To observe the single dose toxicity and repeated dose toxicity of benvitimod, and to provide evidence for clinical administration and drug safety.

Single dose toxicity: The animals were given benvitimod 2 000 mg·kg^-1 (mice) or 500 mg·kg^-1 (rabbits) by subcutaneous injection. After administration, the animals were continuously observed for 14~15 days, and the toxic reaction and deaths were recorded. Repeated dose toxicity: benvitimod was administered subcutaneously to rats at doses of 40, 100, and 200 mg·kg^-1·d^-1 and to rabbits at doses of 30, 60, 150 mg·kg^-1·d^-1 for 6 months and observed for 1 month after the end of administration. The general conditions of the experimental animals were observed daily, and the body weight and food intake of the experimental animals were measured weekly. Twenty-four hours after the last administration, 50% of the animals (male and female) in each group were taken for hematology, blood biochemistry and pathology examination. The remaining animals were discontinued for 1 month, and the corresponding indexes were checked as before.

In the study of single dose toxicity, the NOAEL dose of benvitimod was 2 000 mg·kg^-1 on mice and 500 mg·kg^-1 on rabbit. In the study of repeated dose toxicity, after 6 months of subcutaneous injection, the NOAEL dose of benvitimod was 200 mg·kg^-1 on rats and 150 mg·kg^-1 on rabbit.

The results indicated that benvitimod had good safety in the clinical dosage.

To study the response of patients of acute exacerbation of chronic obstructive pulmonary disease with different fractional exhaled nitric oxide (FENO) levels to glucocorticoid.

A total of 105 patients with acute exacerbation of COPD who met the inclusion and exclusion criteria were collected and divided into high FENO group (FENO >25 ppb) and low FENO group (FENO≤25 ppb) according to the FENO level at admission. Routine blood, CRP, blood gas analysis and other related indicators and CAT scores of patients were determined on the first day after admission. All patients were given systemic glucocorticoids for five days, and the rest of the treatment was correspondingly given in combination according to the guideline recommendations. After the treatment of 6 days, blood routine detection of two groups of patients, such as CRP, blood gas result and CAT scores, was recorded again. The changes of CAT score and various indexes before and after the treatment were statistically analyzed. The difference of CAT between the two groups was statistically significant (P<0.001).

There was no significant difference in CAT scores between the two groups on the 6th day of treatment (P>0.05). The CAT scores of high FENO group and low FENO group after treatment were lower than those before treatment, with the difference statistically significant (P<0.001).

The patients with high FENO level before treatment have better response to the overall treatment and better clinical symptom improvement, which indicates that FENO may be a predictor of treatment response in patients with acute exacerbation of COPD.

To investigate whether β-caryophyllene (BCP) can reduce cerebral ischemia-reperfusion injury (CIR) in rats via activating heat shock factor 1 (HSF1)/heat shock protein 70 (HSP70) pathway.

Male SD rats were randomly assigned to the sham operation group, model group, BCP low, medium, and high dose groups (204,306,408 mg·kg^-1), BCP (306 mg·kg^-1)+Kribb11 intervention group, and Kribb11 intervention group. The suture method was used to create a rat model of CIR injury, and the neurobehavioral score was recorded 24 hours after the reperfusion. The volume of the cerebral infarct was measured using 2,3,5-triphenyltetrazolium chloride staining, and the pathological changes of cortical neurons were observed using hematoxylin-eosin staining and Nissl staining. Western blotting was applied to detect protein expressions of HSP70, HSF1, p-HSF1, Chop, Caspase 3, Bcl2, and Bax in rat brain cortex; immunofluorescence staining was used to detect protein expressions of p-HSF1 and HSP70; and Tunel staining to evaluate cell apoptosis level. Malondialdehyde level in cortical tissue (MDA), activities of total superoxide dismutase (SOD) and Caspase 3 were measured using a chemical colorimetric technique.

Compared to the model group, the β-caryophyllene administration group indicated a lower cerebral infarct volume in rats (P<0.01), a lower level of MDA and Caspase 3 activity in the tissue (P<0.01,P<0.05), a decreased expression of Bax, Chop, and Caspase 3 protein (P<0.01), a decreased occurrence of cell apoptosis, and increased protein expressions of HSF1, p-HSF1, HSP70, and Bcl 2 in the tissue (P<0.01), and substantially greater SOD activity in the tissue (P<0.01), reducing ischemia-reperfusion injury. Compared with the BCP group, Kribb11 in the BCP+Kribb11 group antagonized the curative effect of BCP, the protein expressions of HSF1, p-HSF1 and HSP70 were significantly reduced (P<0.05, P<0.01), and tissue oxidation stress levels increased, cortical cell death increased, and ischemia-reperfusion injury aggravated.

In rats, β-caryophyllene can alleviate cerebral ischemia-reperfusion injury in rats by reducing oxidative stress and minimizing cell apoptosis, which is associated with the activation of the HSF1/HSP70 pathway.

To evaluate the pharmacokinetic characteristics of Jinzhen oral liquid and compare the difference of the absorption and metabolism after single and multiple administrations in rats.

An ultra-high performance liquid chromatography coupled to triple-stage quadrupole mass spectrometer (UPLC-TSQ-MS) was applied to established the method for simultaneous determination of baicalin and wogonoside in rat plasma. Healthy rats were administered a single dose (3.228, 6.456, and 12.912 g·kg^-1) and multiple dose (6.456 g·kg^-1) of Jinzhen oral liquid (crude drug) by oral gavage. The content of target components in plasma at different time points was determined, and the pharmacokinetic parameters were calculated using the non-compartmental model.

The two components in the plasma sample have good linear relation (r>0.99). RSDs of their extraction recovery rate and matrix effect are both <15%, the intra- and inter-batch precision and accuracy, and stability meet the requirements of biological sample analysis. After single administration of Jinzhen oral liquid, the areas under the concentration-time curve AUC_(0-t) of baicalin and wogonoside show a good positive correlation with dose (R²>0.9), and their t_1/2z and CL_z/F have no significant difference at different doses. Compared with a single administration, their absorption and metabolism process are basically the same, and their AUC_(0-t) and t_1/2z have no significant difference after multiple administration.

A stable and reliable UPLC-TSQ-MS quantitative method for baicalin and wogonoside was established. And two components of Jinzhen oral liquid show linear dynamics characteristics in rats between 3.228 and 12.912 g·kg^-1 (crude drug), and there is no accumulation after multiple administrations, revealing the rationality of the clinical dosage of the preparation.

A new type of ginsenoside was semi-synthesized by D-ribose and ginsenoside DQ using glycosyl trichloroacetimide ester method. Its in vivo and in vitro anti-tumor activity and its mechanism of action were studied, and the metabolic pathways and products were analyzed by serum metabolomics.

Using D-ribose and ginsenoside DQ as raw materials, new ginsenoside derivatives were synthesized by chemical methods, and their structures were identified. The effects on S180 cells, human lung adenocarcinoma SPC-A-1 cells, anti-tumor activity in A549 cells and inhibition to mouse S180 tumor cells were determined by MTT method. Its anti-tumor mechanism was explored based on cell metabolomics analysis.

For the first time, a new ocotillol-type ginsenoside, 12-riboside-pseudoginsengenin DQ (RPDQ), was semi-synthesized by chemical methods, and was identified as (20S, 24S)-12-O-α-D-ribofuranosyl-Dama-20,24-epoxy-3β,12β, 25-triol, the yield is 38.6%, and the purity is 99.1%. MTT detection of RPDQ can significantly inhibit the proliferation of three kinds of tumor cells. In vivo experiments demonstrated that RPDQ inhibited solid tumors in tumor-bearing mice, improved the histomorphology of tumor cells, reduced the spleen and thymus indices in tumor-bearing mice and prolonged the survival days of mice. Metabolomics results showed that RPDQ exerted its anti-tumor effects by regulating seven metabolic pathways, including arachidonic acid metabolism, glycerophospholipid metabolism and tryptophan metabolism. Sixteen biomarkers were identified through principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) screening, and a network of signaling pathways related to the anti-tumor effects of RPDQ in mice was investigated.

The synthesis of RPDQ provides a reference for the synthesis and activity research of such ginsenoside derivatives. RPDQ shows good anti-tumor activity, which provides a theoretical basis and data support for the further research and development of pseudoginsengenin.

Quercetin enteric nanoparticles were prepared by electrostatic spray technology, and the preparation process was optimized by central composite design-response surface methodology.

The ethanol solution of quercetin/Eudragit L100 (1∶1, w/w) was prepared using Eudragit L100 as an enteric coating material. The effects of solution concentration, electrostatic spray voltage, spraying speed and receiving distance on the particle size were investigated. On the basis of single factor test results, the optimal process parameters were selected by central composite design-response surface methodology. The nanoparticles were evaluated by scanning electron microscope, X-ray powder diffraction and differential thermal analysis. The equilibrium solubility and dissolution of quercetin nanoparticles were determined in the solution of pH 1.2 and pH 6.8.

The optimum preparation conditions are Quercetin/Eudragit L100 concentration of 0.48%, spray voltage of 29.9 kV, spray speed of 0.44 mL·h^-1 and receiving distance of 23.18 cm. The prepared enteric nanoparticles were spherical with an average diameter of (251.1±7.8) nm. The results of X-ray powder diffraction and differential thermal analysis showed that quercetin was amorphous in nanoparticles. The equilibrium solubilities of quercetin enteric nanoparticles were 1.069 and 6.827 μg·mL^-1 in pH 1.2 and pH 6.8 solution, respectively, and the dissolutions of quercetin enteric nanoparticles at 2 h were 15.1% and 83.9% in pH 1.2 and pH 6.8 solution, respectively.

Quercetin enteric nanoparticles prepared by electrostatic spraying had a good enteric effect.

To analyze the clinical medication characteristics of zedoary turmeric oil injection based on real world data, and to provide reference for its clinical rational medication.

Based on the data of 894 cases treated with zedoary turmeric oil injection extracted from the HIS system of 12 hospitals in China, the general data and medication status of the patients were described and analyzed by using frequency analysis method. The visual correlation analysis of the original diseases and combined medication status of 894 patients was carried out by using VOSviewer software and python program.

Among 894 patients who were administered zedoary turmeric oil injection, the frequency of upper respiratory tract infection was the highest, and the overall effective rate of treatment was 99.55%. Among the 894 cases, 11.52% were over the prescribed dropping rate, and 3 cases of adverse reactions were reported. In the aspect of combined use of zedoary turmeric oil injection, the solvent is mainly 5% glucose injection (73.60%), and it is mostly combined with Reduning injection and ambroxol hydrochloride injection.

zedoary turmeric oil injection has important application value in the treatment of respiratory and digestive system-related diseases. However, there are occasional mild adverse events, which may be related to the non-standard infusion operation. The existing data is limited, and the effectiveness and safety of zedoary turmeric oil injection in clinical application still need to be further improved. The reevaluation of the effectiveness and safety of traditional Chinese medicine injection should be strengthened after being listed. Also, higher quality evidence support should be provided for the clinical rational use of traditional Chinese medicine injection such as zedoary turmeric oil injection.