A chemical fingerprint is an important mean for quality control of traditional Chinese medicine (TCM); however, there is much redundant information in a conventional fingerprint that can affect its availability and accuracy. In this work, the antibacterial biopotency of Scutellariae Radix (Huangqin, HQ) was determined according to the parallel line method of quantitative response. HPLC was adopted to detect the chemical fingerprint of HQ; Grey relational analysis (GRA) was used to identify the primary effective components. The results showed that the antibacterial biopotency of 15 batches of HQ ranged from 0 to 1 000 U·g^-1 and the average potency was 556.29 ±258.57 U·g^-1 (1 U is equivalent to the bacteriostatic activity of 2.25 μg gentamicin). There were 34 characteristic peaks in the fingerprints of the samples and their similarities were 0.255-0.991. Eight components (P33, P30/baicalein, P19/baicalin, P15, P29, P34, P31/wogonin and P28) are positively related to antibacterial biopotency and selected from the top ten components of the grey correlation sequence to define the antibacterially effective components fingerprint of HQ. This fingerprint can clearly distinguish the commodity specification and grade, and can also characterize the morphology, components and the bacteriostatic potency differences of HQ. In summary, we established an antibacterially effective components fingerprint which provides simplified information on the antibacterial activity of Scutellariae Radix and could significantly improve the efficacy, specificity, and discriminative ability of the fingerprint for HQ, and could be a useful reference for the comprehensive quality evaluation of other TCM.

The objective of this work was to develop a bioassay to quantify the antiplatelet aggregation activity of hirudo for quality evaluation and control. Antithrombin activity of hirudo extracted by high temperature decoction was determined by thrombin titration. Antiplatelet aggregation activity of hirudo was determined through pharmacodynamic experiments in vitro and in vivo using a bioassay we developed for quantifying inhibition of platelet aggregation. Methodological investigation was carried out and the titers of 12 batches of hirudo samples were determined. During the experiment, the disposal of animals is in accordance with the ethical standards of animal experiments. The results showed that the antithrombin activity of hirudo decocted at high temperature decreased significantly and almost lost its activity. Hirudo inhibited platelet aggregation and results in vivo and in vitro were consistent. These assays were employed to test 12 batches of hirudo. The results demonstrated that the biopotency of 12 batches was 113.49, 96.13, 121.22, 127.33, 83.48, 108.72, 131.41, 127.95, 76.90, 126.27, 132.89 and 573.53 U·mg^-1. The method was reliable and reproducible and can be used to assess the quality of hirudo.

In recent years, chimeric antigen receptor T cells (CAR-T) have been viewed as a target for successful treatment of hematologic malignancies. However, targeting conventional CAR-T cell has a series of side effects, such as cytokine storm, on-target off-tumor effect and neurotoxicity during treatment, and these side effects threatened patients' life. The extracellular domain of conventional CAR-T is a fixed single-chain variable fragment (scFv) that only targets one specific antigen, and once the tumor antigen is mutated or disappears, the CAR-T cell will fail. In recent years, a number of different switchable CAR-T cells have emerged. The design of switchable CAR-T cells is divided into two aspects:CAR-T cell and molecular switch respectively, and the activation of CAR-T is completely dependent on the switch. It is not only universal, but also decreases the side effect of conventional CAR-T through controlling the molecular switch. We summarized the existing sCAR-T to provide an idea for CAR-T design and optimization, and lay a foundation for entering sCAR-T into clinical practice.

Chuanxiong Qingfengteng mixture (CQM) is an analgesic developed based on clinical evidence and traditional Chinese medicine theory, which majorly consists of Ligusticum chuanxiong and Sinomenium acutum extracts. The current study aims to establish an UHPLC-UV method for the quantification of sinomenine and ligustrazine after CQM administration to rats, mice and cells, and to study the brain permeability of sinomenine and ligustrazine. The selectivity, linearity, accuracy, precision and stability of the established method demonstrated that it was suitable for the determination of sinomenine and ligustrazine in biological samples such as plasma, brain tissue and cellular fluid. After CQM was intravenously administered to rats and mice, both sinomenine and ligustrazine were detected in the brain from 5 min-2 h. The CSF/plasma partition coefficients (K_{p, C/P}) of each component were higher than those of brain tissue/plasma partition coefficient (K_{p, B/P}), the K_{p, C/P} and K_{p, B/P} of ligustrazine were higher than those of sinomenine. The concentrations between CSF and brain tissue were strongly correlated (Pearson's R>0.86, P < 0.001). The unbound fraction in plasma of sinomenine and ligustrazine was 78.92% and 34.07%, respectively. The plasma protein binding rates displayed concentration-independent behavior within their respective in vivo concentration ranges. After CQM co-cultured with Caco-2 cell monolayers, the apparent permeability coefficient (P_app) of sinomenine and ligustrazine were 1.30×10^-6 and 3.64×10^-6 cm·s^-1, respectively, following into the range of the intermediate and high permeability compounds. The efflux ratio (P_{app(basolateral→apical)}/P_{app(apical→basolateral)}) of sinomenine and ligustrazine were 0.67 and 0.85, respectively. When combined with P-glycoprotein inhibitor, the P_app of each component did not increase. In conclusion, the UHPLC-UV assay was successfully applied for the brain permeability study of CQM, the components of CQM can be quickly distributed to cerebrospinal fluid and pass through the blood-brain barrier. The brain permeability of ligustrazine is higher than that of sinomenine. The transmembrane transport of sinomenine and ligustrazine may not be affected by efflux transporters. All animal care and use complied with the Regulations for the Administration of Affairs Concerning Experimental Animals approved by the State Council of the People's Republic of China. All animal studies were implemented according to protocols, which were reviewed and approved by the Institutional Animal Care and Use Committee at Experimental Research Center, China Academy of Chinese Medical Sciences.

This study aimed to investigate the influence of combinating Huangqi with Fuzi on the pharmacokinetics of six Aconitum alkaloids, i.e. aconitine (AC), hypaconitine (HA), mesaconitine (MA), benzoylaconine (BAC), benzoylhypaconine (BHA) and benzoylmesaconine (BMA). The plasma concentrations of the drugs were determined by LC-MS for dose response and time dependent curves. The pharmacokinetic parameters were calculated by DAS 3.3, and SPSS 12.0 was used to analyze the differences of main pharmacokinetic parameters between the two groups. Comparing with Fuzi group, the AUC_0-t and AUC_0-∞ of six alkaloids in Fuzi-Huangqi group was significantly decreased, the CL_z/F of six alkaloids except HA was significantly increased; the C_max was decreased and the t_max was prolonged in 3 monoester alkaloids, and the apparent volume of distribution of BMA and MA (V_z/F) increases. These data indicated that Huangqi can inhibit the absorption of aconite alkaloids, induce the distribution of aconite alkaloids to the whole body, and accelerate the elimination of aconite alkaloids. The animal experiment scheme in this study has been approved by the Experimental Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine.

This study aimed to determine the protective effect of Qizhi hypoglycemic tablet (QZHGT) on foot ulcer in diabetic rats and explore its possible mechanism. Diabetes was induced by streptozotocin injection in rats. The rats received QZHGT (780 mg·kg^-1), metformin hydrochloride tablet (Metf, 200 mg·kg^-1) or glibenclamide tablet (Glib, 1.5 mg·kg^-1) alone via intragastric administration once a day for three months. Food ulcer was prepared by foot skin excision after drug therapy lasted for two months, and the dynamic changes in food ulcer healing were determined. During the experiment, blood glucose, serum levels of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS), factor Ⅲ (FⅢ) and four coagulation parameters[thrombin time (TT), activated partial thromboplatin time (APTT), prothrombin time (PT), fibrinogen (FIB)] were detected. Finally, the protective mechanisms of QZHGT against diabetes and foot ulcer were analyzed by network pharmacology, and immunohistochemistry was used to confirm the expression of transforming growth factor-β (TGF-β) and nuclear factor κB (NF-κB) in pancreatic tissue. All animal procedures were approved by the Animal Experimentation Ethics Committee of Henan University (permission number HUSAM 2016-288). The results showed that the lasting hyperglycemia, polydipsia, polyphagia, polyuria and body weight lost took place in model rats compared to those in normal rats. These model rats also showed an increase in serum VEGF and iNOS, FⅢ, TT, APTT and PT, and a reduction in FIB and wound healing. Metf or Glib significantly improved hyperglycemia, polydipsia, polyphagia, polyuria and emaciation, but failed to ameliorate hypercoagulation and wound healing. QZHGT showed a similar effect on polydipsia, polyphagia, polyuria and emaciation to Metf or Glib, although it was inferior to them in hypoglycemic action. Importantly, QZHGT significantly improved hypercoagulation and wound healing, and attenuated serum VEGF and iNOS. Network pharmacology revealed that QZHGT decreased hyperglycemia through "insulin resistance pathway", improved coagulation status through "HIF-1 signaling pathway", prevented diabetic foot ulcers through "VEGF signaling pathway", "MAPK signaling pathway" and "NF-κB signaling pathway". Immunohistochemistry showed that QZHGT could inhibit the expression of TGF-β and NF-κB in pancreatic tissue to maintain islet function in diabetic rats. In summary, these data suggest that QZHGT can prevent pancreatic injury for adjunctive hypoglycemia and diabetic foot ulcer treatment, and is a better preventive and therapeutic drug for diabetic foot ulcer.

The chemical constituents were isolated and purified by column chromatography and semi-preparative reversed-phase high performance liquid chromatography with silica gel, MCI and polyamide in order to study the chemical constituents of dried flowers of Osmanthus fragrans var. aurantiacus. Their structures were identified by the physical and chemical properties and one-dimensional nuclear magnetic resonance (¹H-, ¹³C-NMR, DEPT), two-dimensional nuclear magnetic resonance (¹H-¹H COSY, non-decoupled HSQC, HSQC, HMBC), UV, IR and high resolution mass spectrometry data. One new compound (1) and five known compounds (2-6) were isolated from 95% ethanol extract of dried broccoli. They were identified as (9S)-9-hydroxymengastigm-5-en-4-one-9-O-primeveroside (1), oleanolic acid (2), forsythiaside (3), 2-(4-hydroxyphenethyl)-ethanol-(6-acetyl)-β-D-glucopyranoside (4), salidroside (5), and acteoside (6). Compounds (2-6) were isolated from this plant for the first time.

To explore the application of an effect-constituents index (ECI) for the quality evaluation of rhubarb, we carried out the simultaneous determination of 12 chemical components by ultra-performance liquid chromatography and used the ICR mouse constipation model to determine the diarrhea biopotency of these 12 components. With the diarrhea biopotency of sennoside A as a reference, the diarrhea biopotency weight coefficient of each chemical component was obtained. A multi-component chemical quantitative analysis combined with the biopotency weight coefficients for rhubarb was developed, named the diarrhea ECI. Animal experiment ethics requirements were approved by the Animal Experimental Ethics Committee of the 302 Hospital of the People's Liberation Army (Grant Number:IACUC-2015-012). The results showed that there were significant differences in the content of the 12 chemical components in different batches of processed products of rhubarb. Especially worthy of attention was the content of aloe-emodin-8-O-β-D-glucoside in sample Rh03, nearly 40-fold higher than that in Rh07 (4.79 vs 0.12 mg·g^-1), and the content of rhein-8-O-β-D-glucoside in sample Rh03, nearly 45 times higher than that in Rh07 (3.56 vs 0.08 mg·g^-1). The actual measured diarrhea biopotencies of the 12 chemical components ranged from 61.65 ±4.28 to 233.84 ±5.58 U·mg^-1. The calculated diarrhea effect-constituents indices of 16 rhubarb samples ranged from 1.07 (Rh15) to 19.38 (Rh03), and the actual measured diarrhea biopotencies of 16 rhubarb samples based the ICR mouse constipation model ranged from 23.84 U·g^-1 (Rh16) to 310.94 U·g^-1 (Rh05). The correlation between the diarrhea ECIs and the actual measured diarrhea biopotencies of 16 rhubarb samples was good (r=0.969 5), suggesting that the diarrhea effect-constituents indices may be the most suitable for evaluating the quality of different rhubarbs with regard to diarrhea.

Xiaojin pills, the first choice for clinical treatment of breast hyperplasia, were selected to explore the suitability of a bioactivity assay with chemical fingerprinting for the development of an overall quality evaluation assay. The liposoluble and water-soluble fraction fingerprints of Xiaojin pills were established. The ability to inhibit platelet aggregation and the rate of inhibition of cyclooxygenase-2 (COX-2) for 16 batches of Xiaojin pills from several manufacturers was analyzed; the chemical fingerprints of these samples were correlated with the bioactivity and chemical analysis. The animal protocol was approved by the Committee on the Ethics of Animal Experiments of Affiliated Hospital of Chengdu University of Traditional Chinese Medicine Approval, ID:2018BL-002. Results showed that the antiplatelet aggregation activity of 16 batches was 0.712-1.278 U·mg^-1, with a relative standard deviation (RSD) of 15.4%. COX-2 inhibition was 52.07%-68.95% and the RSD was 8.91%. The results showed that there was little difference in the biological effects of these samples. However, the chemical fingerprint consistency of these 16 batches of Xiaojin pills was poor, and the similarity of nearly half of the samples was less than 0.9. The total peak area of Xiaojin pills was 32.74%-165.37% across samples, showing very poor chemical consistency. In order to explore the reasons for the poor chemical consistency despite good consistency in the biological assays, the fingerprint chromatogram was analyzed by multivariate statistical analysis. The main chromatographic peaks were identified. The results showed that the similarity of Xiaojin pills was mainly determined by the prominent chromatographic peaks 17, 18, 20, 23 and 27 in the liposoluble fingerprints, which were identified from Liquidambaris resina and Angelica sinensis Radix. However, Liquidambaris resina and Angelicae sinensis Radix had almost no anti-platelet aggregation activity or COX-2 inhibitory effect at the normal prescription ratio. As a result, the ability to utilize chemical fingerprints to evaluate the quality consistency of Xiaojin pills is limited. The selection of biological evaluation methods that reflect clinical efficacy could make up for the shortcomings of chemical evaluation methods for quality assessment, and provide new ideas and methods for the overall quality evaluation of complex Chinese patent medicines.

Pickering emulsion is a new type of emulsion which is stabilized by the adsorption of solid particles on the interface of emulsion droplets. In recent years, its applications in pharmacy have attracted more and more attention because of its higher resistance to coalescence and better safety than traditional surfactant emulsions. The Pickering emulsion was first used for topical administration to reduce skin irritation of surfactants and promote transdermal absorption of drugs. Recently, new oral and injectable Pickering emulsions have also been reported, which can promote oral absorption of insoluble drugs, improve stability of drugs, control drug release, targeted-delivery drugs, and serve as the carrier for novel immunological adjuvants. All these studies show Pickering emulsion a promising drug delivery system. However, its development in pharmacy is still in its infancy. There are many factors influencing the preparation of Pickering emulsions. But there is no systematic analysis of these factors up to now. In this review, we gave an overview of Pickering emulsions from their application in pharmaceutical field, preparation and evaluation, focusing on the effects of solid particles, oil phase, preparation technology and interaction of various factors on the fabrication of Pickering emulsions. The challenges and future directions of this exciting and rapidly expanding research area were further commented on, in order to provide reference for the in-depth study of Pickering emulsion drug delivery systems.