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 improving hematopoietic function of rats with blood deficiency syndrome by Shengxuebao mixture

Background:Shengxuebao mixture(SXBM)is a novel herbal drug approved by China State Food and Drug Administration for the treatment of Leukopenia and iron deficiency anemia caused by radiotherapy and chemotherapy.Methods:To explore the mechanism of SXBM in treating blood deficiency syndrome(BDS).Firstly,network pharmacology and in vivo experiments were used to screen candidate targets and important signaling pathways of SXBM,GO functional enrichment and KEGG pathway analysis were performed.Secondly,a BDS rat model was established to verify the results of the analysis of network pharmacological enrichment.Histopathology and routine peripheral blood examination were observed.The expressions of tumor necrosis factor-α,interleukin(IL)-6,HIF-1αand NF-κB were detected by Western blot,and the expressions of IL-6,IL-1βwere detected by ELISA.Results:62 bioactive components,66 potential targets and 131 signaling pathways of BDS were successfully identified by network pharmacology.Molecular docking simulation techniques showed that key targets tumor necrosis factor-α,IL-6,IL-1βcan dock well with crucial components,and the BDS-related signaling pathways HIF-1 and JAK-STAT play a vital role.The combined model experiment of acetylphenylhydrazine and cyclophosphamide showed that the model group had obvious blood deficiency,and the histopathology and blood routine were effectively restored after administration.Our findings indicate that SXBM’s therapeutic effect on BDS primarily involves the mediation of the HIF-1α/NF-κB signaling pathway and the regulation of hematopoietic factor expression.Conclusion:This study not only affirmed the protective properties of SXBM against BDS but also provided insights into a potential mechanism for blood replenishment in the treatment of BDS using SXBM.

Gut microbial diversity analysis using Illumina sequencing for functional dyspepsia with liver depression-spleen deficiency syndrome and the interventional Xiaoyaosan in a rat model

AIM To investigate gut microbial diversity and the interventional effect of Xiaoyaosan(XYS) in a rat model of functional dyspepsia(FD) with liver depression-spleen deficiency syndrome. METHODS The FD with liver depression-spleen deficiency syndrome rat model was established through classic chronic mild unpredictable stimulation every day. XYS group rats received XYS 1 h before the stimulation. The models were assessed by parameters including state ofthe rat, weight, sucrose test result and open-field test result. After 3 wk, the stools of rats were collected and genomic DNA was extracted. PCR products of the V4 region of 16 S rD NA were sequenced using a barcoded Illumina paired-end sequencing technique. The primary composition of the microbiome in the stool samples was determined and analyzed by cluster analysis.RESULTS Rat models were successfully established, per data from rat state, weight and open-field test. The microbiomes contained 20 phyla from all samples. Firmicutes, Bacteroidetes, Proteobacteria, Cyanobacteria and Tenericutes were the most abundant taxonomic groups. The relative abundance of Firmicutes, Proteobacteria and Cyanobacteria in the model group was higher than that in the normal group. On the contrary, the relative abundance of Bacteroidetes in the model group was lower than that in the normal group. Upon XYS treatment, the relative abundance of all dysregulated phyla was restored to levels similar to those observed in the normal group. Abundance clustering heat map of phyla corroborated the taxonomic distribution. CONCLUSION The microbiome relative abundance of FD rats with liver depression-spleen deficiency syndrome was significantly different from the normal cohort. XYS intervention may effectively adjust the gut dysbacteriosis in FD.

Penicillium marneffei chylous ascites in acquired immune deficiency syndrome:A case report

Penicillium marneffei （R marneffei） infection usually occurs with skin, bone marrow, lung or hepatic involve- ment. However, no cases of P. mameffei infection with chylous ascites have been reported thus far. In this re- port, we describe the first case of acquired immune de- ficiency syndrome （AIDS） which has been complicated by a P. marneffei infection causing chylous ascites. We describe the details of the case, with an emphasis on treatment regimen. This patient was treated with am- photericin B for 3 mo, while receiving concomitant ther- apy with an efavirenz-containing antiretroviral regimen, but cultures in ascitic fluid were persistently positive for P. marneffei. The infection resolved after treatment with high-dose voriconazole （400 mg every 12 h） for 3 too. R marneffei should be considered in the differential di- agnosis of chylous ascites in human immunodeficiency virus patients. High-dose voriconazole is an effective, well-tolerated and convenient option for the treatment of systemic infections with R marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.

Serum Levels of Interleukin-1 Beta, Interleukin-6 and Melatonin over Summer and Winter in Kidney Deficiency Syndrome in Bizheng Rats

Objective To observe the seasonal changes in serum levels of interleukin-1 beta(IL-1β), interleukin-6(IL-6) and melatonin(MT) in Bizheng rat model, and explore the relationship between MT and the pathogenesis of rheumatoid arthritis. Methods One hundred and sixty Sprague-Dawley rats were randomly divided into four groups in summer(n=80) and winter(n=80) respectively: normal group, collagen-induced arthritis(CIA) model group, operation group, and sham-operation group(n=20 in each group). The CIA model group was injected with collagen emulsion at the base of the tail to induce arthritis. The rats in the operation group received pineal gland resection, and 7 days after the first operation, underwent testectomy or oophorectomy. The rats in the sham-operation group were operated to ligature the sagittal sinus, without extracting the pineal gland. After the operations, the operation group and the sham-operation group both were immunized as the CIA group was. The serum levels of IL-1β, IL-6 and MT in different groups were measured by radioimmunoassay. Results Compared with the normal group, the serum levels of IL-1β and IL-6 increased in the CIA model, operation, and sham-operation groups both in summer and in winter(IL-1β in summer, P=0.008, P<0.01, P=0.012; IL-1β in winter, P=0.019, P<0.01, P=0.027; IL-6 in summer, P=0.028, P<0.01, P=0.024; IL-6 in winter, P=0.006, P<0.01, P=0.008). In the operation group, the serum levels of IL-1β and IL-6 in winter were higher than in summer, but with no statistically significant differences(P=0.844, 0.679). Compared with the normal group, the serum level of MT significantly increased in summer and winter in both the CIA model group(P=0.002, 0.008) and the sham-operation group(P=0.003, 0.007), while significantly decreased in the operation group(P=0.023, 0.003). There was no significant difference in MT level in the operation group between summer and winter(P=0.947). Conclusions The increase of serum levels of IL-1β and IL-6 may exacerbate the inflammatoryreaction and cause a more severe condition in the rheumatoid arthritis. The concentrations of IL-1β, IL-6, and MT correspond with the change of seasons, confirming that there are connections between nature and human body.

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.

Effect of long-acting testosterone undecanoate treatment on quality of life in men with testosterone deficiency syndrome： a double blind randomized controlled trial

This study aimed to investigate the effect of intramuscular injection of testosterone undecanoate on overall quality of life （QoL） in men with testosterone deficiency syndrome （TDS）. A randomized controlled trial over a 12-month period was carried out in 2009. One hundred and twenty men aged 40 years and above with a diagnosis of TDS （serum total testosterone 〈12 nmol 1-1 and total Aging Male Symptom （AMS） scores ≥ 27） were invited to participate. Interventions comprised intramuscular injection of either placebo or 1000 mg testosterone undecanoate, given at weeks O, 6, 18, 30 and 42. This paper presents the secondary analysis of QoL changes measured in the scores of Short-Form-12 （SF-12） scale at baseline, weeks 30 and 48 after the first injection. A total of 56/60 and 58/60 men from the active treatment and placebo group, respectively, completed the study. At week 48, before adjusting for baseline differences, the QoL of men in the treatment group improved significantly in five out of the eight domains on SF-12. The physical health composite scores improved 4.0 points from a baseline of 41.9±7.0 in the treatment group compared to 0.8 point from a baseline of 43.7--7.1 in the placebo group （F=3.652, P=0.027）. The mental health composite scores improved 4.4 points from a baseline of 37.1±9.0 in the treatment group compared to 1.0 points from a baseline of 37.6±7.9 in the placebo group （F=4.514, P=-0.018）. After adjusting for baseline differences, significant improvement was observed in mental health composite scores, but not in physical health composite scores. LQng-acting testosterone undecanoate significanUy improved the mental health component of QoL in men with TDS.

Recent topics related to testosterone deficiency syndrome n Japan

Androgens, the levels of which decrease with ageing, play many physiological roles in various organs. Testosterone deficiency syndrome （TDS） has received widespread attention in the last several years. First-line treatment for TDS should be testosterone replacement therapy （TRT）, which is reported to improve several TDS symptoms. Recently, a clinical practice manual for TDS was written and published by a collaborative team from the Japanese Urological Association and the Japanese Society for the Study of the Aging Male to recommend standard procedures for the diagnosis, treatment, prevention and monitoring of adverse reactions to TRT and for post-treatment assessment. In this manual, intramuscular injection of testosterone enanthate or human chorionic gonadotropin and the testosterone gel ＇Glowmin＇ were recommended as TRT. Currently, two topics related to TDS are being focused on in Japan： the relationship between TDS and metabolic syndrome and treatment options for eugonadal patients with TDS symptoms. In this review, the possibility of TRT for metabolic syndrome as well as the relationship between testosterone and adiponectin, which is a key molecule in metabolic syndrome, is discussed. Finally, the possibility of herbal medicines as a treatment option for patients with TDS is addressed, especially for eugonadal patients, because eugonadal men with TDS symptoms account for approximately 30% of the general population. The increase in the levels of several cytokines, such as IL-8, IL-13, interferon.y and tumor necrosis factor-α, after herbal medicine treatment may be the reason for this efficacy.

High Density Lipoprotein Phospholipids as a Marker of Coronary Heart Disease of Shen-Yang Deficiency Syndrome

Objective: To seek a new biochemical index for diagnosis of coronary heart disease (CHD) of shen-Yang deficiency syndrom (CHD-SYD). Methods: Sixty-one patients with CHD were divided into 3 groups according to their TCM Syndrome type, 10 patients in the group without Xin-Qi deficiency (Group A), 25 in the group with Xin-Qi deficiency but without Shen-Yang deficiency (Group B) and 26 in the group both with Xin-Qi deficiency and Shen-Yang deficiency (Group C). Levels of 17-hydroxy-corticoste-roid in urine (urinary 17-OHCS) per 24 hrs, and serum level of high density lipoprotein cholesterol (HDL-C) and high density lipoprotein phospholipid (HDL-PL) in them were determined in synchrostep and compared with those in the control group of 23 healthy aged persons, urinary 17-OHCS per 24 hrs was taken as the diagnostic standard to screen a new index for diagnosis of Shen-Yang deficiency Syndrome, and preliminary appraisal to the index was made. Results: Serum HDL-PL in the CHD-SYD patients( Group C) was 616+157 mg/L, which was obviously lower than that in the patients of Group A and B. With low HDL-PL(<650 mg/L) used as the index to diagnose CHD-SYD, the sensitivity was 73%, the specificity 86% and the accuracy 80%. Conclusion: HDL-PL <650 mg/L could be adopted as an index for CHD-SYD diagnosis, which is simple and practical.

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.

Analysis on Characteristics of Typical Syndromes of Acquired Immune Deficiency Syndrome Based on the Feature Selection Method

Objective:To discover the population characteristics of the syndrome types of Acquired Immune Deficiency Syndrome.Methods:Data mining method for feature selection was used.Results:Main symptoms based on feature selection are as follows,deficiency of both qi and blood(pale complexion,fear of cold,easy to catch a cold,pale tongue,weak pulse);liver depression and qi stagnation with effulgent fire(anxiety,insomnia,chest and hypochondrium,irregular menstruation,thin and whitish coating on the tongue,stringy pulse);dual deficiency of qi and yin(low-grade fever and night sweating,yellow urine,pale complexion,dysphoria with feverish sensation in chest,dry cough with less phlegm,weakness,dizziness,dry and red tongue,little coating,thread and rapid pulse);deficiency of spleen and kidney,dampness pathogen blockage(diarrhea,loose stool,eat less and abdominal nausea,abdominal pain,sallow complexion,nausea,vomiting,loss of hair,deafness and tinnitus,pale tongue with whitish coating,deep and thready pulse,slippery and rapid pulse);qi deficiency with blood stasis(weakness,spontaneous sweating,dry mouth without desire to drink,easy to catch a cold,shortness of breath,sallow complexion,eat less and loose stools,dim tongue quality,hesitant pulse).Conclusion:Based on the feature selection method,we can find the main characteristics of Acquired Immune Deficiency Syndrome,and provide objective reference for clinical diagnosis and treatment.

Investigation of perceived stigma among people living with human immunodeficiency virus/ acquired immune deficiency syndrome in Henan Province, China

Purpose:To investigate the level of and factors influencing perceived stigma and discrimination among people living with human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(PLWHA)in Henan Province.Methods:In total,161 PLWHA from Zhengzhou and Zhenping were investigated using the Berger HIV stigma scale.Results:The mean Berger stigma scale score was 105.70±15.20,indicating a middle stigma level.Among the four subscales of the Berger stigma scale,the disclosure concerns score was highest,while the negative self-image score was lowest.Multivariate analyses showed that factors influencing perceived HIV stigma included the level of education and route of infection.Conclusion:The level of perceived HIV stigma and discrimination among PLWHA in Henan Province is moderate and was affected by the level of education and route of infection.Special intervention should be established to address this problem.

Age-related changes in prevalence and symptom characteristics in kidney deficiency syndrome with varied health status:a cross-sectional observational study

Objective:This study aimed to reveal the age-related changes in prevalence and symptom characteristics in kidney deficiency syndrome(KDS)with varied health status.Methods:This cross-sectional observational study was conducted in6 hospitals.Investigators queried participants aged 20e79 about their health,including symptoms if any,and completed questionnaires to collect participants responses.Prevalence,severity,and frequency of KDS and other relevant parameters were observed and recorded.Comparative analysis of countable variables,including prevalence,was performed by frequency analysis and c2 test and expressed as a composite ratio.Comparative analysis of quantitative scores of the severity and frequency of symptoms was performed by the rank-sum test.Regression analysis of the correlation of KDS with potential contributing factors was performed by non-conditional binary logistic stepwise regression of numerical variables.Results:Prevalence of KDS in healthy and unhealthy participants correlated with increasing age(P<0.05).In those with chronic disease,KDS prevalence was comparatively high,but the trend was not obvious.KDS prevalence in participants age 20e39 showed an increasing trend with deteriorating health(P<0.05).Compared to healthy individuals,KDS prevalence in subhealthy persons and those with chronic disease showed an increasing trend(P<0.05)in the 40e59 and 60e79 age groups,whereas there was no difference between subhealthy persons and those with chronic disease age 40e59 and 60e79.Symptom severity scores of KDS showed an increasing trend with increasing age and deteriorating health status(P<0.05).Higher symptom frequency scores were also positively correlated with increasing age(P<0.05),but health status deterioration was not significantly correlated(P>0.05).Age,health status,lower back pain,shin soreness or heel pain,tinnitus or deafness,hair loss or loose teeth,incomplete bladder emptying or incontinence,and sexual dysfunction or infertility were potential factors contributing to KDS(P<0.05),but age was the only independent variable for which OR>1.Moreover,the distribution of typical KDS-related symptoms showed dramatic regularities.Conclusion:Prevalence and symptom characteristics of KDS were found to increase consistently with increasing age and deteriorating health status.Kidney deficiency may be an important mechanism of aging in the subhealthy and chronic disease states.

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.

Hypothesizing That Pediatric Autoimmune Neuropsychiatric Associated Streptococcal (PANDAS) Causes Rapid Onset of Reward Deficiency Syndrome (RDS) Behaviors and May Require Induction of “Dopamine Homeostasis”

Pediatric autoimmune neuropsychiatric disorders associated with group A streptococcal infections (PANDAS) is a concept that is used to characterize a subset of children with neuropsychiatric symptoms, tic disorders, or obsessive-compulsive disorder (OCD), whose symptoms are exacerbated by group A streptococcal (GAS) infection. PANDAS has been known to cause a sudden onset of reward deficiency syndrome (RDS). RDS includes multiple disorders that are characterized by dopaminergic signaling dysfunction in the brain reward cascade (BRC), which may result in addiction, depression, avoidant behaviors, anxiety, tic disorders, and/or OCD. According to research by Blum et al., the dopamine receptor D2 (DRD2) gene polymorphisms are important prevalent genetic determinants of RDS. The literature demonstrates that infections like Borrelia and Lyme, as well as other infections like group A beta-hemolytic streptococcal (GABHS), can cause an autoimmune reaction and associated antibodies target dopaminergic loci in the mesolimbic region of the brain, which interferes with brain function and potentially causes RDS-like symptoms/behaviors. The treatment of PANDAS remains controversial, especially since there have been limited efficacy studies to date. We propose an innovative potential treatment for PANDAS based on previous clinical trials using a pro-dopamine regulator known as KB220 variants. Our ongoing research suggests that achieving “dopamine homeostasis” by precision-guided DNA testing and pro-dopamine modulation could result in improved therapeutic outcomes.

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 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.

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.

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.