Quantitative predictive model for screening optimal processing methods of Polygonati rhizoma.

Polygonati rhizoma (Huangjing in Chinese) is a common clinical tonic with the traditional effects of tonifying Qi, nourishing Yin. However, the lack of precise control of processing parameters has led to the uneven quality of processed Huangjing. A prediction model using the CRITIC method optimizes processing by correlating method, component contents, and biological activity, ensuring consistent quality and efficacy.

Layperson assessment of smile lines and upper lip combined images in smile esthetics.

STATEMENT OF PROBLEM: The esthetic assessment of smile lines by laypersons is a subject of ongoing debate. However, smile lines often appear with different types of upper lip curvature, which further complicates the esthetic assessment process, and studies on this combination are lacking. PURPOSE: The purpose of this clinical study was to investigate a layperson's esthetic perception of smile lines and upper lip combined images. MATERIAL AND METHODS: Twenty-six smile images resulting from combinations of 3 upper lip types, 4 anterior smile line types, and 3 posterior smile line types were generated by an image editing software program. Eighty-three laypersons (39 men and 44 women; 18 to 35 years of age) completed rating images using a visual analog scale. Unattractive smiles were designated to be those with scores <50 and attractive ones with scores ≥50. Data were analyzed using 1-way analysis of variance and Bonferroni post hoc tests (α=.05). RESULTS: High anterior smile line with gingival display >4 mm obtained significantly lower scores of <50 when combined with all upper lip curvatures (upward: 28.29 ±22.79, straight: 38.74 ±23.00, downward: 30.67 ±22.25, P<.01). High anterior smile lines with gingival display ≤4 mm combined with upward and straight upper lip curvature images obtained significantly higher scores, and all were ≥50 (upward: 63.24 ±22.22, straight: 61.40 ±21.58, P<.01). CONCLUSIONS: From a layperson's perspective, high anterior smile lines with gingival display >4 mm combined with any lip type were determined to be unattractive. If gingival display was ≤4 mm combined with both upward and straight lip types, the smile was assessed as attractive.

A novel recombinant human microplasminogen induced complete posterior vitreous detachment without morphological change of retina in juvenile rabbits.

Vitreomacular traction syndrome results from persistent vitreoretinal adhesions in the setting of partial posterior vitreous detachment (PVD). Vitrectomy and reattachment of retina is an effective therapeutic approach. The adhesion between vitreous cortex and internal limiting membrane (ILM) of the retina is stronger in youth, which brings difficulties to induce PVD in vitrectomy. Several clinical investigations demonstrated that intravitreous injection of plasmin before vitrectomy could reduce the risk of detachment. In our study, a novel recombinant human microplasminogen (rhµPlg) was expressed by Pichia pastoris. Molecular docking showed that the binding of rhµPlg with tissue plasminogen activator (t-PA) was similar to plasminogen, suggesting rh µPlg could be activated by t-PA to generate microplasmin (µPlm). Moreover, rhµPlg had higher catalytic activity than plasminogen in amidolytic assays. Complete PVD was found at vitreous posterior pole of 125 µg rhµPlg-treated eyes without morphological change of retina in juvenile rabbits via intraocular injection. Our results demonstrate that rhµPlg has a potential value in the treatment of vitreoretinopathy.

[Research status and strategy of quality control of medicinal and edible food].

As China is implementing "Healthy China" strategy, medicinal and edible food has attracted unprecedented attention due to the dual attributes of food and medicine. However, there is a lack of the quality control standard and the existing quality control research cannot fully reflect the dual attributes of medicinal and edible food, which consequently restrict the development of medicinal and edible food industry. This study reviewed the research status and proposed the strategy of quality control in line with the dual attribu-tes of medicinal and edible food, and clarified the research contents of quality control of medicinal and edible food of different types to provide references for the follow-up quality control of medicinal and edible food.

[Anti-osteoarthritis components and mechanism of Fufang Duzhong Jiangu Granules].

Osteoarthritis is a common disease characterized by degenerative lesions of articular cartilage in the elderly.Fufang Duzhong Jiangu Granulues(FDJG), a classical prescription for the treatment of osteoarthritis, has the effects of nourishing liver and kidney, nourishing blood and sinew, and dredging collaterals and relieving pain.In this study, molecular simulation technology was combined with molecular biology methods to explore and verify the potential pharmacodynamic substances and molecular mechanism of FDJG in the treatment of osteoarthritis.Arachidonic acid(AA) metabolic pathway is a typical anti-inflammatory pathway, and secretory phospholipase A2 group ⅡA(sPLA2-ⅡA), 5-lipoxygenase(5-LOX), cyclooxygenase-2(COX-2), and leukotriene A4 hydrolase(LTA4 H) are the key targets of the pathway.Therefore, in this study, based on the pharmacophores and molecular docking models of the four key targets in AA pathway, a total of 1 522 chemical components in 12 medicinals of FDJG were virtually screened, followed by weighted analysis of the screening results in combination with the proportions of the medicinals in the prescription.The results showed that mainly 73 components in the preparation could act on the above four targets, suggesting they might be the potential anti-osteoarthritis components of FDJG.Considering the predicted effectiveness, availability, and compatibility of the medicinals, coniferyl ferulate, olivil, and baicalin were selected for further verification.Specifically, lipopolysaccharide(LPS)-induced RAW264.7 inflammatory cell model was used to verify the anti-inflammatory activity of the three components.The results showed that the three can effectively inhibit the release of NO, supporting the above selection.In addition, targets 5-LOX, COX-2, and LTA4 H had high activity, which suggested that they may be the key anti-osteoarthritis targets of FDJG.The comprehensive activity values of Eucommiae Cortex, Achyranthis Bidentatae Radix, Ginseng Radix et Rhizoma, Lycii Fructus, and Astragali Radix were much higher than that of other medicinals in the prescription, indicating that they may be the main effective medicinals in FDJG acting on the AA pathway.In this study, the potential anti-osteoarthritis components of FDJG were obtained.Moreover, it was clarified that the anti-osteoarthritis mechanism of FDJG was to act on LOX and COX pathway in AA metabolic pathway, which provided a reference for the study of pharmacodynamic substances and molecular mechanism of FDJG.

[Study on mechanism of Rehmanniae Radix Praeparata for treatment of osteoarthritis based on network pharmacology and molecular docking].

The mechanism of Rehmanniae Radix Praeparata against osteoarthritis was investigated based on network pharmacology, molecular docking, and in vitro experiments in the present study. Osteoclast models were established via receptor activator of nuclear factor-κB ligand(RANKL) and macrophage colony-stimulating factor(M-CSF) inducing RAW264.7 cells. Further, the influence of Rehmanniae Radix Praeparata on the activity of tartrate-resistant acid phosphatase(TRAP) was evaluated and the efficacy of Rehmanniae Radix Praeparata in the treatment of osteoarthritis was verified. The active components of Rehmanniae Radix Praeparata were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and literature, and the potential targets of the components were collected from SwissTargetPrediction. Osteoarthritis disease targets were searched in Online Mendelian Inheritance in Man(OMIM), Therapeutic Target Database(TTD), GeneCards, and DisGeNET. The intersection targets of Rehmanniae Radix Praeparata and osteoarthritis were obtained by Venny platform. The protein-protein interaction(PPI) network was constructed by Cytoscape 3.8.2, and key targets were obtained based on topology algorithm. The Database for Annotation, Visualization and Integrated Discovery(DAVID) was used to perform Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Finally, the mRNA expression of the key targets was determined by RT-qPCR and the binding activity between the components and key targets was validated by molecular docking. The results showed that Rehmanniae Radix Prae-parata inhibited the TRAP activity, thus inhibiting bone resorption by osteoclasts and treating osteoarthritis. By network pharmacology, 14 active components of Rehmanniae Radix Praeparata and 126 intersection targets were obtained. The network pharmacology enrichment results revealed 432 biological processes and 139 signaling pathways. Key targets such as proto-oncogene tyrosine-protein kinase Src(SRC), signal transducer and activator of transcription 3(STAT3) and transcription factor p65(RELA) were obtained according to the degree in topological analysis. SRC was highly expressed in osteoclasts, which accelerated the development of osteoarthritis. Therefore, SRC was selected for subsequent verification, and Rehmanniae Radix Praeparata decreased the gene expression level of SRC. The molecular docking showed that acteoside, isoacteoside, raffinose had good bonding activity with SRC, suggesting that they might be the critical components in treating osteoarthritis. In conclusion, Rehmanniae Radix Praeparata can inhibit bone resorption by osteoclasts and balance the metabolism of articular cartilage and subchondral bone via acting on SRC, thus playing a therapeutic role in osteoarthritis. In addition, Rehmanniae Radix Praeparata may exert overall efficacy on osteoarthritis through other targets such as STAT3 and RELA, and other related pathways such as PI3 K-AKT and IL-17 signaling pathways.

[Study on discovery of efficacy markers for Dachaihu Decoction and its action mechanism].

Dachaihu Decoction is a classical Chinese herbal prescription that is effective in harmonizing lesser yang and purging internal accumulated heat. At present, it has been widely used in clinical practice, and the resulting outcomes are satisfactory. However, its quality indicators and action mechanism are still not clear. Therefore, this paper explored the efficacy markers of Dachaihu Decoction and its action mechanism based on literature mining, molecular biology, and network pharmacology, so as to better control its quality and ensure its clinical efficacy. The efficacy markers of Dachaihu Decoction were predicted and analyzed according to the "five principles" for Q-markers of Chinese herbs. Then the anti-inflammatory activity of the efficacy markers of Dachaihu Decoction was evaluated with Griess reagent after the establishment of RAW264.7 cell inflammation model in vitro with lipopolysaccharide(LPS). The potential targets of efficacy markers were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), ChEMBL, and SwissTargetPrediction, followed by the construction of the protein-protein interaction(PPI) network of the efficacy markers of Dachaihu Decoction. Topological, GO, and KEGG enrichment analysis was carried out to construct the "key target-signaling pathway-biological process" network, thus elucidating the action mechanism of the efficacy markers of Dachaihu Decoction. Saikosaponin B_2, baicalin, baicalein, wogonoside, neohesperidin, naringin, hesperidin, and paeoniflorin were considered as the potential efficacy markers of Dachaihu Decoction. The anti-inflammatory activity evaluation showed that the potential efficacy markers effectively inhibited the release of NO, exhibiting good anti-inflammatory activities. As demonstrated by network pharmacology, the efficacy markers of Dachaihu Decoction regulated the inflammatory response by acting on MAPK and NF-κB signaling pathways, the carbohydrate metabolism by HIF-1 and PI3 K-AKT signaling pathways, and the lipid metabolism by AMPK and PI3 K-AKT signaling pathways. This study discovered the efficacy markers of Dachaihu Decoction based on literature mining combined with molecular biological experiments and explored its action mechanism at the molecular level based on network pharmacology, which would provide reference for the quality control of Dachaihu Decoction and scientific basis for its clinical application.

[Identification of active components in Xuefu Zhuyu Decoction based on targets of blood-activating function].

As a classic prescription for promoting blood circulation to remove blood stasis, Xuefu Zhuyu Decoction(XFZYD) is widely used in clinical practice and has notable curative effect. Based on the key targets of activating blood circulation, this study identified the active components of XFZYD to reveal the material basis. The components of XFZYD were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The molecular docking models were built for the blood-activating targets obtained from the previous study with the components of XFZYD. The top five active components with measurability for each target were selected as the potential blood-activating components in the prescription. The efficacy of the prescription can embody key pharmacological and high-content components. In this study, anti-platelet aggregation activity was used to characterize the effect of activating blood, and the in vivo experiments were conducted to verify the accuracy of the active components. A total of 210 chemical components of XFZYD were screened out from TCMSP and docked with the key targets with the function of activating blood. Ligustrazine, acteoside, naringin, etc. were selected as the potential active components for activating blood in XFZYD. The anti-platelet aggregation activity of the combination of Chuanxiong Rhizoma, Rehmanniae Radix, Aurantii Fructus, Glycyrrhizae Radix et Rhizoma, and Carthami Flos was 9.82%±5.11%. Compared with that in the control group, the platelet aggregation induced by adenosine diphosphate(ADP) was significantly inhibited in the test group(P<0.01), which verified the accuracy of the active components. This study can guide the research on the material basis of XFZYD and provide insights into the development and utilization of the classical prescription.

[Analysis on targets of regulating Qi and activating blood based on activity spectrum of targets].

The traditional Chinese medicines(TCM) for activating blood circulation and the TCM for regulating Qi are often used in combination in clinical practice. However, their mechanisms are still unclear. The activity spectrum of targets can fuse the active components, targets and intensity of action, which provides support for the discussion of efficacy targets. The chemical components of common TCM sets for activating blood circulation and regulating Qi, as well as the negative sets not for activating blood circulation and re-gulating Qi were obtained from the database of TCM. By the similarity analysis of chemical components in TCM for activating blood circulation and DrugBank database, the predicted targets of chemical components in TCM for activating blood circulation were obtained, and the similarity value of the two was taken as the activity value of the active components and predicted targets. Then, the component-target activity value was weighted. The activity values of herb acting on the same target were fused to construct activity spectra of targets of the herbs for activating blood circulation, herbs for regulating Qi and negative herbs. The targets whose activity values of activating blood circulation and regulating Qi were higher than those of negative herbs were selected as potential targets of efficacy. Protein-protein interaction networks were constructed for topological, GO and KEGG enrichment analysis to determine the key targets of efficacy of activating blood circulation and regulating Qi. The component-target activity information collected from DrugBank database contained 4 499 compounds, 627 targets and 11 295 action relationships. The activating blood function protein-protein interaction network contained 206 nodes and 1 728 edges, while the regulating Qi function protein-protein interaction network contained 230 nodes and 986 edges. The enrichment analysis of topology, GO and KEGG showed that TCM for activating blood circulation mainly exerted its anti-inflammatory, neuroprotective and angiogenic effects on signaling cascade pathway mediated by VEGF/VEGFR2, ERK signaling pathway, calcium signaling pathway and PI3 K-AKT signaling pathway, and the key targets included mitogen activated protein kinases 3(MAPK3), proto-oncogene tyrosine-protein kinase Src(SRC), mitogen activated protein kinases 1(MAPK1), epidermal growth factor receptor(EGFR), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform(PIK3 CA), peroxisome proliferators-activated receptor gamma(PPARG), nitric oxide synthase 3(NOS3), prostaglandin G/H synthetase 2(PTGS2), matrix metalloproteinase-9(MMP9), and vascular endothelial growth factor A(VEGFA). TCM for regulating Qi mainly exerted anti-inflammatory and neuroprotective effects by acting on MAPK signaling pathway and PI3 K-AKT signaling pathway, and the key targets included mitogen activated protein kinases 8(MAPK8), SRC, mitogen activated protein kinases 14(MAPK14), and RAC-alpha serine/threonine-protein kinase(AKT1), mitogen activated protein kinases 3(MAPK3). Based on the activity spectrum of targets, the targets of the TCM for activating blood and the targets of the TCM for regulating Qi were analyzed to provide reference for the study of efficacy targets of TCM, and also provide some scientific basis for clinical application.

[Potential therapeutic effect of Saussureae Involucratae Herba on breast cancer and its mechanism based on network pharmacology].

As one of the most commonly diagnosed cancers in the world, female breast cancer is induced by the high level of estrogen. Saussureae Involucratae Herba(SIH), a gynecological medicinal, regulates estrogen-induced diseases. However, the therapeutic effect of SIH on breast cancer has not been reported. Therefore, this study aims to explore the potential efficacy of SIH on breast cancer based on in vitro experiment and network pharmacology. The inhibitory effect of SIH water extract on proliferation and migration of breast cancer MDA-MB-231 cells was examined. The result demonstrated SIH water extract significantly suppressed the proliferation of breast cancer cells(IC_(50)=6.47 mg·mL~(-1)) and also restricted the migration. A total of 39 components of SIH were retrieved from traditional Chinese medicine database(TCMD) and 160 targets of SIH were screened by target fishing with the PharmaDB database. The Online Mendelian Inheritance in Man(OMIM) was used to establish a 1 001-targets data set of breast cancer. Based on the overlaps(45) of targets between SIH and breast cancer, a protein-protein interaction(PPI) network was built to analyze the interactions among these targets with STRING platform and Cytoscape. Finally, through topology and GO and KEGG analysis, 8 targets, 101 pathways and 85 biological processes were found to involve the treatment of breast cancer by SIH. SIH may exert the anti-breast cancer effect by regulating cell cycle, inhibiting proliferation, migration and adhesion of cancer cells, and modulating estrogen receptor. This study clarified the mechanism of SIH in treating breast cancer, which lays a foundation for the further development of SIH.

[Material manufacturability classification in high shear wet granulation process of Chinese medicine].

The high shear wet granulation(HSWG) process of Chinese medicine has a complicated mechanism. There are many influencing factors that contribute to this process. In order to summarize the manufacturability of different kinds of materials in HSWG, this paper constructed a material library composed of 11 materials, including 4 Chinese medicine extracts and 7 pharmaceutical excipients. Each material was described by 22 physical parameters. Several binders were employed, and their density, viscosity and surface tension were characterized. Combining empirical constraints and the principle of randomization, 21 designed experiments and 8 verification experiments were arranged. The partial least squares(PLS) algorithm was used to establish a process model in prediction of the median granule size based on properties of raw materials and binders, and process parameters. The surface tension and density of binders, as well as the maximum pore saturation were identified as key variables. In the latent variable space of the HSWG process model, all materials could be divided into three categories, namely the Chinese medicine extracts, the diluents and the disintegrants. The granulation of Chinese medicine extracts required low viscosity and low amount of binder, and the resulted granule sizes were small. The diluent powders occupied a large physical space, and could be made into granules with different granule sizes by adjusting the properties of binders. The disintegrants tended to be made into large granules under the condition of aqueous binder. The combination use of material database and multivariate modeling method is conducive to innovate the knowledge discovery of the wet granulation process of Chinese medicine, and provides a basis for the formulation and process design based on material attributes.

[Mechanism of Wuwei Ganlu in treatment of knee osteoarthritis:a study based on network pharmacology and molecular docking].

Wuwei Ganlu, a formula for medicated bath, consists of medicinal materials of Ephedra sinica, Platycladus orientalis, Myricaria squamosa, Artemisia carvifolia, and Rhododendron anthopogonoides, which is effective in inducing perspiration, resisting inflammation, relieving pain, regulating yellow water disease, and activating blood circulation. On this basis, a variety of formulas for Tibetan medicated bath have been derived for the treatment of diseases in internal organs, joints, nerves, etc. Modern studies have confirmed that Wuwei Ganlu has a good therapeutic efficacy on knee osteoarthritis(KOA). The present study explored the mechanism of Wuwei Ganlu in treating KOA based on network pharmacology and molecular docking. Firstly, the chemical components of Wuwei Ganlu were obtained through literature mining and database retrieval, and corresponding potential targets were predicted according to the BATMAN-TCM database. The protein-protein interaction(PPI) network was obtained after the potential targets were input into the STRING database. The network function modules were analyzed by the Molecular Complex Detection(MCODE) algorithm, and the functions of the modules were annotated to analyze the action mode of Wuwei Ganlu. Secondly, the related targets of KOA were collected through the DisGeNET database, and the overlapping targets were confirmed to analyze the mechanism of Wuwei Ganlu in treating KOA. Finally, the key targets were selected for molecular docking with the main components of Wuwei Ganlu to verify the component-target interaction. A total of 550 chemical components and 1 365 potential targets of Wuwei Ganlu were obtained. PPI analysis indicated that this formula could exert the effects of oxidation-reduction, inflammation resistance, bone absorption, bone mineralization, etc. Nineteen common targets were obtained from the intersection of potential targets of Wuwei Ganlu and KOA disease targets. It was found that the Wuwei Ganlu mainly acts on nuclear factor-κB(NF-κB), interleukin-1 beta(IL1ß), tumor necrosis factor(TNF), IL6, IL1 receptor antagonist(IL1 RN), and prostaglandin-endoperoxide synthase-2(PTGS2) to treat KOA. Among the 550 chemical components of Wuwei Ganlu, 252 potential active components were docked with TNF and 163 with PTGS2, indicating good binding of the components with potential key targets. The study preliminarily explored the mechanism of Wuwei Ganlu in treating KOA to provide a reference for the further development and utilization of Tibetan medicated bath that has been included in the UN Intangible Cultural Heritage.

RGD-hirudin-based low molecular weight peptide prevents blood coagulation via subcutaneous injection.

Thromboembolic disease is a common cardio-cerebral vascular disease that threatens human life and health. Thrombin not only affects the exogenous coagulation pathway, but also the endogenous pathway. Thus, it becomes one of the most important targets of anticoagulant drugs. RGD-hirudin is an anticoagulant drug targeting thrombin, but it can only be administered intravenously. We designed a low molecular weight peptide based on RGD-hirudin that could prevent blood clots. We first used NMR to identify the key amino acid residues of RGD-hirudin that interacted with thrombin. Then, we designed a novel direct thrombin inhibitor peptide (DTIP) based on the structure and function of RGD-hirudin using homology modeling. Molecular docking showed that the targeting and binding of DTIP with thrombin were similar to those of RGD-hirudin, suggesting DTIP interacted directly with thrombin. The active amino acids of DTIP were identified by alanine scanning, and mutants were successfully constructed. In blood clotting time tests in vitro, we found that aPTT, PT, and TT in the rat plasma added with DTIP were greatly prolonged than in that added with the mutants. Subcutaneous injection of DTIP in rats also could significantly prolong the clotting time. Thrombelastography analysis revealed that DTIP significantly delayed blood coagulation. Bio-layer interferometry study showed that there were no significant differences between DTIP and the mutants in thrombin affinity constants, suggesting that it might bind to other sites of thrombin rather than to its active center. Our results demonstrate that DTIP with low molecular weight can prevent thrombosis via subcutaneous injection.

Ultrasonographic evaluation of gastric emptying after ingesting carbohydrate-rich drink in young children: A randomized crossover study.

BACKGROUND: A recent consensus statement in Europe has suggested that the fasting time for clear liquid in children can be shortened to 1 hour before a surgery. However, the study to show that 1-hour fasting time for clear fluids is safe in young children is still lacking. This study aimed to investigate the gastric emptying time for carbohydrate-rich drink and regular 5% glucose solution in children aged 3-7 years. METHODS: After overnight fasting, individuals were randomly assigned to ingest 5 mL kg-1 of either carbohydrate-rich drink or 5% glucose solution. One week later, the same subjects were asked to ingest the other one. Ultrasonography was performed to examine the gastric contents. Gastric antral cross-sectional area was measured, and the gastric fluid volume was calculated before and after fluid ingestion within 120 minutes. The primary outcome was the gastric emptying time for both the clear fluids calculated using the antral cross-sectional area and logarithms of gastric fluid volume. The degrees of thirst and hunger of two drinks were evaluated using a visual analogue scale as the secondary outcomes. RESULTS: Data from 16 individuals were analyzed. In the glucose solution group, the antral cross-sectional area and logarithms of gastric fluid volume returned to baseline at 30 minutes after ingestion. However, in the carbohydrate-rich drink group, the median [interquartile range; range] antral cross-sectional area (3.69 [2.64-5.15; 1.83-8.93] cm2 vs 2.41 [2.10-2.96; 1.81-4.37] cm2 , P < .001) and mean (95% confidence interval) logarithms of gastric fluid volume (2.54 [2.30-2.79] mL vs 2.12 [1.94-2.30] mL, P = .048) were still higher than at 60 minutes and returned to the baseline values at 90 minutes after ingestion, respectively. The degree of thirst was lower in the glucose solution group than that in the carbohydrate-rich drink group. CONCLUSIONS: Gastric emptying of carbohydrate-rich drink is slower than that of 5% glucose solution but the residual gastric fluid volume is low one hour after ingestion of 5 mL kg-1 of either fluid.

[Discovery and application of traditional Chinese medicine efficacy markers based on systematic traditional Chinese medicine].

The quality marker(Q-marker) of traditional Chinese medicine(TCM) is a new concept of TCM quality control proposed in recent years. It is a hot issue in the research of modern Chinese medicine. The TCM efficacy is a high-level summary of the TCM therapeutic effect under the guidance of TCM theory. On this basis, it is of considerable significance to explore the TCM efficacy marker for the TCM modernization. However, the traditional research strategy based on the single herb and decoction piece in macro TCM level, or the drug research strategy based on the biological effect of the targets, is quite different from the characteristics of multiple components of TCM, as well as the weak and low-selective effect of Chinese medicine ingredients on targets. Therefore, how to select representative ingredients to characterize the TCM overall efficacy is a problematic point in establishing TCM efficacy markers. In this paper, the concept and method of Q-marker were introduced into the study of Chinese medicine efficacy. The research method for systematic TCM was used to systematically discuss the connotation of TCM efficacy markers, the principles of discovery and determination, common research ideas and techniques by taking the representative research results as an example. This study provides new ideas for the research and discovery of TCM efficacy markers.

[Study on efficacy markers of Salviae Miltiorrhizae Radix et Rhizoma for promoting blood circulation and remving blood stasis based on systematic traditional Chinese medicine].

Traditional Chinese medicine for promoting blood circulation and removing blood stasis has been widely used in clinical practice. However, due to the diversity of the composition of traditional Chinese medicine and the complexity of its interaction with human body, it is difficult to apply traditional quality control ingredients to characterize its overall efficacy. Systematic traditional Chinese medicine is an effective method for studying the efficacy of traditional Chinese medicine, embodying the dialectical unity of holism and reductionism. Salviae Miltiorrhizae Radix et Rhizoma is a common traditional Chinese medicine for promoting blood circulation and removing blood stasis. In this study, we constructed a multi-dimensional network of "efficacy-pharmacological efficacy-targets-components" based on systematic traditional Chinese medicine, and discussed the discovery of the efficacy markers of Salviae Miltiorrhizae Radix et Rhizoma for promoting blood circulation and removing blood stasis. Firstly, based on the Chinese medicine efficacy-pharmacology database, the most relevant pharmacological actions(boundary) for promoting blood circulation and removing blood stasis(function) were obtained, and the target sets(structure) of the corresponding pharmacological action were obtained by the DrugBank database. Then, STRING database was used to construct protein-protein interaction network(relationship) of targets related to promoting blood circulation and removing stasis, and key targets(elements) in the network were selected by evaluating topological parameters of targets. Finally, the potential efficacy markers of Salviae Miltiorrhizae Radix et Rhizoma were predicted by molecular docking based on the key targets of promoting blood circulation and removing blood stasis. The results demonstrated that salvianolic acid B, salvianolic acid A, tanshinone Ⅱ_A and tanshinone Ⅰ were the potential markers of Salviae Miltiorrhizae Radix et Rhizoma on promoting blood circulation and removing blood stasis. Salvianolic acid B, salvianolic acid A, tanshinone Ⅱ_A had been reported to have anti-platelet aggregation, anti-thrombotic, cardiovascular protection and some other pharmacological functions. Based on systematic traditional Chinese medicine, we have preliminarily predicted the efficacy markers of Salviae Miltiorrhizae Radix et Rhizoma in promoting blood circulation and removing blood stasis in this study, providing a research method for the discovery of efficacy markers and a reference for the overall quality control of traditional Chinese medicine.

[Study on components efficacy of Salviae Miltiorrhizae Radix et Rhizoma based on systematic traditional Chinese medicine].

This paper aimed to establish efficacy systems of tanshinones and salvianolic acids, two representative substances in Salviae Miltiorrhizae Radix et Rhizoma by using literature mining and biological network construction, based on systematic traditional Chinese medicine theory. The systematic study on the efficacy of traditional Chinese medicine was carried out from the basic unit, the structure and relationship between the basic units, the boundary of the research object and the function of the system, so as to explain the overall efficacy of the two kinds of components at the molecular level. Firstly, we collected the elements of the efficacy systems of these two kinds of components by literature mining, and defined their boundaries based on biological processes. After that, the structure of the efficacy systems was clarified according to the relationship in the KEGG database. Finally, the function of the efficacy systems was analyzed from the level of pharmacology, pharmacodynamics, and efficacy, revealing the scientific connotation of traditional Chinese medicine efficacy system. The results showed that there were 201 targets(elements), 12 target sets(boundary), and 12 pathway networks(structure) in salvianolic acids' efficacy system. Meanwhile, there were 189 targets(elements), 11 target sets(boundary), and 11 pathway networks(structure) in tanshinones' efficacy system. The results suggested that the functions of salvia-nolic acids' and tanshinones' efficacy systems were different in pharmacology and pharmacodynamics from aspects of elements, boundary, relationship and structure, but they were same in functional level as both of them could promote blood circulation, remove blood stasis, clear away heart-fire, relieve restlessness, and soothe the nerves. Based on systematic traditional Chinese medicine, we constructed the efficacy system of two representative components in Salviae Miltiorrhizae Radix et Rhizoma in this paper, elucidated the overall efficacy and builded the bridge between reductionism and holism in traditional Chinese medicine.

[Exploration of potential efficacy markers of Astragali Radix for invigorating Qi based on systematic traditional Chinese medicine].

Astragali Radix is the elixir for invigorating Qi, with the effects of invigorating Qi, promoting Yang and nourishing the body. With the deepening researches on the chemical constituents of Astragali Radix, it is used more extensively in clinical application. Based on systematic traditional Chinese medicine theory, in this paper, we characterized the effect of Astragali Radix on invigo-rating Qi from the molecular level, and explored the markers of Astragali Radix on invigorating Qi. Through TCMSP and ChEMBL databases, the active components-targets database of Astragali Radix was constructed to clarify the targets(elements) involved in Astragali Radix's Qi invigorating efficacy system. According to the relationship between the targets, the protein interaction network was constructed, and the network modules(structure) were divided according to the theoretic clustering algorithm molecular complex detection(MCODE), and the boundary of the Qi invigorating efficacy system was defined by the pharmacological function of Astragali Radix. The active components of Astragali Radix for invigorating Qi were characterized from the aspects of composition, target and efficacy. The results showed that eight key components of Astragali Radix, such as hederagenin, quercetin, calycosin, formononetin, jaranol, isorhamnetin, astragalosideⅢ, and 9,10-dimethoxypterocarpan-3-O-ß-D-glucoside, could act on eight functional modules composed of 17 key targets, and participate in G-protein coupled receptor protein signaling pathway, regulation of lipid metabolic process, positive regulation of nitrogen compound metabolic process, positive regulation of programmed cell death, fatty acid metabolic process and other biological processes to produce pharmacological effects such as regulating immune function, strengthening heart, protecting myocardial cells, improving material metabolism, and antioxidation effects, thus playing the role of invigorating Qi. Based on the systematic Chinese medicine theory, this study explored the effective markers of Astragali Radix at the level of molecular network, which provided new ideas for the interpretation of the effective substance basis of systematic traditional Chinese medicine and the quality control of traditional Chinese medicine. In the future, it can focus on the compatibility research of these components, and then carry out more in-depth studies on the efficacy of Astragali Radix in invigorating Qi, and strengthen the development of the corresponding pharmacological mechanism and related preparations.

[Discovery of intervention effect of Chinese herbal formulas on COVID-19 pulmonary fibrosis treated by VEGFR and FGFR inhibitors].

Since February 2020, a large number of patients infected with new coronavirus has been cured and discharged with the controlling of epidemic. Pulmonary fibrosis, which may be one of the sequela caused by COVID-19, not only brings dyspnea and deterioration of lung function, but also affects patients' life because of its high mortality and poor prognosis. Vascular endothelial growth factor receptor(VEGFR) and fibroblast growth factor receptor(FGFR) can inhibit the proliferation, activation and migration of fibroblasts by regulating the signal transduction pathway involved in the process of pulmonary fibrosis. Chinese herbal formulas pose a good therapeutic effect on pulmonary fibrosis. Present study explores the intervention effect on pulmonary fibrosis of traditional Chinese medicine(TCM) by screening the potential inhibitors of VEGFR and FGFR. The docking models of VEGFR and FGFR were established to obtain the potential active ingredients which were filtered by the docking score. According to 2 prescriptions in the Protocol for the diagnosis and treatment of coronavirus disease 2019(7th edition)and 9 prescriptions in Traditional Chinese medicine prescriptions for treating blight, 959 and 1 047 potential ingredients were obtained as the inhibitors of VEGFR and FGFR respectively with the screening thres-hold set as eighty percent of the docking score of the initial ligands. The potential herbs were then filtered by the components with a hit rate higher than 30%, such as Scutellariae Radix, Adenophorae Radix, Pinelliae Rhizoma, Coicis Semen, etc. To discuss the rule of TCM in the treatment of pulmonary fibrosis, the networks of TCM-channel tropism and TCM-efficacy of the potential herbs was constructed. The potential herbs for treating pulmonary fibrosis mostly belong to lung(degree=14) and spleen(degree value=8), and the efficacy is focused on reinforcing deficiency(degree=9). Qiyin Prescription and Buzhong Yiqi Decoction contain the largest number of the potential herbs. The main symptom of COVID-19 is damp-heat stagnating in the lung, which always causes impairment of body fluid and Qi. Clinical observation shows that patients in the recovery period are mostly at the status that the remaining virus toxicity is not exhausted while the vital Qi have not recovered. The results of this study are expected to provide references for clinical medication in preventing and treating pulmonary fibrosis caused by COVID-19.

[Study on efficacy markers of heat-clearing and detoxifying effect of Lonicerae Japonicae Flos based on systematic traditional Chinese medicine].

Lonicerae Japonicae Flos has a long history of heat-clearing and detoxifying effect. The description of its efficacy in Chinese Pharmacopoeia of past dynasties is relatively stable, and it is an excellent carrier for the study of efficacy markers. Guided by the theory of systematic traditional Chinese medicine, heat-clearing and detoxifying effect efficacy system of Lonicerae Japonicae Flos was taken as an example in this study to clarify the elements(active ingredients) of Lonicerae Japonicae Flos in heat-clearing and detoxifying efficacy system, determine the boundary(signal pathway), establish the structure(system dynamics model), identify the system functions corresponding to pharmacology, efficacy and effects(heat-clearing and detoxifying effect), and explore the application of system dynamics model in the discovery of efficacy markers of traditional Chinese medicine. In this paper, the dynamic models of interleukin 1(IL-1) and interleukin 6(IL-6) in vivo were established to predict the expression of related factors in IL-1 and IL-6 signaling pathways of different components and their combinations in Lonicerae Japonicae Flos by dynamic network, so as to find the effective markers of heat-clearing and detoxification of Lonicerae Japonicae Flos. The results showed that the lower the concentration of chlorogenic acid, the higher the inhibition rate of Jun N-terminal kinase(JNK) at downstream of IL-1 by the combination of chlorogenic acid and linalool; the higher the concentration of luteolin in IL-6 pathway, the higher the inhibition rate of C-reactive protein(CRP) at downstream of IL-6 by the combination of chlorogenic acid and luteolin. It revealed that the potential efficacy markers of Lonicerae Japonicae Flos in heat-clearing and detoxifying effect based on IL-1 signaling pathway were chlorogenic acid and linalool, and the potential efficacy markers of Lonicerae Japonicae Flos in heat-clearing and detoxifying effect based on IL-6 signaling pathway were chlorogenic acid and luteolin. This study provided methodological guidance for the discovery of efficacy markers of traditional Chinese medicine.