Coronary heart disease (CHD) is one of the leading causes of death in the world and has become a major public health problem worldwide. CHD belongs to the category of "chest stuffiness" in traditional Chinese medicine, and the blood stasis syndrome is the most common syndrome.Danhong injection is prepared from the extract of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos. It has the functions of promoting blood circulation and removing blood stasis. It has anti-inflammatory damage, anti-apoptosis, protection of vascular endothelium, inhibition of platelet aggregation, anti-hyperlipidemia, anticoagulation, improvement of blood rheology and other effects.It also could improve myocardial ischemia and relieve angina symptoms.Danhong injection is widely used in various stages of CHD, including stable angina pectoris, unstable angina pectoris, acute myocardial infarction, postoperative percutaneous coronary intervention(PCI), ischemic cardiomyopathy, CHD with arrhythmia, CHD with hyperlipidemia, CHD with heart failure and CHD with diabetes.

Danhong injection (DHI) and ceftriaxone sodium were used in combination based on their experimental uses in clinic. This study was designed to investigate the impact of ceftriaxone on pharmacokinetics and pharmacodynamics of the phenolic acids from DHI. After administration of DHI for 7 d, ceftriaxone (CFTX) was combined with DHI for the next 7 d in adult male Sprague-Dawley (SD) rats. All the drugs were administered through caudal vein. UHPLC-TQ-MS was applied in determining the plasma concentration of p-coumaric acid (p-CA), salvianolic acid D (SaD), rosmarinic acid (RA) and salvianolic acid B (SaB). The pharmacokinetic parameters of the combination group or the Danhong injection alone group were calculated by statistical moment method, C_max and the average of the area under the curve AUC_0-t using 90% confidence interval of the bioequivalence and bioavailability degree module in DAS 3.2.8 statistic software. The results showed that C_max of p-CA, SaD, RA and SaB were unqualified within 90% confidence intervals for bioequivalence statistics. And the results showed that AUC_0-t of SaD, RA and SaB within 90% confidence intervals for bioequivalence statistics were unqualified. There were no significant difference in the t_max (P>0.05). The results of anticoagulation in vivo showed that the international normalized ratio (INR), prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) were significantly increased when combined with CFTX (P<0.05 or P<0.01). The results in antithrombotic effects revealed that the thromboxane B₂ (TXB₂) level in serum was significantly decreased (P<0.01) in the combination group compared with Danhong injection alone. However, there was no significant difference in antiplatelet effects. These results suggest that CFTX may enhance the anticoagulation and antithrombotic effects of DHI through altering pharmacokinetics and pharmacodynamics in SD rats.

To explore the regularity of traditional Chinese medicine(TCM) prescriptions for cardio-cerebrovascular diseases,the core drug groups with common therapeutic effects on cerebrovascular diseases represented by stroke and cardiovascular diseases represented by coronary artery disease were extracted,and their consistency and difference in the treatment of different diseases were analyzed.A total of 388 Chinese patent medicines were collected for the treatment of cerebrovascular diseases,cardiovascular diseases and cardio-cerebrovascular diseases.The dominant and recessive patterns of Chinese patent medicines in clinical use were found by "frequency analysis","compatibility analysis" and "network analysis" respectively.According to the findings of the three parts,Salviae Miltiorrhizae Radix et Rhizoma,Chuanxiong Rhizoma,Carthami Flos and Astragali Radix have a high frequency of use in the treatment of brain disease,heart disease and both,with frequent combined medication.Data mining confirmed the core drug combinations for the treatment of cerebral and cardiac vascular diseases,so as to reveal the similarities and differences in the drug use of Chinese medicine for these diseases,and provide a basis for the rational use of traditional Chinese medicine in clinical practice.This analysis also defines a new direction for the future development of prescription combinations for different indications of cerebral and cardiac diseases.
Cardiovascular Diseases ; drug therapy ; Cerebrovascular Disorders ; drug therapy ; Data Mining ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Prescriptions

Objective To understand the malaria epidemiological characteristics of Shandong Province in 2017, so as to provide the evidences for formulating targeted prevention and control strategy and measures. Methods The data of malaria cases of Shandong Province in 2017 were collected from the Information Management System for Infectious Diseases Report and Information Management System for Parasitic Diseases Control and Prevention. The epidemiological characteristics of malaria situation and the diagnosis and treatment of malaria cases were analyzed. Results There were 209 malaria cases reported in 2017, all of them were imported cases, and 205 cases (98.09%) were imported from African countries. Among them, 155 cases (74.16%) were falciparum malaria cases. Totally 16 cities had cases reported in 2017, and 154 cases (73.68%) were reported in 6 cities (Yantai, Jining, Weihai, Dezhou, Qingdao, and Tai’an). The malaria cases distributed in 17 cities, and there were 110 cases distributed in 4 cities, namely Yantai, Tai’an, Weihai, and Qingdao, which accounted for 56.41% of the total cases in Shandong Province. Both the median time from onset to seeing a doctor and the median time from seeing a doctor to being diagnosed were one day. Totally 12.92% of the cases went to visit a doctor 7 days later after they had symptoms and 10.53% of the cases were diagnosed 7 days later after the first visit to a doctor. Conclusions At present, the prevention and control of the imported malaria is the focus of malaria control in Shandong Province. According to the central tendency of the malaria situation, the health education and propaganda among the high risk groups and the training on the diagnosis and treatment among medical workers should be strengthened, so as to prevent the risk of reappearance of local cases in the past malaria endemic regions, and to ensure the goal of malaria elimination been achieved on schedule.

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. Trial Registration ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
China ; Crotonates ; administration & dosage ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; therapeutic use ; Multicenter Studies as Topic ; Multiple Sclerosis ; drug therapy ; metabolism ; Proportional Hazards Models ; Toluidines ; administration & dosage ; adverse effects ; therapeutic use

BACKGROUNDThe molecular mechanisms of Shenxianshengmai (SXSM), a traditional Chinese medicine, on bradycardia have been incompletely understood. The study tried to investigate the gene expression profile and proteomics of bradycardia rabbits' hearts after SXSM treatment.

METHODSTwenty-four adult rabbits were randomly assigned in four groups: sham, model, model plus SXSM treatment, and sham plus SXSM treatment groups. Heart rate was recorded in all rabbits. Then, total RNA of atria and proteins of ventricle were isolated and quantified, respectively. Gene expression profiling was conducted by gene expression chip, and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to confirm the results of gene expression chip. We used isobaric tags for elative and absolute quantitation and Western blotting to identify altered proteins after SXSM treatment.

RESULTSThere was a constant decrease in the mean heart rate (32%, from 238 ± 6 beats/min to 149 ± 12 beats/min) after six weeks in model compared with that in sham group. This effect was partially reversed by 4-week SXSM treatment. Complementary DNA microarray demonstrated that the increased acetylcholinesterase and reduced nicotinic receptor were take responsibility for the increased heart rate. In addition, proteins involved in calcium handling and signaling were affected by SXSM treatment. Real-time RT-PCR verified the results from gene chip. Results from proteomics demonstrated that SXSM enhanced oxidative phosphorylation and tricarboxylic acid (TCA) cycle in ventricular myocardium to improve ATP generation.

CONCLUSIONSLong-term SXSM stimulates sympathetic transmission by increasing the expression of acetylcholinesterase and reduces the expression of nicotinic receptor to increase heart rate. SXSM also restored the calcium handling genes and altered genes involved in signaling. In addition, SXSM improves the ATP supply of ventricular myocardium by increasing proteins involved in TCA cycle and oxidation-respiratory chain.

Animals ; Bradycardia ; drug therapy ; metabolism ; physiopathology ; Drugs, Chinese Herbal ; therapeutic use ; Heart Rate ; drug effects ; Proteomics ; Rabbits ; Random Allocation ; Reverse Transcriptase Polymerase Chain Reaction

The Concurrent treatment of the brain and heart (CTBH) theory is proposed based on traditional Chinese medical theory and clinical practice. In this study, a framework for the pharmacological research platform was established to investigate the principles of concurrent treatment of the brain and heart. The platform for CTBH includes several key techniques for network modeling, discovery of active substances, dissecting mechanism of action and investigation of pharmacokinetic property of TCM. Taking network modeling of CTBH as an example, using database search, literature mining, network construction and module analysis, the that network modules closely associated with the pathological progress of cardiovascular and cerebrovascular diseases were identified, while further functional enrichment analysis of these modules indicated that the key biological processes included oxidative stress, metabolism and inflammation. GSK3B, NOTCH1, CDK4 were identified as key nodes in these network modules. The above-mentioned platform was applied to construct component-biomolecules network of Danhong injection for the identification of common targets and pathways. Among them, GSK3B had the highest correlation with the composition of Danhong injection in the network, and the biological function of whose cluster was related to cell oxidative stress. Based upon results of network analysis, validation experiments suggested that Danhong injection significantly improved the survival rate of oxidative injured myocardial cells and nerve cells, and the protective effect was related to the increase of phosphorylated GSK3β protein expression. Moreover, extracts of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos exerted the synergisticcytoprotective effect. The results indicated that the mechanism of treatment of cardiovascular and cerebrovascular diseases of Danhong injection could be studied through network modeling and other methods. In summary, the proposed pharmacological platform provided a feasible way for revealing the mechanism of CTBH by using modern scientific methods.