Establishment of multiple evidence-integrated evaluation and prediction method for "toxic" Chinese medicines / 中国中药杂志

Traditional Chinese medicine(TCM) carries the experience and theoretical knowledge of the ancients, and the use of "toxic" Chinese medicines is a major feature and advantage of TCM. "Toxic" Chinese medicines have unique clinical value and certain medication risk under the guidance of TCM theories such as compatibility for detoxification and treatment based on syndrome differentiation. In recent years, the safety events of Chinese medicines have occurred frequently, which has made the safety of Chinese medicine a public concern in China and abroad. However, limited by conventional cognitive laws and technical methods, basic research on toxicity of Chinese medicines fails to be combined with the clinical application. As a result, it is difficult to identify the clinical characteristics of, predict toxic and side effects of, or form a universal precise medication regimen for "toxic" Chinese medicines, which restricts the clinical application of them. In view of the problem that the toxicity of "toxic" Chinese medicines is difficult to be predicted and restricts the clinical application, the evidence-based research concept will provide new ideas for safe applcation of them in clinical practice. The integrated development of multiple disciplines and techniques in the field of big data and artificial intelligence will also promote the renewal and development of the research models for "toxic" Chinese medicines. Our team tried to propose the academic concept of evidence-based Chinese medicine toxicology and establish the data-intelligence research mode for "toxic" Chinese medicines and the intelligent risk prediction method for medicinal combination in the early stage, which provided methodological supports for solving the above problem. Thus, on the basis of summarizing the research status and problems of the clinical medication regimen of "toxic" Chinese medicines, our team took the evidence-based toxicology of TCM as the core concept, and tried to construct the multiple-evidence integrated evaluation and prediction method for "toxic" Chinese medicine, so as to guide the establishment of the non-toxic medication regimen of "toxic" Chinese medicines. Specifically, through the analysis of multivariate data obtained from the basic research, the evidence-based toxicology database of Chinese medicines and the individualized "toxicity-effect" intelligent prediction platform were built based on the disease-syndrome virtual patients, so as to identify the clinical characteristics and risks of "toxic" Chinese medicines and develop individualized medication regime. This study is expected to provide a methodological reference for the establishment of medication regimen and risk prevention strategy for "toxic" Chinese medicines. The method established in this study will bridge clinical research and basic research, enhance the transformation of the scientific connotation of attenuated compatibility, promote the development of evidence-based Chinese medicine toxicology, and ensure the clinical safety of "toxic" Chinese medicines.

Effect of Combined Therapy of Lung and Intestine on VIP and p38 MAPK Signaling Pathways in Bronchial Asthma Mice / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effects of the combined therapy of lung and intestine， a common treatment for pulmonary diseases in traditional Chinese medicine （TCM）， on bronchial asthma mice， and further detect the changes of vasoactive intestinal peptide （VIP） and p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway-related proteins which are closely related to the pathogenesis of asthma， in order to elucidate the mechanism of the combined therapy of lung and intestine in the treatment of bronchial asthma. MethodA total of 60 Kunming mice were randomly divided into normal group， model group， dexamethasone group （0.5 mg·kg-1·d-1）， TCM group （2.73 g·kg-1·d-1）， and lung-intestine treatment group （6.825 g·kg-1·d-1）， 12 mice in each group. All mice except the normal group were sensitized by ovalbumin to induce bronchial asthma. After 30 days of intragastric administration， serum and lung tissue samples were obtained. The content of VIP， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the serum of mice in each group was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of TNF-α， IL-6， and p38 MAPK in lung tissues of mice were detected by real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of TNF-α， IL-6， p38 MAPK， and phosphorylated p38 MAPK （p-p38 MAPK） in lung tissues of mice were assayed by Western blot （WB）. ResultCompared with the normal group， the model group showed decreased content of serum VIP （P<0.05）， increased content of TNF-α and IL-6 （P<0.05）， up-regulated mRNA levels of TNF-α， IL-6， and p38 MAPK， and elevated protein levels of TNF-α， IL-6， and p-p38 MAPK/p38 MAPK in lung tissues （P<0.05）. Compared with the model group， the treatment groups exhibited increased content of serum VIP， TNF-α， and IL-6 （P<0.05）， down-regulated mRNA levels of TNF-α， IL-6， and p38 MAPK， and lower protein levels of TNF-α， IL-6， and p-p38 MAPK/p38 MAPK in lung tissues （P<0.05）. As compared with the lung-intestine treatment group， the serum TNF-α and IL-6 levels in the dexamethasone group were increased （P<0.05）， and the mRNA and protein levels of TNF-α and IL-6 in lung tissues were down-regulated （P<0.05）， while the levels of p38 MAPK， VIP mRNA， and p-p38 MAPK/p38 MAPK protein in lung tissues were up-regulated （P<0.05）. The serum VIP， TNF-α， and IL-6 levels in the TCM group were decreased （P<0.05）， and the mRNA levels of TNF-α， IL-6， p38 MAPK and protein levels of TNF-α， IL-6， p-p38 MAPK/p38 MAPK in lung tissues were up-regulated （P<0.05）， while the level of VIP mRNA in lung tissues was down-regulated （P<0.05）. ConclusionThrough increasing endogenous VIP and inhibiting the excessive activation of p38 MAPK signaling pathway， the combined therapy of lung and intestine can reduce the release of inflammatory factors， inhibit pulmonary inflammation response， and treat bronchial asthma.

Status Quo and Analysis of the Cardiovascular Clinical Practice Guidelines/Expert Consensuses of Chinese and Integrative Medicine: A Systematic Review / 中国结合医学杂志

OBJECTIVE@#To describe and analyze the status quo of cardiovascular clinical practice guidelines or expert consensuses including both Chinese medicine (CM) and integrative medicine, through systematic literatures searching and quality assessment.@*METHODS@#Data bases including Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, Wanfang Data, China Science and Technology Journal Database were searched for published CM or integrative cardiovascular clinical practice guidelines or expert consensuses. The website www. medlive.cn was also retrieved as supplementary. The clinical practice evaluation tool AGREE II was used to assess the quality of included guidelines or consensuses.@*RESULTS@#A total of 31 relevant clinical practice guidelines or expert consensuses were included, covering diagnosis, treatment, Chinese patent and patient fields. Common cardiovascular diseases like coronary heart diseases, heart failure and arrhythmia were also involved. Through analysis it was found that both the quantity and quality of included guidelines have been improved year by year. A total of 4 evidence-based clinical practice guideline has been found, one of which was a guideline project plan. Except that, the remaining 27 reports were all consensus-based guidelines. The scores of each field, from highest to lowest, were clarity of presentation (58%), scope and purpose (54%), stakeholder involvement (28%), rigor of development (21%), applicability (13%) and editorial independence (8%).@*CONCLUSIONS@#Although clinical practice guidelines in cardiovascular domain of Chinese have gained increasing concern, with both quantity and quality improved, there is still huge gap in methodology and reporting standards between CM guidelines and international ones. On the one hand, it is essential to improve and standardize the methodology of developing CM guidelines. On the other hands, the evaluation system of evidence and recommendation with CM characters should be developed urgently.

Whether Syndrome Differentiation Affects Treatment Result: Study Protocol of MaZiRenWan () for Functional Constipation in A Randomized Controlled Trial / 中国结合医学杂志

BACKGROUND@#Syndrome is one of the most important concepts in Chinese medicine (CM) theory. However, it was not well accounted in most of randomized controlled trials (RCTs).@*OBJECTIVES@#To determine whether CM syndrome differentiation affects the treatment results, functional constipation (FC) was selected as a target disease, and MaZiRenWan (, MZRW), a classic CM formula commonly used for constipation with excessive heat syndrome, was selected for study.@*METHODS@#It is an 18-week prospective double-blinded, doubledummy RCT, including 2-week run-in, 8-week treatment and 8-week post treatment follow-up. A total of 120 FC patients diagnosed as excessive heat syndrome will be recruited from the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and the Baokang Affiliated Hospital of Tianjin University of Traditional Chinese Medicine. Patients will be randomly allocated into fixed MZRW (f_MZRW) granule group, modified MZRW (m_MZRW) granule group or bisacodyl group. For m_MZRW group, no more than two herbal granules can be added according to the syndrome differentiation for individual participants. The primary end point is the mean of complete spontaneous bowel movements (CSBMs) per week during the treatment period. Secondary end points include mean of CSBMs per week during follow-up, stool form, global symptom improvement, constipation and constipation-related symptoms assessment, CM syndrome change, and reported adverse events.@*DISCUSSION@#This trial is designed to evaluate the effectiveness of these three interventions for FC patients with the CM syndrome of excessive heat, and to determine the change of CM syndrome and the progress of disease during the treatment course. The results are important to explore whether syndrome differentiation is important for the therapeutic effect of a formula on a disease. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-TRC-13003742); protocol version: MZRW/NSFC-81173363 (2015.05.04)].

Strategy and Path of Precision and Evidence-based Medicine Promoting the Rational and Legal Application of Traditional Chinese Medicine Injection / 世界科学技术-中医药现代化

There are two major problems in the clinical application of Traditional Chinese Medicine injection: inadequate instruction for clinical medication and unreasonable clinical application. The key of the problem is the lack of precise and evidence-based research. In view of the current problems, we should adopt the strategy of government drug administration department leading and gradually taking shape that a multi-collaboration platform of medical institutions, researchers and enterprises to jointly carry out precise and evidence-based research. The specific implementation path is the precise clinical positioning, improving monitoring and assessment system of adverse drug reactions. The medical institutions fully put into the evidence. Chinese medicine injection will be clear and specific in clinical location, with clear mechanism. Survival of the fittest enhances the core competitiveness of Chinese medicine injections and makes contributions to the cause of protecting human life and health.

Problems of Using Traditional Chinese Medicine Injections in Clinical Practice and the Suggestions about Making the Package Inserts / 世界科学技术-中医药现代化

In clinical practice, the application of Traditional Chinese Medicine injections (TCMIs) has several problems, for example, at some time, the components are complicated, the ingredients and pyrogen are uncontrollable, the usage, the dosage, and the drug interactions are unclear and the method of application is also ambiguous and non-standard. The factors have restricted the development of TCMIs. Based on the policies of the TCMI package inserts since 2006, this paper takes consideration of the problems and gives suggestions of making strict, normal and evidence-based TCMI package inserts.

Applylication of new type combined fragments: nrDNA ITS+ nad 1-intron 2 for identification of Dendrobium species of Fengdous / 药学学报

In this study, 17 kinds of Dendrobium species of Fengdous including 39 individuals were collected from 4 provinces. Mitochondrial gene sequences co I, nad 5, nad 1-intron 2 and chloroplast gene sequences rbcL, matK amd psbA-trnH were amplified from these materials, as well as nrDNA ITS. Furthermore, suitable sequences for identification of Dendrobium species of Fengdous were screened by K-2-P and P-distance. The results showed that during the mentioned 7 sequences, nrDNA ITS, nad 1-intron 2 and psbA-trnH which had a high degree of variability could be used to identify Dendrobium species of Fengdous. However, single fragment could not be used to distinguish D. moniliforme and D. huoshanense. Moreover, compared to other combined fragments, new type combined fragments nrDNA ITS+nad 1-intron 2 was more effective in identifying the original plants of Dendrobium species and could be used to identify D. huoshanense and D. moniliforme. Besides, according to the UPGMA tree constructed with nrDNA ITS+nad 1-intron 2, 3 inspected Dendrobium plants were identified as D. huoshanense, D. moniliforme and D. officinale, respectively. This study identified Dendrobium species of Fengdous by combined fragments nrDNA ITS+nad 1-intron 2 for the first time, which provided a more effective basis for identification of Dendrobium species. And this study will be helpful for regulating the market of Fengdous.

Establish research model of post-marketing clinical safety evaluation for Chinese patent medicine / 中国中药杂志

The safety of Chinese patent medicine has become a focus of social. It is necessary to carry out work on post-marketing clinical safety evaluation for Chinese patent medicine. However, there have no criterions to guide the related research, it is urgent to set up a model and method to guide the practice for related research. According to a series of clinical research, we put forward some views, which contained clear and definite the objective and content of clinical safety evaluation, the work flow should be determined, make a list of items for safety evaluation project, and put forward the three level classification of risk control. We set up a model of post-marketing clinical safety evaluation for Chinese patent medicine. Based this model, the list of items can be used for ranking medicine risks, and then take steps for different risks, aims to lower the app:ds:risksrisk level. At last, the medicine can be managed by five steps in sequence. The five steps are, collect risk signal, risk recognition, risk assessment, risk management, and aftereffect assessment. We hope to provide new ideas for the future research.

Anti-inflammatory and immunoregulatory effects of Yupingfeng powder on chronic bronchitis rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the anti-inflammatory and immunoregulatory effects of Yupingfeng (, YPF) Powder and its components in rats.</p><p><b>METHODS</b>A rat chronic bronchitis (CB) model was developed using lipopolysaccharide (LPS) combined with bacillus Calmette Guerin (BCG). YPF, simple recipe Astragalus membranaceus (Fisch.) Bge (AM) and Astragalus membranaceus (Fisch.) Bge plus rhizome of Atractylodes macrocephala Koidz (AM+RA) decoction were administered (intragastric administration, once a day for 21 days) to rats, to prevent and treat CB. Immunoregulatory and anti-inflammatory effects of YPF, AM and AM+RA were tested by serum pharmacology in vitro on splenic lymphocytes of normal rats and alveolar macrophages of CB rats.</p><p><b>RESULTS</b>Inflammation in the pulmonary tissue and the bronchus of CB rats was significantly reduced in the YPF-treatment groups, AM and AM+RA groups demonstrating the efficacy of YPF. Serum samples collected at different times from rats after administration of YPF, AM and AM+RA demonstrated increased proliferation of splenic lymphocytes with area under the effect curve (AUE) of 552.6%, 336.3% and 452.0%, respectively. Treatment of alveolar macrophages with serum samples in YPF, AM or AM+RA group inhibited interleukin-8 (IL-8) in the cell culture media, and the effect was much better in the YPF group compared with AM or AM+RA group, with a higher maximal effect (Emax, P<0.05) and larger AUE (P <0.01 and P<0.05). Moreover, serum from rats treated with AM or AM+RA had similar efficacy, while the efficiency was lower than that treated with YPF.</p><p><b>CONCLUSION</b>YPF demonstrated anti-inflammatory and immunoregulatory effects in a rat model of CB, and timedependent relationships were demonstrated in vitro.</p>

Optimization of formulas of Quban gel by uniform design / 中国中药杂志

<p><b>OBJECTIVE</b>To optimize formulas of Quban gel.</p><p><b>METHOD</b>The U6 (6(2) x 3) uniform design was adopted to optimize gel formulas, with rheological parameters, such as viscosity and yield value in room temperature, viscosity and yield value in average temperature of skin, thixlotropy.</p><p><b>RESULT</b>The optimum proportion of matrix was made of 1.0 g carbomer 940, 5 mL glycerin and pH value 5-6.</p><p><b>CONCLUSION</b>The regression model for gel matrix quality and gel rheological parameters was established to directly reflect the impacting effect of various factors, and provide certain preference basis for the screening of gel matrix formulas. Quban gel prepared by the method was evenly distributed, moderately viscous and highly thixotropic</p>

Percutaneous permeability study for patches Shangshi Zhitong on different kinds of bases / 中国中药杂志

<p><b>OBJECTIVE</b>To study the percutaneous permeability of patches Shangshi Zhitong on different kinds of bases with the permeation percentage of brucine, strychnine and atropine.</p><p><b>METHOD</b>Using modified Franz difusion to investigate the penetration quantity of brucine, strychnine and atropine. The contents of brucine, strychnine and atropine were determined by HPLC.</p><p><b>RESULT</b>The average accumulative permeation percentage of brucine, strychnine and atropine on new base were 53.25%, 74.52% were 34.32%, respectively, and on old base are 54.90%, 50.24%, 46. 54%, respectively.</p><p><b>CONCLUSION</b>The new base benefits the lipophilic drugs and releases more stably.</p>

Demethylbellidifolin prevents nitroglycerin tolerance via improved aldehyde dehydrogenase 2 activity.

The aim of this study was to investigate the effect of demethylbellidifolin (DMB), a major xanthone compound of Swertia davidi franch, on nitroglycerin (NTG) tolerance. In the in vivo portion of the study, pretreatment of Sprague-Dawley rats with NTG (10 mg/kg) for 8 days caused tolerance to the depressor effect of NTG. This was evident because the depressor effect of NTG (150 microg/kg, I. V.) was almost completely abolished in the tolerant rats. The tolerance could be diminished by treatment with DMB. In the in vitro study, the exposure of aortic rings of Sprague-Dawley rats to NTG (10 microM) for 30 min caused tolerance to the vasodilating effect of NTG. The tolerance is evident because of a substantial right shift of the NTG concentration-relaxation curves. This shift was reduced by pretreatment of the aortic rings with DMB. In cultured human umbilical vein endothelial cells (HUVECs), incubation of NTG for 16 h increased reactive oxygen species (ROS) production, attenuated cyclic guanosine monophosphate (cGMP) levels and decreased the activity of aldehyde dehydrogenase 2 (ALDH-2), the main enzyme responsible for NTG bioactivation. All the effects mentioned above were prevented by co-incubation with DMB. In conclusion, DMB prevents NTG tolerance via increasing ALDH-2 activity through decreasing ROS production.

Application of thermoplastic elastomer in hot-melt pressure sensitive adhesives for transtermal drug delivery / 中国中药杂志

Development of drug dosage forms to a great extent depends on the development of drug auxiliary materials. The development of a new type of polymeric drug auxiliary materials will bring on the developing of a novel dosage forms technology and a flood of new drug dosage forms. Thermoplastic elastomer is a new type of drug polymeric auxiliary materials, at present, which has a broad application in the field of hot-melt pressure sensitive adhesives. This review mainly discussed a new transtermal Chinese drug delivery system, including matrix composition of the formula, modified thermoplastic elastomer for hot-melt pressure sensitive adhesives and their development prospects in the traditional Chinese drug delivery system. It suggested that thermoplastic elastomer of hot-melt pressure sensitive adhesives has broad development prospects in the field of the transtermal drug delivery system for traditional Chinese medicine.

[Inhibitory effect of reinioside C on LOX-1 expression induced by ox-LDL].

OBJECTIVE: To investigate the effect of reinioside C (RC) on the expression of lectin-like oxidized low density lipoprotein receptor (LOX)-1 mRNA and LOX-1 protein induced by oxidized low density lipoprotein (ox-LDL) in cultured human umbilical vein endothelial cells (HUVEC). METHODS: HUVECs were cultured with ox-LDL (50 mg/L) for 24 h in the absence or presence of RC (1, 3, and 10 micromol/L). The expressions of LOX-1 mRNA and LOX-1 protein were examined by RT-PCR and Western-blot. RESULTS: Incubation with ox-LDL (50 mg/L) significantly raised the expression of LOX-1 mRNA and LOX-1 protein,which was concentration-dependent. CONCLUSION: RC can inhibit the increased expression of LOX-1 mRNA and LOX-1 protein induced by ox-LDL in HUVECs.

Inhibitory effect of reinioside C on LOX-1 expression induced by ox-LDL / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of reinioside C (RC) on the expression of lectin-like oxidized low density lipoprotein receptor (LOX)-1 mRNA and LOX-1 protein induced by oxidized low density lipoprotein (ox-LDL) in cultured human umbilical vein endothelial cells (HUVEC).@*METHODS@#HUVECs were cultured with ox-LDL (50 mg/L) for 24 h in the absence or presence of RC (1, 3, and 10 micromol/L). The expressions of LOX-1 mRNA and LOX-1 protein were examined by RT-PCR and Western-blot.@*RESULTS@#Incubation with ox-LDL (50 mg/L) significantly raised the expression of LOX-1 mRNA and LOX-1 protein,which was concentration-dependent.@*CONCLUSION@#RC can inhibit the increased expression of LOX-1 mRNA and LOX-1 protein induced by ox-LDL in HUVECs.