[Evidence mapping analysis of clinical research on traditional Chinese medicine in treatment of vertigo].

In this study, the evidence map system was used to sort out the clinical research evidence on traditional Chinese medicine(TCM) treatment of vertigo and understand the evidence distribution in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Web of Science were searched for the clinical randomized controlled trial(RCT) and systematic reviews/Meta-analysis on TCM treatment of vertigo in recent five years, and the evidence was analyzed and presented in the form of text and charts. The Cochrane handbook for systematic reviews of interventions was used to evaluate the quality of the clinical RCT, and the AMSTAR mea-surement tool was used to evaluate the quality of the systematic reviews/Meta-analysis. A total of 382 RCTs and eight systematic reviews/Meta-analysis were included. In recent five years, the number of published articles has been on the rise. There were many intervention measures and TCM therapies for vertigo. Outcome indicators mainly included clinical efficacy, TCM syndrome score, vertigo score, occurrence of adverse reactions, and effective rate. The overall quality of clinical RCT and systematic reviews/Meta-analysis was low. Most studies have proven the potential efficacy of TCM in treating vertigo, but there was still no clear clinical evidence of efficacy. The results show that TCM has advantages in the treatment of vertigo, but there are also problems. More high-quality studies are still lacking, suggesting that more large-sample and multi-center RCT should be conducted in the future, and the quality of relevant syste-matic reviews/Meta-analysis should be improved to fully explore the advantages of TCM in the treatment of vertigo, and provide strong support for the effectiveness and safety of TCM in the treatment of vertigo.

[Rapid identification of components in Wuzhuyu Decoction using UHPLC Q-Exactive Orbitrap MS~n and molecular network technology].

Wuzhuyu Decoction, the classical formula recorded in the Treatise on Febrile Diseases(Shang Han Lun), has been included in the Catalogue of Ancient Classic Prescriptions(the First Batch). Consisting of Euodiae Fructus, Ginseng Radix et Rhizoma, Zingiberis Rhizoma Recens, and Jujubae Fructus, it is effective in warming the middle, tonifying deficiency, dispelling cold, and descending adverse Qi, and is widely applied clinically with remarkable efficacies. For a classical formula, the chemical composition is the material basis and an important premise for quantity value transfer. This study aimed to establish a rapid identification method of chemical components in Wuzhuyu Decoction by high-resolution mass spectrometry(HR-MS) and molecular network. AQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) was used for sample separation, and acetonitrile-0.1% formic acid in water was used as mobile phases for gradient elution. Q-Exactive Orbitrap MS data were collected in positive and negative ion modes, and GNPS molecular network was plotted according to the similarity of MS/MS fragmentation modes. Cytoscape 3.6.1 was used to screen molecular clusters with similar structures. Finally, the chemical components of Wuzhuyu Decoction were rapidly identified according to the controls, as well as the information of retention time, accurate relative molecular weight of HR-MS, and MS/MS multistage fragments. A total of 105 chemical components were identified in Wuzhuyu Decoction. This study can provide data for the follow-up quality control, standard substance research, and pharmacodynamic material research on Wuzhuyu Decoction, as well as references for the rapid qualitative analysis of the chemical components of Chinese medicine.

[Analysis of adverse reactions' factors to Danhong injection--nested case control study by using hospital centralized monitoring data].

To study the adverse reactions' factors to Danhong injection in the real world. A multi-center, large sample and prospective hospital centralized monitoring method was adopted, and 30 888 cases of Danhong injection from 37 national 3A hospitals were collected to carry out a nested case control design study. These cases were divided into adverse reaction group and non-adverse group. Single factor logistic regression and multiple factor logistic regression were used to analyze data, and investigate the correlation between adverse reaction and gender, allergy history, methods of administration, and combined drug use. One hundred and eight cases of adverse reactions in 30 888 patients were determined, with an incidence of 0.35%. The results showed that Danhong injection combined with other medication(potassium mendoxine magnesium, thymic peptide, celecoxib, fumarate bisoprolol) with history of adverse reactions including scephalosporin allergy and proprietary Chinese medicine allergies had more adverse reactions than the control group(P<0.05, estimated coefficient>0), indicating that these six factors were the risk factors for the adverse reaction of Danhong injection. The adverse reaction of Danhong injection combined with the aspirin was less than that in the control group(P<0.05, estimated coefficient<0), indicating that the aspirin was a non-risk factor for the adverse reaction of Danhong injection. All the above results indicate that the adverse factors to Danhong injection include scephalosporin allergy, patent Chinese medicine allergy, Danhong injection combined with medication(potassium mendoxine magnesium, thymic peptide, celecoxib, fumarate bisoprolol), suggesting special attention shall be paid in clinical application.

Time-dependent variation of pathways and networks in a 24-hour window after cerebral ischemia-reperfusion injury.

BACKGROUND: Cerebral ischemia-reperfusion injury may simultaneously result in functional variation of multiple genes/pathways. However, most prior time-sequence studies on its pathomechanism only focused on a single gene or pathway. Our study aimed to systematically analyze the time-dependent variation in the expression of multiple pathways and networks within 24 h after cerebral ischemia-reperfusion injury. RESULTS: By uploading 374 ischemia-related genes into the MetaCore software, the variation in the expression of multiple pathways and networks in 3 h, 12 h, and 24 h after cerebral ischemia-reperfusion injury had been analyzed. The conserved TNFR1-signaling pathway, among the top 10 pathways, was consistently enriched in 3 h, 12 h, and 24 h groups. Three overlapping pathways were found between 3 h and 12 h groups; 2 between 12 h and 24 h groups; and 1 between 3 h and 24 h groups. Five, 4, and 6 non-overlapping pathways were observed in 3 h, 12 h, and 24 h groups, respectively. Apart from pathways reported by earlier studies, we identified a novel pathway related to the time-dependent development of cerebral ischemia pathogenesis. The process of apoptosis stimulation by external signals, among the top 10 processes, was consistently enriched in 3 h, 12 h, and 24 h groups; 2, 1, and 2 processes overlapped between 3 h and 12 h groups, 12 h and 24 h groups, and 3 h and 24 h groups, respectively. Four, 5, and 5 non-overlapping processes were found in 3 h, 12 h and 24 h groups, respectively. The presence of apoptotic processes was observed in all the 3 groups; while anti-apoptotic processes only existed in 3 h and 12 h groups. Additionally, according to node degree, network comparison identified 1, 8,and 5 important genes or proteins (e.g. Pyk2, PKC, E2F1, and VEGF-A) in 3 h, 12 h, and 24 h groups, respectively. The Jaccard similarity index revealed a higher level of similarity between 12 h and 24 h groups than that between 3 h and 12 h groups. CONCLUSION: Time-dependent treatment can be utilized to reduce apoptosis, which may activate anti-apoptotic pathways within 12 h after cerebral ischemia-reperfusion injury. Pathway and network analyses may help identify novel pathways and genes implicated in disease pathogenesis.

Dynamic Changes in Phenotypic Groups in Patients with Stable Angina Pectoris after Treatment with Xinxuekang Capsule: A Randomized Controlled Trial.

OBJECTIVE: To reveal the cutoff point and influencing factors in the dynamic change in phenotypic group in patients with stable angina pectoris (SAP) after Xinxuekang capsule treatment. METHODS: Five hundred and seventy-six SAP patients were randomly assigned to receive Xinxuekang (XXK) capsules or Compound Danshen (CDS) tablets for 8 weeks. Global similarity degree analysis and nonlinear mixed effects modeling (NONMEM) were employed to reveal the cutoff points and influencing factors in dynamic changes in the SAP phenotypic group. The phenotypic group was defined as the six phenotypes in SAP, including angina, choking sensation in the chest, palpitations, dark purple lips, ecchymosis on the tongue, and fine-choppy pulse, which were quantitatively evaluated on Days 0, 14, 28, 42, and 56. RESULTS: Variation in the six individual phenotypes and distribution of the SAP phenotypic profile were similar between the two experimental groups, but cutoff points for changes in the SAP phenotypic group were 7.28 and 10.73 weeks in XXK and CDS groups, respectively. Degree of severity of SAP as well as study site significantly affected the tendency for change in the SAP Xueyu Zheng in both XXK and CDS treatment groups. Different Chinese patent drugs affected the tendency for change in phenotypic group in patients with SAP. XXK was superior to CDS in controlling a clinical phenotypic group. CONCLUSION: Based on global similarity degree analysis and NONMEM, the cutoff point and influencing factors in phenomic variation of SAP may be determined, to improve the development and modification of treatment regimens.

Convergent and divergent pathways decoding hierarchical additive mechanisms in treating cerebral ischemia-reperfusion injury.

INTRODUCTION: Cerebral ischemia is considered to be a highly complex disease resulting from the complicated interplay of multiple pathways. Disappointedly, most of the previous studies were limited to a single gene or a single pathway. The extent to which all involved pathways are translated into fusing mechanisms of a combination therapy is of fundamental importance. AIMS: We report an integrative strategy to reveal the additive mechanism that a combination (BJ) of compound baicalin (BA) and jasminoidin (JA) fights against cerebral ischemia based on variation of pathways and functional communities. RESULTS: We identified six pathways of BJ group that shared diverse additive index from 0.09 to 1, which assembled broad cross talks from seven pathways of BA and 16 pathways of JA both at horizontal and vertical levels. Besides a total of 60 overlapping functions as a robust integration background among the three groups based on significantly differential subnetworks, additive mechanism with strong confidence by networks altered functions. CONCLUSIONS: These results provide strong evidence that the additive mechanism is more complex than previously appreciated, and an integrative analysis of pathways may suggest an important paradigm for revealing pharmacological mechanisms underlying drug combinations.

Synergistic mechanism of gene expression and pathways between jasminoidin and ursodeoxycholic acid in treating focal cerebral ischemia-reperfusion injury.

AIM: Jasminoidin and ursodeoxycholic acid are 2 bioactive compounds extracted from Chinese medicine that have been proven to exert a synergistic effect as a combined administration for the treatment of stroke. The aim of this study was to reveal the pharmacogenomic mechanism of this synergistic effect of jasminoidin and ursodeoxycholic acid. METHODS: One hundred and fifteen mice with brain damage, induced by focal cerebral ischemia/reperfusion, were divided into 5 groups: jasminoidin-treated, ursodeoxycholic acid-treated, combination-treated, vehicle group, and sham-operated group. Comparative analysis of stroke-related gene expression profiles and Kyoto Encyclopedia of Genes and Genomes pathways among the 3 treatment groups were performed to reveal the mechanism of this synergistic effect. RESULTS: This study demonstrated that (1) treatment with jasminoidin alone caused similar changes in the pattern of gene expression as those treated with the combination; (2) jasminoidin treatment and the combination treatment had more overlapping changes in gene expression and activated pathways than the ursodeoxycholic acid treatment; (3) Hspa1a and Ppm1e were only up-regulated in the combination-treated group; (4) the nonoverlapping genes Fgf12, Rarα, Map3k4, paxillin (PXN) in the combination-treated group were markedly expressed, and P53 pathway was obviously activated in the combination-treated group. CONCLUSION: These findings may suggest that jasminoidin is the major component of the combination, and the combination plays an important role of the synergistic effect in up-regulating expression of gene Hspa1a, genes Fgf12, Rarα, Map3k4 and down-regulating gene PXN, as well as activating P53 pathway.

Comparison of the network structural characteristics of calcium signaling pathway in cerebral ischemia after intervention by different components of Chinese medicine.

OBJECTIVE: To explore the network control mechanism of the calcium signaling pathway in cerebral ischemic injury after intervention by the main components of Qingkailing (see text), i.e. Baicalin, Jasminoidin and their combination. METHODS: Thirty mice were randomly divided into 5 groups, a baicalin group, a Jasminoidin group, a baicalin plus Jasminoidin group, a nimodipine group, and a model group (n = 6). The global cerebral ischemia-reperfusion mouse model was established. The mice were administrated respectively by injection of baicalin, Jasminoidin, mixture of baicalin and Jasminoidin, and nimodipine into the caudal vein, with the model group given no any drug. Three hours after operation, the brain was removed and sectioned. After calculation of cerebral ischemic area by 2,3,5-triphenyltetrazolium staining, the percentage of infarct volume was calculated. The total RNA of the mouse brain tissue was extracted to obtain the whole genome expression profile, and the differentially expressed genes related to the calcium signaling pathway was analyzed with Bayesian network structures. RESULTS: Compared with the model group, the ischemic area was significantly reduced in the baicalin group, the Jasminoidin group, the Baicalin plus Jasminoidin group (all P < 0.05). The ischemic area in the baicalin plus Jasminoidin group was smaller than the other three groups (all P < 0.01). In the gene regulatory network structures of calcium signaling pathway, the average length and equitability were the highest in the baicalin plus Jasminoidin group, followed by the nimodipine group. CONCLUSION: Compared with a single component, combination of Baicalin and Jasminoidin can more obviously intervene in the overall expression of calcium signaling pathway, and the mechanism is related with the aggregation characteristic of the gene expression network.

Fusion of core pathways reveals a horizontal synergistic mechanism underlying combination therapy.

Combination therapies have recently been shown to be more effective than monotherapies that may provide synergistic effects in the treatment of stroke, but its selective mechanism still remains unclear. Based on the median-effect method, the combination therapy of jasminoidin and ursodeoxycholic acid had a synergic effect on reducing the infarct volume. The numbers of up- or down-regulated genes by at least 1.5-fold in the vehicle, jasminoidin, ursodeoxycholic acid, and the combination of jasminoidin and ursodeoxycholic acid treatment groups were 228, 95, 136, and 101, respectively. According to clustering and principal component analysis, the pattern of gene expression in the combination group was similar to that of jasminoidin group rather than ursodeoxycholic acid group. Based on these nine top sequences in the combination group excluding four overlapping pathways (MAPK-ERK, Kitlg, Icam1-Ap1, and prolactin), the jasminoidin group had four (PRLR-STAT1, AcvR2-AcvR1B, ACVR1/2A-SMAD1, GHR-NF-κB) contributing pathways, and the ursodeoxycholic acid group had one (IL-6) contributing pathway. Based on the multiple-pathway-dependent comparison analysis (MPDCA), it may lead to the conclusion that jasminoidin possibly contributes more important pharmacological effect in the combined treatment as jasminoidin regulated 80% of the pathways that the combination group mediated. The study reveals a horizontal synergistic effect by optimizing the fusion of more pathways from the compounds with more contribution to the combination therapy. Rather than selecting compounds only based on experience in the past, this study would give a new insight into the systematic strategies for designing synergistic combination therapies.

[Microarray and research of Chinese medications: pharmcogenomics of Chinese medications].

The mechanism of Chinese medications have some characteristic such as multi-pathway, multi-components, multi-targets and so on, which decide the direction of systems research. In the recent years, microarrays be concerned with the relative field of Chinese medications for its superiority of highthough, parallel and high-density. This paper mainly generalize the approach of these methods in the recent three years, such as finding effective target of Chinese medications, effective part of Chinese medications, checkup of Chinese medications, screening new drugs and so on. We suggest the concept of Pharmacogenomics of Chinese medications with the guidance of the theory of Chinese medications for further development of Chinese medications.

[Survey on factors influencing the use of suitable techniques on Chinese medicine in the countryside in 10 provinces].

OBJECTIVE: To study the effective factors and difficulties in the application of Suitable Technique of Chinese Medicine(STCM) in the countryside. METHODS: A survey on current situation was carried out on incumbency doctors in 12 cities with a self-designed questionnaire. RESULTS: In 1387 available questionnaire, 51.8% of the doctors agreed with the active application of some STCM in the countryside while 42.8% thought that they could be promoted. Factors as age,titles of professional, jobs and holding a diploma had close relation with their attitude to the application of techniques in their cities (P < 0.01). CONCLUSION: Suitable technique of CM could be adopted by the rural doctors working at the grassroot healthcare unit, suggesting that these techniques should be popularized step by step.