[Mechanism of atractylenolide â ¢ in alleviating H9c2 cell apoptosis through ROS/GRP78/caspase-12 signaling pathway based on molecular docking].

This study aims to investigate the effect of atractylenolide Ⅲ(ATL-Ⅲ) on hydrogen peroxide(H_2O_2)-induced endoplasmic reticulum stress and apoptosis of H9 c2 cells via the ROS/GRP78/caspase-12 signaling pathway.The binding activity of ATL-Ⅲ to GRP78 was determined by molecular docking.The result showed that ATL-Ⅲ had a good binding activity to GRP78, and the binding activity of ATL-Ⅲ was stronger than that of its specific inhibitor.The endoplasmic reticulum stress model of H9 c2 was established by H_2O_2(100 µmol·L~(-1)) treatment.Five groups were designed: blank control group, model group, and ATL-Ⅲ(15, 30, and 60 µmol·L~(-1)) groups.Apoptosis was detected by Hoechst/PI double staining and flow cytometry.The levels of superoxide dismutase(SOD), malondialdehyde(MDA), and lactate dehydrogenase(LDH) were measured by colorimetry.The levels of reactive oxygen species(ROS) and calcium(Ca~(2+)) in cytoplasm were determined by the fluorescence probe DCFH-DA and the calcium fluorescence probe Flou-4, respectively.The protein levels of GRP78, caspase-12, and caspase-3 were determined by Western blot, and the mRNA levels of GRP78 and caspase-12 by RT-qPCR.N-acetyl-L-cysteine(NAC) and 4-phenylbutyric acid(4-PBA) were respectively used to inhibit ROS and GRP78, and then the mechanism of ATL-Ⅲ in protecting the cells from endoplasmic reticulum stress induced by H_2O_2 were deduced.ATL-Ⅲ(15, 30, and 60 µmol·L~(-1)) decreased the apoptosis rate and ROS, MDA, and LDH levels(P<0.01), increased the SOD activity(P<0.01), and down-regulated the protein levels of GRP78, caspase-12, and caspase-3 and the mRNA levels of GRP78 and caspase-12(P<0.05).The addition of NAC decreased the apoptosis rate and ROS, MDA, GRP78, caspase-12, and caspase-3 levels(P<0.01), while it elevated the SOD level(P<0.01).The addition of 4-PBA also decreased the apoptosis rate and the levels of GRP78, caspase-12, caspase-3, and Ca~(2+)(P<0.01).The effect of inhibitors were consistent with that of ATL-Ⅲ.In conclusion, ATL-Ⅲ can protect H9 c2 cardiomyocytes by regulating ROS/GRP78/caspase-12 signaling pathway to inhibit H_2O_2-induced endoplasmic reticulum stress and apoptosis.

Atractylenolide III Attenuates Apoptosis in H9c2 Cells by Inhibiting Endoplasmic Reticulum Stress through the GRP78/PERK/CHOP Signaling Pathway.

The objective of this study was to determine the effect of atractylenolide III (ATL-III) on endoplasmic reticulum stress (ERS) injury, H9c2 cardiomyocyte apoptosis induced by tunicamycin (TM), and the GRP78/PERK/CHOP signaling pathway. Molecular docking was applied to predict the binding affinity of ATL-III to the key proteins GRP78, PERK, IREα, and ATF6 in ERS. Then, in vitro experiments were used to verify the molecular docking results. ERS injury model of H9c2 cells was established by TM. Cell viability was detected by MTT assay, and apoptosis was detected by Hoechst/PI double staining and flow cytometry. Protein expression levels of GRP78, PERK, eIF2α, ATF4, CHOP, Bax, Bcl-2, and Caspase-3 were detected by Western blot. And mRNA levels of GRP78, CHOP, PERK, eIF2α, and ATF4 were detected by RT-qPCR. Moreover, the mechanism was further studied by using GRP78 inhibitor (4-phenylbutyric acid, 4-PBA), and PERK inhibitor (GSK2656157). The results showed that ATL-III had a good binding affinity with GRP78, and the best binding affinity was with PERK. ATL-III increased the viability of H9c2 cells, decreased the apoptosis rate, downregulated Bax and Caspase-3, and increased Bcl-2 compared with the model group. Moreover, ATL-III downregulated the protein and mRNA levels of GRP78, CHOP, PERK, eIF2α, and ATF4, consistent with the inhibition of 4-PBA. ATL-III also decreased the expression levels of PERK, eIF2α, ATF4, CHOP, Bax, and Caspase-3, while increasing the expression of Bcl-2, which is consistent with GSK2656157. Taken together, ATL-III could inhibit TM-induced ERS injury and H9c2 cardiomyocyte apoptosis by regulating the GRP78/PERK/CHOP signaling pathway and has myocardial protection.

Liquiritin inhibits H2 O2 -induced oxidative stress injury in H9c2 cells via the AMPK/SIRT1/NF-κB signaling pathway.

Heart failure (HF) is a serious disease with high mortality. Oxidative stress plays a vital role in its occurrence and development. Licorice is commonly used to treat HF in traditional Chinese medicine. Liquiritin, the main ingredient of licorice, has antioxidant and anti-inflammatory properties, but the mechanism against oxidative stress in cardiomyocytes has not been reported. Establishment of oxidative damage model in H9c2 cells by hydrogen peroxide (H2 O2 ). Liquiritin (5, 10, 20 µmol/L) could significantly prevent the loss of cell viability and decrease the apoptosis rate. It can reduce the levels of reactive oxygen species (ROS), malonedialdehyde (MDA), lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and increase the activity of ATP, superoxidedismutase (SOD), glutathione peroxide (GSH-px), glutathione reductase (GR) and catalase (CAT) to alleviate oxidative stress and inflammation in a dose-dependent manner. Liquiritin was found to be related to AMP-Activated Protein Kinase (AMPK) pathway by molecular docking. Western blotting (WB) and quantitative reverse transcription PCR (RT-qPCR) confirmed that liquiritin could promote AMPKα phosphorylation and sirtuin 1 (SIRT1) protein expression, and inhibit phosphorylation of nuclear factor kappa B p65 (NF-κB p65). Compound C, EX 527, and PDTC can reverse the effects of liquiritin, indicating that its antioxidant effect is achieved by regulating AMPK/SIRT1/NF-κB signaling pathway. PRACTICAL APPLICATIONS: Heart failure is one of the most common cardiovascular diseases, and its treatment remains a worldwide problem. Licorice is a food and dietary supplement that has been used widely in traditional Chinese medicine (TCM). Liquiritin is one of the main active components of licorice, which has antioxidant and anti-inflammatory pharmacological effects. This study revealed the mechanism of licorice against oxidative damage of H9c2 cardiomyocytes, and provided a scientific basis for liquiritin as an antioxidant in the treatment of heart failure.

[A preliminary pharmacophylogenetic study of Solanaceae medicinal plants containing tropane alkaloids].

The Solanaceae plants distributed in China belong to 105 species and 35 varietas of 24 genera. Some medicinal plants of Solanaceae are rich in tropane alkaloids(TAs), which have significant pharmacological activities. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, pharmacological activities, and biosynthetic pathways of TAs in Solanaceous plants were summarized. Besides, the phylogeny of medicinal plants belonging to Solanaceae was visualized by network diagram. Fourteen genera of Solanaceae plants in China contain TAs and have medical records. TAs mainly exist in Datura, Anisodus, Atropa, Physochlaina, and Hyoscyamus. The TAs-containing species were mainly concentrated in Southwest China, and the content of TAs was closely related to plant distribution area and altitude. The Solanaceae plants containing TAs mainly have antispasmodic, analgesic, antiasthmatic, and antitussive effects. Modern pharmacological studies have proved the central sedative, pupil dilating, glandular secretion-inhibiting, and anti-asthma activities of TAs. These pharmacological activities provide a reasonable explanation for the traditional therapeutic efficacy of tropane drugs. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, and modern pharmacological activities of TAs-containing species in Solanaceae were analyzed for the first time. Based on these data, the genetic relationship of TAs-containing Solanaceae species was preliminarily discussed, which provided a scientific basis for the basic research on TAs-containing solanaceous species and was of great significance for the development of natural medicinal plant resources containing TAs.

Comparing Smartphone Apps for Traditional Chinese Medicine and Modern Medicine in China: Systematic Search and Content Analysis.

BACKGROUND: Traditional Chinese medicine (TCM) is an integral part of mainstream medicine in China, with theories and practices that are completely different from modern medicine. TCM should not be ignored or confused with modern medicine in the analysis of the Chinese health care system, including the analysis of mobile health (mHealth) apps. To date, differences between TCM apps and modern medicine apps have not be systematically investigated. OBJECTIVE: The aim of this study was to systematically compare the quality of apps for TCM and modern medicine in China. METHODS: In December 2020, we searched iOS (iTunes) and Android (Tencent, Oppo, and Huawei app stores) platforms for all mHealth apps and then categorized them as TCM or modern medicine apps if they were included in the final analysis. The included apps were downloaded on smartphones and assessed by 2 reviewers on the following 4 aspects: (1) data in the app stores, including user ratings, download counts, cost, target users, and year of last update; (2) functionality; (3) quality of the app content as determined by the Mobile App Rating Scale (MARS); and (4) analysis of the app privacy and security. RESULTS: In total, 658 apps were analyzed, including 261 TCM medicine apps and 397 modern medicine apps. The average download count of modern medicine apps (approximately 5 million) was more than 10 times that of TCM apps (approximately 400,000). Regarding functionalities, 64.7% (257/397) of modern medicine apps provided telemedicine (74/261, 28.4% in TCM apps), 62.7% (249/397) provided registration (70/261, 26.8% in TCM apps), and 45.6% (181/397) provided communication (38/261, 14.6% in TCM apps). A larger proportion of TCM apps provided prescription and medication management (144/261, 55.2% in TCM apps versus 168/397, 42.3% in modern medicine apps). The majority of modern medicine apps (329/397, 82.9%) combined ≥3 functionalities compared with one-third of TCM apps (93/261, 34.6%). We then selected 81 top apps for quality and safety assessment (41 TCM apps and 40 modern medicine apps). Of these, the mean overall MARS score of TCM apps (2.7, SD 0.5) was significantly lower than modern medicine apps (3.6, SD 0.4). Almost all modern medicine apps (38/40, 95%) addressed privacy and security by providing a privacy policy and describing how to protect personal data, but less than half of the TCM apps (18/41, 44%) described this information (P<.001). CONCLUSIONS: The different functionalities reflect the distinct innate characteristics of these two medical systems. Although great progress has been made and the Chinese mHealth market size is large, there still exist many opportunities for future development, especially for TCM.

New development and update on China Bioanalysis Forum.

This article provides an update on new development of China Bioanalysis Forum (CBF). CBF became a member association of Chinese Pharmaceutical Association (CPA) at the end of 2019. The official ceremony and first scientific symposium were held in Shanghai on 18 September 2020. The president of Chinese Pharmaceutical Association and representatives from industry, Contract Research Organization (CRO), hospitals and academic institutes attended the ceremony. Seven experts in the field gave presentations on various topics including Drug Metabolism and Pharmacokinetics (DMPK) and bioanalytical support in drug discovery and development as well as experience in Traditional Chinese Medicine research. With the continuous growth of research and development in China, it is well acknowledged that bioanalysis provides critical support for new innovative medicines and generic drug development in the region.

A preliminary pharmacophylogenetic study of Solanaceae medicinal plants containing tropane alkaloids / 中国中药杂志

The Solanaceae plants distributed in China belong to 105 species and 35 varietas of 24 genera. Some medicinal plants of Solanaceae are rich in tropane alkaloids(TAs), which have significant pharmacological activities. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, pharmacological activities, and biosynthetic pathways of TAs in Solanaceous plants were summarized. Besides, the phylogeny of medicinal plants belonging to Solanaceae was visualized by network diagram. Fourteen genera of Solanaceae plants in China contain TAs and have medical records. TAs mainly exist in Datura, Anisodus, Atropa, Physochlaina, and Hyoscyamus. The TAs-containing species were mainly concentrated in Southwest China, and the content of TAs was closely related to plant distribution area and altitude. The Solanaceae plants containing TAs mainly have antispasmodic, analgesic, antiasthmatic, and antitussive effects. Modern pharmacological studies have proved the central sedative, pupil dilating, glandular secretion-inhibiting, and anti-asthma activities of TAs. These pharmacological activities provide a reasonable explanation for the traditional therapeutic efficacy of tropane drugs. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, and modern pharmacological activities of TAs-containing species in Solanaceae were analyzed for the first time. Based on these data, the genetic relationship of TAs-containing Solanaceae species was preliminarily discussed, which provided a scientific basis for the basic research on TAs-containing solanaceous species and was of great significance for the development of natural medicinal plant resources containing TAs.

[Variety textual research of Mongolian medicine of "saradma"].

Mongolian medicine is an indispensable part in developing traditional Mongolian medicine. This study is aimed to provide a basis for the formulation of clinical and Mongolian medicinal materials standards by clarifying the original plant and species collation of Mongolia medicine of "saradma". Mongolian herbal medicine, as an important part of Mongolian medicine, is needed to study the authentic Mongolian medicine, in order to exert the best therapeutic effect in the application. The Mongolian medicine of "saradma" is a kind of medicinal material for diuresis, reinforcing kidney, and eliminating edema, for which comes from the roots, stems, leaves, flowers, fruits, seeds and other parts of medicinal plant. The ancient books of Mongolian medicine are the most important reference the research of Mongolian medicine varieties. This review adopts the method of inductive comparison of ancient books in order to summarize the conclusion of Mongolian medicine of "saradma". According to the investigations, Mongolian medicine of "saradma" type is mainly Leguminosae plant, Oxytropis latibracteata, Hedysarum multijugum, Thermopsis barbata, Astragalus membranaceus, Vicia amoena, O. caerulea, Astragalus bhotanensis, Hedysarum sikkimense. Compared with modern works, it is found that the drug has a wide range of resources distribution and application. It can be used for the treatment of cold edema, hot edema, nephrogenic edema, edema, swelling and likes caused by different diseases. Based on the research of Mongolian medicine of "saradma" varieties, it was found that the most commonly used varieties in Inner Mongolia were cayan saradma, xara saradam and sira saradma all of which are all top-grade drugs that reduce swelling.

[Study on traditional processing method of Mongolian medicine and excipient usage based on data mining].

This paper explores Mongolian medicine processing methods and the use regularity of excipient by text mining techniques. Relevant books of Mongolian medicine processing were consulted to collect data on Mongolian medicine processing methods and excipient, and select data based on processing methods and excipient noun frequency statistics. Microsoft Excel 2010 software was used for statistical analysis and mining for the usage regularity of different types of Mongolian medicinal materials in different periods. And Cytoscape 3.6.1 software was used for visual presentation. The topological analysis showed the top five processing methods were net production, development, frying, calcining and cooking, and the top five processing excipient were fresh milk, wine, urine, cream and mineral borax. Frequency analysis showed that the plant medicinal materials were mostly recorded in the 18~(th) and 21~(st) centuries, especially in the 21 st century; the processing methods mostly contained water processing, repair processing and other methods. The mineral medicinal materials were mostly recorded in the 18~(th), 19~(th) and 21~(st) centuries; most of the processing methods were the fire processing method. The animal medicinal materials were recorded in the 18~(th), 19~(th) and 21~(st) century; the fire processing method occupied a major position, and the repair processing and the grinding processing were markedly increased in the 21~(st) century. In the use of excipient, liquid excipient were mostly used in plant medicines. Solid excipient were most commonly used in the 18~(th) century. Animal excipient were mostly used during the processing in the 18~(th) century. The use of liquid excipient gradually increased in the 19~(th) and 21~(st) centuries. This study summarizes the traditional processing methods of Mongolian medicine and the usage regularity of excipient, defines the characteristics of Mongolian medicine processing methods and excipient, and the characteristics of the combination of medicinal materials and excipient, so as to provide reference for the clinical use of Mongolian medicine.

The Pharmacological Effects and Health Benefits of Platycodon grandiflorus-A Medicine Food Homology Species.

Platycodon grandiflorus is a widely used edible, traditional Chinese medicinal herb. It is rich in saponins, flavonoids, phenolic acids, and other compounds. It contains a large number of fatty acids such as linoleic acid (up to 63.24%), a variety of amino acids, vitamins, and multiple essential trace elements. P. grandiflorus has several biological applications, such as in hypotension, lipid reduction, atherosclerosis, inflammation, relieving cough and phlegm, promoting cholic acid secretion, and as an antioxidant. Further, P. grandiflorus is often used in the development of cold mixed vegetables, canned vegetables, preserved fruit, salted vegetables, and cosmetics in northeast China, South Korea, Japan, and Korea. In this paper, the active chemical components and the health benefits of P. grandiflorus have been reviewed, providing new ideas for the further development of nutraceutical products to prevent and manage chronic diseases.

Study on traditional processing method of Mongolian medicine and excipient usage based on data mining / 中国中药杂志

This paper explores Mongolian medicine processing methods and the use regularity of excipient by text mining techniques. Relevant books of Mongolian medicine processing were consulted to collect data on Mongolian medicine processing methods and excipient, and select data based on processing methods and excipient noun frequency statistics. Microsoft Excel 2010 software was used for statistical analysis and mining for the usage regularity of different types of Mongolian medicinal materials in different periods. And Cytoscape 3.6.1 software was used for visual presentation. The topological analysis showed the top five processing methods were net production, development, frying, calcining and cooking, and the top five processing excipient were fresh milk, wine, urine, cream and mineral borax. Frequency analysis showed that the plant medicinal materials were mostly recorded in the 18~(th) and 21~(st) centuries, especially in the 21 st century; the processing methods mostly contained water processing, repair processing and other methods. The mineral medicinal materials were mostly recorded in the 18~(th), 19~(th) and 21~(st) centuries; most of the processing methods were the fire processing method. The animal medicinal materials were recorded in the 18~(th), 19~(th) and 21~(st) century; the fire processing method occupied a major position, and the repair processing and the grinding processing were markedly increased in the 21~(st) century. In the use of excipient, liquid excipient were mostly used in plant medicines. Solid excipient were most commonly used in the 18~(th) century. Animal excipient were mostly used during the processing in the 18~(th) century. The use of liquid excipient gradually increased in the 19~(th) and 21~(st) centuries. This study summarizes the traditional processing methods of Mongolian medicine and the usage regularity of excipient, defines the characteristics of Mongolian medicine processing methods and excipient, and the characteristics of the combination of medicinal materials and excipient, so as to provide reference for the clinical use of Mongolian medicine.

Variety textual research of Mongolian medicine of "saradma" / 中国中药杂志

Mongolian medicine is an indispensable part in developing traditional Mongolian medicine. This study is aimed to provide a basis for the formulation of clinical and Mongolian medicinal materials standards by clarifying the original plant and species collation of Mongolia medicine of "saradma". Mongolian herbal medicine, as an important part of Mongolian medicine, is needed to study the authentic Mongolian medicine, in order to exert the best therapeutic effect in the application. The Mongolian medicine of "saradma" is a kind of medicinal material for diuresis, reinforcing kidney, and eliminating edema, for which comes from the roots, stems, leaves, flowers, fruits, seeds and other parts of medicinal plant. The ancient books of Mongolian medicine are the most important reference the research of Mongolian medicine varieties. This review adopts the method of inductive comparison of ancient books in order to summarize the conclusion of Mongolian medicine of "saradma". According to the investigations, Mongolian medicine of "saradma" type is mainly Leguminosae plant, Oxytropis latibracteata, Hedysarum multijugum, Thermopsis barbata, Astragalus membranaceus, Vicia amoena, O. caerulea, Astragalus bhotanensis, Hedysarum sikkimense. Compared with modern works, it is found that the drug has a wide range of resources distribution and application. It can be used for the treatment of cold edema, hot edema, nephrogenic edema, edema, swelling and likes caused by different diseases. Based on the research of Mongolian medicine of "saradma" varieties, it was found that the most commonly used varieties in Inner Mongolia were cayan saradma, xara saradam and sira saradma all of which are all top-grade drugs that reduce swelling.

Effectiveness of Integrative Medicine Therapy on Coronary Artery Disease Prognosis: A Real-World Study.

OBJECTIVE: To evaluate the effectiveness of integrative medicine (IM) on patients with coronary artery disease (CAD) and investigate the prognostic factors of CAD in a real-world setting. METHODS: A total of 1,087 hospitalized patients with CAD from four hospitals in Beijing, China were consecutively selected between August 2011 and February 2012. The patients were assigned to two groups based on the treatment: Chinese medicine (CM) plus conventional treatment, i.e., IM therapy (IM group); or conventional treatment alone (CT group). The endpoint was major adverse cardiac events [MACE; including cardiac death, myocardial infarction (MI), and revascularization]. RESULTS: A total of 1,040 patients finished the 2-year follow-up. Of them, 49.4% (514/1,040) received IM therapy. During the 2-year follow-up, the total incidence of MACE was 11.3%. Most of the events involved revascularization (9.3%). Cardiac death/MI occurred in 3.0% of cases. For revascularization, logistic stepwise regression analysis revealed that age ⩾ 65 years [odds ratio (OR), 2.224], MI (OR, 2.561), diabetes mellitus (OR, 1.650), multi-vessel lesions (OR, 2.554), baseline high sensitivity C-reactive protein level ⩾ 3 mg/L (OR, 1.678), and moderate or severe anxiety/depression (OR, 1.849) were negative predictors (P<0.05); while anti-platelet agents (OR, 0.422), ß-blockers (OR, 0.626), statins (OR, 0.318), and IM therapy (OR, 0.583) were protective predictors (P<0.05). For cardiac death/MI, age ⩾ 65 years (OR, 6.389) and heart failure (OR, 7.969) were negative predictors (P<0.05), while statin use (OR, 0.323) was a protective predictor (P<0.05) and IM therapy showed a beneficial tendency (OR, 0.587), although the difference was not statistically significant (P=0.218). CONCLUSION: In a real-world setting, for patients with CAD, IM therapy was associated with a decreased incidence of revascularization and showed a potential benefit in reducing the incidence of cardiac death or MI.

Effectiveness of Integrative Medicine Therapy on Coronary Artery Disease Prognosis: A Real-World Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the effectiveness of integrative medicine (IM) on patients with coronary artery disease (CAD) and investigate the prognostic factors of CAD in a real-world setting.@*METHODS@#A total of 1,087 hospitalized patients with CAD from four hospitals in Beijing, China were consecutively selected between August 2011 and February 2012. The patients were assigned to two groups based on the treatment: Chinese medicine (CM) plus conventional treatment, i.e., IM therapy (IM group); or conventional treatment alone (CT group). The endpoint was major adverse cardiac events [MACE; including cardiac death, myocardial infarction (MI), and revascularization].@*RESULTS@#A total of 1,040 patients finished the 2-year follow-up. Of them, 49.4% (514/1,040) received IM therapy. During the 2-year follow-up, the total incidence of MACE was 11.3%. Most of the events involved revascularization (9.3%). Cardiac death/MI occurred in 3.0% of cases. For revascularization, logistic stepwise regression analysis revealed that age ⩾ 65 years [odds ratio (OR), 2.224], MI (OR, 2.561), diabetes mellitus (OR, 1.650), multi-vessel lesions (OR, 2.554), baseline high sensitivity C-reactive protein level ⩾ 3 mg/L (OR, 1.678), and moderate or severe anxiety/depression (OR, 1.849) were negative predictors (P<0.05); while anti-platelet agents (OR, 0.422), β-blockers (OR, 0.626), statins (OR, 0.318), and IM therapy (OR, 0.583) were protective predictors (P<0.05). For cardiac death/MI, age ⩾ 65 years (OR, 6.389) and heart failure (OR, 7.969) were negative predictors (P<0.05), while statin use (OR, 0.323) was a protective predictor (P<0.05) and IM therapy showed a beneficial tendency (OR, 0.587), although the difference was not statistically significant (P=0.218).@*CONCLUSION@#In a real-world setting, for patients with CAD, IM therapy was associated with a decreased incidence of revascularization and showed a potential benefit in reducing the incidence of cardiac death or MI.

Structure-based Inhibitor Design for the Intrinsically Disordered Protein c-Myc.

Intrinsically disordered proteins (IDPs) are associated with various diseases and have been proposed as promising drug targets. However, conventional structure-based approaches cannot be applied directly to IDPs, due to their lack of ordered structures. Here, we describe a novel computational approach to virtually screen for compounds that can simultaneously bind to different IDP conformations. The test system used c-Myc, an oncoprotein containing a disordered basic helix-loop-helix-leucine zipper (bHLH-LZ) domain that adopts a helical conformation upon binding to Myc-associated factor X (Max). For the virtual screen, we used three binding pockets in representative conformations of c-Myc370-409, which is part of the disordered bHLH-LZ domain. Seven compounds were found to directly bind c-Myc370-409 in vitro, and four inhibited the growth of the c-Myc-overexpressing cells by affecting cell cycle progression. Our approach of IDP conformation sampling, binding site identification, and virtual screening for compounds that can bind to multiple conformations provides a useful strategy for structure-based drug discovery targeting IDPs.

[Effect and mechanism of recombinant hirudin on atherosclerotic plaques in apolipoprotein E knockout (ApoE(-/-)) mice].

OBJECTIVE: To explore the effect and mechanism of hirudin on atherosclerotic plaques in apolipoprotein E knockout (ApoE(-/-)) mice. METHODS: Totally 24 ApoE(-/-) mice, 7-8 weeks old were fed with high fat diets. They were randomly divided into the recombinant hirudin treatment group (drug group) and the model group according to body weight and different dens, 12 in each group. Twelve C57BL/6J mice, 7-8 weeks old fed with high fat diet were recruited as the normal control group. Recombinant hirudin (0.25 mg/kg) was intraperitoneally injected to mice in the drug group from the 10th week old once every other day for five successive weeks. Equal volume of normal saline was injected to mice in the model group. Mice in the normal control group received no treatment. All mice were sacrificed after fed with high fat diet until they were 20 weeks old. Serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), high-sensitive C-reactive protein (hs-CRP), E-selectin, interleukin-6 (IL-6), and stromal metalloproteinase-2 (MMP-2) were detected. The plaque/lumen area and extracellular lipid composition/ plaque area were analyzed by HE staining and morphometry. Changes of signaling molecules in store-operated calcium channels, including stromal interacting molecule 1 (STIM1), Orail protein, and transient receptor potential channel 1 (TRPC1) were determined by Western blot. Results Lipid plaque formed in the aorta vessel wall of 20-week old mice in the model group. Compared with the normal control group, serum levels of TC, TG and LDL increased (P<0.01), hs-CRP, E-selction, IL-6, and MMP-2 obviously increased (P<0.01, P<0.05) in the model group; expression levels of STIM1, TRPC1, and Orail significantly increased (P<0.01). Compared with the model group, the plaque/lumen area and the extracellular lipid composition/plaque area significantly decreased in the drug group (P<0.05, P<0.01); serum levels of TC and LDL, hs-CRP, E-selction, IL-6, and MMP-2 obviously decreased (P<0.05, P<0.01); expression levels of STIM1, TRPC1, and Orail were significantly down-regulated (P<0.05, P<0.01). CONCLUSION: Hirudin could significantly improve lipids and endothelial functions of ApoE(-/-) mice, down-regulate expression levels of STIM1, Orai1, and TRPC1, and thus delaying the occurrence and development of atherosclerosis.

Effect and mechanism of recombinant hirudin on atherosclerotic plaques in apolipoprotein E knockout (ApoE(-/-)) mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect and mechanism of hirudin on atherosclerotic plaques in apolipoprotein E knockout (ApoE(-/-)) mice.</p><p><b>METHODS</b>Totally 24 ApoE(-/-) mice, 7-8 weeks old were fed with high fat diets. They were randomly divided into the recombinant hirudin treatment group (drug group) and the model group according to body weight and different dens, 12 in each group. Twelve C57BL/6J mice, 7-8 weeks old fed with high fat diet were recruited as the normal control group. Recombinant hirudin (0.25 mg/kg) was intraperitoneally injected to mice in the drug group from the 10th week old once every other day for five successive weeks. Equal volume of normal saline was injected to mice in the model group. Mice in the normal control group received no treatment. All mice were sacrificed after fed with high fat diet until they were 20 weeks old. Serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), high-sensitive C-reactive protein (hs-CRP), E-selectin, interleukin-6 (IL-6), and stromal metalloproteinase-2 (MMP-2) were detected. The plaque/lumen area and extracellular lipid composition/ plaque area were analyzed by HE staining and morphometry. Changes of signaling molecules in store-operated calcium channels, including stromal interacting molecule 1 (STIM1), Orail protein, and transient receptor potential channel 1 (TRPC1) were determined by Western blot. Results Lipid plaque formed in the aorta vessel wall of 20-week old mice in the model group. Compared with the normal control group, serum levels of TC, TG and LDL increased (P<0.01), hs-CRP, E-selction, IL-6, and MMP-2 obviously increased (P<0.01, P<0.05) in the model group; expression levels of STIM1, TRPC1, and Orail significantly increased (P<0.01). Compared with the model group, the plaque/lumen area and the extracellular lipid composition/plaque area significantly decreased in the drug group (P<0.05, P<0.01); serum levels of TC and LDL, hs-CRP, E-selction, IL-6, and MMP-2 obviously decreased (P<0.05, P<0.01); expression levels of STIM1, TRPC1, and Orail were significantly down-regulated (P<0.05, P<0.01).</p><p><b>CONCLUSION</b>Hirudin could significantly improve lipids and endothelial functions of ApoE(-/-) mice, down-regulate expression levels of STIM1, Orai1, and TRPC1, and thus delaying the occurrence and development of atherosclerosis.</p>

Effects of acupuncture at ST36 (Zusanli) on attention networks in healthy subjects / 中华行为医学与脑科学杂志

Objective To investigate the effects of acupuncture at bilateral ST36 (Zusanli) on attention networks in healthy subjects.Methods The attention network test was used to compare the effects of after acupuncture at ST36 with the effects of before acupuncture on the efficiency of three anatomically defined attention networks:alerting,orienting,and executive control in 40 health university students.Results The alerting network effect was significantly higher (t=4.125,P＜0.001) after acupuncture ((45.60±3.49) ms) than before acupuncture ((33.20±2.88) ms).The executive control network efficiency was significantly higher (t=2.638,P＜0.05) after acupuncture ((87.97±4.21) ms) than before acupuncture ((97.67±4.66) ms).The orienting network efficiency was higher after acupuncture than before acupuncture,but there was no significant difference (P＞0.05).The average reaction time was significantly lower (t=4.848,P＜0.001) after acupuncture ((559.13 ± 10.66) ms) than before acupuncture ((590.57±12.80) ms).Conclusions These results suggest that there are selective enhancements of the alerting and executive control networks after acupuncture,while the orienting network is spared.

Treatment of Postherpetic Neuralgia by Surround Needling with Electric Stimulation / 针灸推拿医学（英文版）

Twenty-nine cases of postherpetic neuralgia of herpes zoster were treated by the surround needling with electric stimulation, and the better therapeutic effect was obtained, the total effective rate was 93.1%.

Clinical research of qingkailing soft capsules in treating acute upper respiratory infection / 中国中药杂志

<p><b>OBJECTIVE</b>To discuss the efficacy of Qingkailing soft capsules in treating acute fever, and the relationship between symptoms-effect and time effect.</p><p><b>METHOD</b>Qingkailing soft capsules was taken orally, 4 times a day, 1.6 g each time. Shuanghuanglian kou fu liquid was taken as control. 129 patients with acute upper respiratory tract infection were recruited.</p><p><b>RESULT</b>There were 73.34% of patients cured by Qingkailing soft capsules and 43.59% cured by Shuanghuanglian kou fu liquid. The efficacy of the former was better than that of the latter (P < 0.05). The efficacy of Qingkailing soft capsules in treating Fengrexing was better than that in Fenghanxing (P < 0.05). The efficacy of Qingkailing soft capsules in reducing rapid pulse and adding moderate pulse was more remarkable than Shuanghuanglian kou fu liquid (P < 0.05). Taking Qingkailing soft capsules seldom induced mild gastrointestinal disturbance.</p><p><b>CONCLUSION</b>Qingkailing soft capsules showed good result in the treatment of acute upper respiratory tract infection with less adverse effect.</p>