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.

Clinical Observation of the Therapeutic Effects of Wenzhong Hewei Formula in Treating Spleen and Stomach Qi Deficiency Syndrome in Internal Medicine Diseases

Objective:To observe the clinical efficacy and safety of Wenzhong Hewei Formula in treating spleen and stomach qi deficiency syndrome in internal medicine diseases.Methods:Sixty patients with spleen and stomach qi deficiency syndrome admitted to the hospital from April 2022 to June 2023 were randomly divided into observation and control groups,with 30 patients in each group.The control group received conventional internal medicine treatment,while the observation group was additionally treated with Wenzhong Hewei Formula on the basis of conventional treatment.Both groups were treated for 4 weeks.Results:The total effective rate of treatment in the observation group was higher than that of the control group(P<0.05).After treatment,the traditional Chinese medicine syndrome scores of both groups were significantly lower than before treatment,with the observation group showing a more pronounced reduction(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Wenzhong Hewei Formula can effectively improve clinical symptoms in patients with spleen and stomach qi deficiency syndrome,enhance clinical efficacy,and have a high level of safety,making it worthy of clinical promotion.

The prescription rule analysis of the New Theory on Spleen Dampness Syndrome by Academician TONG Xiaolin

Objective To analyze the basic characteristics,drug features,prescription rules,and drug-symptom relationships of patients in the splenic deficiency and impairment stage,by data mining of medical records under the New Theory on Spleen Dampness Syndrome(Pi Dan Xin Lun,《脾瘅新论》).Methods Medical records listed in the“New Theory on Spleen Dampness Syndrome-Under-standing and Treatment of Metabolic Syndrome from the Perspective of Traditional Chinese Medicine”,and which were diagnosed with the spleen dampness syndrome at the splenic de-ficiency and impairment stage,during January 2004 and December 2016 were selected.These patients’data,including basic information,clinical symptoms,laboratory examination res-ults,traditional Chinese medicine(TCM)and western medicine diagnoses,treatment meth-ods,prescriptions,etc.,were collected.The collected data were subsequently compiled into a medical record database using the Epidata 3.1 data management software,followed by the use of Apriori algorithm provided in the SPSS Modeler 14.2 statistical software to investigate the association rules between drug-drug,drug-symptom,and drug-western medicine indices.Results(i)A total of 51 medical records were included,involving 17 types of syndromes.Among them,the top three with frequency≥3 included“Phlegm and blood stasis,and thoracic obstruction”“Deficiency-weakness of the spleen Qi,and static blood blocking collat-erals”,and“Deficiency-weakness of the spleen Qi,and static blood blocking collaterals”.Al-ternatively,of the 14 treatment methods,the top three treatments with frequency of≥3 in-cluded“Activating Yang and eliminating turbidity,and removing phlegm and dredging chan-nel blockage”“Strengthening the spleen and benefiting Qi,and eliminating phlegm to activ-ate the channels”,and“Warming Yang and benefiting Qi,and expelling cold to remove ob-structions”.Among the 15 prescriptions,the top three used with frequency≥3 included Huangqi Guizhi Wuwu Tang(黄芪桂枝五物汤),Gualou Xiebai Banxia Tang(瓜蒌薤白半夏汤),and Ganjiang Huangqin Huanglian Renshen Tang(干姜黄芩黄连人参汤).Lastly,of the 83 drugs used for a total of 476 times,those with frequency≥15 included Huanglian(Coptid-is Rhizoma),Huangqi(Astragali Radix),Jiudahuang(Wine-processed Rhei Radix et Rhizoma),Jixueteng(Spatholobi Caulis),Shengjiang(Zingiberis Rhizoma Recens),Huangqin(Scutellariae Radix),and Guizhi(Cinnamomi Ramulus).(ii)For the drug-drug associations,under the criteria of support≥15%and confidence=100%,seven second-order association rules,seven third-order rules,and six fourth-order roles were identified.The top-ranking rule of each was“Huangqin(Scutellariae Radix)→Huanglian(Coptidis Rhizoma)”“Ganjiang(Zingiberis Rhizoma)+Huangqin(Scutellariae Radix)→Huanglian(Coptidis Rhizoma)”,and“Baishao(Paeoniae Radix Alba)+Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatho-lobi Caulis)→Huangqin(Scutellariae Radix)”,respectively.Alternatively,the drug-symptom associations were analyzed under the criteria of support≥5%and confidence=100%,which derived eight second-order association rules,31 third-order rules,and 30 fourth-order rules.The top-ranking association rule of each order was“Huangqi(Astragali Radix)→Limb ed-ema”“Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatholobi Caulis)→Limb numbness and pain”,and“Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatholobi Caulis)+Huangqi(As-tragali Radix)→Limb numbness and pain”,respectively.Similarly,the drug-western medi-cine index associations were investigated under the criteria of support≥5%and confidence=100%,and five second-order association rules,16 third-order rules,and 16 fourth-order rules were identified.In this category,the top-ranking association rule of each order was“Qinpi(Fraxini Cortex)→Uric acid”“Huanglian(Coptidis Rhizoma)+Ganjiang(Zingiberis Rhizoma)→Glycated hemoglobin”,and“Huanglian(Coptidis Rhizoma)+Ganjiang(Zing-iberis Rhizoma)+Huangqin(Scutellariae Radix)→Glycated hemoglobin”,respectively.Conclusion Through association rule mining,this study objectively and quantitatively demonstrated the drug-drug,drug-symptom,and drug-physicochemical index associations of patients with the spleen dampness syndrome at the splenic deficiency and impairment stage treated by Academician TONG Xiaolin.The results indicated that treatment for these patients adopted the“state-target”syndrome differentiation method.The drug combination was characterized by“small prescriptions”,targeting both the patient’s symptoms and signs(syndrome target)and western medicine indices(treatment target).This study could provide references for future research on the academic thoughts and medical experience of Academi-cian TONG Xiaolin.

CLINICAL STUDY ON SPLEEN-STOMACH-REINFORCING MOXIBUSTION TREATMENT OF DIARRHEA-TYPE IRRITABLE BOWEL SYNDROME

In the present paper, the therapeutic effect of spleen- stomach- reinforcing moxibustion for treatment of irritable bowel syndrome (IBS) is observed and its underlying mechanisms on immunity are analyzed. A total of 72 IBS patients are randomly divided into moxibustion group (n= 46) and acupuncture group (control group, n = 26). Acu-points used are Zhongwan (CV 12), Qihai (CV 6) and Zusanli (ST 36), etc. Serum IgG, IgA and IgM contents, blood T-lympocytes (T3+, T4+, T8+) counts, T4+ /T8+, cancer embryonic antigen (CEA) content, serum IL-2 and slL-2R contents are assayed for evaluating changes of the immunocompetence. After two courses of treatment (24 sessions), results show that in moxibustion group, 25 cases (54.35%) are cured, 17 experience improvement in clinical symptoms and 4 have no apparent changes, with an effective rate of 91.30% ; in control group, 8 cases (30. 78%) are cured, 12 experience improvement and 6 have no marked improvement, with an effective rate of 76.92% . The therapeutic effect of moxibustion is significantly superior to that of acupuncture (P<0.01). In addition, moxibustion can effectively rectify abnormal immune function and stabilize human's immunity. This research provides a reliable experimental basis for clinical application of 'principal prescription of moxibustion for reinforcing the spleen and stomach'.

Exosomes promote the invasion and metastasis of hepatocellular carcinoma cells via an integrin-dependent manner in the spleen-deficient state

Background:To investigate the detailed mechanism underlying the pro-metastatic effect of spleen deficiency(SD)syndrome on hepatocellular carcinoma(HCC).Methods:In the present study,our model was established based on an HCC mouse model induced by diethylnitrosamine using reserpine to induce SD.Exosomes were isolated and purified from mouse plasma samples using an exosome isolation kit.Subsequently,we verified the pro-metastatic effects of exosomes from the HCC mice with SD on HCC cells by transwell assays,wound healing assays,phalloidin staining in vitro,and lung metastasis assay of mice in vivo.Finally,we further explored the detailed mechanism underlying the pro-metastatic effect of exosomes from the HCC mice with SD on HCC cells.Results:We found that SD promoted the malignant progression of HCC in mice.Exosomes from HCC mice with SD enhanced the invasion and metastasis of HCC cells in vitro and in vivo.Mechanistically,upregulation of integrinα1,integrinβ1,and integrinβ5 seemed to play a key role in mediating the pro-metastatic effect of exosomes isolated from the HCC mice with SD,which was largely abrogated upon co-treatment with a broad-spectrum integrin inhibitor.Conclusion:Our findings demonstrated that exosomes promote the invasion and metastasis of HCC cells via an integrin-dependent manner in the spleen-deficient state that would contribute to our better understanding of the role of SD in HCC progression in traditional Chinese medicine,and thus management of the disease.

Biological basis of “depression with liver-qi stagnation and spleen deficiency syndrome”: A digital gene expression profiling study

Objective:To investigate the biological basis of“depression with liver-qi stagnation and spleen deficiency syndrome”.Methods:A digital gene expression profiling method was conducted to explore global changes in the mRNA transcriptome in a rat model of depression with liver-qi stagnation and spleen deficiency syndrome.Real-time quantitative polymerase chain reaction(q-PCR)was performed to verify the five genes most interest based on the Kyoto Encyclopedia of Genes and Genome(KEGG)analysis.Sini San,which disperses stagnated liver qi and strengthens the spleen,was administered to the model rats to observe whether it could reverse these genetic changes in the liver.Results:Forty-six differentially expressed genes were identified.Three of the five genes of most interestdHnf4a,Hnf4g and Cyp1a1dbased on KEGG analysis,were confirmed by realtime q-PCR.Sini San reduced the gene expression changes of Hnf4a,Hnf4g and Cyp1a1 in the rat model.Conclusions:Hnf4a,Hnf4g and Cyp1a1 are involved in“depression with liver-qi stagnation and spleen deficiency syndrome”.These findings indicate that depressed rats with liver-qi stagnation and spleen deficiency syndrome are at risk of liver diseases.Furthermore,our results will inform exploration of the etiology of depression and help in the development of effective therapeutic strategies.

Study on the Characteristics of Gut Microbiota in Chronic Hepatitis B(CHB)Patients with Damp Heat Syndrome and Liver Depression and Spleen Deficiency Syndrome

Objective:This study was designed to explore the characteristics of gut microbiota in CHB patients with two most common traditional Chinese medicine(TCM)Syndromes—damp heat syndrome and liver depression and spleen deficiency syndrome.Methods:According to the diagnostic criteria of Western medicine,TCM and screening exclusion criteria,65 cases of CHB with damp heat syndrome and 28 cases of CHB with liver depression and spleen deficiency syndrome were finally included in the study.All the basic information was gathered and the fresh fecal samples were collected for 16S rDNA sequencing.16S rDNA of gut microbiota was sequenced using Illumina hiseq 2,500 high-throughput sequencing platform.Based on the optimized sequence,Operational Taxonomic Units(OTU)clustering analysis and taxonomic annotation were carried out.Results:The difference in relative abundance of gut microbiota was significant between damp heat syndrome and liver depression and spleen deficiency syndrome in CHB patients.Cyanobacteria was only found in damp heat syndrome.The relative abundance of Erysipelotrichia and Subdoligranulum were higher in liver depression and spleen deficiency syndrome,while the relative abundance of Rhodospirillales,Alphaproteobacteria and Lachnospira were higher in the damp heat syndrome.LDA Effect Size(LEfSe)analysis showed that Lachnospira,Olsenella and Subdoligranulum had significant difference in species among the two TCM syndromes.Conclusion:The different characteristics of gut microbiota in the two TCM syndromes of CHB patients may play an important role in syndrome formation of TCM,which provides a new field of vision for the accurate diagnosis and treatment of TCM.

Clinical study on fire needle acupuncture treating irregular menstruation with spleen deficiency syndrome

Objective:To observe the clinical efficacy of fire needle acupuncture in treating irregular menstruation with spleen deficiency syndrome.Methods:60 patients with spleen deficiency-irregular menstruation were randomly divided into treatment group and control group of 30 each.In the treatment group,fire needle acupuncture was used to insert into Guanyuan,Qihai,Pishu,Sanyinjiao,Zusanli and Taibai points,while the filiform needle was used to needle the corresponding acupoints in the control group.After 8 weeks of treatment,menstrual cycle,menstrual period,menstrual volume,irregular menstrual symptom score and spleen deficiency symptom score were recorded.Results:Both treatments could effectively improve the menstrual cycle,menstrual period and menstrual volume,but there was no statistical significance between the two groups(P>0.05).Both treatments were effective in regulating the symptoms of menstruation,and fire needle acupuncture was better than filiform needle(P<0.05).Both treatments relieved the symptoms of spleen deficiency,and fire needle acupuncture was better than filiform needle(P<0.05).In terms of overall curative effect,the curative effect of fire needle acupuncture therapy was significantly better than filiform needle therapy,and the difference was statistically significant(P<0.05).Conclusion:Fire needle acupuncture therapy could effectively regulate menstrual volume of patients with irregular menstruation of spleen deficiency syndrome,and relieve the symptoms of traditional Chinese medicine.

Potential Mechanism and Application of Strengthening the Spleen, Clearing Heat and Dampness in Treatment of Gastroesophageal Reflux Disease

Gastroesophageal reflux disease(GERD)is one of refractory digestive disease in clinic characterized by high prevalence,complex and recurrent symptoms.Traditional Chinese medicine(TCM)has a significant effect on the treatment of GERD.Spleen deficiency and damp-heat syndrome becomes one of the main syndrome patterns of GERD adapting with the changes of modern lifestyle.Although the therapy of strengthening the spleen,clearing heat and dampness is widely used in treatment of GERD,further studies still need to be conducted.The article comprehensively analyses the theoretical basis,mechanism and clinical efficacy of the therapy in order to provide more ideas for clinical treatment.

Efficacy of Pidan Jianqing decoction in treatment of type 2 diabetes with spleen deficiency and damp-heat syndrome

Introduction:This study aimed to assess the clinical efficacy of Pidan Jianqing decoction in the treatment of type 2 diabetes.Methods:A total of 72 patients with type 2 diabetes differentiated as spleen deficiency with damp-heat syndrome were randomly assigned to a treatment group(n=35)or control group(n=32).Patients in the control group received diet and exercise guidance and medication in the form of 0.5 g metformin hydrochloride tablets,while patients in the treatment group received Pidan Jianqing decoction in addition to the treatment given to the control group.Efficacy was evaluated after 8 weeks of treatment.Results:Efficacy was 91.4%in the treatment group versus 68.8%in the control group,which was a statistically significant difference(P<0.05).Significant group differences were also noted in the number of patients with improvement in symptoms such as dry mouth and polydipsia,frequency of urination and polyuria,abdominal distention and loss of appetite,fatigue and weakness,and sticky stools(all P<0.05),with greater improvement in the treatment group compared to the control group.The fasting blood glucose(FBG)and 2 h postprandial blood glucose levels significantly improved in both groups after treatment(P<0.05);however,there was no significant difference in glycated hemoglobin levels before and after treatment in both groups.Conclusion:Pidan Jianqing decoction can lower blood glucose levels and improve symptoms in patients with type 2 diabetes.

Study of establishing disease-syndrome combined with animal model for immune thrombocytopenic purpura without additional conditions

Objective:To explore the feasibility of establishing the disease-syndrome combined animal model for immune thrombocytopenic purpura(ITP)without additional conditions.Methods:Three batches of data related to the ITP model mice obtained by replication at different time were analyzed,and whether the APS-injected model mice replicated through the passive immune modeling method could simulate the pathogenesis and clinical characteristics of human ITP was evaluated according to the differentiation criteria for diseasesyndrome combined model.Results:The APS-injected replicated ITP model mice possessed the following traits:(1)Compared with the normal group,the platelet count was significantly decreased,and coagulation time was significantly increased in the model group(P<.01).(2)Compared with the normal group,the medullary thrombocytogenous megakaryocytes were significantly decreased(P<.05,.01,.001).(3)The APS-injected sites and other parts of the model mice had spontaneous hemorrhage.(4)Behavioral changing signs were observed 1 week after the modeling(i.e.low activity,delayed activity,poor appetite,skin petechia/hemorrhage and spontaneous hemorrhage at the injected sites or other parts),and were getting more and more severe.Conclusion:According to the syndrome differentiation criteria for disease-syndrome combined model of ITP,the APS-injected animal model of ITP replicated through the passive immune modeling method without additional conditions possesses the characteristics of disease-syndrome combined model.It provides an ideal tool for the development of traditional Chinese medicine pharmacology experiment.

The mechanism of Astragalus membranaceus in treating peritoneal fibrosis by intervening the key syndrome and pathology based on Q-marker theory

Objective:To evaluate the mechanism of Astragalus membranaceus(AM)by intervening peritoneal mesothelial cells(PMCs),epithelial-mesenchymal transition(EMT),and spleen deficiency syndrome(SDS)in peritoneal fibrosis(PF),we base on employing the strategy of Q-marker theory combination network pharmacology method.Methods:First,we obtained the Q-markers of AM by searching the relevant literature and its pharmacological information was collected based on SwissADME.The SwissTargetPrediction and pharmmaper were employed to predict its potential target.Secondly,GeneCards,DisGeNET,and OMIM databases were employed to search the related targets of EMT,SDS,and PF.VENNY2.1 tool was employed to obtain the intersection targets of AM and the three;then the“AM potential target-SDS-EMT-PF”Venn diagram was constructed.The common targets of AM,EMT and SDS were uploaded to the STRING database and obtained the PPI protein interaction network map.Cytoscape 3.7.2 was employed to evaluate the core target of PPI network.PATHER and Metascape databases were used to analyze protein type,GO biological process,and KEGG pathway.Finally,a network diagram of the“TCM-component-disease target-pathway”was drawn.Results:A total of 10 AM Q-makers were screened out,corresponding to 335 targets of AM,2,728 targets of SDS,373 of EMT,and 612 PF targets were found.Among them,there are 155 common AM targets related to SDS and EMT.Key targets such as ALB,AKT1,VEGFA,TNF,EGFR,CASP3,SRC,STAT3,HSP90AA1,and ESR1 were obtained.The core drug include quercetin,astragalosideIII,Calycosin-7-O-beta-D-glucoside,astragalosideIV,etc.The types of PPI proteins include protein modification enzymes,metabolite transferases,transmembrane signal receptors,etc.Biological processes include the regulation of kinase activity,the positive regulation of transferase activity,and the regulation of kinase activity.The key pathways may include PI3K-Akt signaling pathways,the non-smad pathway of the TGF-βsignaling pathway,and the AGE-RAGE signaling pathway.Conclusion:AM could prevent and treat PF through a multi-component multi-target-multi-path mechanism.Astragalus saponins may be the main component types of AM intervening EMT pathology by strengthening the spleen and nourishing Qi.AstragalosideIV and astragalosideIII may be the constituents that can invigorate the spleen and replenish Qi.The results of this study contribute to a more comprehensive understanding of the critical components and mechanisms of AM by intervening SDS and EMT in the treatment of PF.

Clinical observation of treatment of infantile diarrhea due to spleen deficiency using five-step pediatric tuina of Huxiang school

Objective:To observe the clinical efficacy of treating infantile diarrhea due to spleen deficiency with five-step pediatric tuina of Huxiang school.Methods:Using a randomized controlled trial design,sixty eligible kids with diarrhea due to spleen deficiency were randomized into an observation group and a control group,with 30 cases in each group.The observation group was intervened by the five-step pediatric tuina method of Huxiang school,and the control group received conventional tuina treatment.The intervention was conducted once a day,consecutive 5-day treatment as 1 course,at a 2-day interval between courses,successively for a total of 4 courses.Changes in the primary and secondary symptoms of diarrhea due to spleen deficiency were observed,and the clinical efficacy was evaluated.Results:After treatment,the scores of primary and secondary symptoms and the general score of diarrhea due to spleen deficiency were improved;the improvements in fecal form and frequency,decreased appetite,bloating after meals and fatigue and sluggishness were more significant in the observation group than in the control group.Conclusion:The five-step pediatric tuina method of Huxiang school and conventional tuina both can improve the primary and secondary symptoms in infantile diarrhea due to spleen deficiency,while the former one can produce more significant efficacy.

Chinmedomics facilitated quality-marker discovery of Sijunzi decoction to treat spleen qi deficiency syndrome

Sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of years.However,the quality control (QC) standards of SJZD are insufficient.Chinmedomics has been designed to discover and verify bioactive compounds of a variety of formularapidly.In this study,we used Chinmedomics to evaluate the SJZD's efficacy against SQDS to discover the potential quality-markers (q-markers) for QC.A total of 56 compounds in SJZD were characterized in vitro,and 23 compounds were discovered in vivo.A total of 58 biomarkers were related to SQDS,and SJZD can adjust a large proportion of marker metabolites to normal level and then regulate the metabolic profile to the health status.A total of 10 constituents were absorbed as effective ingredients that were associated with overall efficacy.We preliminarily determined malonyl-ginsenoside Rb2 and ginsenoside Ro as the q-markers of ginseng;dehydrotumulosic acid and dihydroxy lanostene-triene-21-acid as the q-markers of poria;glycyrrhizic acid,isoglabrolide,and glycyrrhetnic acid as the q-markers of licorice;and 2-atractylenolide as the q-marker of macrocephala.According to the discovery of the SJZD q-markers,we can establish the quality standard that is related to efficacy.

Efficacy of Gastrosis No.1 Compound on Functional Dyspepsia of Spleen and Stomach Deficiency-Cold Syndrome:A Multi-Center,Double-Blind,Placebo-Controlled Clinical Trial

To assess the efficacy and safety of Gastrosis No.1 compound in the treatment of functional dyspepsia with Spleen （Pi） and Stomach （Wei） deficiency-cold syndrome. Methods： A randomized, double-blind, placebo-controlled trial was performed in 5 centers. Patients with functional dyspepsia （FD） of Spleen-deficiency and qi-stagnation syndrome （162 cases） were randomly assigned to groups given Chinese herbal medicine （CHM） Gastrosis No.1 compound or placebo in a 2：1 ratio. This trial included a 4-week treatment period and a 4-week follow-up period. The outcomes were the dyspepsia symptom scores （measured by total dyspepsia symptom scale and single dyspepsia symptom scale） and syndromes of traditional Chinese medicine score （measured by traditional Chinese medicine syndrome scale）. The outcomes were noted at weeks 0, 4 and 8. Results： Compared with patients in the placebo group, patients in the CHM group showed significant improvement in the dyspepsia symptom scores as rated by patients and investigators （P〈0.01）, and also showed improvement in syndromes of traditional Chinese medicine score （P〈0.01）. No serious adverse event was reported. Safety tests obtained after 4 weeks of treatment showed no abnormal values. Conclusion： CHM Gastrosis No.1 compound was effective and safe in the treatment of functional dyspepsia with Spleen and Stomach deficiency-cold syndrome.

Effects of different doses of ginger-partitioned moxibustion on trefoil factor 1,mucin 5AC and epidermal growth factor receptor in rats with spleen deficiency syndrome

To observe the effects of different doses of ginger-partitioned moxibustion on serum trefoil factor 1 （TFF1） and mucin 5AC （MUCSAC） levels, as well as the expression of epidermal growth factor receptor （EGFR） in gastric mucosa of rats with spleen deficiency syndrome, therefore, to explore the possible mechanism and the dose-effect characteristics of ginger-partitioned moxibustion in spleen deficiency syndrome. Methods： Seventy-five SPF grade Sprague-Dawley （SO） rats were randomly divided into a blank control group （group A）, a model group （group B）, a 3 moxa-cone ginger-partitioned moxibustion group （group C1）, a 6 moxa-cone ginger-partitioned moxibustion group （group C2） and a 9 moxa-cone ginger-partitioned moxibustion group （group C3） using random number table method, 15 rats in each group. Except group A, rats in the other groups received intragastric administration of 4 ~C 200% concentrated Da Huang （Radix et RhizomaRhei） to prepare spleen deficiency syndrome model. After successful modeling, rats in group B received no treatment; rats in group C1, C2 and C3 were treated with 3, 6 and 9 moxa-cone ginger-partitioned moxibustion at Zusanli （ST 36）and Zhongwan （CV 12） respectively for 8 continuous days. The general symptom score of rats was observed. The serum levels of TFF1 and MUC5AC were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of EGFR protein in gastric mucosa was detected by immunohistochemistry. Results： After the treatment, compared with group A, the spleen deficiency symptom score was increased in group B, the levels of serum TFF1 and MUC5AC, the EGFR protein expression in gastric tissues of group C1, C2 and C3 were significantly increased （all P〈0.01）; compared with group B, the spleen deficiency scores were decreased in group C1, C2 and C3, and the serum levels of TFF1 and MUC5AC, as well as EGFR protein expression in gastric tissues were increased （all P〈0.01）. Compared with group C1, the spleen deficiency scores were decreased in group C2 and C3, the serum levels of TFF1 and MUC5AC, and the expression of EGFR protein in gastric tissues were increased （all P〈0.01）, however, there was no significant difference between group C2 and C3 （all P〉0.05）. The mechanism may be related to the increase of serum TFF2 and MUC5AC levels and activation of EGFR protein. Conclusion： Ginger-partitioned moxibustion can improve the symptoms, as well as promote the proliferation and repair of gastric mucosa in rats with spleen deficiency. The therapeutic efficacy of 6 or 9 moxa-cone ginger-partitioned moxibustion is better than that of 3 moxa-cone ginger-partitioned moxibustion, while the efficacies are equivalent between 6 and 9 moxa-cone Ringer-Dartitioned moxibustion groups.

Appraisal of treatment outcomes in integrative medicine using metabonomics:Taking non-alcoholic fatty liver disease with spleen deficiency syndrome as an example

Objective:Appraisal of treatment outcomes in integrative medicine is a challenge due to a gap between the concepts of Western medicine(WM)disease and traditional Chinese medicine(TCM)syndrome.This study presents an approach for the appraisal of integrative medicine that is based on targeted metabolomics.We use non-alcoholic fatty liver disease with spleen deficiency syndrome as a test case.Methods:A patient-reported outcome(PRO)scale was developed based on literature review,Delphi consensus survey,and reliability and validity test,to quantitatively evaluate spleen deficiency syndrome.Then,a metabonomic foundation for the treatment of non-alcoholic fatty liver disease with spleen deficiency syndrome was identified via a longitudinal interventional trial and targeted metabolomics.Finally,an integrated appraisal model was established by identifying metabolites that responded in the treatment of WM disease and TCM syndrome as positive outcomes and using other aspects of the metabonomic foundation as independent variables.Results:Ten symptoms and signs were included in the spleen deficiency PRO scale.The internal reliability,content validity,discriminative validity and structural validity of the scale were all qualified.Based on treatment responses to treatments for WM disease(homeostasis model assessment of insulin resistance)or TCM syndrome(spleen deficiency PRO scale score)from a previous randomized controlled trial,two cohorts comprised of 30 participants each were established for targeted metabolomics detection.Twenty-five metabolites were found to be involved in successful treatment outcomes to both WM and TCM,following quantitative comparison and multivariate analysis.Finally,the model of the integrated appraisal system was exploratively established using binary logistic regression;it included 9 core metabolites and had the prediction probability of 83.3%.Conclusion:This study presented a new and comprehensive research route for integrative appraisal of treatment outcomes for WM disease and TCM syndrome.Critical research techniques used in this research included the development of a TCM syndrome assessment tool,a longitudinal interventional trial with verified TCM treatment,identification of homogeneous metabolites,and statistical modeling.

Effect of herbal cake-partitioned moxibustion on MEK1/2 and ERK1/2 expressions of gastric tissues in rats with spleen deficiency syndrome

Objective： To observe the effect of herbal cake-partitioned moxibustion on the expressions of mitogen-activated protein kinase （MEK：1/2） and extracellular regulatory protein kinase （ERK：1/2） in gastric tissues of rats with spleen deficiency syndrome, and to explore the possible mechanisms of herbal cake-partitioned moxibustion in treating spleen deficiency syndrome. Methods： Sixty Sprague-Dawley （SD） rats were randomly divided into a blank control group （group A）, a model group （group B）, a ranitidine group （group C）, and a herbal cake-partitioned moxibustion group （group D） by random digit, 15 rats in each group. Rat models of spleen deficiency syndrome were made by intragastric administration of 4℃ 200% concentrated Da Huang （Radix et Rhizoma Rhei）. After successful modeling, the rats in group C were treated with 25 mg/（kg.bw） ranitidine by intragastric adminstration and rats in group D were treated with herbal cake-partitioned moxibustion at Zusanli （ST 36） and Zhongwan （CV 12）, for 8 d. Excepted for rats in group A, all the other rats were treated with indomethacin at 5 mg/（kg.bw） at 8：00 a.m. on the second day after finishing all the intervention and sacrificed 7 h later to isolate the stomach. Histopathological changes of the gastric tissues were observed under light microscope after hematoxylin-eosin （HE） staining. The protein expressions of MEK：1/2 and ERK：1/2 in the gastric tissues were detected by immunohistochemistry. Results： After intervention, the gastric mucosal injury in group B was significantly severer than that in group A, with large breakage and ablating; the damage of gastric mucosa was decreased in group C compared with group B; the gastric mucosal surface remained relatively complete, and the status of breakage and ablating was significantly improved. After intervention, compared with group A, the protein expressions of MEK：1/2 and ERK：12 in gastric tissues of the other groups were significantly higher （P〈0.01）. Compared with group B, the protein expressions of MEK：1/2 and ERK：1/2 in group C and D were significantly higher （all P〈0.01）. Compared with group C, the protein expressions of MEK：1/2 and ERK：1/2 in group D were significantly higher （P〈0.01）. Conclusion： Herbal cake-partitioned moxibustion promotes the repair of gastric mucosa in rats with spleen deficiency syndrome, via improving protein expressions of MEK：1/2 and ERK：1/2 in gastric tissues, as well as activating MEK/ERK signaling pathway.

Screening the effective components in treating dampness stagnancy due to spleen deficiency syndrome and elucidating the potential mechanism of Poria water extract

Poria is an important medicine for inducing diuresis to drain dampness from the middle energizer.However,the specific effective components and the potential mechanism of Poria remain largely unknown.To identify the effective components and the mechanism of Poria water extract(PWE)to treat dampness stagnancy due to spleen deficiency syndrome(DSSD),a rat model of DSSD was established through weight-loaded forced swimming,intragastric ice-water stimulation,humid living environment,and alternate-day fasting for 21 days.After 14 days of treatment with PWE,the results indicated that PWE increased fecal moisture percentage,urine output,D-xylose level and weight;amylase,albumin,and total protein levels;and the swimming time of rats with DSSD to different extents.Eleven highly related components were screened out using the spectrum-effect relationship and LC-MS.Mechanistic studies revealed that PWE significantly increased the expression of serum motilin(MTL),gastrin(GAS),ADCY5/6,p-PKAα/β/γcat,and phosphorylated cAMP-response element binding protein in the stomach,and AQP3 expression in the colon.Moreover,it decreased the levels of serum ADH,the expression of AQP3 and AQP4 in the stomach,AQP1 and AQP3 in the duodenum,and AQP4 in the colon.PWE induced diuresis to drain dampness in rats with DSSD.Eleven main effective components were identified in PWE.They exerted therapeutic effect by regulating the AC-cAMP-AQP signaling pathway in the stomach,MTL and GAS levels in the serum,AQP1 and AQP3 expression in the duodenum,and AQP3 and AQP4 expression in the colon.

Efficacy and Safety of Jianpi Jieyu Decoction for Patients with Mild-to-Moderate Depression of Xin(Heart)-Pi(Spleen)Deficiency Syndrome:A Multi-centre Randomized Controlled Study

Objective:To evaluate the efficacy and safety of Jianpi Jieyu Decoction(JJD)for treating patients with mild-to-moderate depression of Xin(Heart)-Pi(Spleen)deficiency(XPD)syndrome.Methods:In this multi-center,randomized,controlled study,140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019.They were randomly divided into JJD group and paroxetine group by using a random number table,with 70 cases in each group.The patients in the JJD group were given JJD one dose per day(twice daily at morning and evening,100 m L each time),and the patients in the paroxetine group were given paroxetine(10 mg/d in week 1;20 mg/d in weeks 2-6),both orally administration for a total of 6 weeks.The primary outcome was the change of 17-item Hamilton Depression Rating Scale(HAMD-17)score at week 6 from baseline.The secondary outcomes included the Hamilton Anxiety Scale(HAMA)score,Traditional Chinese Medicine Symptom Scale(TCMSS),and Clinlcal Global Impression(CGI)scores at the 2nd,4th,and 6th weekends of treatment,HAMD-17 response(defined as a reduction in score of>50%)and HAMD-17 remission(defined as a score of 7)at the end of the 6th week of treatment.Adverse events(AEs)were also recorded.Results:From baseline to week 6,the HAMD-17 scores decreased 10.2±4.0 and 9.1±4.9 points in the JJD and paroxetine groups,respectively(P=0.689).The HAMD-17 response occurred in 60%of patients in the JJD group and in 50%of those in the paroxetine group(P=0.292);HAMD-17 remission occurred in 45.7%and 30%of patients,respectively(P=0.128).The differences of CGI scores at the 6th week were not statistically significant(P>0.05).There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week(P=0.001 and P=0.014).The HAMA scores declined 8.1±3.0 and 6.9±4.3 points from baseline to week 6 in the JJD and paroxetine groups,respectively(P=0.905 between groups).At 4th week of treatment,there was a significant difference in HAMA between the two groups(P=0.037).TCMSS decreased 11.4±5.1,and 10.1±6.8 points in the JJD and paroxetine groups,respectively(P=0.080 between groups).At the 6th week,the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group(7.14%vs.22.86%,P<0.05).Conclusion:Compared with paroxetine,JJD was associated with a significantly lower incidence of AEs in patients with mild-tomoderate depression of XPD syndrome,with no difference in efficacy at 6 weeks.(Trial registration No.Chi CTR2000040922).