Targeted nano-drug delivery system (TNDDS) offers prominent advantages in drug delivery for treatment of hepatocellular carcinoma, targeting the tumor site via ligand-receptor interaction. TNDDS reduces the dosage of drug to fulfill the therapeutic index requirement, improving pharmacokinetics and biodistribution. Besides, it can sustain drug release for several days after single-dose administration. In recent years, glycyrrhetinic acid (GA) attracts much attention as a highly efficient ligand targeting to liver tumor. The superiority of GA is mainly reflected in its combination of efficient liver tumor targeting, superior anti-tumor activity and favorable biocompatibility. GA-based TNDDS to liver tumor possesses high site-specificity and therapeutic efficiency for chemotherapeutic drugs or genetic materials delivering. This paper focuses on the basic theory of GA as a ligand targeting to liver tumor and the researches advances in the development of GA-based nano-delivery systems. Through the review and summary in this paper, it is expected to systematically present current progress of GA-based liver tumor TNDDS for interested researchers, and provide references for the development of new delivery systems.

OBJECTIVE To establish a quality consistency evaluation method reflecting the overall pharmacodynamic characteristics of multi-batch Chinese medicine compound preparations. METHODS Establish a drug absorption simulating system(DASS) standardized absorption biomimetic system module using a flipped intestinal sac model, and prepare intestinal absorption samples of Danggui buxue tang from different sources and batches; Drawing on the concept of consistency evaluation of biopharmaceuticals, a cell biological effect characterization module was established using Real-time cell analysis(RTCA) to monitor the cell response curves of 15 batches of Danggui buxue tang samples. RESULTS The combination of DASS-RTCA was used to extract the characteristic parameters of time-dependent cell response patterns (TCRPs) maps from 15 batches of Danggui buxue tang samples. The RSD of each characteristic parameter was less than 5.1%, indicating that the differences in cell effect characterization of Danggui buxue tang (DBT) were small and the similarity of TCRPs maps was high. Through similarity analysis, cluster analysis, radar chart analysis, etc., it is reflected that the quality of different batches of DBT has high consistency. CONCLUSION The quality consistency evaluation method established by DASS-RTCA can reflect the overall quality of the preparations and provide new ideas and methods for the evaluation of batch-to-batch quality consistency of traditional Chinese medicines.

OBJECTIVE This study aimed to investigate the role and potential mechanisms of Icotinib (ICO) on pulmonary fibrosis. METHODS C57BL/6 mice were randomly divided into Sham group, PF group, ICO 30 mg·kg^-1 group and ICO 60 mg·kg^-1 group, 8 rats in each group. A mouse model of PF was induced by intratracheal injection of bleomycin (3 mg·kg^-1). Hematoxylin-eosin staining and Masson trichrome staining for lung tissues were performed to observe the pathological alterations and collagen deposition. Immunohistochemical detection of lung tissue collagen type Ⅰ (collagen Ⅰ) expression. In vitro, the lung epithelial cells were divided into control group, epidermal growth factor (EGF) group, EGF combined with ICO (0.1, 1, 10 mmol·L^-1) groups. The protein expression of E-cadherin, α-SMA and nuclear transfer of NF-κB p65 were detected by immunofluorescence. The protein levels of Collagen Ⅰ, E-cadherin, α-SMA, Vimentin, phosphorylation epidermal growth factor receptor (p-EGFR), p-IκBα, p-NF-κB p65 and nuclear NF-κB p65 were detected by Western blot analysis in lung tissue and (or) cells. RESULTS The results demonstrated that ICO inhibited bleomycin-induced collagen deposition, reduced type Ⅰ collagen expression, alleviated bleomycin-induced EMT (increased E-cadherin expression and decreased Vimentin and α-SMA expression), and decreased phosphorylation of EGFR, IκBα, NF-κB p65 and nuclear translocation of NF-κB p65 in vivo. Furthermore, incubation of lung epithelial cells with EGF activated EMT and EGFR/NF-κB signaling pathway, and these effects were reversed by ICO In vitro. CONCLUSION In conclusion, ICO attenuates EGF-induced EMT in lung epithelial cells and bleomycin-induced pulmonary fibrosis in mice by downregulating EGFR/NF-κB pathway.

OBJECTIVE To establish a quantitative proton nuclear magnetic resonance (qHNMR) method for determination of the reference standards of moxifloxacin hydrochloride impurities A, B, C and D. METHODS Proton nuclear magnetic resonance (¹H-NMR) spectra of four reference standards of impurities were obtained in dimethylsulfoxide-d₆ (DMSO-d₆) or chloroform-d (CDCl₃) using a nuclear magnetic resonance spectrometer. The internal standard was 1,3,5-trimethoxybenzene. All ¹H-NMR spectra for quantitative analysis were measured with noesyigld1d pulse sequence using the following experimental parameters: 32 number of scans (NS), relaxation delay time (D1) of 30 s, 25 ℃ testing temperature. RESULTS The quantitative peak signals of four moxifloxacin hydrochloride impurities and 1, 3, 5-trimethoxybenzene were well separated on ¹H-NMR spectra, and the linear relationship was good within the linear range (r²>0.999 4). The injection precision and repeatability of the method were good. The contents of four reference standards of impurities determined by qHNMR method were basically consistent with those determined by mass balance method. CONCLUSION The established qHNMR method is accurate, reliable, simple, fast, which provides a new way for content determination of these impurities and can also be used as a mutual verification method for the calibration results of these reference substance by the mass balance method.

OBJECTIVE To explore the feasibility of using cyclic olefin polymer (COP) as packaging material for human albumin products. METHODS Human albumin products were stored in COP bottles. Under the conditions of long-term stability (2-8 ℃ for 24 months) and accelerated stability [(25±2) ℃ for 12 months], the key quality indexes of albumin and the probable extracts of COP material were analyzed, and the seal integrity of COP packages was tested. RESULTS Under both test conditions, the appearance, visible foreign matter, numbers of insoluble particles, pH, purity, polymer content, residual aluminum content, protein content, activity of prekallikrein activator and abnormal toxicity of the albumin products all conformed to the quality standards and met the requirements of Chinese Pharmacopoeia. In the products, the contents of molybdenum, nickel, methylbenzene, and cyclohexane that may be produced by COP bottles were all lower than the quality standard limits. Moreover, the human albumin packaging container assembled by COP bottle, halogenated butyl rubber plug and aluminum-plastic combination cap showed excellent package integrity. CONCLUSION COP can be used in the storage and transport of human albumin.

Ginkgo biloba has been widely used to treat diseases such as blood stasis blocking collaterals, chest pain, stroke, and hemiplegia. Ginkgo biloba extract 50 (GBE50) is the fifth generation of Ginkgo biloba extract (GBE). The chemical components of GBE50 include total flavonoids and terpene lactones. GBE50 shows multiple pharmacological effects such as anti-inflammatory, antioxidant stress, and antiplatelet aggregation. In clinic, it has been widely used in vascular-related diseases such as coronary heart disease, angina pectoris, stroke, and vascular dementia. The authors review the studies on the material basis, clinical application, and mechanism of GBE50, and mainly focus on the research progress in pharmacological mechanism. These might provide a fresh perspective and idea for research on GBE50 in the treatment of vascular-related diseases.

OBJECTIVE To excavate the key genes of drought stress response of A.sinensis, and carry out the comparative analysis with the transcriptome data of the main cultivars ‘Mingui 1’ and ‘Mingui 2’ of Angelica sinensis (Oliv.) Diels. METHODS With the fresh leaf and root tissues of two cultivars of A.sinensis as materials, a cDNA library was constructed. The Illumina HiSeq^TM 4000, a second-generation high-throughput sequencing platform, was used for sequencing analysis, and key enzyme genes in response to drought stress were screened from differentially expressed genes(DEGs). RESULTS A total of 584 423 236 clean reads were obtained from transcriptome sequencing, in which the percentage of Q20 (base amount ≥20%) and Q30 (base amount ≥30%) were above 97.47% and 92.64%, and the GC content ranged from 42.78% to 43.15%. A total of 1 894 DEGs were screened from the leaves and roots of two cultivars of A.sinensis, the numbers of which were 674 and 1 220, respectively, and they had 338 shared DEGs. The GO enrichment results showed that the annotation classification of DEGs of two cultivars of A.sinensis in the same tissue part mainly included cellular process, metabolic process and catalytic activity. KEGG analysis found that the DEGs were significantly enriched in plant-pathogen interaction, MAPK signaling pathway-plant, phenylpropanoid biosynthesis and plant hormone signal transduction pathways. The detailed classification annotation results were consistent with the trends of GO and KEGG analysis. Based on the functional annotation results, 60 drought resistance genes were excavated. HVA22C, KRP1, PUB23, DREB1B and Bp10 were selected to verify their expression levels by qRT-PCR. and the results showed their genes expression level were consistent with the transcriptome sequencing gene expression trends. CONCLUSION The two cultivars of A.sinensis have some differences in drought resistance pathways such as abscisic acid regulation, osmoregulation, scavenging of reactive oxygen species and regulation of other functional proteins, and the screened drought resistance genes can provide data references for further research on the molecular mechanisms of A.sinensis in response to drought stress.

OBJECTIVE To optimize the formulation of nicorandil thermosensitive nasal gel (NIC-TNG) and further evaluate its quality. METHODS With gelling temperature and gelling time as observation indexes, the blank formulation composition of NIC-TNG was first optimized by central composite design-response surface method. Franz transdermal diffusion cell method was then used to screen the ideal permeation enhancer by using ex vivo nose mucosa of sheep as test model. The effect of pH on the chemical stability of NIC aqueous solution was investigated to establish the suitable pH of NIC-TNG. Lastly, NIC-TNG was prepared and its main quality items such as the gelation temperature and time, pH, labeled contents of the drug and preservative, cumulative erosion rate, cumulative drug release, and in vitro drug release were studied, respectively. Meanwhile, the effect of temperature on the viscosity, expansion coefficient and water holding capacity of NIC-TNG were investigated. RESULTS The optimized formulation of NIC-TNG consisted of 25 mg·mL^-1 NIC, 172.1 mg·mL^-1 F127, 5.0 mg·mL^-1 F68, 3.8 mg·mL^-1 HPMC, 5.0 mg·mL^-1 chlorobutanol and suitable amount of purified water. The gelation temperature and time, pH, labeled content of NIC and preservative were found to be 30.92 ℃, 40.82 s, 6.42, 99.18% and 98.72%, respectively. There was a good linear correlation between the in vitro cumulative erosion rate, cumulative drug release of NIC-TNG and time (r≥0.999 6). Furthermore, the in vitro release of NIC from the nasal gel showed obvious sustained release characteristics. Temperature exhibited obvious effect on the viscosity of the nasal gel. Finally, NIC-TNG showed low expansion coefficient and good water-holding capacity. CONCLUSION NIC-TNG will be expected to have good clinical application prospects due to its advantages such as reasonable formulation composition, simple preparation process, stable and controllable quality, convenient use and obvious sustained drug release behavior.

OBJECTIVE To establish the cell model of reporter gene for detecting histamine phosphate. METHODS The plasmids of human histamine phosphate H1 receptor (H1R), H2 receptor (H2R) and the response elements of G protein-coupled receptor alpha subunits, including Gs, Gi or Gq, cloned with reporter gene were co-transfected into HEK293 cells. The transfected ratio of the plasmid was optimized. Subsequently, the expression and function of H1R and H2R were verified by detecting the change of cAMP content and cellular [Ca²⁺] after the effect of agonists. The chemiluminescence activities of HEK293 cells transfected with H1R and/or H2R under different concentrations of histamine were compared. Finally, the cell model was verified by adding histamine phosphate into compound amino acid injection, succinyl gelatin injection, and enoxaparin sodium solution to simulate the detection and calculating the recovery rate. RESULTS When the amount of three plasmids was 1∶1∶10, the response value of cells to histamine phosphate was higher, this ratio was used for subsequent transfection. The changes of cAMP and Ca²⁺contents in cells verified the overexpression of H1R and H2R and the function of reporter gene response element. When the concentration of histamine phosphate was higher than 0.64 nmol·L^-1, the chemiluminescence value of cells overexpressing H1R and H2R reporter genes (H1R/H2R-Luc cells), was higher than that of other groups (P<0.05). This cell model was used to detect the histamine phosphate added in amino acid injection, succinyl gelatin injection, and enoxaparin sodium solution. The recovery rates were between 88%-121% when the concentration of histamine phosphate was between 3.2-400 nmol·L^-1. CONCLUSION The H1R/H2R-Luc cells constructed successfully in the present study would be used for the detection of histamine phosphate.

OBJECTIVE To explore the characteristic and microscopic features of Perillae Folium and Perillae Folium sum Cacumen and provide reference for the identification of Perillae Folium and Perillae Folium sum Cacumen. METHODS Characteristic identification and microscopic identification of 6 batches of Perillae Folium and Perillae Folium sum Cacumen were carried out. Samples were collected at different growing stages, including seeding stage, vegetative growth stage and reproductive stage. RESULTS For Perillae Folium collected at different growthing stages, the transverse sections of leaf veins were compared. As plant grows into older stages, more areas of the leaf veins appeared purple color. Additionally, the color of excited luminescence varied between Perillae Folium collected at different growing stages. These phenomena could be utilized to differentiate between Perillae Folium collected at different growing stages. Next, this experiment explored the microscopic difference of Perillae Folium and its counterfeit, Perillae Folium sum Cacumen. The leaf surface characters of Perillae Folium and Perillae Folium sum Cacumen were found to appear in different shapes. The density of peltare glandular hair and capitate glandular hair, as well as the numerical value of stomatal index ratio (lower/upper surface), was observed to be different between two kinds of leaves. CONCLUSION Through this experiment, the characteristic and microscopic features of Perillae Folium and Perillae Folium sum Cacumen are summarized, offering a reference for the supervision inspection, clinical application and standard revision of Perillae Follium.