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 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.

Consensus on diagnostic criteria for Yin deficiency syndrome in hypertension:a modified Delphi study

OBJECTIVE:To reach consensus on the diagnostic criteria for Yin deficiency syndrome in hypertension(YDSH)patients by a modified Delphi method.METHODS:Our study was consistent with T/CACM 1032-2017.The methodology of RAND/UCLA appropriateness was used to develop consensus guidance statements.A nationwide panel of experienced clinical experts from 19 provinces was constructed.These experts were all prominent in Traditional Chinese Medicine(TCM)of cardiovascular diseases.This consensus process consisted of two rounds of questionnaires and a final round of consultation to analyze the weight score of each item.Moreover,the data extraction process is carried out independently by third-party researchers(LIANG Junya,SUN Yang,and DU Xiaona).When there is disagreement in all three rounds,the expert panel group(odd number)are invited to vote,and the one with more votes wins.In the questionnaires,participants were asked to rate the appropriateness of each syndrome item using a nine-point Likert scale.The consensus was defined as a panel median rating 1-3 or 7-9 without disagreement.And then the diagnostic criteria of YDSH were formed according to the weight score in the final round.RESULTS:Twenty-eight experts(84.8%)participated in the first round,and thirty-one(93.9%)finished the second round.After two rounds,the consensus of YDSH was reached on 11 items(25.6%),including symptoms,signs,and pulse condition.Twenty-one experts(63.6%)completed the final round in which they used a grading system for each item.Red tongue with scanty fur had the highest weighting(22.8%),followed by heat in the palms and soles(20.1%).CONCLUSIONS:The consensus-based diagnostic criteria for YDSH,formed by a modified Delphi method,can be widely incorporated in TCM.A further clinical study will be conducted to analyze the diagnosis value and cut-off score of our YDSH criteria.

Correlation between constitution of Yin deficiency syndrome and polymorphism of HLADQA1 / treatment response of Peg-IFNα therapy in HBeAg positive chronic hepatitis B patients

Objective To observe the correlation between constitution of yin deficiency syndrome(YDS)and polymorphism of HLA-DQA1/treatment response of Peg-IFNαtherapy in HBe Ag positive chronic hepatitis B(CHB)patients,and to explore constitution of Chinese medicine(CM)in response to interferon therapy.Methods Totally 120 HBe Ag positive CHB patients who were

Liver metabolomic characteristics in three different rat models of Yin deficiency based on ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry

OBJECTIVE:To investigate the mechanism of Yin deficiency syndrome(YDS) by analyzing the liver metabolomic characteristics of three different Yin deficiency rat models METHODS:Following the TCM etiology,for clinical features and pathological manifestations of modern medicine,three kinds of animal models of Yin deficiency were induced and replicated.Totally 48 Sprague-Dawley(SD) male rats were randomly divided into blank group,irritation induced model group,Fuzi-Ganjiang induced model group,and thyroxine-reserpine induced model group.After successful development of model,the ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry was carried out to detect metabolites in each group.The metabolites of rat liver were analyzed for the characteristics of their biomarkers.The pathway enrichment analysis and metabolic network construction were performed through various online databases including Metabolite Biology Role,Human Metabolome Database,MetaboAnalyst,and Kyoto Encyclopedia of Genes and Genomes.RESULTS:The SD rats in the experimental group showed symptoms like less weight gain,reduced diet and water intake,high body temperature,increased liver and kidney indexes,and abnormal liver and kidney tissue morphology.Moreover,the rats showed high increased levels of serum cyclic adenosine monophosphate,estradiol,alanine transaminase,and aspartate aminotransferase and decreased levels of cyclic guanosinc monophosphate and testosterone.We found four key interrelated metabolic pathways in the liver tissue metabolomics,including the biosynthesis of pantothenic acid and coenzyme A,and metabolism of alpha-linolenic acid metabolism,glycerophospholipid metabolism,and sphingolipid.CONCLUSION:The liver and kidney YDS is closely related to the biosynthesis of pantothenic acid and CoA and abnormal metabolism of α-linolenic acid,glycerophospholipid,and sphingolipid in SD rats.

Study on Molecular Mechanism of Liver Yang Ascending Syndrome in Hypertension

Objective: To investigate the molecular mechanism of Liver Yang Ascending Syndrome (LYAS) in hypertension. Methods: The plasma norepinephrine (NE), epinephrine (E) contents in patients with LYAS or Liver and Kidney Yin Deficiency Syndrome (LKYDS) of hypertension and normal controls were determined by high performance liquid chromatography-electrochemical detector (HPLC-ECD). The polymorphism of tyrosine hydroxylase (TH) gene in the three groups were analysed by Southern Blot assay. The polymorphism of TH and monoamine oxidation A(MAO-A), monoamine oxidation B(MAO-B) gene microsatellite in these groups were analysed by polymerase chain reaction (PCR)-SSCP. At the same time, the LYAS model was established by administering Aconitum preparation (AP) to spontaneous hypertension rats (SHR). The adrenal gland medulla of the experimental animal was examined for their TH expression at the protein level after ABC immuno-histochemical staining with the TH monoclonal antibody (McAb). The adrenal TH gene mRNA expression was demonstrated by in situ hybridization with the synthetized TH oligonucleic acid probe. The results of immuno-histochemistry and in situ hybridization were analyzed with the image analysis system (IAS). Results: The plasma NE and E contents in patients with LYAS were more obviously increased than those in LKYDS and normal controls. The TH gene amplified and the type A1 TH microsatellite D11S4046 was markedly higher in the LYAS group than those in the other groups. The TH mRNA protein expression in the adrenal tissue of the AP induced LYAS model in SHR elevated. Conclusion: The LYAS of hypertension has the characters as amplified TH gene and increased TH mRNA and protein expression, which suggested that the overexpression of TH is probably the mechanism of LYAS in hypertension.