Q-marker is a new concept of quality control for traditional Chinese medicine. Since its introduction in 2016, it has received extensive support and participation from researchers and manufactures of the entire industry. In order to establishing the research level of quality markers, normative research model, we review the proposed core theory and research methods of Chinese medicine quality markers. The definition and scientific connotation of Chinese medicine quality markers are analyzed. The core theories and research methods of quality markers are summarized from five aspects:"effectiveness", "specificity", "transfer and traceability", "compatibility environment" and "measurability" of quality markers. This paper aims to provide useful theoretical and methodological guidance for studying Chinese medicine quality markers.

The quality of traditional Chinese medicine (TCM) is the lifeline for TCM industry. The development of artificial intelligence (AI) has provided new means for the quality management of Chinese medicinal materials (CMM). In this paper, we take the quality marker (Q-marker) as a breakthrough point, focused on the research strategy from chemical markers to Q-markers, picked up the characteristics of the Q-markers from the near infrared spectrum (NIRS), and explored the feasibility of establishing the NIRS assay based on Q-marker. After integrated the biological activity detection and artificial neural network algorithm, we try to establish the relationship between the spectral properties of NIRS and specific efficacy of the CMM. Finally, the bottlenecks will be solved that related to the transmission and traceability of quality attributes in the process of TCM production, quantity change, overall quality management and so on. This system is going to improve TCM quantity scientific and intelligent supervision, and promote the upgrading of traditional TCM industry.

The quality control of traditional Chinese medicine provides the premise of its modernization and globalization. Currently, the dual quality control based on chemical benchmark and effect benchmark has been recognized domestically and internationally. Research efforts have lead to establishment of a series of effective quality control methods based on chemical components, medicinal properties, microscopic characteristics, material constituents and pharmacodynamic targets. In the study of quality control based on chemical benchmarks, fruitful results on fingerprints, DNA barcodes, and quality markers have been achieved. However, due to a variety of factors, such as growth period, origin, growth environment and preparation process of traditional Chinese medicine, the quality control of traditional Chinese medicine based on chemical benchmarks remains difficult to fully reflect the quality of traditional Chinese medicine. At present, there is still a dispute on how to accurately reflect the quality of traditional Chinese medicines based on chemical benchmarks. For example, the index components selected in the Chinese medicine quality standards are difficult to totally reflect all the components of Chinese medicine, and the relevance between the index components versus therapeutic effect is not yet clear. In view of the complex signal network by cascade reaction and crosstalk of multi-signaling pathways within an organism, and the coordinated regulation of multi-components and multi-targets of traditional Chinese medicine, there may be different components regulating the same signal network or situations where the amount of certain chemical components within a range is not sufficient to cause a change in the signal network. Therefore, the quality control of traditional Chinese medicine based on the effect benchmark may be a useful supplement to the quality standard of traditional Chinese medicine. This paper proposes a Q-biomarker research strategy based on the effect benchmark in order to provide a methodological reference for the quality control research of traditional Chinese medicine.

The quality definition of traditional Chinese medicine (TCM) is a hot area in modern research of TCM. In recent years, the characteristics of one herb with multiple effects have been widely accepted and studied. The typical opposite-effect of herbs is considered as a special part of one herb with multiple effects, and was summarized in this paper. Sanqi was used as an example of opposite-effect herbs for developing the strategies and approaches on the Q-markers. The traditional opposite-effect should be studied by modern pharmacological research methods. The correlation of the chemical components with the opposite effects should be established in order to verify the material basis and evaluate the mechanism including targets and pathways. The unique characteristics of chemical components should be analyzed and defined. Finally, the Q-markers of the opposite effect herb will be confirmed. This paper provides a useful reference for the precise quality control of herbal opposite-effects.

The chemical composition of traditional Chinese medicine (TCM) compounds is complex, the treatment is broad, and the quality control indexes cannot accurately reflect the functional properties. According to the above problems, the authors take the research process of quality markers of Qizhiweitong granules as an example to innovate the research ideas and technical methods, and constructed five progressive steps of TCM compounds quality control and evaluation model:"based on function, to figure out the attending", "components and pharmacodynamics correlation, multiple components with multiple effects", "to analyze the components, and systematically integrate them", "spectrum and effect correlation, from a spectrum to see the efficiency", and "from the content-effect colour atla to see the quality". Based on the multiple effects of components, multiple components of multi-effect pharmacological efficacy evaluation system were established. All-time isobaric multiwavelength fusion fingerprint technology was improved and developed. "Spectrum-effect colour atla" software was research and developed for the first time, to realize the "visualization" of TCM efficacy. The aim of this work is to provide an exploratory solution for the integrated quality control of TCM compounds.

Atherosclerosis refers to vascular pathological changes in which vascular lumen was narrowed or blocked by cholesterol or fat existed in vascular endothelium, which could induce serious cardiovascular events. The pathogenesis of atherosclerosis is complicated extremely. Vascular endothelial dysfunction initiated the plague formation and deterioration, which determined the prognosis of atherosclerosis. Circular RNA (circRNA) is a special endogenous non-coding RNA, which has become a research hotpot in the field of non-coding RNA. This review aims to bring together the recent research on the pathogenesis and pathological process of endothelial dysfunction, and the regulative effect of circRNA on it. Our article will provide new targets and new ideas for the research and development of anti-atherosclerosis drugs.

Depression, a global disease with various pathogenic factors, is seriously affecting human physical and mental health. In Chinese traditional medical theory, the disease belongs to the category of "Yu Zheng". At present, on the one hand, adverse reactions to antidepressant western medicine are becoming more and more prominent. On the other hand, the study of their antidepressant active ingredients and compatibility mechanisms has become a difficult field in the traditional Chinese medicine compounds due to their complexity. The Chinese antidepressant herb-pairs has become a hot topic in the field of antidepressant research. Herb-pair is the core of traditional Chinese medicine compound. In addition, the compound itself is a herb-pair. The study of traditional Chinese antidepressant herb-pairs is more conducive to clarify the compatibility mechanism of herb interaction and the mechanism of antidepressants on the body.Therefore, this paper systematically expounds antidepressant herb-pairs from the study of material, pharmacokinetics and efficacy, which aims at providing theoretical support for the compatibility mechanism of antidepressant herb-pairs and the research of new antidepressant drugs.

Ionic liquids are not limited to the traditional use of solvents because of their high permeability and excellent physicochemical and unique biological properties. Nowadays, with the deep understanding of their toxicity and biocompatibility, ionic liquids have been tailored as novel solutions to address potential problems of marketed drugs. Based on the research and development of modified new drugs, ionic liquids have been incorporated into drug synthesis and emerged as attractive environmental-friendly reaction media with milder reaction conditions, higher yields and easier reaction workups and drug delivery systems. In addition, they have been designed for effective drug carriers removing undesirable properties of solid drugs. Further, ionic liquids forming active pharmaceutical ingredients dedicated to the liquefaction of drugs for promising clinical applications.

Anti-tumor intervention using a combination of drugs shows unique advantages in research and clinical practice. Active ingredients of Chinese herbal medicines can offer many advantages, such as high efficiency, low toxicity, wide effect and multiple targets. At present, the combination active ingredients of Chinese herbal and chemotherapy drugs have attracted increased attention. Nano-drug delivery system provides a good carrier platform for anti-tumor drugs. Nano-carrier-mediated drug combination is a promising strategy. In this paper, we review the mechanisms of the anti-tumor effects of active ingredients of traditional Chinese medicine combined with chemotherapeutic drugs and consider the advantages of drug-loaded nanoparticles, the types and characteristics of carriers. The aim is to provide a reference for the research of effective regimen for anti-tumor therapy.

The blood-brain barrier (BBB) not only maintains the stability of the environment within the central nervous system by controlling the transport of substances on both sides of the blood and brain, but also plays an important role in the R&D of new drugs for neurological disorders. The establishment of an in vitro high-fidelity model to study BBB function is imperative for assessing barrier permeability of drugs and xenobiotics. However, the complexity of the BBB structure makes it difficult to replicate with an in vitro model. Compared to the traditional in vitro BBB model, the BBB-on-chip provides certain advantages in miniaturizing the system, reducing the amount of cells and medium required, and allowing simultaneously induction of shear stress. We review here the BBB-on-chip models from their establishment and characterization to applications in research of neuroinflammation, brain tumor and drug evaluation.

The research is aimed to investigate the effect of genistein (GEN) on the apoptosis in lipopolysaccharide (LPS)-activated RAW264.7 cells and explore the pharmacological mechanism of GEN anti-atherosclerosis (AS). RAW264.7 cells were activated by LPS, the level of TNF-α and IL-6 mRNA were detected by qRT-PCR, the expression of COX-2 and iNOS were detected by Western blot. RAW264.7 cells were pretreated with GEN for 2 h, and then incubated with LPS for 24 h. After that, CCK8 kit was used for the cell viability, Annexin V-FITC/PI kit for the apoptosis of cell. qRT-PCR was used to detect the level of CHOP, caspase-3 and miR-21. Western blot was used to detect the expression of CHOP and caspase-3. Results showed that LPS (1 000 ng·mL^-1) increased the expression of TNF-α, IL-6, COX-2 and iNOS in RAW264.7 cells compared with that in control group. GEN inhibited the cell activity and the level of miR-21, promoted the expression of CHOP and caspase-3 in LPS-activated RAW264.7 cells in a dose-dependent manner. miR-21 up inhibited the expression of CHOP and caspase-3 in LPS-activated RAW264.7 cells and this process was reversed by GEN treatment. miR-21 down promoted the expression of CHOP and caspase-3, which were further enhanced by GEN. These results indicate that GEN promotes the apoptosis of RAW264.7 cells activated by LPS through down regulating miR-21 and activating endoplasmic reticulum (ER) stress pathway.

To investigate the potential hypoglycemic effect of nanosuspensions of honokiol and explore the underlying mechanisms, a high fat diet (HFD) was studied in C57BL/6J mice divided into five groups:normal diet (ND), HFD, HFD/honokiol-sodium carboxymethyl cellulose (CMC-Na) (Hono-CMC, 100 mg·kg^-1), HFD/honokiol-Nano (Hono-Nano, 80 mg·kg^-1), HFD/metformin (HFD/Met, 200 mg·kg^-1). Fasting blood glucose (FBG) and body weights (BW) of mice were measured every seven days. After 30-day treatment, an oral glucose tolerance test (OGTT) was performed, and blood and tissue samples were collected for analysis. All animal experiments were approved by the Research Animal Care Committee of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. The data showed Hono-Nano and metformin reduced FBG, BW, and markedly improved OGTT of mice compared to HFD group (P < 0.05). Hono-CMC produced nonsignificant impact on FBG, BW of mice, while OGTT of mice was improved by Hono-CMC (P < 0.05). Meanwhile, none of these treated groups showed significant effects on regulating serum insulin levels, but all of them exhibited decreased serum glucagon levels notably compared to the HFD group (P < 0.05). Western blot analysis revealed that honokiol up-regulated levels of p-AMPK and p-FOXO1 in liver tissue of HFD mice (P < 0.05), which resulted in activation of AMPK and inhibition of FOXO1. Moreover, the expression of PEPCK (a key enzyme of gluconeogenesis) was decreased by honokiol (P < 0.05). Taken together, our findings demonstrate that nanosuspension of honokiol is more effective than CMC-Na-suspension of honokiol on blood glucose controlling in HFD mice. The hypoglycemic effects of honokiol might rely on suppressing hepatic gluconeogenesis via activating AMPK and inhibiting FOXO1.

To investigate the effect of scutellarin (Scu) on diabetic cardiomyopathy in mice, type 2 diabetes mellitus was induced by intraperitoneal injection of 50 mg·kg^-1 streptozotocin (STZ) into a high-fat diet. Scu was injected intraperitoneally. After 8 weeks, fasting blood glucose and serum biochemical parameters were measured. Masson staining was performed on myocardial tissue. The expression levels of Nrf2, NFκB, AKT and p-AKT in myocardium of mice were observed by Western blot. All the procedures were approved by the Laboratory Animal Ethics Committee of the Peking Union Medical College. The results showed that Scu significantly decreased the heart-body ratio, increased myocardial contractile function, decreased the level of myocardial fibrosis and the expression of collagen I and collagen Ⅲ in myocardium of diabetic mice. Scu can effectively reduce the levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), malondialdehyde (MDA) in serum of diabetic mice, increase the level of antioxidant enzymes in serum, and inhibit the release of inflammatory factors. Further studies showed that Scu significantly increased Nrf2 nuclear translocation, inhibited NFκB nuclear translocation and increased AKT phosphorylation. It indicates that Scu has significant effect on diabetic cardiomyopathy in mice.

This study was designed to compare the antithrombotic effects of salvianolic acid A and aspirin. The anti-platelet aggregation and anticoagulant effects of salvianolic acid A and aspirin in vitro and in vivo were investigated in normal rats. The anti-cerebral ischemia and anti-platelet aggregation effects of salvianolic acid A and aspirin were also investigated in rats with thrombotic cerebral ischemia. All animal care and experimental procedures were reviewed and approved by the Animal Ethics Committee of Chinese Academy of Medical Sciences. The results of antiplatelet aggregation in vitro and in vivo showed that salvianolic acid A could mildly inhibit adenosine diphosphate (ADP), arachidonic acid (AA) and thrombin (THR)-induced antiplatelet aggregation in a dose-dependent manner, while aspirin played a strong inhibitory effect on AA-induced platelet aggregation in vivo. The effects of salvianolic acid A and aspirin on the coagulation system were similar. At the same time, the results of maximum platelet aggregation rate (MAR) in the rat cerebral ischemia model[MAR_ADP=(41.67±4.55)%, MAR_AA=(53.22±2.83)%, MAR_THR=(73.33±5.04)%] indicated that salvianolic acid A could mildly inhibit ADP and AA-induced antiplatelet aggregation[MAR_ADP=(26.13±4.60)%, MAR_AA=(35.53±13.73)%, P < 0.01], while aspirin played a strong inhibitory effect on AA-induced platelet aggregation[MAR_AA=(8.13±2.99)%]. Salvianolic acid A (10 mg·kg^-1) significantly improved the neurological function, cerebral infarction volume[(10.77±7.80)%] and brain edema[(79.72±0.83)%] compared with the model group[(43.50±12.69)%, (82.25±0.89)%] (P < 0.01), while the effect of aspirin (100 mg·kg^-1) was not obvious. The above results suggest that compared with aspirin, salvianolic acid A provided a mild inhibitory effect on platelet aggregation and protected against cerebral ischemia induced by thrombus. Therefore, salvianolic acid A has a good application prospect in the prevention and treatment of thrombotic diseases.

This study offers preliminary insight into the phytoestrogen activity and mechanism of rehmapicrogenin. In this study, we characterized the estrogenic activity of rehmapicrogenin using immature female mice in vivo and MCF-7 cell proliferation assay in vitro. All the procedures for the care of the mice were conducted in accordance with the Regulations of Experimental Animal Administration issued by the State Committee of Science and Technology of the People's Republic of China. Uterine wet weight/body mass ratios, Western blot assay for estrogen receptor, and serum estrogen levels of estradiol (E₂), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were investigated. The effects of rehmapicrogenin, and the estrogen receptor antagonist ICI182, 780, the estrogen receptor alpha antagonist MPP, the estrogen receptor beta antagonist THC, the G-protein coupled receptor 30 antagonist G15 combined with rehmapicrogenin on cell proliferation were examined in MCF-7 cells. Rehmapicrogenin (50 mg·kg^-1) treatments demonstrated significant estrogenic activity by promoting the development of uterus in immature female mice, as well as increasing the expression of estrogen receptor alpha (ERα) and G-protein coupled receptor 30 (GPR30) at the protein level in uterus, and decreasing FSH and LH compared with the control group. Meanwhile, rehmapicrogenin (6 and 8 μmol·L^-1) promoted the proliferation of MCF-7 cells, which were significantly antagonized by ICI182, 780, MPP and G15. This study demonstrates rehmapicrogenin exerts estrogenic effects through ERα and GPR30.

To assess the therapeutic effect of Tao Hong Si Wu decoction (THSWD) on glucocorticoid-induced osteoporosis and its mechanism, the standard products of nine active components in THSWD were accurately weighed and the reserve liquid of standard product was prepared. Then a series of concentration standard liquid was obtained by dilution, and the standard curve was established. The formula of THSWD was proportionally extracted and the nine active components were determined by high performance liquid chromatography (HPLC). Naturally mated to obtain zebrafish embryos after incubation, the zebrafish larvae were cultured in blank E₃ medium until the 3 days post fertilization (DPF), then divided into control group (blank E₃ medium), prednisolone (PNSL) group (25 μmol·L^-1 PNSL), disodium ethydronate (DE) group (15 μmol·L^-1 DE and 25 μmol·L^-1 PNSL), THSWD group (0.1, 1.0 or 10.0 μg·mL^-1 THSWD and 25 μmol·L^-1 PNSL), 15 in each group. The culture was continued until the 10 DPF. The zebrafish was anesthetized and sacrificed, stained with alizarin red S, then the bone staining was observed under a microscope. Quantitative analysis of bone mineralization area and cumulative optical density. Expression of alkaline phosphatase (AKP), type Ⅰ collagen (type Ⅰ), runt-related transcription factor 2 (RUNX-2), osteoprotegerin (OPG), tartrate-resistant acid phosphatase 5b (TRACP) and osteocalcin (OCN) were assessed by quantitative real-time PCR. The mineral contents in zebrafish were measured using inductively coupled plasma-mass spectrometry. In the THSWD water extract, the content of 9 compounds in descending order was as follows:gallic acid > hydroxysafflor yellow A > chlorogenic acid > senkyunolide H > ferulic acid > caffeic acid, senkyunolide Ⅰ > coumaric acid > benzoic acid. Compared with the control group, treatment of zebrafish with 25 μmol·L^-1 prednisolone significantly reduced the area of mineralized bone and cumulative optical density, and the expression of AKP, type Ⅰ, RUNX-2, OPG, OCN gene was also significantly reduced. The levels of Ca, P, K, Mg, Zn and Fe in zebrafish were reduced by 2.8, 2.4, 13.8, 6.6, 8.0 and 8.8 times, respectively. Compared with the prednisolone group, after treating with THSWD, the area of mineralized bones and cumulative optical density value of zebrafish increased significantly and was dose-dependent, and the expression of related genes also increased. The Ca, P, K, Mg, Zn, Fe levels were significantly higher than the prednisolone group. Result show that THSWD has the potential to reverse the effect of glucocorticoid osteoporosis, the mechanism of which is to enhance the activity of osteoblast, promote the expression of bone gelatin and bone mineralization, and increase bone mass.

A mouse model of cholestatic liver fibrosis was established by bile duct ligation (BDL) method. The effect of ginsenoside Rg1 in the disease progress and the mechanism of cholestatic liver fibrosis are investigated in this mouse model. All animal experiments in this paper have been approved by the Unit Ethics Committee. Analysis of serum biochemical indicators and pathological sections assessed liver function, liver damage and fibrosis in mice. Immunohistochemistry and Western blot assays were used to detect vascular cell adhesion molecule-1 (VCAM-1) in BDL-induced mice. Nuclear factor-κB (NF-κB) and inflammatory factors were detected to investigate related mechanism of Rg1. The results showed that expression of VCAM-1 was up-regulated and peaked at 7 days, followed by decreased expression, but still efficiently expressed compared to the sham-operated group. Compared with the model group, 40 mg·kg^-1·d^-1 Rg1 treatment reduced serum aspartate transaminase (AST), alanine transaminase (ALT) and total bilirubin (T.Bili) levels (P < 0.05 or P < 0.01) and liver function damage, alleviated BDL-induced liver fibrosis, significantly down-regulated the expression of VCAM-1 (P < 0.05), and inhibited the inflammatory response. In addition, Rg1 significantly reduced NF-κB p65 level in the cellular nucleus (P < 0.05). This study demonstrates that VCAM-1 is dynamically altered during BDL-induced liver fibrosis. Rg1 could dampen inflammation and alleviate cholestatic liver fibrosis via regulation of the NF-κB/VCAM-1 pathway. The results provide an experimental basis for Rg1 application for treating liver fibrosis.

We were interested in ascertaining differences in developmental neurotoxicity in normal and blood-stasis pregnant mice administered orally Rhizoma Curcumae and the underlying molecular biology mechanisms of any differences. To answer these questions, a blood stasis model was induced by being immersion in ice water. C57BL/6 mice with blood stasis, normal C57BL/6 mice, Nrf2 knock out (KO) mice with blood stasis were randomized into control groups and Rhizoma Curcumae exposure groups. The pregnant mice were administered Rhizoma Curcumae during pregnant day 5 to day 18. The neurodevelopment reflex was examined by the positive occurring time of avoidance precipice reflex tests. Measurement of glutathione (GSH) in brain of the offspring was performed by colorimetric assays. Transcription factor NF-E2-related factor 2 (Nrf2), glutamate cysteine ligase catalytic subunit (GCLc), and glutamate cysteine ligase modifier subunit (GCLm) mRNA and protein expression in brain of the offspring were examined by real-time RT-PCR and Western blot, respectively. All animal care and experiments procedures were reviewed and approved by the Animal Care and Use Committee of Qiqihar Medical College. Our results demonstrated for the first time evidence that C57BL/6 mice treated with Rhizoma Curcumae (10.0 g·kg^-1) extended the positive occurring time of avoidance precipice reflex tests of offspring mice compared with the normal control group (P < 0.05). We could not find any significant change in that of blood-stasis pregnant mice offspring compared with the normal control group (P>0.05). Compared with the normal control group, level of glutathione, mRNA and protein expression of Nrf2, GCLc, and GCLm significantly increased in brain of the offspring of blood-stasis pregnant mice (all P < 0.05). However, mice treated with Rhizoma Curcumae (10.0 g·kg^-1) did not change those of offspring (all P>0.05). Knock out Nrf2 using CRISPR/Cas9 extended the positive occurring time of avoidance precipice reflex tests of offspring of blood-stasis pregnant mice (P < 0.05). To conclude, developmental neurotoxicity of the blood-stasis pregnant mice to Rhizoma Curcumae was weaker than that of the normal pregnant mice. Cold-induced Nrf2 activation has important roles in "YOU-GU-WU-YUN" phenomenon of Rhizoma Curcumae.

Ten novel oleanolic acid (OA) derivatives containing urea or thiourea group were designed and synthesized, the chemical structures were confirmed by ¹H NMR, ¹³C NMR and HR-MS. All of these compounds were evaluated for the inhibitory activity against growth of HepG2 and SGC7901 cells. The results showed that compounds I₃ and Ⅱ₃ exhibited significant antitumor activities with IC₅₀ of 9.4 and 5.5 μmol·L^-1, respectively. Molecular docking studies showed that all these compounds exhibit inhibitory ability against mTOR kinase. Compounds I₃ and Ⅱ₃ were further evaluated for the inhibitory activity against mTOR kinase. The results showed that I₃ and Ⅱ₃ exhibited strong inhibitory effect on mTOR kinase with IC₅₀ values of 0.83 and 0.26 μmol·L^-1.

Chemical constituents from the ethanol extract of Radix Angelicae Pubescentis was isolated and purified through Diaion HP-20 macroporous, silica gel column chromatography, gel filtration over Sephadex LH-20 and preparative HPLC. Two new sesquiterpenoid derivatives were identified as angesesquid A (1) and angesesquid B (2), and their structures were determined. In vitro degeneration model of primary rat disc chondrocytes was used to evaluate the anti-inflammatory activity of these two compounds. The results showed that compounds 1 and 2 had no anti-proliferation effect. Both compounds inhibited the release of NO, but had no inhibitory activity for the release of PGE₂. This finding implies that both of these two new sesquiterpenoids could moderately inhibit the inflammatory reaction to some extent.

To determine relative molecular weight of astragalus polysaccharides (APs), we used Shodex GS620 gel permeation chromatographic column and differential refraction detector (GPC-RI) with dextran as a reference. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and GPC combined with multi-angle laser light scattering detection (GPC-MALLS) were also used.GPC-RI measure showed four peaks of APs, with the M_w of 1 380 000, 231 000, 18 000, and 480, respectively. Three main peaks were found by GPC-RI-MALLS with the M_w as 1 148 000, 180 000, and 43 000, respectively. Strong signals in 155 000 and 18 000 were detected by MALDI-TOF-MS, which also indicated the sugar moieties of the APs as hexoses. From our study, we found that the GPC-RI method with universal correction is most suitable for M_w determination of the APs. Nevertheless, the three methods should be combined and contrasted with each other to obtain accurate information in research of polysaccharides from Chinese medicine.

Though red yeast rice (RYR) has been used as medicine for centuries, few study has been reported about its biological activities related to traditional medicinal application and marketed RYR showed poor consistency in quality. In this study, with comprehensive investigation of their production processes and field acquisition samples including those from genuine producing area, an ultra performance liquid chromatographic (UPLC) method was firstly established to discriminate RYR for different applications based on their secondary metabolites fingerprint. It was performed on a CAPCELL CORE AQ column (100 mm×4.6 mm, 2.7 μm), with PDA (range:200-650 nm, extracted:237 nm) and ELSD detection. The mobile phase used was water (A) and acetonitrile (B) both containing 0.1% formic acid at gradient elution (0-15 min, 50% B→85% B (linear); 15-16 min, 85% B→50% B (linear) and maintained until 21 min), with a flow rate of 0.5 mL·min^-1. The method established was fully validated in agreement with guidelines of Chinese Pharmacopeia. Common metabolites were found in RYR for same application and the fingerprints of RYR for food coloring or brewing from various manufacturers had similarities above 0.90. Meanwhile, significant differences were observed among the fingerprints for various applications and discrimination could be achieved by principal component analysis (PCA). Lovastatin was absence in RYRs for food coloring or brewing, and the fingerprint of traditional medicinal RYR was similar to that of RYR for brewing. However, standardization was required for RYR containing lovastatin because of their significant differences from various manufacturers in fingerprints and lovastatin content. The results demonstrated the feasibility to discriminate RYR for different applications by the secondary metabolites fingerprint method established in this study, which provides a scientific basis to investigate the relationship between biological activities of medicinal RYR and their corresponding secondary metabolites, and further aid their quality standardization and improvement.

Nifedipine, a calcium channel antagonist, is metabolized mainly by CYP3A4 to dehydronifedipine. A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine nifedipine and dehydronifedipine in human plasma using d₆-nifedipine/d₆-dehydronifedipine as internal standards. After extraction from the plasma by protein precipitation, the analytes and internal standard were separated on a Hypersil Gold C₁₈ (50 mm×2.1 mm, 1.9 μm). The mobile phase consisted of methanol and 5 mmol·L^-1ammonium acetate aqueous solution (0.1% formic acid). Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 347.3→254.1 for nifedipine, m/z 345.2→283.9 for dehydronifedipine, m/z 353.3→257.1 for d₆-nifedipine, m/z 351.2→286.9 for d₆-dehydronifedipine. The method had a linear calibration curves over the concentrations of 0.10-80.0 ng·mL^-1 for nifedipine and 0.050-40.0 ng·mL^-1 for dehydronifedipine. The validated LC-MS/MS method has been successfully used study pharmacokinetic interactions of apatinib (CYP3A4 inhibitor) and nifedipine (CYP3A4 substrate) in human. This clinical trial was approved by the society of ethics and conducted in the first hospital of China medical university.

In this paper, multifunctional silver-graphene quantum dot nanoparticles coated with phospholipids (ADG-DDPC) were prepared and their properties were evaluated in vitro. Cationic phospholipids 1, 2-diolefinoxy-3-trimethy-laminopropane (DOTAP) was absorbed first onto the surface of the core of silver nanoparticle (AgNPs) through the mutual attraction between the positive and negative charge. Based on the principle of phase transformation and hydrophobic interaction, dstearyl-phosphatidylglycolamine-polyethylene-glycol-cyclic-cRGD peptide (DSPE-PEG₂₀₀₀-cRGD) self-assembled onto the outlayer of DOTAP of AgNPs. A stable multifunctional nano-preparation was formed and its ultraviolet absorption, particle size distribution, morphology, in vitro release behavior, ability to kill cancer cells and cell uptake were studied. The maximum UV absorption of the synthesized nanometer preparation was about 400 nm. Malvern particle size meter and transmission electron microscope showed that the particle size of the nano-preparation was about 30-40 nm and its particle size distribution was uniform. The in vitro release of nano-preparation was positively correlated with the concentration of H₂O₂. The IC₅₀ value of AgNPs for tumor cells was (347.78±0.06) ng·mL^-1, and the IC₅₀ value of ADG-DDPC for tumor cells was (209.68±0.09) ng·mL^-1, indicating that ADG-DDPC possessed a stronger cytotoxicity than that of AgNPs. Cell uptake experiment showed that ADG-DDPC could be absorbed by tumor cells and exhibited fluoresce inside those cells. In conclusion, ADG-DDPC was successfully prepared, and in vitro characterization study pointed to that the nano-preparation exhibits a higher antitumor activity than AgNPs.

In order to determine the differences in structure and optimum isolation conditions of Glycyrrhiza uralensis endophytes from different habitats, plate-separation method was used to identify endophytes in G. uralensis from Gansu, Ningxia, Inner Mongolia, Xinjiang, and Beijing. The isolation parameters were defined by investigating various concentrations and sterilization time of NaClO solution. The strains were identified by morphological and molecular biological methods. The results showed that 5% NaClO solution and sterilization time of 5 min were the optimal surface sterilization conditions. Among 129 strains of G. uralensis from 5 producing areas, 438 strains of endophytic fungi were isolated and belonged to 5 orders, 7 genera, and 11 species. Among them, 4 taxa were firstly isolated from the licorice in China. Fusarium was a common genus among the 5 regions. There were differences in the composition and structure of the endophytic fungi of G. uralensis from different habitats. Diversity analysis showed that the endophytic fungi diversity in Gansu was the highest and that of Beijing was the lowest. The comprehensive analyses indicated that the endophytic fungi of G. uralensis are diverse, and there were differences among the number, composition and population of endophytic fungi in five producing areas of Gansu, Ningxia, Inner Mongolia, Xinjiang and Beijing.

Hypophosphatemia is a common metabolism disease in humans. Fibroblast growth factor 23 (FGF23) inhibits phosphate reabsorption by targeting on the renal tubules. FGF23^C-tail contains 73 amino acids from C-terminus of FGF23, serves as an inhibitor of FGF23, and can increase phosphate reabsorption. Therefore, FGF23^C-tail is an important drug for hypophosphatemia. In this paper, we constructed a fusion protein of FGF23^C-tail with HSA, and investigated the expression of the fusion protein in the Pichia pastoris system. The recombinant gene was constructed by fusion PCR. A high-yield strain was selected by G418 resistance and fermentation yield, and the expression yield was 43.7 mg·L^-1 in flask. In 5 L fermenters, the highest expression yield could reach 265.6 mg·L^-1. FGF23^C-tail-HSA could be used as an inhibitor for FGF23, and could significantly increase blood phosphorus levels in rats. The procedures for care and use of animals were approved by the Ethics Committee of YiChun University. This paper provided a basis research for further studying physiological activity of FGF23^C-tail-HSA.