Conventional chemotherapy drugs, molecularly targeted drugs, and immune checkpoint inhibitors are the major constituents of anti-tumor drugs in clinical settings at present. Molecularly targeted drugs specifically target the key proteins, genes, or signal transduction pathways in tumor cells which are essential for initiation and development of tumor, resulting in selective activity to induce cell death or growth inhibition. Molecularly targeted drugs have emerged as the mainstream in the research and development of anti-tumor drugs due to its high selectivity and low toxicity. Natural products refer to the chemical constituents or metabolites originated animals, plants, or microorganisms, which have been recognized as one of the important sources of drug discovery with abundant resources and diversified structures. At present, a number of molecularly targeted anti-tumor drugs derived from natural products or their derivatives have been approved for cancer therapy or in clinical trials. This review will summarize the molecularly targeted anti-tumor drugs derived from natural products or their derivatives according to their different cellular targets, and also outline the molecular mechanism, progress, and perspectives of these drugs.

It is now widely accepted that platelet aggregation plays an important role in physiological hemostasis and pathological thrombosis associated with cardiovascular and cerebrovascular diseases. Anti-platelet aggregation drug research is also a hot spot of current research. The biggest challenge of antiplatelet therapy has been the molecular overlap of the hemostasis and thrombosis, leading to a serious risk of bleeding. Recent studies have emphasized the importance of shear stress generated from blood flow, which will primarily drive platelet activation and aggregation in thrombosis. So if we can take advantage of the differences between the physiological and pathological vascular blood flow environment, the development of selective anti-platelet therapy may be a safer treatment for cardiovascular and cerebrovascular diseases. In this review, we discuss the underlying mechanisms of shear-induced platelet activation. Later, we summarize the effects and mechanisms of compounds and traditional Chinese medicine on shear-induced platelet activation. The aim is to provide a reference for the study of biological pharmacology of traditional Chinese medicine for promoting blood circulation and removing blood stasis.

Fibrosis is a pathological process characterized by tissue scars and can occur in many organs of the human body. Organ fibrosis is manifested by increased fibrous connective tissue and reduced parenchymal cells in organ tissues, which can lead to destruction of organ structures and reduced function, which seriously endangers human health. Current strategies for treating organ fibrosis include:blocking the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway, anti-inflammatory, regulating the sphingosine kinase 1/sphingosine-1-phosphate (SK1/S1P) signaling pathway, antagonizing vasoactive peptide receptors, enzyme inhibitors, kinase inhibitors, inhibitors of cellular signaling pathway, regulation of metabolic pathways, and mesenchymal stem cell therapy. In the review, the treatment strategies for organ fibrosis and the latest developments in the research of anti-organ fibrosis drugs are summarized to provide a reference for the development of anti-organ fibrosis drugs.

Coronaviruses (CoVs) are associated with some mammalian infectious diseases, which have caused several outbreaks of respiratory system infectious diseases in recent years. There is no effective vaccine or approved drug treatment against coronaviruses, and the development of anti-coronavirus agents is an urgent priority. Phenothiazines are a class of antipsychotic drugs, which were found that they have some other biological activities, like promising antibacterial, antifungal, anticancer, antiviral, etc. They can be used for drug repurposing. This review summarizes current researches on the potential anti-coronavirus activity of phenothiazine, discusses the mechanisms and some research difficulties, and provides a foundation for developing anti-coronavirus drugs which use phenothiazine as the lead compound.

Applying poly(ADP-ribose) polymerase inhibitors (PARPi) to the treatment of cancers with homologous recombination deficiency (HRDness) has been a great advance in the field of molecular therapeutics. However, in the clinic patients lacking the specific mutations or developing reverse mutations in the process of PARPi treatment may not benefit from PARPi monotherapy. Therefore, targeting homologous recombination (HR) repair with molecularly targeted agents is becoming an attractive research focus and is raising the concept of "chemical HRDness". HR repair is an evolutionarily conserved and extensively regulated process that employs sister chromatids as the template to repair DNA double-strand breaks with high fidelity. In addition to directly targeting HR components, modulation of regulatory pathways controlling HR repair is effective in achieving the "HRDness" phenotype; this includes modulation of the cell cycle checkpoint regulatory pathway, the phosphatidylinositol 3-kinase (PI3K) signaling pathway, the chromatin remodeling pathway, etc. Targeting HR repair can not only result in "synthetic lethality" when combined with PARPi, but also sensitizes cancers to traditional radio/chemotherapy and novel immunotherapy. In this review we describe the HR repair pathway and its regulatory pathways, summarize the preclinical and clinical outcomes of targeting HR repair, discuss the remaining problems in this field and provide a prospective on its application in tumor therapy.

Tumor cells can metabolize glucose through glycolysis to intermediates for biomacromolecule synthesis by inhibiting the activity of the pyruvate dehydrogenase complex (PDC) in mitochondria. In this process, pyruvate dehydrogenase kinases (PDKs) play a key role. The inhibition of the activity of PDKs can effectively block this metabolic pathway, activate mitochondrial oxidative metabolism, and induce tumor cell apoptosis. PDK inhibitors have become a research hotspot in medicinal chemistry, and novel structures targeting classical binding sites have been synthesized. In this paper, recent research progress on PDK inhibitors is reviewed to provide information on these latest entities and to explore their clinical applicability.

Resveratrol possesses a wide range of biological activities, such as anti-cancer, anti-oxidation, induction of apoptosis, etc., but its poor drug properties, rapid metabolism, low target selectivity and bioavailability limit its application value. Studies have shown that modification of the structure of natural compounds can improve their pharmacological activities. To improve the bioavailability of resveratrol, many researchers have undertaken the synthesis and activity evaluation of resveratrol derivatives and analogues. They have modified the phenolic hydroxyl groups, double bonds and benzene ring of resveratrol so as to further understand the interactions among functional groups and its structure-activity relationship. In this paper, we review the chemical structures, synthetic methods and mechanisms of biological activity of resveratrol monomer derivatives as well as their related therapeutic applications, especially in the anticancer area over the last decade. This will provide some reference value for the further research and development of resveratrol-related drugs.

Based on Chinese clinical guidance for COVID-19 pneumonia diagnosis and treatment (7^th edition), the metabolism and pharmacokinetics of drugs used in clinical treatment of COVID-19 were reviewed. The antiviral drugs include remdesivir, chloroquine/hydroxychloroquine, lopinavir/ritonavir, favipiravir, arbidol, baicalin, baicalein and forsythin. Among them, the metabolism and pharmacokinetics of arbidol, baicalin and forsythin are the research results of the author's laboratory. This article aims to provide reference for the efficacy evaluation and rational drug use of COVID-19.

Xenograft mice are preclinical animal models of tumors and are widely utilized in anti-tumor research. PK/PD modeling of anti-tumor agents is an approach that can capture the time profile of the "dose-plasma concentration-biomarker level-tumor volume" process based on experimental data from xenograft mice using a non-linear mixed-effect model. PK/PD modeling can help optimize the dosing regimen for anti-tumor therapy, evaluate any synergistic effect and help identify an optimal schedule for combination therapy, as well as providing a preliminary estimate of a drug's efficacy and anti-tumor potency in the human body. PK/PD modeling can also help by quantitatively explaining the mechanism of the tumor-inhibitory effect as indicated by changes in biomarker levels after a drug acts on its target. This article provides a systematic summary of the background, application range, and limitations of the mainstream anti-tumor agent PK/PD models. Recent advances in model structure development are reviewed in detail. Finally, we discuss promising applications of PK/PD models in anti-tumor medicine development from the perspective of a drug's mechanism of action, optimization of combination therapy schedules, and their clinical translation.

In recent years, layer-by-layer self-assembly (LbL) has developed rapidly. It has been widely used in various industries such as medicine and metallurgy because of its simplicity, flexibility and controllability. In the study of drug delivery system, hollow microcapsules constructed by LbL method as drug carrier have great advantages in drug release, circulation in vivo and bioavailability, providing a technical platform for targeted drug release. In this paper, we summarize the types of film-forming materials and the driving force used in LbL technology, the way of loading drug into hollow micro capsule, and the variety of loaded drugs. We focus on the release mechanism, its evaluation and safety evaluation of self-assembled film as drug carrier in vivo and in vitro. The review shows the great application prospect of LbL technology in the field of drug delivery.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein system exerts genome editing effect through cleaving DNA double strands using RNA-guided endonuclease. Double-strand breaks were repaired via homology directed repair (HDR) or nonhomologous end joining (NHEJ), accompanied by insertions, deletions or replacements into the genome. As a powerful tool, CRISPR/Cas system has provided tremendous convenience for basic researches and may pave the path to treat genetic diseases and cancers. Genome editing could be achieved only when both CRISPR RNA and Cas protein are delivered into nucleus of target cell. Compared with physical and viral delivery, nonviral delivery of CRISPR/Cas system possesses unique advantages in terms of safety, loading capacity and preparation. Hence, many researchers have devoted themselves to the development of nonviral vectors with high delivery efficiency which is important for the application and translation of the promising technology. Advances on cationic liposomes, lipid like nanoparticles, cationic polymers, AuNPs, vesicles, polypeptides, proteins and so on have been made. We will give a brief introduction to the mechanism of CRISPR/Cas9, problems faced by nonviral delivery of CRISPR/Cas9 system in forms of plasmid, mRNA and protein; examples of non-viral vectors, hoping to give some hints on design of safe and efficient nonviral vectors for genome editing.

Photodynamic therapy (PDT) has attracted wide attention due to its unique advantages such as minimal invasiveness, high efficiency and high selectivity, and its ability to induce anti-tumor immune response. However, the treatment process is heavily dependent on the oxygen content of the treatment site, and the widespread oxygen deficiency in malignant tumors severely limits its efficacy. In addition, PDT-mediated oxygen depletion exacerbates tumor hypoxia, which further reduces its therapeutic effect. In recent years, many researches have been devoted to overcoming this problem. This paper summarized various strategies based on tumor hypoxic PDT in recent years, discussing the advantages and disadvantages of these strategies, and analyzing the main challenges and future directions of PDT in the treatment of tumors, so as to provide references for the in-depth study of photodynamic therapy of tumors.

Philadelphia chromosome (Ph) positive (Ph⁺) B cell acute lymphoblastic leukemia (B-ALL) is the most common genetic abnormality associated with B-ALL and has been shown to confer the worst prognosis to both children and adults. Increasing evidence has revealed that high tribbles homologue 3 (TRIB3) expression contributes to multi-cancer development and progression, but the underlying role and molecular mechanisms of TRIB3 in Ph⁺ B-ALL remain unclear. Here, we report that TRIB3 expression was enhanced in Ph⁺ B-ALL patient samples and positively associated with the expression of breakpoint cluster region-Abelson tyrosine kinase (BCR-ABL). We further demonstrated that deletion of TRIB3 attenuated the progression of Ph⁺ B-ALL by reducing BCR-ABL expression. Mechanistically, TRIB3 interacted with lysosomal cysteine proteinase cathepsin Z (CTSZ) to suppress CTSZ-mediated BCR-ABL degradation, which enhanced BCR-ABL activity, causing high proliferation of Ph⁺ B-ALL cells. Thus, our study indicated that inhibiting the expression of TRIB3 to regulate BCR-ABL kinase activity may be exploited as an additional target therapy for Ph⁺ ALL. Procedures for animal study were performed with approval of the Animal Care and Use Committee of the Chinese Academy of Medical Sciences and Peking Union Medical College. The procedure of human leukemia sample was approved by the Ethics Committee of Chinese Academy of Medical Sciences and Peking Union Medical College (KT2019055-EC-1).

The aim of this study was to evaluate the effects and mechanisms of berberine (BBR) against dexamethasone (Dex)-induced metabolic disorders. 3T3-L1 cells were differentiated by Dex treatment and then treated with BBR (2.5, 5, 10 μmol·L^-1). Lipid accumulation was detected using oil-red O staining. After review and approval of the ethics committee of the Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences, C57BL/6N mice were randomly divided into three groups. In the BBR treatment group, mice were subcutaneously implanted with an osmotic pump containing Dex and gavaged with BBR (100 mg·kg^-1·day^-1) for 4 weeks. The model control group was implanted with a Dex osmotic pump with no other treatment. Mice given a saline-filled osmotic pump were used as a negative control. During the study, food intake and body weight were measured weekly. Subcutaneous fat and visceral fat was detected by MRI. At the end of the experiment the plasma levels of total cholesterol (CHO), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), glucose (Glu), and muscle mass were measured. The expression of peroxisome proliferator-activated receptor γ (PPARγ) and AMP-activated protein kinase α (AMPKα) in 3T3-L1 cells and epididymal fat of C57BL/6N mice was evaluated through RT-PCR and Western blot analysis. The results showed that BBR inhibited Dex-induced adipocyte differentiation in 3T3-L1 preadipocytes by up to 23% in a dose-dependent manner. In C57BL/6N mice, berberine alleviated hyperlipidemia and hyperglycemia and reduced visceral fat accumulation induced by Dex. The results from RT-PCR and Western blot analysis showed that BBR reduced PPARγ expression and increased the phosphorylation of AMPKα in 3T3-L1 cells as well as in adipose tissue. Berberine might alleviate Dex-induced metabolic disorder and visceral fat accumulation by modulating PPARγ and AMPK expression.

Possible mechanisms by which Polygonati rhizoma opposes atherosclerosis (AS) were identified by network pharmacology and molecular docking analyses. The Traditional Chinese Medicine Database (TCMD) and the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) were utilized to identify the likely active components of Polygonati rhizoma. The potential targets set of Polygonati rhizoma were predicted with the PharmaDB database and the Swiss TargetPrediction database. The targets set for AS was retrieved by OMIM, DisGeNET and NCBI Gene database. We used the STRING platform to construct a protein-protein interaction network of the intersectional targets and performed visual analysis in Cytoscape. The key targets of Polygonati rhizoma in AS were searched by network topology and the resulting GO and KEGG enrichment was analyzed by Clue GO. In addition, the key targets were verified by molecular docking in Discovery Studio 4.0. A total of 45 active ingredients and 51 potential targets were obtained in the treatment of AS. The results of the topology analysis included five key targets:serum albumin, mitogen-activated protein kinase 3, mitogen-activated protein kinase 1, proto-oncogene tyrosine-protein kinase Src and matrix metalloproteinase-9. The 131 GO items showed that the biological process mainly involved the steroid receptor, cell response to steroid stimulation, the phosphatidylinositol-3 kinase signal pathway, and others. The KEGG pathway analysis included 37 pathways, which were closely related to peroxisome proliferation activated receptor signaling pathway, platelet activation pathway, vascular endothelial growth factor pathway, hypoxia inducible factor pathway and adhesion connection pathway. The results of molecular docking proved that the combined activity of the components with potential key targets is excellent. This study proposes mechanisms by which Polygonati rhizoma might act to reverse or minimize AS and provides a scientific basis for clinical research on Polygonati rhizoma.

To investigate the therapeutic effect of artesunate on mouse cytomegalovirus pneumonia, the BALB/c-nu mice were infected with murine cytomegalovirus-green fluorescent protein (MCMV-GFP) by nose dropping method. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Guangzhou Medical University. The BALB/c-nu mice were randomly divided into five groups:control group, MCMV pneumonia group, and artesunate (60, 120, and 240 mg·kg^-1) groups. The survival rate, weights, and virus loads in lungs among the groups were observed. The degree of histopathologic changes in lungs was assessed directly by hematoxylin-eosin (HE) assay. MCMV-GFP expression was assessed by immunofluorescence. In addition, reverse transcription polymerase chain reaction (RT-PCR) analysis was performed to investigate the content of major immediate early 1 (Mie1) mRNA, and enzyme-linked immunosorbent assay (ELISA) was used to detect the changes of inflammatory factors, interleukin 10 (IL-10), IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis was used to detect the expression of the changes of nuclear factor-kappa B (NF-κB) signaling pathways in total proteins. Compared with MCMV group, artesunate (120 mg·kg^-1) significantly increased body weights of MCMV-infected nude mice over 30 days, and decreased the viral titer in lung homogenate, lung inflammation, and histological severity. Moreover, the administration of artesunate (120 mg·kg^-1) could downregulate the expression of phospho-NF-κB (p-NF-κB) p65 in the lungs of mice. The present study suggested that artesunate can protect the immunocompromised mice from MCMV-induced interstitial pneumonia via downregulating NF-κB signaling pathway, thus attenuating inflammation in the lungs.

We used network pharmacology and molecular docking to investigate the molecular mechanism of Lishi-Kuijie decoction (KJF) in the treatment of ulcerative colitis (UC). Chemical components and targets related to the 13 herbs of Chinese Materia Medical in KJF were searched through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The UC-related targets were identified through OMIM, DisGeNet and GeneCards databases. Using Cytoscape 3.7.2 software a drug-compound-disease-target network was established. The target interaction network and core target for KJF against UC was built and selected based on the String database and topological parameters. Using the R package clusterprofile in Bioconductor, the intersection genes and the disease-drug intersection targets were transformed to Entrez gene ID, followed by gene ontology biological process enrichment analysis and KEGG pathway annotation analysis. The KJF compound-UC target network contained 149 compounds, 108 corresponding targets and 12 core targets (including signal transducer and activator of transcription 3, interleukin 6, tumor necrosis factor, c-x-c motif chemokine ligand 8, interleukin 2, etc.). We identified 2 371 GO terms and 155 pathways (mainly involving IBD, PI3K-ATK, NF-kappa B, TNF, Toll-like receptor signaling pathway) as determined by enrichment analysis. Molecular docking, used with the key molecular factors and the core targets, revealed stable binding for IL2, TNF-α, MAPK1 and RELA. These results suggest the possible molecular mechanism of KJF in treatment of UC and lay the foundation for further characterization of the components and their mechanisms.

In this study, the effect of benzo[α]pyrene (BaP) on chaperone-mediated autophagy (CMA) in a simulated hypoxia environment was observed and the relationship to heat shock protein 90 (HSP90) was clarified. With HSP90 inhibitor geldanamycin (GA) and HSP90α silenced, the mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α), HSP90, heat shock cognate protein 70 (HSC70), and lysosomal associated protein 2A (LAMP-2A) of A549 cells on hypoxic environment by BaP were tested. Alkaline comet experiment, immunofluorescence γ-H2AX focus experiment, quantitative real-time PCR (qPCR), and Western blot analyses were used to clarify the relationship between the DNA damage of different concentrations of BaP in A549 cells and the mRNA and protein expression of CMA-related factors. The results show that hypoxia can promote the expression of mRNA and protein of CMA-related factors in A549 cells. This study found that BaP has an inhibitory effect on CMA under the hypoxic environment. The inhibition or silencing of HSP90 will enhance the inhibitory effect of BaP on CMA. In a normoxic environment, BaP causes DNA damage and promotes CMA.

Three butylphthalide derivatives were isolated from the Rhizome of Ligusticum chuanxiong using a series of isolation and purification approaches including macroporous resin, ODS-A column, Sephadex LH-20 and preparative HPLC. These structures were elucidated based on extensive spectroscopic data (UV, IR, HR-ESI-MS and NMR) and identified as (3Z, 3aE)-(6R, 7R, 2'S)-6-hydroxy-7-(2-carboxyl-2-hydroxyethylthio)-3-(2-hydroxybutylidene)-4, 5, 6, 7-tetrahydro-phthalide (1), (3Z, 3aZ)-3-butylidene-6, 7-dihydroxy-4, 5, 6, 7-tetrahydro-phthalide 7-O-α-D-glucopyranosyl-(1→2)-β-D-fructo-furanoside (2) and 3-(3-β-D-glucopyranosyloxy-butylidene)-7-hydroxy-phthalide (3).

Peptidyl-prolyl cis-trans isomerase Pin1 is over-expressed in prostate cancer cells and the level of expression correlates with the malignancy grade and prognosis in patients. In this work, twenty-one 2-(1H-benzimidazol-2-ylthio) acetic acid derivatives were designed and prepared with the aid of the crystal structure of Pin1 and our previous work. The chemical structures of the target compounds were confirmed by ¹H NMR, ¹³C NMR, ESI-MS and IR. The inhibitory activity of compounds 6a-6i and 13a-13i against Pin1 were determined using a protease-coupled assay. The results indicated that twenty compounds were significantly superior to the positive control drug Juglone, and 6g, 6h and 13i exhibited the most potent Pin1 inhibitory activity, with IC₅₀ values at the sub-micromolar level. The in vitro anti-proliferative activities of these analogs were evaluated by the MTT assay and several showed a moderate effect in human prostate cancer PC-3 cells. Molecular docking studies demonstrated that both the benzimidazole skeleton and the thioacetic acid fragment were indispensable for the compounds to interact with key residues in the catalytic domain of Pin1.

A UPCC-Q-TOF-MS method was established to analyze the components of polyoxyethylene 35 castor oil. The separation was performed at 50℃ on a Waters Acquity UPCC system by an Torus Diol column (3.0 mm×100 mm, 1.7 μm) with gradient elution of CO₂ and methanol-acetonitrile (50:50); the flow rate was 1.0 mL·min^-1, the back pressure was 2 000 psi, and methanol containing 2.5 mmol·L^-1 ammonium formate was used as ionization reagent, whose flow rate was 0.2 mL·min^-1. Positive ion electrospray ionization (ESI) mode and MS^E technology were used. The qualitative analyses were carried out by using precise mass information of the parent and product ions and a PCA model was established by UPCC-Q-TOF-MS. L-02 cells and RBL-2H3 cells were used to study the cytotoxicity and histamine release of CrEL samples in vitro. A total of 13 kinds of CrEL components were obtained and their structures were identified by UPCC-Q-TOF-MS, with 255 compounds in total. The percentage content of 13 types of components was calculated by the normalization method. The content of polyoxyethylene glycerol tri-ricinoleate (PGTri-ricinoleate) in all samples was 0.36%-2.80% and the main components were polyethylene glycol, polyethylene glycerol and polyoxyethylene glycerol mono-ricinoleate. All samples have different degrees of cytotoxicity and histamine release, which is negatively correlated with the content of PGTri-ricinoleate and positively correlated with the content of polyoxyethylene glycol fatty acid esters. The UPCC-Q-TOF-MS method is simple and rapid, has strong separation ability and high accuracy. It is suitable for the analysis of CrEL components. It is suggested that the fatty acid composition should be included in the monograph of CrEL for injection to increase the content of PGTri-ricinoleate and decrease the content of polyoxyethylene glycol fatty acid esters, so as to improve the product safety.

Heavy metals and other harmful elements in traditional Chinese medicines inflict serious damage on public health. Therefore, risk assessment of Chinese raw materials has gained increasing attention. To date, few reports have been published on the health risk assessment of heavy metals and harmful elements in Chinese patent medicines. To gain a comprehensive understanding of heavy metals and other harmful elements in Chinese patent medicines and to establish proper limits, residual Pb, Cd, As, Hg, Cu and Cr in 15 054 samples of 295 drugs was analyzed with regard to distribution and variation between elements and dosage forms. In addition, in accord with procedures including hazard identification, hazard characterization, exposure assessment and risk characterization, basic procedures and specific parameters for risk assessment of heavy metals and harmful elements in Chinese patent medicines were clarified based on the health risk assessment of 14 787 samples and 276 drugs. A method and equation for establishing residual limits is proposed. The results show that content and target hazard quotients (THQs) of the investigated elements in all samples showed a skewed distribution approaching 0. Content of Pb, As, Cu, Hg, Cd or Cr in the samples exceeded 100 mg·kg^-1 and the content of Pb, As, or Cu in individual samples exceeded 1 000 mg·kg^-1. THQs of 586 samples and four drugs were above 1. We believe that the health risk of Hg, Pb and As in Chinese patent medicines with dosage forms of pill, capsule, tablet and powder, especially those in raw powder preparations, warrant concern.

The effects of alcohol extracts from roots, stems, leaves, and flowers of Scutellaria Baicalensis Georgi (SBG) on endogenous metabolism in D-gal-induced aging-model rats were investigated by ¹H NMR metabolomics. Results showed that 32 endogenous metabolites were identified in the urine. Combined with the VIP value and t-test, 14 different metabolites were found by multivariate statistical analysis of the spectrum. Compared with the control group, the content of α-ketoglutaric acid, hippuric acid and 3-hydroxybutyrate in the urine of rats in the model group was significantly decreased (P < 0.05) and the content of trimethylamine oxide, glycine, alanine, lactic acid, dimethylglycine, acetate, pyruvate, taurine, allantoin, betaine, N-acetylated glycoprotein was significantly increased (P < 0.05). The metabolites were mainly derived from taurine and hypo-taurine metabolism; glycine, serine and threonine metabolism; pyruvate metabolism; glycolysis/gluconeogenesis; glyoxylic acid and dicarboxylic acid metabolism; and the tricarboxylic acid cycle. The content of differential metabolites in urine samples was altered by the alcohol extracts from the different parts of SBG. Leaves extracts of SBG had the greatest effect on urine metabolites, and mainly affected taurine and hypo-taurine metabolism; glycine, serine and threonine metabolism; and pyruvate metabolism. This study provides a reliable experimental basis for the future development of SBG. This animal experiment was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2016036).

The glycosylation heterogeneity of recombinant human pro-urokinase (pro-UK) was assessed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Firstly, the source of heterogeneity was determined by measuring the M_r of intact protein before and after N-deglycosylation. Glycosylation sites and the proportion of O-glycopeptides then were determined at the peptide level. Finally, the N-glycans were confirmed and quantified using the N-glycan profile. Results show that the structural heterogeneity of pro-UK is mainly caused by glycosylation. All T₁₈ were fucosylated, and 6.4% of S_138/139 was O-glycosylated with two kinds of oligosaccharides with a ratio of 6.0% and 0.4% respectively. All N₃₀₂ positions were N-glycosylated by more than ten types of glycans, among which A2F and A3F accounted for 80% of the total. The assessment of glycosylation heterogeneity of pro-UK will provide a reference for quality standardization.

The aim of this study is to prepare acetaminophen sustained-release tablets by hot melt extrusion 3D printing technology based on the concept of "Quality by Design" (QbD). Firstly, the failure mode and effect analysis (FMEA) was used to determine the critical process parameters (CPPs), then full-factor experimental design was used to analyze the critical quality attributes (CQAs) and to establish the design space. The results showed that the content of plasticizer, the path spacing and the shell numbers are independent variable for the experimental design. The design space was concluded to be plasticizer content:9%, and the shell number:3-5, the path spacing:1.05-1.2 mm. In this study, 3D printing technology was used to prepare acetaminophen sustained-release tablets in accordance with the concept of QbD, which improved the durability of the process and ensured the uniform and controllable quality of the preparation and also provided experimental basis for personalised medicine.

This paper aimed to study the effect of combined co-processing of coating and pore forming on the tableting and tablet properties of traditional Chinese medicine (TCM) extracts together with its applicability. Four TCM extracts were co-processed using fluid bed with hydroxypropyl methyl cellulose (HPMC) as coating agent and ammonium bicarbonate (NH₄HCO₃) as pore-forming agent. Powder properties (such as particle size and size distribution, bulk density, tap density, moisture content) and tablet properties (including tensile strength, compaction ratio, fast elastic stretch, and disintegration time) were measured and compared among the powders. Scanning electron microscopy (SEM) was applied to characterize the surface of particles and tablets. Results showed that the particle size, flowability, and compactibility of the composite particles with HPMC were superior to the parent powders of TCM extracts. These properties of the porous particles with HPMC and NH₄HCO₃ showed further improvements. In addition, the addition of HPMC prolonged the disintegration time of tablets, whereas the pore-forming effect of NH₄HCO₃ could shorten the disintegration time. SEM revealed the changes in the morphology of the composite particles and the pores on the surface of the porous particles and tablets. In conclusion, co-processing with HPMC and NH₄HCO₃ could improve the powder and tablet properties of TCM extract powders, and this method shows certain applicability, which provides a feasible choice for improving the tableting properties of some TCM extract powders.

Bulbophyllum orchids are popular for its ornamental appearance and great medicinal values. However, there is still a lack of research on phylogenetic relationship and species identification for this genus. In this study, the plastome sequences of three medicinal Bulbophyllum orchids (Bulbophyllum affine, Bulbophyllum pectinatum, Bulbophyllum funingense) were sequenced and analyzed. After assembly and annotation, it was found that the plastomes of Bulbophyllum plants encoded a total of 108 genes, including 74 protein-coding genes, 30 tRNA genes and 4 rRNA genes. Based on the analysis of mVISTA and comparison between junctions, it was found that the plastome structure of Bulbophyllum orchids was relatively conserved, and the variation mainly existed in the non-coding regions. Phylogenetic analysis showed that Bulbophyllum orchids were closely related to Dendrobium orchids. SSR analysis of Bulbophyllum showed that most SSRs were located in the intergenic spacer and had the most single nucleotide repeats. In addition, based on the comparative analysis of non-coding sequences, a total of 10 high-variability sequences were screened out, among which the combination of five non-coding region sequences, including psbI-trnS, psbC-trnS, clpP-ex1-psbB, psaJ-rpl33, rpl33-rps18, had the highest sequence variability and could be used in the species identification study of medicinal plants of Bulbophyllum. In conclusion, this study provides a theoretical basis for phylogenetic relationship and species identification of Bulbophyllum orchids through the comparative analysis of plastome sequences of three medicinal plants of the genus Bulbophyllum.