Network pharmacology-based exploration of molecular mechanisms underlying therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure with spleen Qi deficiency syndrome

BACKGROUND Chronic heart failure is a complex clinical syndrome.The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure;however,the underlying molecular mechanism is still not clear.AIM To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure.METHODS The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target genes of chronic heart failure were searched in the Genecards database.The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drugdisease targets,which were then used to construct a key chemical componenttarget network using Cytoscape 3.7.2 software.The protein-protein interaction network was constructed using the String database.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database.Finally,our previously published relevant articles were searched to verify the results obtained via network pharmacology.RESULTS A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified,of which quercetin,kaempferol,7-methoxy-2-methyl isoflavone,formononetin,and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3,MAPK3,AKT1,JUN,MAPK1,TP53,TNF,HSP90AA1,p65,MAPK8,MAPK14,IL6,EGFR,EDN1,FOS,and other proteins.The pathways identified by KEGG enrichment analysis include pathways in cancer,IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,calcium signaling pathway,cAMP signaling pathway,NF-kappaB signaling pathway,AMPK signaling pathway,etc.Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α,IL-6,MAPK,cAMP,and AMPK pathways to affect the mitochondrial structure of myocardial cells,oxidative stress,and energy metabolism,thus achieving the therapeutic effects on chronic heart failure.CONCLUSION The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes,oxidative stress,energy metabolism,and other processes.Future studies are warranted to investigate the role of the IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.

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.

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.

Symptom characteristics and prevalence of qi deficiency syndrome in people of varied health status and ages: A multicenter cross-sectional study

Objective:Aging caused by a deficiency syndrome can be found in ancient and modern traditional Chinese medicine literature.Qi deficiency syndrome(QDS)is a vital factor in the aging process.This study aimed to establish a full-scale trial to evaluate the prevalence,symptom severity,frequency,and distribution of QDS in different age groups and varying health status to elucidate the role of qi deficiency in the aging process and deterioration of health.Methods:This cross-sectional study was conducted in four hospitals in China,and data from 1220 participants were included.The participants,aged between 20 and 79 years,completed questionnaires that recorded prevalence of QDS and severity or frequency of relevant symptoms,then were interviewed by investigators.We used frequency analysis and chi-squared tests to perform comparative analysis of prevalence in different age and health groups;we used a ranksum tests for quantitative analysis of symptoms severity and frequency scores;we performed a regression analysis of correlation between syndrome occurrence and potential factors using nonconditional binary logistic stepwise regression of numerical variables.P<0.05 was considered statistically significant.Results:Prevalence,symptom severity and frequency scores of QDS showed a rising trend when physical condition worsened,rather than when age increased.Health status,fatigue,shortness of breath or no desire to talk,spontaneous sweating,swollen tongue with teeth marks on side,and deficient and weak pulse,rather than increasing age were contributing factors to this syndrome.Distribution of QDS in certain health and age stages showed remarkable irregularities.Conclusions:Qi deficiency may be a contributing factor for sub-health(sub-optimal health)and chronic diseases rather than aging.It may play a crucial role in chronic disease pathogenesis of young and middle-aged people,and in sub-health pathogenesis of older adults.Recognition of the warning signs and symptoms of QDS may lead to early intervention and prevention of subhealth,and chronic diseases.

Serum protein profiles suggest a possible link between qi deficiency constitution and Pi-qi-deficiency syndrome of chronic superficial gastritis

Objective:To identify potential serum protein candidates involved in linking the traditional Chinese medicine(TCM)-defined qi deficiency constitution(QDC)to Pi-qi-deficiency syndrome(PQDS)of chronic superficial gastritis(CSG).Methods:Using participants with the TCM-defined balanced constitution as a control population,labelfree quantitative proteomics was adopted to identify differentially expressed proteins(DEPs)in serum samples from two case populations:case population 1(participants with QDC)and case population 2(patients with PQDS of CSG).The DEPs discovered in both case populations were analyzed to identify common DEPs as potential candidates for proteins involved in the link between QDC and PQDS.Based on Kyoto Encyclopedia of Genes and Genomes pathway(KEGG)and Gene Ontology(GO)enrichment analysis and analysis of proteineprotein interaction networks,we evaluated the possible functions of these potential serum candidates.Results:We discovered 24 and 28 proteins that were differentially expressed in case populations 1 and 2,respectively,compared with the control population.Hierarchical clustering analysis showed that the expression profile of DEPs of individuals from the same population clustered well,while those from different populations were segregated.Furthermore,GO analysis revealed the 10 DEPs that were common to both case populations to be mainly associated with negative regulation of cellular metabolic and immune system processes while KEGG analysis indicated these proteins to be associated with complement and coagulation cascades and peroxisome proliferator-activated receptor signaling.Notably,serum levels of C4b-binding protein beta chain,glycosylphosphatidylinositol-specific phospholipase D1 and MS-F1 light chain variable region proteins were notably higher in the two case populations compared with the control,particularly in the case of CSG with PQDS.Conclusion:The results presented here provide new insights into the molecular mechanisms underlying development of PQDS of CSG from QDC,and suggest candidate serum biomarkers for future application in integrative medicine.

Efficacy of integrative medicine in deficiency of both qi and yin in the rat model of type 2 diabetes

Objective:To establish a rat model of type 2 diabetes(T2DM)manifesting the Chinese medicine syndrome pattern of both qi and yin deficiency for evaluating the efficacy of a Chinese herbal formula(CHF),integrative medicine(IM),and pioglitazone(PIO)on T2DM indicators in the animal model.Methods:The rat model was induced by a high-fat diet(HFD)and streptozotocin(STZ,30 mg/kg).CHF(3.4 g/kg),PIO(2.7 mg/kg),and IM(3.4 g CHF+2.7 mg PIO)were administered to rats once daily for 14 days.Related laboratory parameters were observed.Results:Diabetic rats showed unsmooth fur,alopecia,reduced activity,huddling,somnolence,depression,pale or reddened tongue,damp/dark red tail,and high levels of water and food intake,urine volume,and stool weight,but weakened grip strength.Low levels of serum SOD,Nat-Kt-ATPase,cAMP/cGMP,and a high level of iNOS were observed.Hyperglycemia,hyperinsulinemia,insulin resistance,high levels of serum glucagon/IDE and pancreatic amylin,and low serum and pancreatic SS levels were evident as well.Conclusions:A rat model of T2DM with both qi and yin deficiency was successfully replicated.CHF appeared to be more efficacious than IM and PIO in the rat model of qi and yin deficiency pattern of T2DM,though IM and PIO were each found to have their merits and drawbacks in attenuating T2DM indicators in the rat model.

Establishment and evaluation of a mouse model of bronchial asthma with Yin deficiency syndrome

Objective: To establish and evaluate a mouse model of bronchial asthma with Yin deficiency syndrome. Methods: The mouse model of bronchial asthma with Yin deficiency syndrome was established by the treatment with injecting ovalbumin(OVA) two times to sensitize, inhaling OVA 14 times to stimulate, and using thyroxin through lavage during late stimulation. This model was evaluated through body weight, asthmatic behaviors, respiratory function, autonomous activity, lung pathology, and pulmonary fluid clearance. Results: OVA combined with thyroxin was an appropriate method to induce the mouse model with increased food and water intake, autonomous activity, asthmatic behaviors score, and respiratory rate, decreased body weight, tidal volume, and wet/dry ratio of lung, and changed with pathology of lung tissue. The changes of the above mentioned parameters indicated that the model was the bronchial asthma with Yin deficiency syndrome. Conclusion: The OVA combined with thyroxin is a good pattern to establish a mouse model of bronchial asthma with Yin deficiency syndrome successfully, which can highly simulate the clinical symptoms of this disease.

Screening for blood leukocyte microRNA biomarkers responsible for association between qi deficiency constitution and Pi-qi-deficiency syndrome of chronic superficial gastritis

Objective:To screen for blood leukocyte microRNA(miRNA)biomarkers responsible for the association between the traditional Chinese medicine(TCM)qi deficiency constitution(QDC)and the Pi-qi-deficiency syndrome(PQDS)of chronic superficial gastritis(CSG).Methods:Peripheral blood leukocytes were separated from people of two TCM constitutions(balance and qi deficiency)and from CSG patients with PQDS.Total RNA was isolated from the leukocytes and subjected to subsequent high-throughput miRNA sequencing to identify the miRNAs that are specifically and highly expressed in persons of QDC and CSG patients with PQDS.In addition,the target genes of the associated miRNAs were predicted.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway-based enrichment analyses of these target genes were performed to further evaluate the associated miRNA candidates as potential biomarkers responsible for the association between QDC and PQDS of CSG.Results:Compared with the control group with a balance constitution(P<.05,fold change>1.5 or<0.5),31 and 38 differentially expressed miRNAs were found in persons of QDC and CSG patients with PQDS,respectively.In particular,hsa-miR-145-5p and hsa-miR-146a-3p were highly expressed in both the persons of QDC and CSG patients with PQDS.GO analysis of the target genes of the two common miRNAs showed that they were mainly associated with functions related to synthesis and metabolism,such as cellular nitrogen compound metabolic processes,biosynthetic processes,cellular protein modification processes,and cellular component assembly.KEGG analysis identified the common pathways enriched among the target genes,including the Hippo signaling pathway and the transcriptional misregulation pathway.The common target genes of the two miRNAs seemed to be associated with the spliceosome pathway and the RNA degradation pathway.Conclusion:Hsa-miR-145-5p and hsa-miR-146a-3p may serve as candidate biomarkers responsible for the association between QDC and PQDS of CSG.

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.

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.

Rules of Ren Shunping's prescription for trearing Spleen Deficiency and Qi Stagnation Syndrome of Functional Dyspepsia Based on Data Mining

Objective:To explore the medication rules of Professor Ren Shunping treating spleen deficiency and qi stagnation syndrome of functional dyspepsia,so as to provide reference for clinical prevention and development of new drugs.Methods:The 144 Chinese herbal formulas considered as active prescribed by professor Ren Shunping for the first time treating the patients with spleen deficiency and qi stagnation syndrome of functional dyspepsia were collected,entered into TCM inheritance auxiliary platform(V2.5),and then mined by some data mining methods of the software,such as the association rules and unsupervised entropy hierarchical clustering.Results:This study involved 144 Chinese herbal formulas,including a total of 56 Chinese herbal medicines.Of these Chinese herbal medicines,the herbs of cold and warm nature,and pungent,bitter and sweet in flavors were used in a quite high frequency,all of which act on spleen,stomach,lungs,large intestine,liver and gallbladder meridians.One core Chinese herbal formula was excavated,composed of patchouli,perilla stem,radix bupleuri,scutellaria,ginger pinellia,codonopsispilosula,magnolia bark,tangerine peel,large-headed atractylodes,immature bitter orange,wood incense,fructus amomi,inula britannica chinensis,ginger,medicated leaven,fried rice and fried malt based on the association rules.And a total of 17 groups of core used drugs and 2 groups of new Chinese herbal formulas undiscovered were mined based on unsupervised entropy hierarchical clustering.Conclusion:In treating spleen deficiency and qi stagnation syndrome of functional dyspepsia,professor Ren is good at treating spleen deficiency and qi stagnation syndrome of functional dyspepsia from the perspective of"tong jiang",using the"five-in-one"strategy of strengthening the spleen,evacuating the liver,coming down qi from the stomach,dispersing lung,and bowel-reflexing to treat patients as a whole.And the herbal medicines were light in dose,lovely and mild in nature for the formulars.At the same time,he paid attention to the combination of syndromes and symptoms,and flexible arbitration.

Effect of Huangqi Xiaoke Recipe combined with alprostadil on qi and yin deficiency type diabetic nephropathy and its effect on vascular endothelium and oxidative stress

Objective: To observe the clinical efficacy of Huangqi Xiaoke Decoction combined with alprostadil on qi and yin deficiency type diabetic nephropathy (DN) and its effect on vascular endothelium and oxidative stress. Methods: A total of 72 patients with qi and yin deficiency type DN who were admitted to the diabetes specialist ward and outpatient department of Baoan District Hospital of Shenzhen from January 2017 to July 2018 were enrolled. The patients were divided into the control group and the observation group according to the random number method. 36 cases in each group. Both groups were treated with conventional treatments such as hypoglycemic, hypotensive, lipid-lowering and anti-platelet aggregation. The control group was treated with alprostadil on the basis of conventional treatment. The observation group was given orally on the basis of the control group. Both groups were treated once a day for a total of 4 weeks. Compare the clinical syndrome scores and clinical efficacy of the two groups before and after treatment;fasting blood glucose (FPG), glycosylated hemoglobin (HbA1C), blood lipids (TC, TG, LDL, HDL), serum creatinine (SCr), blood urea nitrogen (BUN Endothelin-1 (ET-1), nitric oxide (NO), von Willebrand factor (vWF);glutathione peroxidase (GSH-Px), superoxide disproportionation The level of enzyme (SOD), malondialdehyde (MDA). Results:The total effective rate of TCM syndromes in observation group was 94.44%, which was significantly different from 72.22% in the control group. The scores of TCM syndromes in the observation group were significantly lower than those in the control group;Compared with the control group, the HDL-C of the observation group did not change much, there was no statistical difference;FBG, HbA1C, SCr, BUN, TC, TG, LDL-C, ET-1, vWF, MDA Significantly decreased, NO, GSH-Px, SOD increased significantly, with significant difference. Conclusion: Huangqi Xiaoke Decoction combined with alprostadil in the treatment of qi and yin deficiency type DN has significant curative effect, which can not only lower blood sugar, regulate blood lipids, improve renal function and clinical symptoms, but also inhibit oxidative stress and protect endothelial function.

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.

Clinical Significance and Changes of ECG in the Patients with Cardiac Deficiency of the Qi and the Yin

In order to explore the changes and clinical significance of ECG in the patients with cardiac deficiency of the Qi and Yin, 124 patients with heart diseases were examined by means of ECG. The results showed that the prevalence of left ventricular hypertrophy in cardiac deficiency of the Qi (CDQ) was obviously higher than that of cardiac deficiency of the Yin (CDY). The higher prevalence of tachycardia occurred in the patients with CDY.The prevalence of the Q - T interval prolongation and abnormalities of ST - T segment in the patients with CDY was also higher than that of CDQ. The difference between two groups suggests that the diagnosis of two syndromes by ECG may be of important value.

Exploring the biological mechanism of qi deficiency syndrome with chronic obstructive pulmonary disease(COPD)based on integrated pharmacology

Objective:To explore the potential biological mechanism of chronic obstructive pulmonary disease(COPD)qi deficiency syndrome,we used the integrated pharmacology network computing platform and carried out experimental verification.Methods:Using an integrated pharmacology strategy to analyze the potential biological targets of COPD qi deficiency syndrome.Based on the established qi deficiency syndrome rat model of COPD,the biological targets of lung and skeletal muscle were detected by electron microscopy,adenosine triphosphate(ATP)content assays,and western blotting.Results:According to the integrated pharmacological results,it was found that the locations of cell components related to COPD qi deficiency syndrome were mainly mitochondria.Electron microscopy results using lung tissue showed that mitochondria in the lipopolysaccharide(LPS group)and pulmonary instillation of LPS combined with cigarette smoke(LPStCS group)were swollen,deformed,and fragmented,with disappearing or broken crista.Results also showed that the total content of ATP in the lung and skeletal muscle of both groups was significantly lower than that in the control group at the 12th week(P<.05).At the 12th week,the expression of dynamin-related protein 1(DRP1)and mitofusin 1(MFN1)protein was significantly difference than that of the control group(P<.05).At the 10th and 14th weeks,changes in fission and fusion proteins in mitochondria of the lung and skeletal muscle were further detected.There was also a significant difference in the expression between the two groups compared to that in the control group at the 10th week and 14th week(P<.05).Conclusion:These findings suggest that the changes in mitochondrial morphology and ATP content and the unbalanced expression of DRP1 and MFN1 might be the key mechanisms underlying qi deficiency syndrome in rats with COPD.

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.

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.

CLINICAL OBSERVATION ON 84 CASES OF VENTRICULAR PREMATURE BEAT WITH DEFICIENCY SYNDROME TREATED BY QI LU TANG

From August 1989 to May 1994, 84 cases of ventricular premature beat (VPB) with deficiency syndrome were treated with our empirical prescription called Qi Lu Tang Decoction for Improving Abnormal Heart Beat). The total effective rate was 88.10%, being significantly different from that of the control group treated with the Western drug propafenone (P

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.

基于糖代谢和胰岛素抵抗评估益气养阴法治疗气阴两虚型2型糖尿病的疗效

目的分析益气养阴法治疗气阴两虚型2型糖尿病对患者糖代谢和胰岛素抵抗评估的影响。方法南京中医药大学附属南京市中西医结合医院2019年6月—2022年3月收治的90例气阴两虚型2型糖尿病患者随机分为胰岛素泵治疗组(45例)和益气养阴治疗组(45例)。益气养阴治疗组采用胰岛素泵强化治疗联合益气养阴法进行治疗,胰岛素泵治疗组单独进行胰岛素泵强化治疗,两组均治疗2周。统计两组治疗2周后的临床疗效及治疗期间不良反应发生情况,比较两组治疗前和治疗2周后中医证候积分、糖代谢情况、胰岛素抵抗情况。结果治疗2周后,益气养阴治疗组总有效率为91.11%(41/45),高于胰岛素泵治疗组[73.33%(33/45),P<0.05]。治疗2周后与治疗前比较,两组口燥咽干、倦怠乏力、失眠、自汗盗汗、五心烦热、气短懒言评分及血清空腹血糖(fasting blood glucose,FPG)、餐后2 h血糖(postprandial 2-hour blood glucose,2 h PG)、糖化血红蛋白(glycated hemoglobin,HbA1c)、空腹胰岛素(fasting insulin,FINS)水平、胰岛素抵抗指数(Homa-IR)降低,益气养阴治疗组低于胰岛素泵治疗组(P<0.05),两组胰岛素敏感指数(insulin sensitivity index,ISI)、胰岛功能指数(Homa-islet)升高,益气养阴治疗组高于胰岛素泵治疗组(P<0.05)。治疗期间,益气养阴治疗组总不良反应发生率与胰岛素泵治疗组比较,差异无统计学意义(P>0.05)。结论气阴两虚型2型糖尿病患者采用益气养阴法进行治疗,可有效改善患者中医证候、糖代谢,降低患者机体胰岛素抵抗程度,具有较好的治疗效果。