiency and blood stasis blocking collaterals syndrome).Methods:62 patients with heart failure(heart and kidney yang deficiency and blood stasis blocking collaterals syndrome)admitted to our hospital from February 2023 to February 2024 were selected and divided into the observation group(n=31)and the control group(n=31)by using the random numerical table method.The control group adopted conventional nursing interventions,and the observation group received the nursing program of the control group with the addition of moxibustion nursing interventions.The nursing effectiveness,quality of life scores,and nursing satisfaction were compared between the two groups.Results:The nursing effectiveness of the observation group was significantly higher than the control group(P<0.05);the quality of life score of the observation group was significantly higher than the control group(P<0.05);the nursing satisfaction of the observation group was significantly higher than that of the control group(P<0.05).Conclusion:The use of moxibustion nursing intervention in patients with heart failure(heart and kidney yang deficiency and blood stasis blocking collaterals syndrome)can effectively relieve the symptoms of abdominal distension,improve patients'quality of life,and increase nursing satisfaction,which has promotion and application values.

Therapeutic effect and apoptosis mechanism of lung-tonifying and expectorant decoction on lung cancer rats with Qi deficiency and blood stasis

Objective:To explore the effect and specific mechanism of lung-tonifying and expectorant decoction on lung cancer rats with Qi deficiency and blood stasis,and aim to provide a new idea on treating the disease with traditional Chinese medicine based on syndrome differentiation.Methods:A total of 60 C57BL/6J male rats were included in the study.The model of Qi deficiency and blood stasis was established in 60 rats by using multiple-factor stimulation.About 10 rats were randomly taken to verify whether the model establishment was successful and the rest of 50 rats were divided into 5 groups with 10 rats each:blank control group,cisplatin group,low dose group,medium dose group and high dose group.The blank control group was treated with normal saline,and cisplatin group was treated with cisplatin while the other three groups were treated with lung-tonifying and expectorant decoction at different doses.The volume change in transplanted tumor,tumor inhibition rate,apoptosis rate,and expression of Bc1-2,Bax.cleaved caspase-3 and cleaved caspase-9 in 5 groups were compared.Results:The rapidest growth rate of transplanted tumor volume was observed in blank control group and the slowest in cisplatin group.The growth rate was gradually decreased with the increasing dose of lung-tonifying and expectorant decoction,and the difference in growth of tumor volume among groups was statistically significant(P<0.05).The cisplatin group showed the highest tumor inhibition rate,with dose-dependent increase(P<0.05).The apoptosis rate in low dose group was higher than blank control group but lower than high dose group(P<0.05).The apoptosis rate in medium dose group was significantly higher man blank control group(P).05).The apoptosis rate in high dose group was significantly higher than control group(P<0.05).The positive expression rates of Bel-2 and Bax in all groups showed statistically significant difference(P<0.05),while expression of cleaved caspase-3 and cleaved caspase-9 in 5 groups was significantly different,with dose-dependent increase(P<0.05).Conclusions:The lung-tonifying and expectorant decoction inhibits the proliferation of tumor cells by inducing and activating the cell apoptosis in treatment of lung cancer with Qi deficiency and blood stasis,probably with good clinical therapeutic effect.

Study of Interference Treatment by Xuesaitong (血塞通) Soft Capsuleon Patients of Nephrosis Syndrome with Qi Deficiency and Blood Stasisduring Dose Reducing Stage of Corticosteroid

Objective: To observe the effect of Xuesaitong (血塞通, XST) soft capsule in interference treatment on patients of nephrosis syndrome (NS) during corticosteroid (CS) dose reducing stage. Methods: Seventy-one NS patients applying prednisone and initiating dose reducing stage were randomized into trial group and control group. On the basis of conventional prednisone dose reduction of both groups, the trial group was given additionally XST, and the treatment course ended with the reduction to maintenance dose. In the course of observation, those who did not comply with the criteria of observation were excluded. Before and after the dose reduction, TCM syndrome scoring, 24 hrs urinary protein amount, blood β2-microglobulin (β2-MG), urinary β2-MG, blood fibrinogen (Fbg), plasma prothrombin time (PT), blood lipid, etc. were observed. Results: The trial group of XST could obviously lower their urinary protein amount and blood lipid level (P<0.05 or P<0.01), markedly improve the blood coagulation parameters (P<0.01), improve the TCM syndrome and CS induced adverse reaction (P<0.05 or P<0.01), also obviously reduced the recurrence rate of NS (P<0.05). Conclusion: XST could obviously improve the clinical symptoms and renal impairment parameters in NS patients during CS dose reduction stage, improve the CS induced adverse reaction and prevent the recurrence of NS.

Preliminary molecular basis of Danggui-buxue-tang on Qi deficiency and blood stasis syndrome

Objective To study the molecular biology mechanism of Danggui-buxue-tang on tonifying Qi and controlling blood circulation through modulation the immune functional genes.Methods Rats were randomly divided into control group,model group,and Danggui-buxue-tang group.Effect of Dang-guibuxue-tang on mRNA expressions of IL-1β,TNF-α,HSP-70,NF-κB,p38MAPK and JNK in blood cells of rats with Qi deficiency and blood stasis were measured with real-time fluorescent quantitative-PCR at 5th,14th and 28th day.And that in artery wall were determined at the 28th day.NF-κB/p65 and p-c-jun protein expressions in rat artery wall were detected by western blotting as well.Results In model group,TNF-α,IL-1β,NF-κB,HSP-70,p38MAPK and JNK mRNA expression in blood cell increased significantly compared with control group.Compared with model group,mRNA expression of IL-1βand JNK decreased significantly;TNF-α decreased at 5th,14th day;HSP-70,p38MAPK decreased at 14th,28th day;NF-κB decreased at 28th day.In model group,TNF-α,IL-1β,NF-κB,p38MAPK and JNK mRNA expression in artery increased compared with control group,excluded HSP-70,and that in Danggui-buxue-tang group decreased significantly.In model group,NF-κB/p65 and p-c-jun protein expression in artery increased compared with control group,and that in Danggui-buxue-tang group decreased significantly.Conclusions The effects of Dang-guibuxue-tang on Qi deficiency and blood stasis syndrome was brought from the regulating of cytokine network at multi-link and multi-target,NF-κB,p38MAPK and JNK signal transduction pathways included.Through which the immune system and whole body reached to a functional balance status.

Serum proteomic approach in patients with Qi deficiency and blood stasis syndrome in coronary heart disease:to explore therapeutic mechanism of Yiqi Huoxue decoction

OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.METHODS The patients with coronary heart disease of Qi deficiency and blood stasis syndrome were treated with Yiqi Huoxue decoction for 3 months,and the changes of cardiac function were observed.61 serum samples(including 29 cases of disease group and 32 cases of Yiqi Huoxue expression group)were analyzed by non labeled proteomics.The disease group was used as the control group,and the protein with expression level difference of more than 1.2 folds(P<0.05)was screened.The molecular function,biological pathway and protein interaction of the different proteins were analyzed by bioinformatics,so as to identify the molecular and biological pathway of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.RESULTS Clinical treatment found that Yiqi Huoxue decoction can improve TCM syndrome score and left ventricular ejection fraction,regulate blood glucose and blood lipid levels,prolong thrombin time,and improve heart function.The results of proteomic quantitative analysis showed that there were 69 proteins with different expression levels in the disease group.Bioinformatics analysis results showed that Yiqi Huoxue decoction may regulate ApoA1,alpha-2 and other proteins to act on HDL assembly,platelet degradation,PI3K Akt signaling pathway,and then play a therapeutic role in coronary heart disease with Qi deficiency and blood stasis syndrome.CONCLUSION Yiqi Huoxue decoction can effectively improved the heart function decline caused by Qi deficiency and blood stasis syndrome of coronary heart disease.It mainly act on energy metabolism and platelet activation pathway by activating HDL assembly and platelet degradation signal pathway proteins.This study can provide reference for the follow-up treatment mechanism of Qi deficiency and blood stasis syndrome of coronary heart disease.

Clinical observation on efficacy of compound of warming yang, descending turbidity and dredging collaterals in the treatment of diabetic kidney disease with Yin-Yang deficiency and blood stasis syndrome

Objective:To observe the clinical efficacy of compound of owarming yang,descending turbidity and dredging collaterals in the treatment of diabetic kidney disease with yin-yang deficiency and blood stasis syndrome.Methods:Seventy-six patients of diabetic kidney disease with yin-yang deficiency and blood stasis syndrome were randomly divided into observation group and control group,thirty-eight cases in each group.The control group was given conventional western medicine treatment,while the observation group took compound of owarming yang,descending turbidity and dredging collaterals orally on the basis of conventional western medicine treatment.The course of treatment covered for one month.Before and after treatment,we observed the scores of traditional Chinese medicine symptoms,indicators of renal function[serum creatinine(Scr),blood urea nitrogen(BUN),microalbuminuria(MALB)],indicators of glucose metabolism[fasting plasma glucose(FPG),2-hour postprandial blood glucose(2hPG),glycosylated hemoglobin(HbAlc)],indicators of hemorheology[plasma viscosity(PV),platelet aggregation rate(PAR),fibrinogen(FIB)],Cystatin-C(Cys-C),C-reactive protein(CRP)in the two groups.Results:After treatment,the clinical effect of the observation group was significantly better than the control group(P<0.05).The scores of traditional Chinese medicine symptoms,indicators of renal function(Scr、BUN、UAER),indicators of glucose metabolism(FPG、2hPG、HbAlc),indicators of hemorheology(PV、PAR、FIB),Cys-C and CRP in the two groups were decreased significantly compared with those before treatment(P<0.05),and the decrease in the observation group was superior to that in the control group(P<0.05).Conclusion:Compound of warming yang,descending turbidity and dredging collaterals has remarkable efficacy in treating of diabetic kidney disease patients with yin-yang deficiency and blood stasis syndrome by alleviating clinical symptoms,glucose metabolism,renal function and microcirculatory disturbance,and the mechanism related to alleviation of microinflammation.

Effects of Lycii Fructus and Salviae Miltiorrhizae on the Syndrome of Deficiency with Blood Stasis in RCS(rdy-/-, p-/-) Rats with Retinitis Pigmentosa: An Intervention Study

Objective To investigate the effects of Lycii Fructus(LF,Gou Qi Zi,枸杞子)and Salviae Miltiorrhizae Radix Ex Rhizoma(SM,Dan Shen,丹参)on the syndrome of deficiency with blood stasis in the RCS(rdy-/-,p-/-)rats with retinitis pigmentosa(RP).Methods A total of 32 RCS(rdy-/-,p-/-)rats were divided into 4 groups(equal amounts of female and male rats in each group):model group treated with 0.9%normal saline,LF group treated with LF formula granules,SM group treated with SM formula granules,and LF and SM(L·S)group treated with LF and SM formula granules.Eight RCS(rdy+/+,p+/+)rats(4 males and 4 females)were treated with 0.9%normal saline to serve as blank group.The contents of E2,PG,P-Selectin,plasma viscosity,whole blood relative index of the high shear rate and fibrinogen content in plasma,and the content of cAMP and cGMP in retinal homogenate were detected.The retina was evaluated by hematoxylin-eosin staining.Results The contents of E2,PG,P-Selectin,plasma viscosity,whole blood relative index of the high shear rate,and fibrinogen content in the plasma of L·S group significantly differed from those of model group(P<0.01),but were similar to those of blank group.The contents of cAMP and cGMP in the retinal homogenate of L·S group significantly differed from those in model group(P<0.01)but were similar to those in blank group(P>0.05).Conclusions LF and SM can effectively treat retinitis pigmentosa by ameliorating the syndrome of deficiency with blood stasis.

Effect of Chanfukang(Chinese Medicine)on Endothelin and Nitric Oxide in Postpartum Cows with Qi Deficiency and Blood Stasis

[ Objective] To observe effect of Chanfukang on vascular endothelial cells of postpartum cows with Oi deficiency and Blood stasis, and to explore the treatment mechanism of Chanfukang. [Method] A total of 58 cows were assigned to four groups. The cows in group 1 and group 2 suffered from Qi deficiency and Blood stasis. The cows in group 1 were gavaged with Chanfukang （0.5 g/kg-BW, 5 d） at 12 h post partum, but the cows in group 2 were not treated. The cows in group 3 were healthy and gavaged with Chanfukang （0.4 g/kg.BW, 5 d） at 12 h post partum. Cows in group 4 were healthy control cows. The plasma endothelin （ET） concentration and serum nitric oxide （NO） concentration were determined before and after parturition, respectively. [ Result ] The plasma ET concentration and serum NO concentration were significantly higher in the cows with Qi deficiency and Blood stasis than in the healthy control cows （P 〈 0.05）. The NO concentration decreased on Day 10 post partum in the cows with Qi deficiency and Blood stasis, but it was still higher than that in the healthy control cows. After taking Chanfukang for 7 d, the ET concentration and NO concentration decreased, and no significant difference was found between the cows with Qi deficiency and Blood stasis treated with Chanfukang and the healthy control cows. [ Conclusion] Chanfukang may relieve Qi deficiency and Blood stasis of postpartum cows through decreasing plasma ET concentration and serum NO concentration.

Yiqi Huoxue Decoction in the treatment of Qi and yin deficiency and stasis type diabetic nephropathy in stageⅢ and its effect on VEGF and TGF-β1

Objective:To observe the efficacy of Yiqi Huoxue Decoction in the treatment of patients with diabetic nephropathy(DN)stageⅢwith qi and yin deficiency and stasis and its effects on vascular endothelial growth factor(VEGF)and transforming growth factor-β(TGF-β1).Methods:Sixty patients with stage DN of Qi-yin deficiency and stasis type DN who were treated in the Endocrinology Department of the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from September 2018 to December 2019 were selected as the research subjects.The remainder method was used to divide them into 30 cases in the observation group and 30 cases in the control group.Patients in both groups were referred to the guidelines and expert consensus for general treatment of DN(hypogl-ycemic,antihypertensive,lipid-lowering,etc.).The control group was given pancreatic kallikrein enteric-coated tablets orally once,120U,3 times a day,and the observation group was given The traditional Chinese medicine Yiqi Huoxue Decoction was taken orally,one dose daily,twice a day in the morning and evening;the two groups intervened continuously for 8 weeks.Detect blood FPG,PBG,HbA1c,β2-MG,BUN,SCr,VEGF,TGF-β1,and urine mALB and UACR levels before and after treatment,and calculate eGFR before and after treatment in both groups;observe changes in TCM syndrome scores in the two groups,Compare its clinical efficacy.Results:After 8 weeks of treatment,the total clinical effective rate of patients in the observation group was 93.3%,which was significantly different from the control group of 76.6%(P<0.05);the TCM syndrome scores in the observation group were significantly lower than those before treatment and in the control group(P<0.05);The levels of FPG,HbA1c,PPG,mALB,β2-MG,UACR,VEGF,and TGF-β1 in the observation group were significantly lower than those in the control group,with significant differences(P<0.05).The levels of SCr and BUN in the observation group were significantly lower.Compared with before treatment,eGFR increased,but there was no signi-ficant difference(P>0.05).Conclusion:Yiqi Huoxue Decoction for the treatment of patients with DN typeⅢqi-yin deficiency and stasis type,not only helps to lower blood sugar levels,improve TCM syndromes,but also can reduce early renal damage,reduce urine albumin,and delay kidney function It may be further worsened and has better safety.The mechanism may be related to reducing the levels of VEGF and TGF-β1,thereby delaying the fibrosis of tubulointerstitial scar and inhibi-ting glomerular capillary sclerosis.

Study on syndrome differentiation based on pharmacology of syndrome management system-a case of Qi and Yin deficiency syndrome

Taking the Qi and Yin deficiency syndrome as an example,the research method of pharmacology of syndrome management system was proposed.By means of text mining,systematic pharmacology and target analysis,to attempt to reveal the essence of the corresponding syndrome by studying the drugs and targets of Qi and Yin deficiency.Fourteen Chinese herbs treating Qi and Yin deficiency were retrieved and used more than 30 times,and 9,317 related targets were predicted.The common targets of action were 85.Topological analysis was carried out by using degree centrality,closeness centrality and betweenness centrality to confirm that estrogen receptor(ESR1),tumor necrosis factor(TNF),D(2)dopamine receptor(DRD2),vitamin D3 receptor(VDR),glucocorticoid receptor(NR3C1),acetylcholinesterase(ACHE)and endothelin-1(EDN1)were highly correlated with Qi and Yin deficiency syndrome.Through the target to find Qi and Yin deficiency syndrome corresponding to 17 categories of diseases.A new idea was provided for studying the biological essence of TCM clinical syndrome differentiation.

On the Treatment of Kidney Fibrosis from the Theory of Internal Deficiency of Qi and the Coexistence of Phlegm and Blood Stasis

Traditional Chinese medicine believes that the etiology and pathogenesis of renal fibrosis are characterized by deficiency of the lung,spleen and kidney,and phlegm,blood stasis,dampness and poison.The positive and the evil can influence each other and cause and effect each other,forming the pathological characteristics of the deficiency,the deficiency,the deficiency and the reality.Chinese medicine treatment of the disease has its unique advantages,external and internal injury equal emphasis,correction and dispelling evil and regulation.From the point of view of"deficiency of qi and coexistence of phlegm and blood stasis",the treatment of renal fibrosis can provide theoretical basis for the treatment of the disease.

Pharmacological effects of Paeoniflorin and Albiflorin on IL-3, GM-CSF, IL-6 and TNF-α in the rats of syndrome of stagnation of liver qi and blood deficiency

Objective： To observe the effect of paeoniflorin （PF）, albiflorin （AF） on the hemogram, visceral index and hematopoiesis cytokine in the rats of syndrome of stagnation of liver qi and blood deficiency, and to discuss the material base and mechanism of effect of nourishing blood and smoothing the liver of Baishao （Radix Paeoniae Alba）. Methods： Male SD rats were randomly divided into groups according to the sucrose preference test and body weight （n = 12）. Except the normal control, the other groups were treated with the chronic stress stimulation combined with radiation respectively to establish the model of syndrome of stagnation of liver qi and blood deficiency. The body weight, visceral index and the quantity of Leucocyte, Red Blood Cells, Hemoglobin in peripheral hemogram were monitored, then plasma and serum were separated. Radioimmunoassay was used to analyze the levels of Lnterleukin-3, Granulocyte-macrophage Colony-stimulating Factor, Lnterleukin-6 and Tumor Necrosis Factor-α in plasma. Results： Compared with that of model group, 30 mg·kg^-1 PF and 30 mg·kg^-1 AF of the weight, spleen index, quantity of Leucocyte were increased significantly （P 〈 0.05, P 〈 0.01）. The results of Radioimmunoassay showed that the levels of Interleukin-3 increased （P 〈 0.05, P 〈 0.05） and the levels of Tumor Necrosis Factor-α decreased in both 30 mg·kg^-1 PF and 30 mg·kg^-1 AF groups （P 〈 0.05, P 〈 0.05）. Conclusion： The effect of PF and AF on the regulation of bone marrow hematopoietic system and immune system play a role in the blood of rats with syndrome of stagnation of liver qi and blood deficiency, which suggests that both of them are the main active ingredients of nourishing blood and smoothing the liver of Baishao.

A Clinical Study on the Treat ment of Chronic Pelvic Inflammation of Qi-stagnation with Blood Stasis Syndrome by Penyanqing Capsule (盆炎清胶囊)

Objective： To observe the clinical efficacy of Penyanqing Capsule （盆炎清胶囊, PYQC） in treating pelvic inflammation of Qi-stagnation with blood stasis syndrome. Methods： The randomized, single blinded, parallel positive drug controlled method was adopted, with 82 patients assigned into two groups by envelop method. The 42 patients in the treated group received PYQC 3 times a day, 4 capsules each time taken orally; the 40 patients in the control group were given orally Fuyankang tablets （妇炎康片, FYKT） 3 times a day, 6 tablets each time. The therapeutic course for both groups was 2 months, and 2 courses of treatment were given successively to observe the comprehensive effect, changes of symptoms and signs before and after treatment. The effects of PYQC on hemorrheological character in part of the patients and on the pathogenetic chlamydia and mycoplasma were also observed. Results： The total effective rate in the treated group was 83.3%, which was insignificantly different from that in the control group （77.5%, P〉0.05）. However, PYQC could significantly lower the hemorrheologic indexes in patients and showed definite influence on the pathogenetic chlamydia and mycoplasma. Conclusion： PYQC has good therapeutic effect in treating chronic pelvic inflammation of Qi-stagnation with blood stasis syndrome, and showed definite effect on chlamydia and mycoplasma.

Study on the relationship between syndrome characteristics degree and inflammatory factor and negative emotional scale in"double heart disease"patients with Qi stagnation blood stasis and heart gallbladder heat stagnation

Objective:To Discuss the correlation between Hypersensitivity C-reactive Protein(Hs-CRP),Total Cholesterol(TC),Triglyceride(TG),negative emotion scale and TCM syndrome scores in“Double Heart Disease”patients with Qi stagnation blood stasis and heart gallbladder heat stagnation.Method:Fifty-two patients in Western Medicine Diagnosis of Double Heart Disease,in TCM syndrome identified as Qi stagnation blood stasis Heart gallbladder heat stagnation syndrome,detects it Hs-CRP,TC,TG levels by ELISA,use TCM Syndromes Scale to evaluate TCM Syndrome,use the Pittsburgh Sleep Quality Index(PSQI)and Self-rating symptom scale(SCL-90)to assess anxiety and sleep levels,analyze the correlation between TCM syndrome scores and Hs-CRP,TC,TG level,PSQI index,SCL-90 index.Result:There was a significant positive correlation between Hs-CRP,TG level and TCM Syndrome scores(P<0.05);TC level was postively correlated with TCM Syndrome scores,but there was no statistical significance(P>0.05);There was a significant positive correlation between PSQI index,SCL-90 index and TCM Syndrome scores(P<0.05).Conclusion:In“Double Heart Disease”patients with Qi stagnation blood stasis and heart gallbladder heat stagnation,there have characteristic syndrome changes in terms of inflammatory factor level,blood lipid level and negative emotion score;Which the above indexes can reflect the severity of TCM syndromes to a certain extent and provide the basis for the effective intervention treatment of TCM.

Study on blood pressure rhythm in hypertensive patients with Yin deficiency syndrome and a random forest model for predicting hypertension with Yin deficiency syndrome

OBJECTIVE: To investigate blood pressure rhythm(BPR)in Yin deficiency syndrome of hypertension(YDSH)patients and develop a random forest model for predicting YDSH.METHODS: Our study was consistent with technical processes and specification for developing guidelines of Evidence-based Chinese medicine clinical practice(T/CACM 1032-2017). We enrolled 234 patients who had been diagnosed with primary hypertension without antihypertensive medications prior to the enrollment. All participants were divided into Yin deficiency group(YX, n = 74) and non-Yin deficiency group(NYX, n = 160).Participants were professionally grouped by three experienced chief Traditional Chinese Medicine(TCM)physicians according to four examinations(i.e.,inspection, listening and smelling, inquiry and palpation).We collected data on 24 h ambulatory blood pressure monitoring(ABPM) and YDSH rating scale. We divided 24 h of a day into 12 two-hour periods [Chen-Shi(7:00-9:00), Si-Shi(9:00-11:00), Wu-Shi(11:00-13:00), Wei-Shi(13:00-15:00), Shen-Shi(15:00-17:00), You-Shi(17:00-19:00), Xu-Shi(19:00-21:00), Hai-Shi(21:00-23:00), ZiShi(23:00-1:00), Chou-Shi(1:00-3:00), Yin-Shi(3:00-5:00), Mao-Shi(5:00-7:00)] according to the theory of “midnight-midday ebb flow”. We used random forest to build the diagnostic model of YDSH, with whether it was Yin deficiency syndrome as the outcome. RESULTS: Compared with NYX group, YX group had more female participants with older age, lower waist circumference, body mass index(BMI), diastolic blood pressure(DBP), and smoking and drinking rate(all P < 0.05). The YDSH rating scores of YX group [28.5(21.0-36.0)] were significantly higher than NYX group [13.0(8.0-22.0)](P < 0.001), and the typical symptoms of YX group included vexing heat in the chest, palms and soles, dizziness, dry eyes, string-like and fine pulse, soreness and weakness of lumbus and knees, palpitations, reddened cheeks, and tinnitus(all P < 0.05). The ratio of non-dipper hypertension in YX group was higher than in NYX group(56.9% vs 44.4%, P = 0.004). Compared with NYX group, 24 h DBP standard deviation(SD), nighttime DBP SD, Si-Shi DBP, Si-Shi mean arterial pressure(MAP), Hi-Shi systolic blood pressure(SBP), Hi-Shi DBP, Hi-Shi MAP, Zi-Shi SBP, Zi-Shi DBP, Zi-Shi MAP, ChouShi SBP SD, Chou-Shi DBP SD, Chou-Shi SBP coefficient of variation(CV) were lower in YX group(all P < 0.05). Binary Logistic Regression analysis showed that the diagnosis of YDSH was positively correlated with age, heart rate, YDSH rating scores, and four TCM symptoms including vexing heat in the chest, palms and soles, string-like and fine pulse, soreness and weakness of lumbus and knees, and reddened cheeks(all P < 0.05), but was negatively correlated with smoking(P﹥0.05). In addition, the diagnosis of YDSH was positively correlated with daytime SBP SD, nighttime SBP SD, nighttime SBP CV, and Hi-Shi SBP CV, but was negatively correlated with 24 h SBP CV, daytime DBP SD, nighttime DBP SD, and Hi-Shi DBP(all P < 0.05). Hi-Shi SBP CV had independent and positive correlation with the diagnosis of YDSH after adjusting the variables of age, gender, course of hypertension, BMI, waist circumference, SBP, DBP, heart rate, smoking and drinking(P = 0.029). Diagnostic model of YDSH was established and verified based on the random forest. The results showed that the calculation accuracy, specificity and sensitivity were 77.3%, 77.8% and 76.9%, respectively. CONCLUSION: The BPR was significantly attenuated in YDSH patients, including lower 24 h DBP SD and nighttime DBP SD, and Hi-Shi SBP CV is independently correlated with the diagnosis of YDSH. The prediction accuracy of diagnosis model of YDSH based on the random forest was good, which could be valuable for clinicians to differentiate YDSH and non-Yin deficiency patients for more effective hypertensive treatment of TCM.

Pharmacokinetics of traditional Chinese syndrome and recipe:a hypothesis and its verification(Ⅰ)

AIM To propose a hypothesis defining theabsorption,distribution,metabolism andelimination of traditional Chinese recipe（TCR）-component in blood of healthy subjects andpatients,and estimate its correctness.METHODS The pharmacokinetics（PK）of samedose of drug was studied in the animal model oftraditional Chinese syndrome（S）and healthyanimals.The classification,terminology,concept and significance of the hypothesis wereset forth with evidence provided in the presentstudy.The hypotheses consisted of traditionalChinese syndrome PK（S-PK）and traditionalChinese recipe PK（R-PK）.Firstly,the observedtetramethylpyrazine（TMP）PK in healthy,chronically reserpinized rats（rat model ofspleen deficiency syndrome,RMSDS）andRMSDS treated with Sijunzi decoction（SJZD）forconfirmation were used to verify S-PK; secondly,the ferulic acid（FA）PK in healthy andhigh molecular weight dextran（HMWD）-inducedrabbit model with blood stasis syndrome（RDBSS）was also used to verify S-PK;andlastly,TMP PK parameters in serum of healthyrats after orally taken Ligusticum wallichii（LW）,LW and Salvia miltiorrhiza（LW&SM）decoctions were compared to verify R-PK.RESULTS The apparent first-order absorption[Ka,（13.61±2.56）h-1,area under the blooddrug concentration-time curve[AUC,（24.88±9.76）μg.h-1mL-1],maximum drug concentration[Cmax,（4.82±1.23）μg·mL-1]of serum TMP inRMSDS were increased markedly（P【0.05）compared with those[Ka=（5.41±1.91）h-1,AUC=（5.20±2.57）μg·h-1·mL-1,Cmax=（2.33±1.77）μg·mL-1]of healthy rats（HR）.Theapparent first-order rate constant for α and βdistribution phase[α=（0.38±0.09）h-1,β=（0.06±0.03）h-1,the apparent first-orderintercompartmental transfer rate constants[K10=（0.24±0.07）h-1,K12=（0.11±0.02）h-1,K21=（0.11±0.02）h-1]of serum TMP in RMSDS weredecreased significantly（P【0.01）comparedwith those[K10=（0.88±0.20）h-1,K12=（1.45±0.47）h-1,K21=（0.72±0.22）h-1]of HR.However,no apparent differences occurredbetween HR and RMSDS treated with SJZD.Theserum FA concentration and its AUC[（5.6690±2.3541）μg·h-1·mL-1] in RMBSS were also higherthan those[AUC=（2.7566±0.8232）μg·h-1·mL-1]of healthy rabbits（P【0.05）.The Ka（11.51±2.82）h-1,AUC（0.84±0.17）μg·h-1·mL-1of LW & SM-derived TMP in serum weremuch lower（P【0.05）than those[Ka=（19.58±4.14）h-1,AUC=（1.27±0.26）μg·h-1·mL-1]ofLW-derived TMP in serum after oral decoctions.CONCLUSION The SDS and blood stasissyndrome state could affect significantly thepharmacokinetic parameters of drugs and theabnormal SDS pharmacokinetic parameters couldbe normalized by SJZD.The combination ofChinese medicine in TCR could reciprocallyaffect the pharmacokinetic parameters of othercomponents absorbed into the systemiccirculation.These results support the S-and R-PK hypothesis.

Efficacy of Yangyin Yiqi Huoxue Granule (养阴益气活血颗粒) in Treatment of Ischemic Stroke Patients with Qi-Yin Deficiency and Blood Stasis Syndrome: A Randomized, Double-Blind, Multicenter, Phase-2 Clinical Trial

Objective To evaluate the efficacy and safety of Yangyin Yiqi Huoxue Granule(养阴益气活血颗粒,YYHG)in the treatment of ischemic stroke(IS)patients with qi-yin deficiency and blood stasis syndrome(QYDBSS),and to explore its effective dosage.Methods The total of 288 patients were randomly assigned to the YYHG high-dose,YYHG low-dose,positive control(administered Xiaoshuantong Granule,XSTG,消栓通颗粒),or placebo control(administered inert granule)groups(72 cases per group)by software-drived competitive block randomization.The trial was conducted for a 28-day period,with a 180-day follow-up period.The primary outcome was the comprehensive curative evaluation,and secondary outcomes were the National Institute of Health Stroke Scale(NIHSS)score,Barthel activities of daily living(ADL)index score,the quality of life index(QLI)score,and the Chinese medicine syndrome(CMS)score.All analyses were done on an intention-to-treat basis.The clinical safety was also assessed.Results The total of 288 participants were recruited between June 1,2008 and September 30,2009,and 287 patients received intervention;the treatment groups were well balanced at baseline.The comprehensive cure rates of YYHG high-dose,low-dose,positive and placebo control groups were 63.38%,31.94%,36.11%and 6.14%,respectively;there was a statistical difference between the two groups(P<0.01),while the high-dose YYHG treatment group was significantly higher than the other 3 groups(P<0.01).The improvement of NIHSS,ADL,QLI and CMS scores of the YYHG high-dose and low-dose groups was significantly better than that of the positive control group and the placebo control group(P<0.05).In terms of improving the classification of the NIHSS scale and the assessment of the ADL scale,the YYHG high-dose group was significantly better than the other three groups(P<0.05),and the YYHG low-dose group was better than the placebo control group(P<0.01).At the same time,except for the QLI score,the high-dose group was better than the low-dose group(P<0.05).In terms of safety,adverse reactions after YYHG treatment were generally mild(3.78%),and no serious adverse reactions have been reported.Conclusion YYHG is safe and effective in the treatment of IS patients with QYDBSS.

Summary and correlation analysis of TCM syndromes in 159 elderly patients with acute myeloid leukemia

Objective:To investigate the characteristics of TCM syndromes in elderly patients with acute myeloid leukemia(AML)at the onset,and to analyze the main syndrome types and their correlation with age,percentage of bone marrow blasts,and genetic prognostic stratification.Methods:A retrospective analysis was performed on 159 AML patients aged over 60 years who were diagnosed and treated in our hospital,and the clinical data were collected and analyzed statistically.Results:In 159 elderly AML patients,the main clinical symptoms were fatigue,poor appetite,conscious fever,and various hemorrhages.The main syndromes were Ying(42.01%),Wei(31.25%),Essential(14.81%)and Blood(11.69%);the syndromes are divided into Qi and Yin deficiency(32.70%),Qi and blood deficiency(30.19%),true Yin deficiency(28.03%)and Qi heat and blood(8.81%).The age difference between the two groups was statistically significant(P<0.001),and the multiple comparison results showed that the age of the Qi-blood deficiency group was younger than the true-Yin deficiency group and the Qi-Yin deficiency group;the percentage of bone marrow blasts was statistically significant in the three groups at the initial diagnosis(P<0.05),multiple comparison results showed that the percentage of bone marrow blasts in the true Yin deficiency group was higher than that in the Qi-blood deficiency group and the Qi-Yin deficiency group;the genetic prognostic stratification of the three groups was statistically significant(P<0.05),multiple comparisons.The results showed that the genetic prognosis of the true Yin deficiency group was poorer than that of the Qi and blood deficiency group and the Qi and Yin deficiency group.Conclusion:The most common clinical symptoms of elderly AML patients are fatigue,the disease is located in the bone marrow,and the disease is Ying,Wei,essence,and blood.With the increase in the patient's age,the TCM syndrome types tend to be more insufficiency of true Yin and deficiency of both Qi and Yin,and the prognosis of patients with insufficiency of true Yin is poor.It provides a directional scientific basis for the treatment of senile AML with integrated traditional Chinese and Western medicine.

Metabonomic phenotype and identification of “heart blood stasis obstruction pattern” and “qi and yin deficiency pattern” of myocardial ischemia rat models

The traditional Chinese medicine concepts of "Xinxueyuzuzheng (heart blood stasis obstruction pattern)" and "Qiyinliangxuzheng (qi and yin deficiency pattern)" for myocardial ischemia rat models were constructed in the present study. Endogenous metabolites in rat plasma were analyzed using the GC/TOF-MS-based metabonomic method. Significant metabolic differences were observed between the control and two model groups, and the three groups were distinguished clearly by pattern recognition. Compared with those of the control, the levels of hydroxyproline, threonic acid, glutamine and citric acid were strikingly up or down-regulated in model rats. The metabolites contributing most to the classification between the two "pattern" rats were identified, such as valine, serine, threonine, ornithine, hydroxyproline, lysine, 2-hydroxybutanoic acid, 3-hydroxybutanoic acid, galactofuranose and inositol. These compounds were indicated as the potential biomarkers. The results suggested that the two "patterns" are involved in dysfunction in oxidative stress, energy metabolism and amino acid metabolism. These findings also provided the substantial foundation for exploring the scientific connotation of these two "Zhengxing (pattern types)" of myocardial ischemia, and "Bianzheng (pattern identification)".