TCM-HIN2Vec:A strategy for uncovering biological basis of heart qi deficiency pattern based on network embedding and transcriptomic experiment

Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD pattern genes using the new strategy,TCM-HIN2Vec,which involves heterogeneous network embedding and transcriptomic experiments.First,a heterogeneous network of traditional Chinese medicine(TCM)patterns was constructed using public databases.Next,we predicted HQD pattern genes using a heterogeneous network-embedding algorithm.We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq.Finally,we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism,signal transduction pathways,and immune processes.Moreover,we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern.Furthermore,herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.Conclusion: Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes,but also deciphering the basis of HQD pattern.Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns,leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.

Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease

Objective:To explore the kidney yang deficiency pattern(KYDP)in a chronic kidney disease(CKD)rat model and the mechanisms underlying the effects of Zhenwu decoction(ZWD)by conducting tran-scriptomic and metabolomic analyses.Methods:Adriamycin(ADR)combined with hydrocortisone(HC)was used to induce CKD with KYDP in rats.ADR was injected into the tail vein twice.HC was injected intramuscularly for 8 weeks.ZWD was administered by gavage for 8 weeks.The general condition was observed,24-h urine protein was detected,serum corticosterone,triiodothyronine,thyroxine,TSH,testosterone,cAMP,and cGMP levels were determined,and pathological analysis was conducted.Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes(DEGs),differentially expressed metabolites(DEMs),and differentially expressed pathways(DEPs).The core DEMs and DEGs were input to Metab-oanalyst 5.0 to identify the pathways affected by ZWD.Results:In the HC group,KYDP symptoms were observed.Compared with control group,the levels of 24-h urine protein,TSH,and cGMP significantly increased(all P<0.01),and corticosterone,triiodothyronine,thyroxine,and cAMP significantly decreased(all P<0.01)in the HC group.After ZWD intervention,the levels of above-mentioned indicators could be reversed to some extent.Pathological analysis in the HC group revealed kidney lesions.DEGs in the ZWD group were mainly associated with pathways such as nucleotide synthesis and endocrine pathways.In the ZWD group,differences in biosynthesis of unsat-urated fatty acids and butanoate metabolism were observed.The following pathways were significantly affected by ZWD:arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.Conclusion:ZWD can be used to treat KYDP in CKD through regulating arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.

Mechanisms of Dihuang(Rehmanniae Radix)in treating diabetic nephropathy complicated with depression based on network pharmacology

Objective To predict the molecular mechanism of Dihuang(Rehmanniae Radix)in the treatment of diabetic nephropathy(DN)complicated with depression based on network pharmacology.Methods The components of Dihuang(Rehmanniae Radix)were identified from the Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP),Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and relevant literature.The component targets were detected by combining the SwissTargetPrediction and Pub Chem databases.Disease targets were collected from the Therapeutic Target Database(TTD),Dis Ge NET,and Ensembl databases with“diabetic nephropathy”and“depression”as keywords.The disease-component targets were mapped using Venny 2.1.0 to obtain potential targets.A protein-protein interaction(PPI)network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database and Cytoscape 3.7.2.The co-expression genes of the key targets were collected based on the COXPRESdb 7.3.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed for potential targets using R language.Target-component docking was verified and evaluated using Discovery Studio 4.5.Results According to the databases and literature reports,Dihuang(Rehmanniae Radix)contained 65 active components,and had 155 related targets for the treatment of DN complicated with depression.PPI screening showed that the key targets included serine/threonine protein kinase 1(AKT1),signal transducer and activator transcription 3(STAT3),interleukin 6(IL-6),mitogen-activated protein kinase 1(MAPK1),and vascular endothelial growth factor A(VEGFA),etc.GO enrichment analysis mainly involved biological processes,such as lipid metabolism,protein secretion regulation,cell homeostasis,and phosphatidylinositol 3 kinase activity.KEGG pathway enrichment analysis included the role of the AGE-RAGE signaling pathway in diabetic complements,insulin resistance(IR),neurotrophin signal path,Toll-like receptor signaling pathway,relaxin signaling pathway,epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs),etc.Molecular docking showed that the target had high affinity for stachyose,manninotriose,verbascose,nigerose,etc.Conclusion Based on network parmacology,this study preliminarily predict the effects of Dihuang(Rehmanniae Radix)in treating DN complicated with depression by regulating inflammation,glucose metabolism,nution nerve,etc.

An innovative method to evaluate the severe level of general Qi deficiency

OBJECTIVE:The study aim was to use existing relevant indexes to establish an index series for the quantitative measurement of Qi deficiency pattern(QDP) in Traditional Chinese Medicine(TCM).METHODS:Seventeen indexes of arterial oxygen saturation(SaO_2),TCM pulse diagnosis,heart rate,and blood pressure were integrated into an index series,and 94 selected subjects were divided into a healthy control group,a mild QDP group,and a typical QDP group.All three groups were then synchronously given a breath-holding(BH) test and index detections using TCM apparatus for auxiliary diagnosis and treatment and a photoplethysmograph.The detections were carried out repeatedly until there was no monotonic change in the value of the minimal SaO_(2d)uring a BH measurement(SaO_(2 min)) or in the duration of BH during a BH measurement(TBH).RESULTS:BH measurement and index detection data from 380 eligible cases were analyzed and a significant intergroup difference was found for 12 indexes.CONCLUSION:An index series for quantitative QDP measurement could comprise the 12 effective indexes:RSaO_(2d)(rate of decline of SaO_(2d)uring a BH measurement),RSaO_(2r)(recovery rate of SaO_2 after a BH measurement),SaO_(2 min),BFV(blood flow velocity),TSaO_(2d)(the time at which SaO_2 started declining during a BH measurement),TBH,TSa_(O2 min)(the time of occurrence of the minimal SaO_(2d)uring a BH measurement),TSa O_(2 max)(the time of occurrence of the maximal SaO_2 after a BH measurement),PTP(pulse-touching pressure),SBP(systolic blood pressure),PWV(pulse wave velocity),and DBP(diastolic blood pressure).Of the indexes,RSaO_(2d)could play akey role in quantitative QDP measurement;RSaO_(2r) and Sa O_2 mincould be used to differentiate the QDP symptom of shortness of breath and as early-warning indexes for chronic obstructive pulmonary disease.BFV,TSaO_(2d),and TBHcould be used to quantitatively assess the QDP symptoms of spontaneous perspiration and shortness of breath.

Clinical observation of acupuncture and moxibustion for functional dyspepsia due to Yang deficiency of the spleen and stomach

Objective To observe the clinical efficacy of acupuncture and moxibustion for functional dyspepsia(FD)due to Yang deficiency of the spleen and stomach.Methods A total of 90 patients meeting the inclusion criteria of FD due to Yang deficiency of the spleen and stomach were randomized into an acupuncture-moxibustion group,an electroacupuncture(EA)group,and a mosapride group by the random number table method,with 30 cases in each group.The mosapride group was treated with mosapride citrate dispersible tablets.The EA group was treated with EA treatment.The acupuncture-moxibustion group was treated with additional moxibustion therapy based on the treatment in the EA group.All three groups took 10 d as one treatment course and 2 courses in total,with a 2-day interval between two courses.The traditional Chinese medicine(TCM)symptoms score,functional digestive disorder quality of life questionnaire(FDDQL)score,oral-colon transit time(OCTT),and serum glucagon-like peptide-1(GLP-1)level was compared before and after treatment among the three groups.And the clinical efficacy was evaluated.Results The total effective rate in the acupuncture-moxibustion group was 96.7%,which was higher than 86.7%in the EA group and 73.3%in the mosapride group,and the total effective rate in the EA group was higher than that in the mosapride group;the inter-group differences were all statistically significant(P<0.05).After treatment,the TCM symptom score in the three groups was lower than that before treatment(P<0.05),and the FDDQL score was higher than that before treatment(P<0.05).The change after treatment in the TCM symptom score in the acupuncture-moxibustion group and the EA group was more significant than that in the mosapride group,and the change in the acupuncture-moxibustion group was more significant than that in the EA group;the inter-group differences were statistically significant(P<0.05).The change after treatment in the FDDQL score in the acupuncture-moxibustion group and the EA group was greater than that in the mosapride group,and the change in the acupuncture-moxibustion group was larger than that in the EA group;the inter-group differences were all statistically significant(P<0.05).After treatment,the OCTT in all three groups was lower than that before treatment(P<0.05),and the serum GLP-1 level was higher than that before treatment(P<0.05);the change after treatment in the OCTT in the acupuncture-moxibustion group and the EA group was more significant than that in the mosapride group,and the change in the acupuncture-moxibustion group was more significant than that in the EA group;the inter-group differences were statistically significant(P<0.05).The change after treatment in the serum GLP-1 level in the acupuncture-moxibustion group and the EA group was greater than that in the mosapride group,and the change in the acupuncture-moxibustion group was larger than that in the EA group;the inter-group differences were statistically significant(P<0.05).Conclusion Acupuncture and moxibustion can improve the clinical symptoms in patients with FD and enhance their quality of life,producing better effects than EA or mosapride alone.Shortening gastrointestinal movement time and increasing gastrointestinal hormone levels may be its mechanism.

Effectiveness of Fuling(Poria) and its extracts against spleen deficiency in rats via tonifying spleen

OBJECTIVE:To observe and explore the effect of Fuling(Poria) in alleviating the spleen deficiency symptom pattern(SDSP).METHODS:We established an animal model of SDS in Sprague-Dawley(SD) rats by treating them with deficiency-inducing factors,including irregular feeding and tail clamping.Mice were administered Fuling(Poria) and its extracts(raw/cooked powder,aqueous/alcohol extract) by gavage once a day for 21 d.The body weight,rectal temperature,and spleen and thymus organ coefficients were calculated.The levels of motilin(MTL),gastrin(GAS),aquaporin 2(AQP2),interleukin 2(IL-2),IL-4,and 5-hydroxytryptamine(5-HT) in the serum and the level of AQP2 in the kidneys were evaluated by enzyme-linked immunosorbent assay.RESULTS:Fuling(Poria) and its extracts did not change the body weight,rectal temperature,and organ coefficients of the spleen and thymus.However,it reduced the levels of MTL and GAS and increased the levels of IL-2 and AQP2.In addition,the levels of IL-4 and 5-HT showed no significant alteration.CONCLUSIONS:These results suggested the crucial function of Fuling(Poria) in SDSP,especially promoting digestive function and water metabolism.

Guilingji capsule(龟龄集胶囊)for Alzheimer's disease:secondary analysis of a randomized non-inferiority controlled trial

OBJECTIVE:To investigate the effectiveness and safety of Guilingji capsule(龟龄集胶囊,GLJC)in treatment of Alzheimer's disease(AD)patients with kidney-marrow deficiency pattern(KMDP)compared with gingko extract tablets.METHODS:This is a secondary analysis of a large-scale multicenter randomized non-inferiority clinical trial.A total of 120 AD patients with KMDP were enrolled in this study.The participants were randomly categorized into two groups:(a)GLJC group(n=60)and(b)gingko group(n=60).The GLJC group was treated with GLJC and gingko extract mimetic tablets,whereas the gingko group received gingko extract tablets and mimetic GLJC.The data on the Mini-Mental State Examination(MMSE),Alzheimer's Disease Assessment Scale-Cognitive Subscale(ADAS-Cog),Activities of Daily Living(ADL),and Chinese Medicine Symptom Scale(CM-SS)was evaluated at 0,12,and 24 weeks of treatment.The serum levels of acetylcholine(Ach),acetylcholinesterase(AchE),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)in the participants were measured before and after 24 weeks of treatment.The safety was based on the incidence of adverse events.RESULTS:Both interventions significantly increased the MMSE scores of the participants and decreased their ADAS-Cog,ADL,and CM-SS scores(P<0.01).Compared with the gingko group,the GLJC group had a higher effective rate of improvement in the symptoms of“amnesia”and“dull expression and slow thinking”at the 12th week and 24th week(P<0.05,P<0.01).In the GLJC group,serum Bcl-2 levels were significantly increased at the 24th week(P<0.05).Serum Bax and AchE levels of the two groups were significantly decreased at the 24th week(P<0.01).No treatmentrelated adverse events were reported in the two groups.CONCLUSIONS:GLJC is equivalent to the gingko extract tablets in terms of improving cognitive function and the quality of life in AD patients with KMDP and has good clinical efficacy and safety.When it comes to improving TCM symptoms and anti-aging,GLJC is even more advantageous.