Effects of Si-Miao-Yong-An decoction on myocardial I/R rats by regulating gut microbiota to inhibit LPS-induced TLR4/NF-κB signaling pathway.

BACKGROUND: Coronary Artery Disease (CAD) is primarily caused by inflammation which is closely linked to the gut microbiota. Si-Miao-Yong-An (SMYA) decoction is a traditional Chinese herbal formula with anti-inflammatory properties that found to be effective against CAD. However, it is still unclear whether SMYA can modulate gut microbiota and whether it contributes to the improvement of CAD by reducing inflammation and regulating the gut microbiota. METHODS: The identification of components in the SMYA extract was conducted using the HPLC method. A total of four groups of SD rats were orally administered with SMYA for 28 days. The levels of inflammatory biomarkers and myocardial damage biomarkers were measured through ELISA, while echocardiography was used to assess heart function. Histological alterations in the myocardial and colonic tissues were examined following H&E staining. Western blotting was performed to evaluate protein expression, whereas alterations in gut microbiota were determined by 16 s rDNA sequencing. RESULTS: SMYA was found to enhance cardiac function and decrease the expression of serum CK-MB and LDH. SMYA was also observed to inhibit the TLR4/NF-κB signaling pathway by downregulating the protein expression of myocardial TLR4, MyD88, and p-P65, leading to a reduction in serum pro-inflammatory factors. SMYA modified the composition of gut microbiota by decreasing the Firmicutes/Bacteroidetes ratio, modulating Prevotellaceae_Ga6A1 and Prevotellaceae_NK3B3 linked to the LPS/TLR4/NF-κB pathway, and increasing beneficial microbiota such as Bacteroidetes, Alloprevotella, and other bacterial species. Moreover, SMYA was found to safeguard the intestinal mucosal and villi structures, elevate the expression of tight junction protein (ZO-1, occludin), and reduce intestinal permeability and inflammation. CONCLUSIONS: The results indicate that SMYA has the potential to modulate the gut microbiota and protect the intestinal barrier, thereby reducing the translocation of LPS into circulation. SMYA was also found to inhibit the LPS-induced TLR4/NF-κB signaling pathway, leading to a decrease in the release of inflammatory factors, which ultimately mitigated myocardial injury. Hence, SMYA holds promise as a therapeutic agent for the management of CAD.

Network pharmacology-based approach to research the effect and mechanism of Si-Miao-Yong-An decoction against thromboangiitis obliterans.

BACKGROUND: Si-Miao-Yong-An decoction (SMYAD) is a conventional therapeutic formula for treat thromboangiitis obliterans (TAO), consisting of four Chinese herbs: Lonicerae japonicae Thunb. (Jinyinhua), Scrophularia ningpoensis Hemsl. (Xuanshen), Angelica sinensis (Oliv.) Diels (Danggui) and Glycyrrhiza uralensis Fisch. (Gancao). However, the mechanism of SMYAD in TAO treatment remains unclear. METHODS: Components, as well as potential targets of SMYAD in TAO therapy, were downloaded from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Subsequently, with the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signalling pathways of the targets enrichment were performed. Next, based on STRING online database, the protein interaction network of vital targets was built and analysed. Molecular docking and calculation of the binding affinity were performed using AutoDock. The PyMOL software was employed to observe docking outcomes of active compounds and protein targets. Based on the predicted outcomes of network pharmacology, in vivo and in vitro tests were performed for validation. In vivo experiment, the TAO rats model was established using sodium laurate injection into the femoral artery. The symptoms as well as pathological changes of the femoral artery were observed. Besides, the predicted targets were verified by the RT-qPCR, in vitro experiment. The cell viability in LPS-induced human umbilical vein endothelial cells (HUVECs) was detected using CCK-8 kit, and the predicted targets were also verified by the RT-qPCR. RESULTS: In the network pharmacology analysis, we obtained 105 chemical components in SMYAD and 24 therapeutic targets. We found that the mechanism SMYAD in TAO therapy was primarily associated with inflammation and angiogenesis by constructing multiple networks. Quercetin, vestitol and beta-sitosterol were important compounds, and interleukin-6 (IL6), MMP9, and VEGFA were key targets. According to molecular docking, active compounds (quercetin, vestitol and beta-sitosterol) and targets (IL6, MMP9 and VEGFA) showed good binding interactions. In in vivo experiment, SMYAD ameliorated the physical signs and pathological changes, inhibited the expression of IL6 and MMP9, and enhanced the expression of VEGFA. In an in vitro experiment, SMYAD increased the cell viability of LPS-induced HUVECs and the expression of VEGFA, and reduced the expression of IL6 and MMP9. CONCLUSIONS: This study showed that SMYAD improves TAO symptoms and inhibits the development of TAO. The mechanism could be associated with anti-inflammatory and therapeutic angiogenesis.

Perspectives of international multi-center clinical trials on traditional Chinese herbal medicine.

With the introduction of various subjects, such as clinical epidemiology and evidence-based medicine, the qualities and levels of Traditional Chinese Herbal Medicine (TCHM) in China improved substantially, and the processes of internationalization of Traditional Chinese Medicine (TCM) are further accelerated. Since, a variety of drug products in China have been approved for marketing in other countries, and approximately 10 products have submitted the IND application to FDA of United States, of which various Chinese herbal preparations such as compound Danshen dripping pills, Xingling granules, and HMPL-004 have been approved to be investigated in phase III clinical trials. In general, multi-center studies of TCHM are increasing with years, but most of the studies are performed in some certain country, and the actual international multi-center clinical trials are very rare. Number of SCI literatures on multi-center clinical trials of TCHM that published in the recent decade also showed increasing tendency with years, despite the evident reduction in the past 2 years due to the influence of COVID-19 pandemic. Of the multi-center clinical trials of TCHM that performed by mainland China and other oversees regions, except for Taiwan, China, nearly 70% were focused on classic Chinese medicinal formulae and Chinese patent medicine, while the other 30% were on dietary supplements and plant extracts. Facing the future, the "human experience" has attracted close attentions from researchers throughout the world. Effectively utilizing the historic "human experience" is an important method to vitalize potential of original scientific and technological resources of TCHM. Performing multi-center clinical trials with high qualities is still an essential method for TCHM in accessing the mainstream medicine market. In addition, it is also required to further improve the evaluation techniques and methods that not only meet the international standards but also meet the characteristics of TCHM. Furthermore, we should also focus on the TCHM specific clinical values and scientific reports.

HJ11 decoction restrains development of myocardial ischemia-reperfusion injury in rats by suppressing ACSL4-mediated ferroptosis.

HJ11 is a novel traditional Chinese medicine developed from the appropriate addition and reduction of Si-Miao-Yong-An decoction, which has been commonly used to treat ischemia-reperfusion (I/R) injury in the clinical setting. However, the mechanism of action of HJ11 components remains unclear. Ferroptosis is a critical factor that promotes myocardial I/R injury, and the pathophysiological ferroptosis-mediated lipid peroxidation causes I/R injury. Therefore, this study explored whether HJ11 decoction ameliorates myocardial I/R injury by attenuating ACSL4-mediated ferroptosis. This study also explored the effect of ACSL4 expression on iron-dependent programmed cell death by preparing a rat model of myocardial I/R injury and oxygen glucose deprivation/reperfusion (OGD/R)-induced H9c2 cells. The results showed that HJ11 decoction improved cardiac function; attenuated I/R injury, apoptosis, oxidative stress, mitochondrial damage, and iron accumulation; and reduced infarct size in the myocardial I/R injury rat model. Additionally, HJ11 decoction suppressed the expression of ferroptosis-promoting proteins [Acyl-CoA synthetase long-chain family member 4 (ACSL4) and cyclooxygenase-2 (COX2)] but promoted the expression of ferroptosis-inhibiting proteins [ferritin heavy chain 1 (FTH1) and glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4)] in the myocardial tissues of the I/R injury rat model. Similar results were found with the OGD/R-induced H9c2 cells. Interestingly, ACSL4 knockdown attenuated iron accumulation, oxidative stress, and ferroptosis in the OGD/R-treated H9c2 cells. However, ACSL4 overexpression counteracted the inhibitory effect of the HJ11 decoction on OGD/R-triggered oxidative stress and ferroptosis in H9c2 cells. These findings suggest that HJ11 decoction restrained the development of myocardial I/R injury by regulating ACSL4-mediated ferroptosis. Thus, HJ11 decoction may be an effective medication to treat myocardial I/R injury.

Jia-Wei-Si-Miao-Yong-An decoction modulates intestinal flora and metabolites in acute coronary syndrome model.

Aims: We assessed the efficacy of the traditional Chinese medicine formulation Jia-Wei-Si-Miao-Yong-An decoction (HJ11) in the treatment of acute coronary syndrome and evaluated its impact on the intestinal microbiota and their metabolites. Methods: An acute coronary syndrome model was established in rats, which were randomly assigned to the model, HJ11 treatment, and atorvastatin treatment groups. Rats were then administered saline solution (model and sham operation control groups) or drugs by oral gavage for 28 d. Echocardiography was performed and serum creatine kinase-MB and cardiac troponin I levels were monitored to examine the cardiac function. Inflammation was evaluated using hematoxylin and eosin staining of heart tissue, and serum interleukin-2, interleukin-6, tumor necrosis factor alpha, and high-sensitivity C-reactive protein measurements. Gut microbiota composition was analyzed via 16S rRNA gene sequencing. Metabolomics was used to determine fecal metabolites and elucidate the modes of action of HJ11 in acute coronary syndrome treatment. Results: HJ11 improved cardiac function and attenuated inflammation in rats with acute coronary syndrome. Relative to the untreated model group, the HJ11-treated group presented normalized Firmicutes/Bacteroidetes ratio and reduced abundances of the bacterial genera norank_f__Ruminococcaceae, Desulfovibrio, Clostridium_sensu_stricto_1, Adlercreutzia, Staphylococcus, Bacteroides, Prevotella, Rikenellaceae_RC9_gut_group, unclassified_o__Bacteroidales, and Ruminococcus_gauvreauii_group. We found 23 differentially expressed intestinal metabolites, and the enriched metabolic pathways were mainly related to amino acid metabolism. We also discovered that asymmetric dimethylarginine levels were strongly associated with cardiovascular disease. Correlation analyses revealed strong associations among intestinal microflora, their metabolites, proinflammatory factors, and cardiac function. Hence, the therapeutic effects of HJ11 on acute coronary syndrome are related to specific alterations in gut microbiota and their metabolites. Conclusion: This work demonstrated that HJ11 effectively treats acute coronary syndrome. HJ11 seems to increase the abundance of beneficial bacterial taxa (Bacteroides and Rikenellaceae_RC9_gut_group), mitigate the risk factors associated with cardiovascular disease, alter bacterial metabolites, lower asymmetric dimethylarginine levels, and effectively treat acute coronary syndrome.

An Automatic Petechia Dots Detection Method on Tongue.

Tongue diagnosis with features like tongue coating, petechia, color, size and so on is of great effectiveness and convenience in traditional Chinese medicine. With the development of image processing techniques, automatic image processing can reduce hospital inspection for patients. However, there are ubiquitous problems of inadequate accuracy in petechia dots detection with previous methods. In this paper, we propose a method of petechia dots detection on tongue based on SimpleBlobDetector function in OpenCV library and support vector machines model, which improves the detective accuracy. We test 128 clinic tongue images and select 9 of the images with plentiful petechia dots for further experiments. Our method achieves mean value of false alarm rate 4.6% and missing alarm rate 11.8%, which have 19.4% and 8.2% reduction respectively compared to previous work.Clinical Relevance-The method can provide detailed information of tongue, which assists doctors to investigate curative effect.

Study on syndrome differentiation strategy of phlegm and blood stasis syndromes of coronary heart disease based on expert consultation on medical cases.

BACKGROUND: It is becoming more and more important to judge whether patients with coronary heart disease (CHD) have phlegm and blood stasis syndromes in the process of traditional Chinese medicine (TCM) diagnosis and treatment of CHD. The syndrome differentiation strategy of phlegm and blood stasis syndromes of CHD is still not standardized, and it is particularly necessary to make syndrome differentiation simpler and more accurate. METHODS: Twenty-eight medical cases that met the criteria, comprising 10 ancient medical cases and 18 modern ones, were selected from the TCM literature, which were then analyzed by 57 experts via questionnaire. Statistical analysis of the data was mainly based on frequency analysis. RESULTS: (I) The average age of the 57 experts from 20 provinces was 48.9±8.5 years; 89.5% were associate professor or above, and 75.4% of them worked at a tertiary hospital. (II) Consistency of expert consultation over medical cases: for the ancient medical cases, the diagnostic consistency rate of phlegm syndrome was 27/34 (79.4%) and additional diagnosis rate of the blood stasis syndrome was 27/57 (47.4%); for the modern medical cases, the consistency rate compared with the original diagnosis of phlegm syndrome was 54/80 (67.5%) and that of blood stasis syndrome was 73/90 (81.1%). (III) The top five experts' diagnostic basics of phlegm syndrome were oppression in the chest, slippery pulse, greasy fur, coughing of phlegm, and chest pain; the top five diagnostic basics of blood stasis syndrome were chest pain, dark tongue, oppression in chest, red tongue, and ecchymosis on tongue. (IV) In the questionnaire consultation on CHD phlegm-blood stasis syndrome cases, the diagnostic basis of "symptom or (and) tongue manifestation" accounted for 12/27 (44.4%) of the diagnostic basics of phlegm syndrome and 28/38 (73.7%) of that of blood stasis syndrome basis. CONCLUSIONS: Modern Chinese medicine experts pay much attention to the diagnosis and treatment of CHD based on TCM pathology theories of phlegm and blood stasis. To collect and detect the patients' symptoms and tongue manifestation is an important strategy of the experts for CHD phlegm and blood stasis syndrome differentiation.

Core Outcome Set for Clinical Trials on Coronavirus Disease 2019 (COS-COVID).

Since its outbreak in December 2019, a series of clinical trials on coronavirus disease 2019 (COVID-19) have been registered or carried out. However, the significant heterogeneity and less critical outcomes of such trials may be leading to a waste of research resources. This study aimed to develop a core outcome set (COS) for clinical trials on COVID-19 in order to tackle the outcome issues. The study was conducted according to the Core Outcome Measures in Effectiveness Trials (COMET) Handbook: Version 1.0, a guideline for COS development. A research group was set up that included experts in respiratory and critical medicine, traditional Chinese medicine (TCM), evidence-based medicine, clinical pharmacology, and statistics, in addition to medical journal editors. Clinical trial registry websites (www.chictr.org.cn and clinicaltrials.gov) were searched to retrieve clinical trial protocols and outcomes in order to form an outcome pool. A total of 78 clinical trial protocols on COVID-19 were included and 259 outcomes were collected. After standardization, 132 outcomes were identified within seven different categories, of which 58 were selected to develop a preliminary outcome list for further consensus. After two rounds of Delphi survey and one consensus meeting, the most important outcomes for the different clinical classifications of COVID-19 were identified and determined to constitute the COS for clinical trials on COVID-19 (COS-COVID). The COS-COVID includes one outcome for the mild type (time to 2019 novel coronavirus (2019-nCoV) reverse transcription-polymerase chain reaction (RT-PCR) negativity), four outcomes for the ordinary type (length of hospital stay, composite events, score of clinical symptoms, and time to 2019-nCoV RT-PCR negativity), five outcomes for the severe type (composite events, length of hospital stay, arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2), duration of mechanical ventilation, and time to 2019-nCoV RT-PCR negativity), one outcome for critical type (all-cause mortality), and one outcome for rehabilitation period (pulmonary function). The COS-COVID is currently the most valuable and practical clinical outcome set for the evaluation of intervention effect, and is useful for evidence assessment and decision-making. With a deepening understanding of COVID-19 and application feedback, the COS-COVID should be continuously updated.

[Exploration on origin of Simiao Yong'an Decoction].

Simiao Yong'an Decoction is composed of Lonicerae Japonicae Flos, Scrophulariae Radix, Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizome, which was chosen as one of the 100 classic prescriptions in Catalogue of Ancient Classics Prescription(the first batch). Through tracing to the source, It was found that the Simiao Yong'an Decoction(but not named) originated from the Shi Shi Mi Lu, and was later cited by books such as Ancient and Modern Book Integration-Full Record of Medical Department and New Edition of Useful Prescriptions. Literature shows that this prescription was not named until first reported in the Effect of Traditional Chinese Medicine on Arterial Embolism Gangrene in 1956 by a journalist LYU Min. This article recorded that SHIJIA Baoshan, a monk from Hebei Province, used self-named "Simiao Yong'an Decoction" to treat local arterial embolic gangrene. After comparison, there was two difference between ancient books and SHIJIA Baoshan's records. Firstly, according to ancient books, the composition and dosage of Simiao Yong'an Decoction is Lonicerae Japonicae Flos 90 g, Scrophulariae Radix 90 g, Angelicae Sinensis Radix 60 g, Glycyrrhizae Radix et Rhizome 30 g", and the ratio is 3∶3∶2∶1. By SHIJIA Baoshan's record, the composition and dosage are: Lonicerae Japonicae Flos 66 g, Scrophulariae Radix 132 g, Angelicae Sinensis Radix 99 g, Glycyrrhizae Radix et Rhizome 33 g, and the ratio changed to 2∶4∶3∶1. Secondly, ancient books show that patients can be healed after taking seven or ten days of the previous prescription, however, it would take 3 or 4 months, even 7 months in SHIJIA Baoshan's records. It can be considered that the previous prescription should be used at the beginning of gangrene, while the modified Simiao Yong'an Decoction by SHIJIA Baoshan is widely used in the middle and late stages of gangrene, even the critical condition, that is the reason for longer treatment and larger dosage. Nowadays, Simiao Yong'an Decoction is not limited to the treatment of gangrene and bulla in clinic. Relevant studies have confirmed that Simiao Yong'an Decoction has the effects such as anti-inflammatory, plaque stabilization, lipid-lowering, vascular protection, improvement of hemorheology, anticoagulation, inhibition of thrombosis and fibrinolysis, etc. In the follow-up, we should carry out the analysis of the compatibility of this four medicines, and redefine the scope of its clinical application under the theory of traditional Chinese medicine.

The therapeutic effects of qigong in patients with chronic obstructive pulmonary disease in the stable stage: a meta-analysis.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is one global disease. Lung function gradually declines. Medication does not fully reverse the airflow limitation. Qigong's role in COPD rehabilitation has been assessed. We aimed to assess the effects of Qigong practised by COPD patients. METHODS: Eligible articles were obtained through a systematic search. The databased were search on October 8, 2017, and the date range of the searches in the electronic databases had no upper limit. The Cochrane risk-of-bias tool was used to evaluate the quality of the eligible studies. Mean differences with 95% confidence intervals were utilized to analyse the results. RESULTS: Ten included studies contained 993 participants. Statistical improvements occurred in the 6-min walk distance (6MWD) (MD, 30.57 m; 95% CI, 19.61-41.53 m; P < 0.00001); forced expiratory volume in 1 s (FEV1) (MD, 0.32 L; 95% CI, 0.09-0.56 L; P < 0.001); forced vital capacity rate of 1 s (FEV1/FVC) (MD, 2.66%; 95% CI, 1.32-2.26%; P = 0.0001); forced expiratory volume in 1 s/predicted (FEV1/pre) (MD, 6.04; CI, 2.58-9.5; P = 0.006); Monitored Functional Task Evaluation (MD, 0.88; 95% CI, 0.78-0.99; P < 0.00001); COPD Assessment Test for exercise (MD, - 5.54; 95% CI, - 9.49 to - 1.59; P = 0.006); Short Form-36 Health Quality Survey (SF-36)-General Health (MD, 5.22; 95% CI, 3.65-6.80; P < 0.00001); and Short Form-36 Health Quality Survey (SF-36)-Mental Health (MD, - 1.21; 95% CI, - 2.75 to 0.33; P = 0.12). CONCLUSIONS: In this meta-analysis of RCTs between ten included studies, we found that Qigong can improve COPD patients in lung function, exercise capacity and quality of life who were in the stable stage.

Establishment of Comprehensive Indicators in TCM Pectoral-qi Case Report Based on Experts Diagnosis and Self-test Technology.

RATIONALE: To establish TCM Pectoral-qi comprehensive indicators and highlight the inner structure among different variables in an objective way, the article uses Partial Least Square Second-order Latent Variable Model (PLS-SLVM) and accomplishes 3 different comprehensive indicators based on both experts diagnosis and self-test data. SLVM includes a measurement model that defines the relationship between observed variables and latent variables and a structure model that imputes relationships between latent variables. The article focuses on PLS as the estimation method. Without normal distribution and independence assumptions, PLS uses objective weighting methods based on the data. Bootstrap method (B = 200) is used to calculate the mean value and standard errors of the PLS estimates. The article chooses the percentile interval to obtain the confidence interval of PLS parameters. PATIENT CONCERNS: The patients were diagnosed by the means of experts diagnosis and self-test technology. On the one hand, the patients want to know the effect of self-test by wearing a kind of instrument. On the other hand, we want to establish TCM Pectoral-qi comprehensive indicators and highlight the inner structure among different variables in an objective way. DIAGNOSES: The group of 59 subjects are the same no matter whether they were diagnosed through TCM Pectoral-qi Assessment Questionnaire of self-test technology. INTERVENTIONS: The same group of 59 subjects keep wearing the instrument for hours and get the self-test data consequently. OUTCOMES: As one of comprehensive indicator establishing methods, PLS-SLVM highlights the structure state among variables and improves the evaluation efficiency. Furthermore, it provides a new tool and method in TCM diseases prevention and health security. LESSONS: As expected, PLS-SLVM is a useful tool due to its nonassumption of normal distribution and independence with consideration of correlation among different variables. Thus PLS-SLVM can be applied in ordinal data from assessment questionnaire and continuous data about physicochemical indexes for the same group of people. It displays that PLS-SLVM builds a connection between TCM experts diagnosis and the self-testing technology.

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease.

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine-based approach was proposed to identify the underlying molecular modules of PSCS complicated with IHD, which could be used for interpreting the pharmacological mechanisms of well-established Chinese herbal formulas (e.g., Tao Hong Si Wu Tang, Dan Shen Yin, Hunag Lian Wen Dan Tang and Gua Lou Xie Bai Ban Xia Tang). In addition, these results delivered novel understandings of the molecular network mechanisms of IHD phenotype subtypes with PSCS complications, which would be both insightful for IHD precision medicine and the integration of disease and TCM syndrome diagnoses.

[Expert consensus on the design and implementation of clinical safety centralized monitoring study of Chinese medical injection].

Along with the increase of clinical application, the safety of traditional Chinese medicine gained more and more attentions. In particular, the safety evaluation of Chinese medical injections has become a mandatory task should be completed by pharmaceutical companies under the supervision of China Food and Drug Administration(CFDA). Due to the weak foundation of previous studies, the safety issues of Chinese medical injections have not been fully understood, and lack of scientific and rational risk management programs. Clinical safety centralized monitoring(CSCM) is an important method for post-market safety evaluation of Chinese medicine. Due to the lack of appropriate norms and procedures, the quality of similar research is uneven, and the results vary. Combined with practical experience with experts' suggestions, we developed this expert consensus on the design and implementation of CSCM from three stages (design, implementation and report) with 20 technical points, which will provide technical support for future CSCM studies.

Bacillus as a potential diagnostic marker for yellow tongue coating.

Observation of tongue coating, a foundation for clinical diagnosis and treatment in traditional Chinese medicine (TCM), is a major indicator of the occurrence, development, and prognosis of disease. The biological basis of tongue diagnosis and relationship between the types and microorganisms of tongue coating remain elusive. Thirteen chronic erosive gastritis (CEG) patients with typical yellow tongue coating (YTC) and ten healthy volunteers with thin white tongue coating (WTC) were included in this study. Patients were provided a 2-course targeted treatment of a herbal medicine Ban Xia Xie Xin decoction, traditionally prescribed for CEG patients with YTC, to evaluate the relationship between tongue coating microbiota and diagnosis of CEG with typical YTC. The tongue coating segregation structure was determined using Illumina Miseq sequencing of the V4-V5 region of the 16S ribosomal RNA gene. Bacillus was significantly observed only in CEG patients with YTC, but not in patients who received the decoction. YTC (n = 22) and WTC (n = 29) samples were collected for bacterial culturing to illustrate the relationship between Bacillus and YTC. The Bacillus positivity rate of YTC samples was 72.7%; Bacillus was not observed in WTC samples. In conclusion, Bacillus was strongly associated with YTC.

Recent Advances and Perspective of Studies on Phlegm Syndrome in Chinese Medicine.

This review paper summarized the current situation of studies on the essence of phlegm syndrome and relation between phlegm syndrome, diseases, and therapeutics based on published English articles. In studies on the essence of phlegm syndrome, omic technologies were used to explore the molecular basis of phlegm syndrome; in studies on relation between phlegm syndrome and diseases, discovery of markers of phlegm syndrome in diseases becomes a hotspot; the distribution of phlegm syndromes in some common chronic diseases was found; in the therapy of phlegm syndrome, two therapeutic models, treatment with CM formula and treatment with a combination of CM formula and Western medicine, were used most frequently. It is certainly that using one omic technology is not able to deal with the complexity of phlegm syndrome and that the use of a combination of multiple omic methods will be a trend in future studies. Meanwhile, for rapidly increasing clinical research quality of phlegm syndrome, a series of agreed criteria, such as syndrome diagnostic criteria and efficacy criteria clinical studies of phlegm syndrome, needed to be established urgently, and there was an urgent need of standardizing syndrome names in English.

[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.

Detection of herb-symptom associations from traditional chinese medicine clinical data.

Background. Traditional Chinese medicine (TCM) is an individualized medicine by observing the symptoms and signs (symptoms in brief) of patients. We aim to extract the meaningful herb-symptom relationships from large scale TCM clinical data. Methods. To investigate the correlations between symptoms and herbs held for patients, we use four clinical data sets collected from TCM outpatient clinical settings and calculate the similarities between patient pairs in terms of the herb constituents of their prescriptions and their manifesting symptoms by cosine measure. To address the large-scale multiple testing problems for the detection of herb-symptom associations and the dependence between herbs involving similar efficacies, we propose a network-based correlation analysis (NetCorrA) method to detect the herb-symptom associations. Results. The results show that there are strong positive correlations between symptom similarity and herb similarity, which indicates that herb-symptom correspondence is a clinical principle adhered to by most TCM physicians. Furthermore, the NetCorrA method obtains meaningful herb-symptom associations and performs better than the chi-square correlation method by filtering the false positive associations. Conclusions. Symptoms play significant roles for the prescriptions of herb treatment. The herb-symptom correspondence principle indicates that clinical phenotypic targets (i.e., symptoms) of herbs exist and would be valuable for further investigations.

Clinical phenotype network: the underlying mechanism for personalized diagnosis and treatment of traditional Chinese medicine.

Traditional Chinese medicine (TCM) investigates the clinical diagnosis and treatment regularities in a typical schema of personalized medicine, which means that individualized patients with same diseases would obtain distinct diagnosis and optimal treatment from different TCM physicians. This principle has been recognized and adhered by TCM clinical practitioners for thousands of years. However, the underlying mechanisms of TCM personalized medicine are not fully investigated so far and remained unknown. This paper discusses framework of TCM personalized medicine in classic literatures and in real-world clinical settings, and investigates the underlying mechanisms of TCM personalized medicine from the perspectives of network medicine. Based on 246 well-designed outpatient records on insomnia, by evaluating the personal biases of manifestation observation and preferences of herb prescriptions, we noted significant similarities between each herb prescriptions and symptom similarities between each encounters. To investigate the underlying mechanisms of TCM personalized medicine, we constructed a clinical phenotype network (CPN), in which the clinical phenotype entities like symptoms and diagnoses are presented as nodes and the correlation between these entities as links. This CPN is used to investigate the promiscuous boundary of syndromes and the co-occurrence of symptoms. The small-world topological characteristics are noted in the CPN with high clustering structures, which provide insight on the rationality of TCM personalized diagnosis and treatment. The investigation on this network would help us to gain understanding on the underlying mechanism of TCM personalized medicine and would propose a new perspective for the refinement of the TCM individualized clinical skills.

Network based integrated analysis of phenotype-genotype data for prioritization of candidate symptom genes.

BACKGROUND: Symptoms and signs (symptoms in brief) are the essential clinical manifestations for individualized diagnosis and treatment in traditional Chinese medicine (TCM). To gain insights into the molecular mechanism of symptoms, we develop a computational approach to identify the candidate genes of symptoms. METHODS: This paper presents a network-based approach for the integrated analysis of multiple phenotype-genotype data sources and the prediction of the prioritizing genes for the associated symptoms. The method first calculates the similarities between symptoms and diseases based on the symptom-disease relationships retrieved from the PubMed bibliographic database. Then the disease-gene associations and protein-protein interactions are utilized to construct a phenotype-genotype network. The PRINCE algorithm is finally used to rank the potential genes for the associated symptoms. RESULTS: The proposed method gets reliable gene rank list with AUC (area under curve) 0.616 in classification. Some novel genes like CALCA, ESR1, and MTHFR were predicted to be associated with headache symptoms, which are not recorded in the benchmark data set, but have been reported in recent published literatures. CONCLUSIONS: Our study demonstrated that by integrating phenotype-genotype relationships into a complex network framework it provides an effective approach to identify candidate genes of symptoms.