Test-Retest Reliability of the Coronary Heart Disease Damp Phlegm and Blood Stasis Pattern Questionnaire: Results from a Multicenter Clinical Trial.

BACKGROUND: Damp phlegm and blood stasis pattern (DPBSP) is the main pattern in coronary heart disease (CHD) patients. To quantify and standardize the diagnosis of DPBSP, questionnaires are usually administered. The CHD Damp Phlegm and Blood Stasis Pattern Questionnaire (CHD-DPBSPQ) is the standard metric for measuring CHD-DPBSP signs and symptoms in practice and clinical research. The CHD-DPBSPQ has moderate diagnostic efficiency, as evidenced by its receiver operating characteristic curves. Furthermore, and high reliability and validity have been shown in some studies but not in a multicenter clinical trial. Our purpose was to evaluate the test-retest reliability of a proprietary CHD-DPBSPQ. METHODS: The CHD-DPBSPQ uses a standard procedure for measuring symptoms. The (interrater) reliability and validity of this questionnaire have been previously studied. Here, we evaluated the test interval and weighted kappa value of items of test-retest (intrarater) reliability of the CHD-DPBSPQ. The test-retest reliability was evaluated by the intraclass correlation coefficient (ICC) for the total CHD-DPBSPQ score and the phlegm domain and blood stasis domain scores. Weighted kappa statistics were calculated for the individual CHD-DPBSPQ items. RESULTS: Using the CHD-DPBSPQ, 79 patients with late-stage CHD who were participating in a multicenter clinical trial were assessed twice. The ICCs for the CHD-DPBSPQ score were as follows: 0.827 for the total CHD-DPBSPQ, 0.778 for the phlegm domain score, and 0.828 for the blood stasis domain score. The reliability was slightly better in patients whose test interval was ≤14 days. The weighted kappa values of individual items showed moderate consistency. CONCLUSIONS: The CHD-DPBSPQ was found to have excellent test-retest reliability in this sample of patients.

Based on Network Pharmacology and RNA Sequencing Techniques to Explore the Molecular Mechanism of Huatan Jiangzhuo Decoction for Treating Hyperlipidemia.

BACKGROUND: Hyperlipidemia, due to the practice of unhealthy lifestyles of modern people, has been a disturbance to a large portion of population worldwide. Recently, several scholars have turned their attention to Chinese medicine (CM) to seek out a lipid-lowering approach with high efficiency and low toxicity. This study aimed to explore the mechanism of Huatan Jiangzhuo decoction (HTJZD, a prescription of CM) in the treatment of hyperlipidemia and to determine the major regulation pathways and potential key targets involved in the treatment process. METHODS: Data on the compounds of HTJZD, compound-related targets (C-T), and known disease-related targets (D-T) were collected from databases. The intersection targets (I-T) between C-T and D-T were filtered again to acquire the selected targets (S-T) according to the specific index. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, as well as network construction, were applied to predict the putative mechanisms of HTJZD in treating hyperlipidemia. Thereafter, an animal experiment was conducted to validate the therapeutic effect of HTJZD. In addition, regulated differentially expressed genes (DEGs) were processed from the RNA sequencing analysis results. Common genes found between regulated DEGs and S-T were analyzed by KEGG pathway enrichment to select the key targets. Lastly, key targets were validated by real-time quantitative reverse transcription PCR (qRT-PCR) analysis. RESULTS: A total of 210 S-T were filtered out for enrichment analysis and network construction. The enrichment results showed that HTJZD may exert an effect on hyperlipidemia through the regulation of lipid metabolism and insulin resistance. The networks predict that the therapeutic effect of HTJZD may be based on the composite pharmacological action of these active compounds. The animal experiment results verify that HTJZD can inhibit dyslipidemia in rats with hyperlipidemia, suppress lipid accumulation in the liver, and reverse the expression of 202 DEGs, which presented an opposite trend in the model and HTJZD groups. Six targets were selected from the common targets between 210 S-T and 202 regulated DEGs, and the qRT-PCR results showed that HTJZD could effectively reverse Srebp-1c, Cyp3a9, and Insr mRNA expression (P < 0.01). CONCLUSION: In brief, network pharmacology predicted that HTJZD exerts a therapeutic effect on hyperlipidemia. The animal experimental results confirmed that HTJZD suppressed the pathological process induced by hyperlipidemia by regulating the expression of targets involved in lipid metabolism and insulin resistance.

Effects of Huatan Jiangzhuo decoction on diet-induced hyperlipidemia and gene expressions in rats.

Huatan Jiangzhuo decoction (HJD) is a combination of six traditional Chinese medicines that were used for lipid metabolism-related disorders, but its efficacy and underlying mechanisms have not been explored by modern research strategies. This study aimed to investigate the therapeutic role of HJD in determining the transcriptome level. Hyperlipidemia model was established by feeding Sprague-Dawley rats with high-fat diet. Differentially expressed genes (DEGs) were detected by high-through transcriptome sequencing, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The total cholesterol (TC) and triglyceride (TG) levels in hyperlipidemia model rats were significantly increased, whereas high-density lipoprotein (HDL) concentration decreased when compared to normal rats, and HJD significantly downregulated TC concentrations and liver coefficient in the hyperlipidemia rats. Histology staining showed that HDJ greatly recovered the lipid accumulation in rat hepatic stellate cells and aortic arch vascular wall thickness of hyperlipidemia rats. One thousand nine hundred and thirty-six DEGs were identified in the HJD-treated hyperlipidemia rats, which were associated with various biological processes and signaling pathways such as peroxisome proliferator-activated receptors, AMP-activated Protein Kinase , and insulin signaling pathways. Quantitative reverse transcription-polymerase chain reaction further confirmed the downregulated expression of cholesterol 7-α-hydroxylase(CYP7A1), liver orphan receptor(LXRα),peroxisome proliferator-activated receptor gamma(PPARγ),andSterol Response Element-Binding Protein 1c(SREBP1c) genes in hyperlipidemia rats treated with HJD. Our data first elucidated the gene expression profile of high-fat diet-induced hyperlipidemia in rats after HJD treatment, and lipid metabolism-related genes (CYP7A1, LXRα, PPARγ, and SREBP1c) may be potentially biomarkers for HJD-alleviated hyperlipidemia.

A Quantitative Diagnostic Method for Phlegm and Blood Stasis Syndrome in Coronary Heart Disease Using Tongue, Face, and Pulse Indexes: An Exploratory Pilot Study.

Objectives: The aim of this study was to establish a quantitative syndrome differentiation model with logistic regression analysis for phlegm and blood stasis syndrome (PBSS) in coronary heart disease (CHD) to offer methodology guidance for the quantitative syndrome differentiation of Traditional Chinese Medicine (TCM). Design: Tongue, face, and pulse information of each subject was obtained using the TCM-intelligent diagnosis instruments. Logistic regression model was used to construct the syndrome diagnosis model. The area under receiver operating characteristic curve (ROC-AUC) was used to evaluate the diagnostic value of the model. Subjects: Among the 141 subjects, 83 belonged to the PBSS group, and 58 belonged to the non-PBSS group. Results: The independent indexes used to predict PBSS in patients with CHD were length of the crack (LC) (p = 0.002), number of ecchymosis (NE) (p < 0.001), length of philtrum (LEP) (p = 0.022), and right hand pulse h1 (Rh1) (p = 0.021). The expression of combining predictor L in this study was L = LC +57.58 NE +4.53 LEP +2.68 Rh1. The ROC curve analysis indicated that the AUC values of LC, NE, LEP, and Rh1 were 0.646, 0.710, 0.619, and 0.613, respectively. The AUC = 0.825 of the syndrome diagnosis model was the largest. Conclusions: The quantitative study of TCM syndrome based on logistic regression analysis provides a good method for the objective analysis and application of TCM syndrome.

Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Huashi Baidu formula in the treatment of COVID-19.

PURPOSE: Huashi Baidu formula (HSBDF) was developed to treat the patients with severe COVID-19 in China. The purpose of this study was to explore its active compounds and demonstrate its mechanisms against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through network pharmacology and molecular docking. METHODS: All the components of HSBDF were retrieved from the pharmacology database of TCM system. The genes corresponding to the targets were retrieved using UniProt and GeneCards database. The herb-compound-target network was constructed by Cytoscape. The target protein-protein interaction network was built using STRING database. The core targets of HSBDF were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The main active compounds of HSBDF were docked with SARS-CoV-2 and angiotensin converting enzyme II (ACE2). RESULTS: Compound-target network mainly contained 178 compounds and 272 corresponding targets. Key targets contained MAPK3, MAPK8, TP53, CASP3, IL6, TNF, MAPK1, CCL2, PTGS2, etc. There were 522 GO items in GO enrichment analysis (p < .05) and 168 signaling pathways (p < .05) in KEGG, mainly including TNF signaling pathway, PI3K-Akt signaling pathway, NOD-like receptor signaling pathway, MAPK signaling pathway, and HIF-1 signaling pathway. The results of molecular docking showed that baicalein and quercetin were the top two compounds of HSBDF, which had high affinity with ACE2. CONCLUSION: Baicalein and quercetin in HSBDF may regulate multiple signaling pathways through ACE2, which might play a therapeutic role on COVID-19.

Development of a Diagnostic Questionnaire for Damp Phlegm Pattern and Blood Stasis Pattern in Coronary Heart Disease Patients (CHD-DPBSPQ).

BACKGROUND: The aim was to develop a diagnostic questionnaire for damp phlegm pattern and blood stasis pattern in coronary heart disease patients (CHD-DPBSPQ). METHODS: The standard procedures of questionnaire development were carried out to develop and assess CHD-DPBSPQ. The patients were assessed using the CHD-DPBSPQ, CHD-DPPQ, and CHD-BSPQ. Four methods were used to select the items on the CHD-DPBSPQ in a pilot study based on data from a Guizhou tertiary grade A hospital. Cronbach's alpha and the split-half reliability, test-retest reliability, content validity, criterion validity, construct validity, and convergent validity were determined in a validation study using a nationwide sample. RESULTS: After item selection, the CHD-DPBSPQ contained 15 items in two domains: the phlegm domain (9 items) and the blood stasis domain (6 items). For the CHD-DPBSPQ, the alpha coefficient was 0.88, the split-half coefficient was 0.90, and the intraclass correlation coefficient was 0.83. The range of the item-level content validity index (I-CVI) was 0.71 to 1.0 and that of the scale-level content validity index/average (Scale-CVI/Ave) was 0.97. The domain scores on the CHD-DPBSPQ were in close relation to the scores on a questionnaire for damp phlegm pattern in coronary heart disease patients (CHD-DPPQ) and a questionnaire for blood stasis pattern in coronary heart disease patient (CHD-BSPQ) (P < 0.01). The root mean square error of approximation (RMSEA) was equal to 0.05 (90% CI: 0.044, 0.059). Convergent validity was demonstrated with a moderate correlation. CONCLUSION: The CHD-DPBSPQ is a reliable and valid instrument.

Diagnostic Accuracy of Chinese Medicine Diagnosis Scale of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease: A Study Protocol.

BACKGROUND: Phlegm and blood stasis syndrome (PBSS) is one of the main syndromes in coronary heart disease (CHD). Syndromes of Chinese medicine (CM) are lack of quantitative and easy-implementation diagnosis standards. To quantify and standardize the diagnosis of PBSS, scales are usually applied. OBJECTIVE: To evaluate the diagnostic accuracy of CM diagnosis scale of PBSS in CHD. METHODS: Six hundred patients with stable angina pectoris of CHD, 300 in case group and 300 in control group, will be recruited from 5 hospitals across China. Diagnosis from 2 experts will be considered as the "gold standard". The study design consists of 2 phases: pilot test is used to evaluate the reliability and validity, and diagnostic test is used to assess the diagnostic accuracy of the scale, including sensitivity, specificity, likelihood ratio and area under the receiver operator characteristic (ROC) curve. DISCUSSION: This study will evaluate the diagnostic accuracy of CM diagnosis scale of PBSS in CHD. The consensus of 2 experts may not be ideal as a "gold standard", and itself still requires further study. (No. ChiCTR-OOC-15006599).

Assessment of Intermingled Phlegm and Blood Stasis Syndrome in Coronary Heart Disease: Development of a Diagnostic Scale.

BACKGROUND: Intermingled Phlegm and Blood Stasis Syndrome (IPBSS) is a common feature in patients with coronary heart disease (CHD). In clinical practice, the diagnostic agreement of clinical doctor of Chinese Medicine (CM) is poor. We previously developed a IPBSS diagnostic scale for use by general practitioner. OBJECTIVES: To assess a IPBSS diagnostic scale that we previously developed for use by non-experts. METHODS: This is a multicenter, prospective study involving eight study sites across China. Eligible patients were adults (≥18 years) with CHD as demonstrated by a history of myocardial infarction, stenosis, or past coronary revascularization. IPBSS was assessed using a scale that consisted of 14 items in two domains (e.g., phlegm and blood stasis). The score range for each item was 0 to 3 points. Maximum total score was 72 points. Diagnostic accuracy was verified using consensus opinion by two independent experts as reference. RESULTS: A total of 1,142 CHD patients were included. IPBSS was established in 729 subjects using the IPBSS diagnostic scale. In ROC curve analyses, at the optimal cut-off of 25.5, the sensitivity and specificity of the IPBSS scale were 67.6% and 72.4%, respectively. The area under the ROC curve was 0.741 (95%CI: 0.711-0.772). CONCLUSIONS: The newly developed IPBSS scoring system showed moderate performance in diagnosing IPBSS in CHD patients. Data from further large-scale diagnostic test accuracy studies are warranted. This trial is registered with ChiCTR-OOC-15006599.

Expert Consensus of Syndrome Differentiation for Phlegm Turbidity Syndrome for Coronary Heart Disease.

OBJECTIVE: The purpose of the study was to form a questionnaire of expert consensus about phlegm turbidity syndrome of coronary heart disease (CHD) using literature method and Delphi method, which could provide the objective evidences for the clinical diagnosis and treatment for CHD. METHOD: The CBM, CNKI, VIP, and PubMed were searched. The articles about phlegm turbidity syndrome for CHD with the definite related four diagnostic data were included. Based on the results of the literature method, two rounds of Delphi method were conducted. The TCM experts about CHD were enrolled. Concentration and coordination index of the experts were used to select the items. RESULTS: Literature method: A total of 118 articles were included. Greasy fur, slippery pulse, chest fullness or chest pain, anorexia, nausea and vomiting, vertigo, excessive phlegm, abdominal fullness, head heaviness, obesity, stringy pulse, physical heaviness, soft pulse, somnolence, fatigue, and pale tongue (16 items) had the relatively high proportion, and they were eligible for Delphi process. Delphi method: A total of 93 experts (22 for the first round, 71 for the second round) were included. The reliability of the items was 0.885 for all the experts. The 16 items were not significantly different between the two rounds (P>0.05). According to the results of mean, frequency, sum of ranks and coefficient of variation, the item of nausea and vomiting, somnolence, pale tongue, and soft pulse were deleted. CONCLUSIONS: The questionnaire of phlegm turbidity syndrome of CHD was established, with good reliability. The sensitivity and specificity of the questionnaire are still necessary to further validate for clinical or scientific use.

Methological quality of systematic reviews and meta-analyses on acupuncture for stroke: A review of review.

OBJECTIVE: To assess the methodological quality of systematic reviews and meta-analyses regarding acupuncture intervention for stroke and the primary studies within them. METHODS: Two researchers searched PubMed, Cumulative index to Nursing and Allied Health Literature, Embase, ISI Web of Knowledge, Cochrane, Allied and Complementary Medicine, Ovid Medline, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang and Traditional Chinese Medical Database to identify systematic reviews and meta-analyses about acupuncture for stroke published from the inception to December 2016. Review characteristics and the criteria for assessing the primary studies within reviews were extracted. The methodological quality of the reviews was assessed using adapted Oxman and Guyatt Scale. The methodological quality of primary studies was also assessed. RESULTS: Thirty-two eligible reviews were identified, 15 in English and 17 in Chinese. The English reviews were scored higher than the Chinese reviews (P=0.025), especially in criteria for avoiding bias and the scope of search. All reviews used the quality criteria to evaluate the methodological quality of primary studies, but some criteria were not comprehensive. The primary studies, in particular the Chinese reviews, had problems with randomization, allocation concealment, blinding, dropouts and withdrawals, intent-to-treat analysis and adverse events. CONCLUSIONS: Important methodological flaws were found in Chinese systematic reviews and primary studies. It was necessary to improve the methodological quality and reporting quality of both the systematic reviews published in China and primary studies on acupuncture for stroke.

[Study on Macrocosmic Diagnostic Criteria for Coronary Heart Disease with Intermingled Phlegm- Blood Stasis Syndrome].

Macrocosmic diagnostic criteria for coronary heart disease (CHD) with phlegm-damp- ness syndrome (PDS) were established after screening based on macrocosmic indices of CHD with PDS after previous literature analyses and experts consultations. The weights of macrocosmic indices of PDS were compared using analytic hierarchy process (AHP). Macrocosmic diagnostic criteria for CHD with intermingled phlegmblood stasis syndrome were studied by combining with diagnostic criteria for CHD patients with blood stasis syndrome (BSS) set by Academician CHEN Ke-ji group.

JinQi-Jiangtang tablet, a Chinese patent medicine, for pre-diabetes: a randomized controlled trial.

BACKGROUND: Pre-diabetes is a growing health concern where a large percentage of these patients develop full type 2 diabetes. Effective interventions on pre-diabetes can prevent or delay the occurrence or development of diabetes. Pharmacodynamics and pre-clinical of JinQi-Jiangtang tablets (JQJT) suggest that it could be benefit for pre-diabetes. METHODS/DESIGN: Randomized controlled trial (RCT) is implemented in this study. The study term is 24 months (12 months for intervention and 12 months for follow up). Participants are recruited from four cities of China: Beijing, Tianjin, Xi'an and Nanning. Four hundred participants are randomized to treatment group (JQJT tablets) and control group (Placebo); two hundred participants each. People being included in this study must have been diagnosed as pre-diabetes via western medicine criteria and traditional Chinese medicine (TCM) criteria. The end-point indexes include: incidence of diabetes mellitus and reversion rate. Primary outcome indexes include: oral glucose tolerance test; insulin releasing test; glycosylated hemoglobin (HA1c). Secondary outcome indexes include: score of the Short Form 36 Health Survey Questionnaire (SF-36); score of TCM symptoms; blood lipid test. Indexes of safety include: general medical examination; blood and urine regular test; electrocardiogram (ECG), liver function (ALT) and renal function (BUN, Creatinine) test; record of adverse event, such as headache, faint, etc. Qualitative control will be implemented and a number of standard operating processes (SOPs) will be formed throughout the study: laboratory quality control measures; compliance control for researchers and participants; researcher training before study; supervision; investigational drug management and others. DISCUSSION: The aim of this study is to evaluate the effectiveness and safety of JinQi JiangTang (JQJT) tablets for the treatment of patients with pre-diabetes. TRIAL REGISTRATION: Chinese clinical trials register ChiCTR-TRC-00000401.