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A Peer-reviewed, open access journal sponsored by TMR publishing group
Editor-in-Chief: Wen-Yuan Gao, PhD. Prof.
ISSN 2624-3075
7Drug Combination Therapy (DCT) is an international peer-reviewed, open access journal sponsored by TMR publishing group. DCT aims to publish unbiased original articles, reviews, letters, news and comment in all areas of drug combination therapy. DCT is dedicated to report the latest advancements and the research done in drug combination along with all the relevant fields, including but not limited to prescription compatibility studies, disassembled formulae studies, drug compatibility synergetic/antergic mechanisms, drug incompatibility/adverse reactions, combination therapy for specific populations, integrated pharmacology studies, system/network pharmacology, big data analysis, systematic evaluation/meta-analysis, omics research, natural products chemistry, pharmaceutical analysis, etc. In order to focus on breakthrough research in a field, DCT insist on publishing special issues around a topic related to drug combination therapy. DCT has been included in CAS databases, EuroPub, J-Gate, Google Scholar, CNKI Scholar, Baidu Scholar, VIP Data, Superstar Journals Database and Traditional Medicine Research Data Expanded. ... More

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Current Issue     05 May 2020, Volume 2 Issue 2 Previous Issue   
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The analgesic, anti-inflammatory, and anti-infection effects of Chai Ge fever relief oral liquid
Shan-Shan Guo, Ya-Xin Wang, Ying-Jie Gao, Sai-Wei Lu, Xiao-Lan Cui
7Drug Combination Therapy. 2020, 2 (2): 45-53.   https://doi.org/10.12032/DCT2020A015
Abstract ( 58 )     PDF (420KB) ( 32 )  
Backgroud: To explore the analgesic, anti-inflammatory, and anti-infective effects of Chai Ge fever relief oral liquid and provide evidence for clinical application of Chai Ge fever relief oral liquid. Methods: In this study, four groups of experiments were designed: analgesic, anti-inflammatory, antiviral, and antibacterial. In the mouse pain model, the analgesic effect of Chai Ge fever relief oral liquid was studied by the writhing method and pain threshold; the anti-inflammatory effect by measuring the level of capillary permeability in the abdominal cavity of mice in different dose groups and the weight of cotton ball granuloma formation in rats; the antiviral effect by measuring the lung index of a pneumonia model of mouse infected with influenza virus; and the antibacterial effect by comparing the difference in the death protection ratio between each dose group and the model group result. Results: In the analgesic experiment, the high and medium dose of Chai Ge fever relief oral liquid could significantly reduce the number of writhing in mice caused by acetic acid, and the pain threshold of mice in the high- and medium-dose groups was significantly increased for 1–3 hours. In the anti-inflammatory experiment, the medium-dose group could significantly inhibit the increase of capillary permeability in the abdominal cavity of mice caused by acetic acid, and the low-dose group could significantly reduce the weight of rat cotton ball granuloma. In the antiviral experiment, the high- and medium- doses of Chai Ge fever relief oral liquid could significantly reduce the lung index of normal mouse pneumonia model of influenza virus infection and achieve a higher inhibition rate. In the anti-infective experiment, the death protection rate of the high-dose group was significantly different from that of the model control group. All three dose groups could significantly prolong the survival days of infected mice. Conclusion: These experimental results prove that in addition to its antipyretic effect, Chai Ge fever relief oral liquid also has analgesic, anti-inflammatory, antiviral, and antibacterial effects.
Mechanism of Qingre Yangyin Chushi Pill in the treatment of gout based on NLRP3/GSDMD pyroptosis pathway
Bo Wen, Cong Ma, Qin Zhang, Yang Shi, Mi-Feng Liu, Xiao-Meng Huo, Wen Gu, Pei-Pei Shao, Ping Tang
7Drug Combination Therapy. 2020, 2 (2): 54-66.   https://doi.org/10.12032/DCT2020A016
Abstract ( 56 )     PDF (918KB) ( 14 )  
Background: The study was conducted with the interest of exploring the effects of Qingre Yangyin Chushi pill as anti-inflammatory agent in gout treatment based on the NLRP3/GSDMD coke death pathway. Methods: In this study, 48 male SD rats were randomly divided into 6 groups, namely model group, blank control group (BC), Qingre Yangyin Chushi pill low-dose treatment group (MSD1), medium-dose treatment group (MSD2), high-dose treatment group (MSD3), and colchicine group (PC), with eight members in each group. The BC and model groups were administered with saline twice a day. The MSD1, MSD2, and MSD3 groups were administered with Qingre Yangyin Chushi pill at a dose of 1.8 g·kg −1 , 3.6 g·kg −1 , and 7.2 g·kg −1 twice a day. The colchicine group was administered with a colchicine suspension at a dose of 0.6 × 10 −3 g kg −1 twice a day for 7 days. After gavage of animals in each group for 4 days, the rats' ankle joints were injected with sodium urate suspension × 3 days to induce a gouty arthritis model. Then, serum and tissue samples were collected on the third and seventh day after gavage. The synovial tissue from the rat ankle joints was taken, and immunohistochemical technique was used to detect NOD-like receptor protein 3 (NLRP3), inflammatory bodies, cysteine protease-1 (Caspase-1), and Gasdermin-D protein (GSDMD) expression. Image-Pro Plus image analysis system was used to measure the average integrated absorbance and calculate IHS. Integral enzyme-linked immunosorbent assay was used to determine the interleukin 1β (IL-1β) and interleukin 18 (IL-18) expression of tumor necrosis factor-α (TNF-α). Western blot was used to detect NLRP3, Caspase-1, GSDMD, and apoptosis-associated speck-like protein containing a CARD (ASC) expression levels. Results: After 48 hours of modeling, compared with the PC group, the arthritis indices of the MSD1, MSD2, and MSD3 groups were insignificant (P > 0.05). The levels of IL-1β, IL-18, and TNF-α were lower in the PC and MSD2 groups compared with the BC group. However, compared with the control group, MSD1, MSD2, and PC groups had lower levels of IL-1β and IL-18. Regarding TNF-α levels (P < 0.05); compared with the PC group, the levels of IL-1β, IL-18, and TNF-α in MSD2 decreased more significantly (P < 0.05). The levels of NLRP3, Caspase-1, GSDMD, ASC, IHS score, and mRNA were lower in the PC and MSD2 groups (P < 0.05) compared with the control group. The MSD1 and MSD2 groups had lower levels of NLRP3, Caspase-1, GSDMD, ASC protein levels, IHS points, and mRNA levels (P <0.05) compared with the PC group. Moreover, NLRP3, Caspase-1, GSDMD, ASC protein levels, IHS points, and mRNA levels were more reduced in the MSD2 group (P < 0.05). Conclusion: Qingre Yangyin Chushi pill can inhibit the activation of the NLPR3 inflammatory complex, reduce the production of GSDMD protein, regulate the occurrence of pyroptosis, reduce the expression of inflammatory factors, and thus reduce arthritis. All these processes are achieved through the NLRP3/GSDMD pathway.
Orginal Article
Study on the therapeutic effect of external application of ShouNian Powder combined with acupuncture at Zhitong acupoint on ICBN syndrome after breast cancer operation
Ning Mao, Yin-Hai Dai, Zhi-Yong Shao, Mao Wang, Jun-Yi Bai, Qian-Qian Liang
7Drug Combination Therapy. 2020, 2 (2): 67-73.   https://doi.org/10.12032/DCT2020A011
Abstract ( 88 )     PDF (441KB) ( 51 )  
Background: To explore the clinical effect of external application of ShouNian Powder combined with acupuncture at Zhitong acupoint in the treatment of intercostobrachial nerve syndrome (ICBNs) after breast cancer operation. Methods: A total of 80 patients with ICBNs who underwent modified radical mastectomy in our hospital from July 2014 to July 2016 were collected and divided into control group and study group according to the different treatment methods of ICBNs. 40 patients in the control group were treated with symptomatic analgesia and 40 patients in the study group were treated with external application of ShouNian Powder combined with acupuncture at Zhitong acupoint to compare and analyze the pain relief, quality of life and analgesic recurrence rate of ICBNs between the two groups. Results: Compared with the control group, the pain relief rate of ICBNs in the study group was higher. The patient satisfaction and long-term quality of life in the study group were better than those in the control group. However, there was no significant difference in postoperative pain recurrence rate. Conclusion: External application of ShouNian Powder combined with acupuncture at Zhitong acupoint can effectively relieve pain and improve quality of life for patients with ICBNs after breast cancer operation, which has a certain popularizing significance in clinical practice.
Analysis on the compatibility rules and mechanism of formulae treatment for COVID-2019 based on the TCM inheritance assistance system and network pharmacology
Zi-Tong Fu, Jia-Xin Huang, Teng-Fei Bai, Guo-Wei Zhang
7Drug Combination Therapy. 2020, 2 (2): 74-88.   https://doi.org/10.12032/DCT2020A018
Abstract ( 172 )     PDF (1248KB) ( 124 )  
Background : On December 8, 2019, Wuhan City, Hubei Province, a new type of coronavirus disease 2019 (COVID-2019) was firstly discovered, and COVID-2019 spread rapidly in China. The number of confirmed cases in various provinces and cities rose sharply in China. In clinical treatment, Chinese medicine treatment showed significant efficacy. Since the outbreak, the National Health Commission (NHS) of China has issued seven editions of the “Pneumonitis Diagnosis and Treatment Program for COVID-2019”, at the same time, most provincial health boards and the Chinese Medicine Administration had also released information on the prevention and control scheme of COVID-2019 by Chinese medicine. The purpose of this study is to explore the compatibility rules of the main drugs in the prescription and the potential mechanism on COVID-2019 pneumonia, in order to provide reference for clinical research and new drug development of COVID-2019. Methods: This article uses the TCM inheritance assistance system and network pharmacology BATMAN-TCM online analysis system to collect and summarize the national “Pneumonitis Diagnosis and Treatment Program for COVID-2019 (trial version sixth)” and formulae for adult treatment from the TCM prevention program of 23 provinces and cities. Results: We found that the most formulae for the treatment of COVID-2019 were modified on the basis of Maxing Shigan decoction and the top 5 high-frequencyn drugs are Xingren (Armeniacae semen amarum), Mahuang (Ephedrae herba), Gancao (Glycyrrhizae radix et rhizoma), Shigao (Gypsum fibrosum), and Haungqin (Radix scutellariae). High frequency traditional Chinese medicines are mainly used for relieving the symptoms, clearing away heat, eliminating dampness, resolving phlegm, relieving cough and asthma, promoting water and dampness, and tonifying deficiency. Warm medicine and bitter medicine are the most frequently used drugs in four Qi attribute and five flavor attribute, respectively. Most of drugs are belong to lung, stomach and spleen channel. Mahuang (Ephedrae herba), Xingren (Armeniacae semen amarum), Gancao (Glycyrrhizae radix et rhizoma), Shigao (Gypsum fibrosum), Cangzhu (Atractylodis rhizama) and Huoxiang (Pogostemonis herba) are the core drugs for treating COVID-2019. The TTD disease enrichment, target and signal transduction pathways of the six drugs showed that pneumonia and asthma were most closely related to COVID-2019. And the inflammatory reaction-related pathways may be the main pathways through which these drugs function. Conclusions: The modified Maxing Shigan decoction is the main prescription for the treatment of COVID-2019. The Xingren (Armeniacae semen amarum), Gancao (Glycyrrhizae radix et rhizoma), Shigao (Gypsum fibrosum), Cangzhu (Atractylodis rhizama) and Huoxiang (Pogostemonis herba) have certain theoretical and experimental basis for the treatment of COVID-2019 through network pharmacology analysis, but further experiments are needed to verify the effects.
Stability and compatibility of common traditional Chinese medicine injections matching with fructose injection
Zhe-Tao Zhang, Xiao Liu, Ze-Yuan Wei, Chao-Liang Tang
7Drug Combination Therapy. 2020, 2 (2): 89-96.   https://doi.org/10.12032/DCT2020B021
Abstract ( 53 )     PDF (334KB) ( 75 )  

In recent years, China has attached great importance to the work of traditional Chinese medicine (TCM), more and more Chinese patent medicines are included in the national medical insurance catalogue, and the clinical application of TCM injections is also increasing. This article reviews a total of 20 literature reports on the compatibility of fructose injections with TCM injections from 2005 to the present, and evaluates the stability based on the appearance, pH, insoluble particles and content changes after compatibility, and provides for the rational use of fructose injections. Theoretical evidence provides options for special patients with special solvent limit.

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  • 2020-06-13

    Analysis on the medication and methods of ancient traditioal Chinese medicine in the prevention of plague
     
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    Background: To analyze the medication and methods of ancient traditional Chinese medicine for the prevention of plague and seasonal pathogen in order to reduce the spread of infectious diseases such as flu and protect the susceptible people. Methods: Search the medication and the methods for preventing plague and seasonal pathogen in the Chinese Medical Code, classify and summarize the methods, perform frequency analysis and efficacy cluster analysis on Chinese medicines of involved medicines. Results: The methods of preventing ancient plague were as follows: burning and fumigating Chinese medicines, medicating nostrils, wearing bags filled with Chinese medicines, oral Chinese medicines and applying medicines to skin. The three main ways for drugs to work were external medication, nostril inhalation, and internal absorption. The Chinese medicines for preventing plague are mostly warm in nature and pungent in flavour, belonging to the spleen, stomach, liver, lung meridian. The three categories of drugs obtained by cluster analysis are C1: drugs for facilitating lung, relieving exterior and dissipating cold, such as Cangzhu (Atractylodis rhizoma)-Qianghuo (Notopterygh rhizoma et radix)-Xixin (Asari radix et rhizoma)-Baizhi (Angelicae dahuricae radix)-Fangfeng (Saposhnikoviae radix)-Zaojiao (Gleditsiae sinensis fructus); C2: drugs for promoting blood circulation and removing blood stasis, such as Xionghuang (Realgar)-Zhusha (Cinnabaris)-Dahuang (Rhei radix rhizoma)-Chuanxiong (Chuanxiong rhizoma)-Jiegeng (Platycodonis radix); C3: drugs for replenishing Qi (it is the most basic element that constitutes human body and maintains life activities in traditional Chinese medicine) and tonifying the spleen, such as Gancao (Glycyrrhizae radix et rhizoma)-Dazao (Jujubae fructus)-Ganjiang (Zingiberis rhizoma)-Rougui (Cinnamomi cortex)-Gansong (Nardostachyos radix et rhizoma)-Chenpi (Citri reticulatae pericarpium)-Baizhu (Atractylodis macrocephalae rhizoma). Conclusion: Through analysis the medication and methods of ancient traditional Chinese medicine for the prevention of plague, we can provide reference for modern research from the original plague prevention methods, and make an important contribution to the use of traditional Chinese medicine in the prevention and treatment of epidemic infectious diseases in modern clinic.
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    Wei-Sen Fan, Wen-Hui Zhang, Yun-Sheng Liu, Xiao-Mei Feng, Zhen-Gao Sun
  • 2020-04-28

    The antipyretic effects of Chai Ge fever relief oral liquid 
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    Background: To verify the antipyretic effect and mechanism of Chai Ge fever relief oral liquid, and to provide evidence for the clinical application of Chai Ge fever relief oral liquid. Methods: By designing three groups of experimental models of yeast-induced rat fever model, endotoxin-induced rabbit fever model, and para-influenza virus-induced rabbit fever model, the antipyretic effect and mechanism of Chai Ge fever relief oral liquid were studied by measuring body temperature before and after treatment and the expressions of protein kinase A (PKA), protein kinase C, arginine vasopressin (AVP), prostaglandin E2 and cyclic adenosine monophosphate (cAMP) in hypothalamus after administration. Results: In the yeast-induced fever model of rats, the body temperature and PKA expression levels in different dose groups of Chai Ge fever relief oral liquid were significantly different from those of the model group 1–3h after treatment. In the rabbit fever model induced by endotoxin, different dosage groups of Chai Ge fever relief oral liquid have obvious antipyretic effect on 1–3h after the model is established, and can significantly reduce the expression of AVP and cAMP in hypothalamus. In the para-influenza virus-induced rabbit fever model, each dose group of Chai Ge fever relief oral liquid has obvious antipyretic effect on 1–2h after the model is established. Conclusion: Chai Ge fever relief oral liquid has good antipyretic effect on fever models induced by yeast, endotoxin and parainfluenza by regulating the expression of PKA, AVP, and cAMP.
    ...
    Shan-Shan Guo, Ya-Xin Wang, Ying-Jie Gao, Sai-Wei Lu, Xiao-Lan Cui
  • 2020-04-27

    Meta-analysis of tonifying kidney and soothing liver traditional Chinese medicine method in the treatment of polycystic ovary syndrome 
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    Background: To systematically evaluate the clinical efficacy of tonifying kidney and soothing liver method in the treatment of polycystic ovary syndrome (PCOS). Methods: The literatures of randomized controlled trials (RCTs) on the treatment of PCOS with traditional Chinese medicine (TCM) published at home and abroad until March 2020 were retrieved, and RCTs on the treatment of PCOS with tonifying kidney and soothing liver method were collected. According to the systematic evaluation method of the Cochrane Collaboration Network, RevMan5.3 software was used to perform quality evaluation and data extraction for meta-analysis of tests that met the inclusion criteria. Results: A total of 30 eligible RCTs were included, including 2244 patients. Meta-analysis results show that the method of tonifying the kidney and soothing liver has certain advantages in the treatment of PCOS. Compared with Western medicine alone group, tonifying the kidney and soothing liver TCM method alone or combined with Western medicine could improve the total effective rate [OR = 3.52, 95% CI (2.67, 4.63), I2 = 0%, P < 0.00001]. It is superior to the control group in improving ovulation rate [OR = 2.01, 95% CI (1.46, 2.78), I2 = 0%, P < 0.0001], pregnancy rate [OR = 2.82, 95% CI (2.28, 3.49), I2 = 0%, P < 0.00001], reducing LH [MD = -2.65, 95% CI (-3.43, -1.88), I2 =92%, P < 0.00001] and ovarian stimulating hormone levels [MD = -0.52, 95% CI (-0.85, -0.18), I2 = 94%, P = 0.002]. There was no statistical difference in reducing serum testosterone levels [SMD = -0.56, 95% CI (-1.22, 0.09), I2 = 96%, P = 0.09] and improving TCM symptoms [MD = -0.09, 95% CI (-4.75, 4.56), I2 = 97%, P = 0.97]. Conclusion: The method of tonifying the kidney and soothing liver has a certain effect in treating polycystic ovary syndrome, but the evidence is still very limited, and a large sample of high-quality randomized controlled studies is still needed in order to make a more rigorous evaluation.
    ...
    Xin Ma, Yu-Liang Zhang, Guo-Wei Zhang
  • 2020-04-22

    Molecular mechanism prediction analysis of Xiaozheng decoction in the treatment of bladder cancer based on network pharmacology 
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    Background: To investigate the mechanism of Xiaozheng decoction in treatment of bladder cancer based on network pharmacology. Methods: Based on the Tradictional Chinese Medicine Systems Pharmacology Database(TCMSP), the active compositions of Xiaozheng decoction were screened. The targets of active components were obtained from TCMSP, Swiss Target Prediction, and STITCH database. By mapping the disease targets of bladder cancer obtained from the DisGeNET and Genecards databases, the potential targets of Xiaozheng decoction for bladder cancer were obtained. The active components of Xiaozheng decoction-targets network was constructed using the Cytoscape software. The target protein interaction (PPI) network was constructed by using the String online platform, which was visualized by Cytoscape software and analyzed by network topology to obtain the key targets of Xiaozheng decoction. GO bioprocess enrichment analysis and KEGG pathway enrichment analysis were performed on key targets of the Xiaozheng decoction by DAVID database. Results: A total of 68 active components and 255 potential targets of Xiaozheng decoction in the treatment of bladder cancer were retrieved and screened out. The key targets were enriched and analyzed by the GO biological pathway, and 135 pathways were obtained, which involved transcriptional process, platelet activation, cell proliferation, and apoptosis. KEGG pathway enrichment analysis revealed 95 pathways, mainly involving cancer pathway, bladder cancer pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, and VEGF signaling pathway. Conclusion: The result of this study showed that Xiaozheng decoction may play its therapeutic role through multiple components, multiple targets and multiple pathways, and preliminarily explored the mechanism of Xiaozheng decoction in the treatment of bladder cancer, laying a foundation for subsequent experimental studies.
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    Wan-Ying Zhang, Jia-Yi Shi, Ying Chen, Miao-Miao Zhang, Guo-Wei Zhang