Novel in-house knowledge-based automated planning system for lung cancer treated with intensity-modulated radiotherapy.

PURPOSE: The goal of this study was to propose a knowledge-based planning system which could automatically design plans for lung cancer patients treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: From May 2018 to June 2020, 612 IMRT treatment plans of lung cancer patients were retrospectively selected to construct a planning database. Knowledge-based planning (KBP) architecture named αDiar was proposed in this study. It consisted of two parts separated by a firewall. One was the in-hospital workstation, and the other was the search engine in the cloud. Based on our previous study, A­Net in the in-hospital workstation was used to generate predicted virtual dose images. A search engine including a three-dimensional convolutional neural network (3D CNN) was constructed to derive the feature vectors of dose images. By comparing the similarity of the features between virtual dose images and the clinical dose images in the database, the most similar feature was found. The optimization parameters (OPs) of the treatment plan corresponding to the most similar feature were assigned to the new plan, and the design of a new treatment plan was automatically completed. After αDiar was developed, we performed two studies. The first retrospective study was conducted to validate whether this architecture was qualified for clinical practice and involved 96 patients. The second comparative study was performed to investigate whether αDiar could assist dosimetrists in improving the quality of planning for the patients. Two dosimetrists were involved and designed plans for only one trial with and without αDiar; 26 patients were involved in this study. RESULTS: The first study showed that about 54% (52/96) of the automatically generated plans would achieve the dosimetric constraints of the Radiation Therapy Oncology Group (RTOG) and about 93% (89/96) of the automatically generated plans would achieve the dosimetric constraints of the National Comprehensive Cancer Network (NCCN). The second study showed that the quality of treatment planning designed by junior dosimetrists was improved with the help of αDiar. CONCLUSIONS: Our results showed that αDiar was an effective tool to improve planning quality. Over half of the patients' plans could be designed automatically. For the remaining patients, although the automatically designed plans did not fully meet the clinical requirements, their quality was also better than that of manual plans.

Icariside II suppressed tumorigenesis by epigenetically regulating the circß-catenin-Wnt/ß-catenin axis in colorectal cancer.

Icariside II, a flavonol glycoside, one of the major components of Traditional Chinese Medicine Herba epimedii. In the present study, we found that Icariside II suppressed the proliferation of CRC by inducing cell cycle arrest and apoptosis in vitro and inhibited tumor growth in vivo. The further mechanism investigation showed that Icariside II suppressed the expression of ß-catenin and led to the functional inactivation of Wnt/ß-catenin signaling. Circß-catenin was considered as a promising candidate for mediating the tumorigenesis and the activation of Wnt/ß-catenin signaling in CRC cells. Furthermore, Icariside II has been proven to suppress the biogenesis of circß-catenin via epigenetically targeting DNA methyltransferases (DNMTs) to decrease global DNA methylation levels in CRC cells. Taken together, our results indicated that Icariside II suppressed tumorigenesis by epigenetically silencing the activation of circß-catenin-Wnt/ß-catenin axis in colorectal cancer. More importantly, the information gained from this study suggest that Icariside II may have great potential to be developed as a therapeutic drug for CRC patients.

Comparative Genome Analysis of Scutellaria baicalensis and Scutellaria barbata Reveals the Evolution of Active Flavonoid Biosynthesis.

Scutellaria baicalensis (S. baicalensis) and Scutellaria barbata (S. barbata) are common medicinal plants of the Lamiaceae family. Both produce specific flavonoid compounds, including baicalein, scutellarein, norwogonin, and wogonin, as well as their glycosides, which exhibit antioxidant and antitumor activities. Here, we report chromosome-level genome assemblies of S. baicalensis and S. barbata with quantitative chromosomal variation (2n = 18 and 2n = 26, respectively). The divergence of S. baicalensis and S. barbata occurred far earlier than previously reported, and a whole-genome duplication (WGD) event was identified. The insertion of long terminal repeat elements after speciation might be responsible for the observed chromosomal expansion and rearrangement. Comparative genome analysis of the congeneric species revealed the species-specific evolution of chrysin and apigenin biosynthetic genes, such as the S. baicalensis-specific tandem duplication of genes encoding phenylalanine ammonia lyase and chalcone synthase, and the S. barbata-specific duplication of genes encoding 4-CoA ligase. In addition, the paralogous duplication, colinearity, and expression diversity of CYP82D subfamily members revealed the functional divergence of genes encoding flavone hydroxylase between S. baicalensis and S. barbata. Analyzing these Scutellaria genomes reveals the common and species-specific evolution of flavone biosynthetic genes. Thus, these findings would facilitate the development of molecular breeding and studies of biosynthesis and regulation of bioactive compounds.

TrMYB4 transcription factor regulates the rutin biosynthesis in hairy roots of F. cymosum.

Fagopyrum cymosum has been considered as a traditional medicinal plant that belongs to Fagopyrum, which has exhibited great pharmaceutical potential due to its abundant flavonoid accumulation. The hairy roots induced by Agrobacterium rhizogenes has been utilized to produce valuable specialized metabolites or reveals plant metabolic processes, whereas the underlying regulatory networks of flavonoid biosynthesis in hairy roots of F. cymosum remained unexplored. Here, the regulatory transcription factor TrMYB4 cloned from Trifolium repens with purple striped leaves was considered to investigate the mechanism of flavonoids biosynthesis in hairy roots of F. cymosum. Results showed that the expression of key genes involved in rutin biosynthesis pathway from TrMYB4 hairy roots were significantly up-regulated compared with non-transgenic hairy roots, while the content of total flavonoids and rutin in TrMYB4 hairy roots also increased consistently. It revealed the TrMYB4 transcription factor could regulate the rutin biosynthesis in F. cymosum. Meanwhile, our research provided a theoretical reference for the industrial production of rutin using F. cymosum hairy roots.

Constituents Isolated from the Leaves of Glycyrrhiza uralansis and Their Anti-Inflammatory Activities on LPS-Induced RAW264.7 Cells.

Licorice, the root and rhizome of Glycyrrhiza uralansis Fisch, is one of the most frequently used Traditional Chinese Medicines in rigorous clinical trials to remove toxins and sputum, and to relieve coughing. However, the aerial parts are not used so widely at present. It has been reported that the aerial parts have many bioactivities such as anti-microbial and anti-HIV activities. In this study, we aimed to discover the bioactive compounds from the leaves of G. uralensis. Four new compounds, licostilbene A-B (1-2) and licofuranol A-B (3-4), together with eight known flavonoids (5-12), were isolated and identified from the leaves of G. uralensis. Their structures were elucidated mainly by the interpretation of high-resolution electrospray mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR) spectroscopic data. Compared with quercetin, which showed a 50% inhibitory concentration (IC50) value of 4.08 µg/mL, compounds 1-9 showed significant anti-inflammatory activities by inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) production with IC50 values of 2.60, 2.15, 3.21, 3.25, 2.00, 3.45, 2.53, 3.13 and 3.17 µg/mL, respectively. The discovery of these active compounds is important for the prevention and treatment of inflammation.

[Quality evaluation of Magnoliae Officinalis Cortex based on combinative method of fingerprint,quantitative analysis of multicomponents and chemometrics].

This study aims to establish a combinative method based on fingerprint,assay of multi-component and chemometrics for quality evaluation of Magnoliae Officinalis Cortex. Twenty batches of samples were determined by UPLC and a common mode of fingerprint was established. The similarities between fingerprints of 20 batches of samples were over 0. 90 and the common mode were evaluated. Eight components were identified as syringing, magnocurarine, magnoflorine, magnoloside B, magnoloside A, honokiol,magnolol,and piperitylmagnolol by comparison with reference substances and their content in samples were simultaneously determined.Based on the results,the fingerprint had good consistency between the same origin and minor diversity between the different sources.Piperitylmagnolol and peak 13 could be used as a distinction with the different sources. According to content of 8 components,Fisher discriminant analysis model was established and different source sample was classified pursuant to the discriminant fraction. It is indicated that simultaneous quantification of multi components coupled with chemometrics analysis could be a well-acceptable strategy to identify and evaluate the quality of Magnoliae Officinalis Cortex.

[Effect of matrine on NO and ADMA metabolism pathways in serum and tissues of mice with lipopolysaccharide-induced intestine tissue inflammation].

OBJECTIVE: To discuss the effect of matrine on nitric oxide (NO) and asymmetric methylarginine (ADMA) metabolism pathways in serum and tissues of mice with lipopolysaccharide (LPS) -induced intestine tissue inflammation. METHOD: Kunming mice were randomly divided into five groups: the normal control group, the LPS group and matrine (80, 40, 20 mg x kg(-1) x d(-1)) groups. The mice were intragastrically administered with drugs for 3 d (distilled water of the same volume for the normal control group and the LPS group). One hour after the last intragastrical administration, normal saline or LPS (1 mg x kg(-1)) were intraperitoneally injected. Twelve hours later, serum and tissues were collected to determine NO and ADMA levels and observe the pathological changes of intestinal tissues. The Western blot method was adopted to detect the protein expressions of arginine methyltransferases 1 (PRMT1) and dimethylarginine dimethylaminohydrolase 2 (DDAH2) in intestinal tissues. RESULT: Compared with the model group, matrine (80, 40, 20 mg x kg(-1) x d(-1)) groups showed lower NO content in serum and tissues, higher ADMA level in serum and increased PRMT1 expression in intestinal tissues, but without effect on DDAH2 expression. CONCLUSION: Matrine could inhibit LPS-induced intestine tissue inflammation in mice. Its action mechanism is related to the decreased NO content in serum and tissues and increased ADMA level in serum and PRMT1 expression in intestinal tissues.

Arbuscular mycorrhizal symbiosis for sustainable cultivation of Chinese medicinal plants: a promising research direction.

Arbuscular mycorrhizal (AM) are symbiotic systems in nature and have great significance in promoting the growth and stress resistance of medicinal plants. During our literature search from the Chinese Scientific Information Database (Chinese National Knowledge Infrastructure, CNKI) we obtained 65 articles with "AM fungi" and "medicinal plant" as the key words, which indicates that in China, research efforts on these topics have been increasing. The main purposes of this review are to discuss the effects of mycorrhiza on the active ingredients of Chinese medicinal plants in comparison with results obtained in other plants in studies conducted by the international research community, and to introduce works published in Chinese journals to international colleagues.

Arbuscular mycorrhizal symbiosis and active ingredients of medicinal plants: current research status and prospectives.

Medicinal plants have been used world-wide for thousands of years and are widely recognized as having high healing but minor toxic side effects. The scarcity and increasing demand for medicinal plants and their products have promoted the development of artificial cultivation of medicinal plants. Currently, one of the prominent issues in medicinal cultivation systems is the unstable quality of the products. Arbuscular mycorrhiza (AM) affects secondary metabolism and the production of active ingredients of medicinal plants and thus influence the quality of herbal medicines. In this review, we have assembled, analyzed, and summarized the effects of AM symbioses on secondary metabolites of medicinal plants. We conclude that symbiosis of AM is conducive to favorable characteristics of medicinal plants, by improving the production and accumulation of important active ingredients of medicinal plants such as terpenes, phenols, and alkaloids, optimizing the composition of different active ingredients in medicinal plants and ultimately improving the quality of herbal materials. We are convinced that the AM symbiosis will benefit the cultivation of medicinal plants and improve the total yield and quality of herbal materials. Through this review, we hope to draw attention to the status and prospects of, and arouse more interest in, the research field of medicinal plants and mycorrhiza.

[Preliminary study in glycyrrhizin content and its influencing factors of wild and cultivated in different region of China].

OBJECTIVE: In order to understand the glycyrrhizin content range in the wild and cultivated Glycyrrhiza uralensis in China and to find the related influencing factors of glycyrrhizin content. METHOD: The glycyrrhizin content of 165 wild and 1 013 cultivated G. uralensis samples from 37 countries in 9 provinces was determined by HPLC, and the effects of the producing region, medicinal parts, cultivation years, soil type and texture on the glycyrrhizin content were analyzed. RESULT AND CONCLUSION: The average glycyrrhizin content was (4.43 +/- 1.32)% in the wild G. uralensis population, and (1.51 +/- 0.49)% in the cultivated and the glycyrrhizin content in the cultivated was less than the minimum sandards in the Chinese Pharmacopoeia. The glycyrrhizin content was significant different in the wild and cultivated G. uralensis in different producing regions, respectively. The glycyrrhizin content in roots and rhizome of the wild G. uralensis had no significant difference, it had no significant difference in the cultivated G. uralensis from 1 to 4 years and it increased rapidly after 5 years, and the effects of the soil types and texture on it were significant.

[Analysis of broad-sense heritability and genetic correlation of production and content of glycyrrhizin of annual Glycyrrhiza uralensis].

OBJECTIVE: To estimate the broad-sense heritability of the production of Glycyrrhiza uralensis and the content of glycyrrhizin as well as the genetic relationship of various growth indexes and biomass indexes, and provide the scientific basis for establishment of high quality licorice cultivate technology system. METHOD: The randomized method was used to assign the provenance trial, the content of glycyrrhizin was determined by HPLC, and the method of classic genetics was applied to estimate the broad-sense heritability and genetic correlation coefficient. RESULT AND CONCLUSION: The content of glycyrrhizin is influenced by the growth environment and gene, but the growth environment is the dominant factor. The estimated result of single sites about broad-sense heritability (h2) showed that the production of G. uralensis (W(u)) and the content of glycyrrhizin was controlled by gene which the broad-sense heritability was 0.663 2, 0.751 1 respectively, they had some potential on genetic modification. The results of genetic analysis correlation showed that the plant height and the stem diameter was positive (P < 0.01) correlated significantly with the production (W(u)) either on phenotype or on genetic, it suggests that the plant height and the stem diameter could be the index above ground to assessment the production of the G. uralensis. The content of glycyrrhizin had a positive correlation with the number of lateral root (P < 0.05), but it had a negative correlation with the plant height, stem diameter, diameter of root top (D(r)), the total biomass (W(t)) and the biomass underground (W(u)) on inheritance. It is suggested that it was difficult to achieve both high content and high yield simultaneously in the genetic improvement, so we should have a deeply thought about the specific improvement target when making the reformed scheme.

[Spectrometric determination of trace elements in anticancer new medicine Fagopyrum dibotrys].

The golden buckwheat Fagopyrum dibotrys produced in Yunnan has a unique anti-cancer effects. It is a main raw material of "Wei Mai ning" capsules which is the national second-class anti-cancer drug. The present paper used (5 : 1) mixed acid as digestive juice to process the sample, and determine the twelve elements including K, Ca, Cu, Na, Mg, Mn, Fe, Zn, Pb, Cr, Cd and Co in the Fagopyrum dibotrys by inductively coupled plasma atomic emission spectrometry(ICP-AES). The detection limits of this method were 0.017-0.084 microg x mL(-1), the RSDs (n = 8) were all 0.09%-1.87%, and the addition standard recoveries(ASR) (n = 8) were 98.2%-107.4% for all elements. The research results showed that there is rich K(1 477.3 microg x g(-1)) in the Fagopyrum dibotrys, there are not harmful elements Cd and Pb, and this result is mainly related to the geochemistry background where the sample lived. The contents of seven remaining kinds of elements ranked as Na (826.1) > Ca (765.2 > Mg (493.4) > Zn (112.7) > Fe (56.5) > Cu (11.4) > Mn (4.49 microg x g(-1)). This result provides some theoretical basis for the study of internal relations between trace elements in Fagopyrum dibotrys and efficacy. It' s also useful for better development and utilization of the resource.

[Effects of N P K on yield and baicalin contents of Scutellaria baicalensis].

OBJECTIVE: To find out the effects of different levels and combinations of nitrogen, phosphorus and potassium on the growth and secondary metabolites of Scutellaria baicalensis. METHODS: The quantities of growth, physiological indicators and baicalin contents in different fertilization treatment were calculated and compared. RESULTS: The growth physiological indicators and baicalin contents of S. baicalensis in complex fertilization treatment were better than those in single element fertilization treatment, and nutrition balance types better than maladjustment type. The reasonebly fertilitzing in complex fertilization treatment, nitrogen could improve the fertilizer efficiency of phosphorus. CONCLUSION: According to the fertilization mathematic model, the optimum fertilization dosage should be primarily defined as N: 22.6-25.0 g/m2, P: 30.6-44.6 g/m2, K: 5.4-21.4 g/m2, that is 2N:3P:1K.

[Present situation and prospects of special fertilizer for traditional Chinese medicine herbs].

OBJECTIVE: To find out the present situation and the development trend special fertilizer of the traditional Chinese medicina plants. METHOD: By consulting a great deal of literatures on special fertilizer and fertilization on traditional Chinese medicine herbs, and based on the scientific research and manufacture experience of the author, and the theoretic actuality of the researches on the fertilization of traditional Chinese medicine herbs, the present study of the special fertilizer inside and outside of our country was analyzed. CONCLUSION: The view points of developing special fertilizer for Chinese traditional medicine were put forward, and the development trend of special fertilizer for traditional Chinese medicine herbs was forecasted.

[The investigation of the licorice resources in northeast China].

OBJECTIVE: To find out the licorice(Glycyrrhiza uralensis) distribution area, resource complexion and resource reserves of northeast China, to analyze the cause of the swing of the pendulum of resources, to put forward the countermeasure of resource protection and to provide evidence for the establishment of relative statutes. METHOD: Combination of visit-inquisition and sample-square investigation involving the resource complexion of the 32 counties and cities in the northeast China wasmade. RESULT AND CONCLUSION: The east distribution boundary and the whole distribution current of licorice in the northeast China were determined the northeast licorice distributing region was compartmentalized into three typical sub-regions, and the licorice population character and artificial disturbing status in main counties of every sub-region were described. The licorice reserves were also figured out. At the same time, the nature and the artificial factors that influenced the swing of the pendulum of licorice resource were analyzed, and the correlative safeguard measure was brought forward.