The use of traditional dressings, such as gauze, cotton and bandages, has been gradually reduced in medical practice due to their disadvantages, including poor permeability and the tendency to cause secondary injuries during replacement. In contrast, functional hydrogels have attracted much attention due to their excellent biocompatibility, high water retention, ease of introduction of functional components and accelerated wound healing. This paper describes the mechanisms of skin wound healing and the properties of different types of wound dressings. It summarizes the research progress in functional hydrogels constructed by physical or chemical crosslinking over the past five years. Additionally, it offers insights into the future development trends of functional hydrogels.

OBJECTIVE To investigate the safety of the tetravalent influenza vaccines adjuvanted with PEG6000 and cationic [2,3-dioleoxypropyltrimethylammonium chloride(DOTAP)∶1,2-dioleoyl phosphatidylcholine(DOPC)]-modified liposomes. METHODS Mice were divided into five groups∶ PBS negative control group, blank neutral liposome group, PEG6000 liposome group, cationic 4∶1 liposome group, and vaccine stock solution group. Abnormal toxicity test, acute toxicity test, and long-term toxicity test were performed. The general behavior, body weight, food intaking, viscera index, morphology, and blood indexes of mice were recorded to evaluate the safety of the vaccines adjuvanted with PEG6000 and cationic-modified liposomes. RESULTS Abnormal toxicity test∶ within 7 days after injection, all mice were alive with weight gaining and without abnormal symptoms. Acute toxicity test∶ 0.5 mL (hemagglutinin content 15 μg) was injected intraperitoneally, and no abnormal reaction or death was observed within 14 d. Long-term toxicity test∶ The mice were inoculated with 0.2 mL of hemagglutinin (6 μg) at 0, 14 and 28 d respectively. The mice were executed in the acute phase (3 d after the last immunization) and the recovery phase (14 d after the last immunization). No abnormal conditions and death were observed in the mice during the experiment period, and their body weight increased. Hematological examination and blood biochemical indexes fluctuated within the normal range, no toxic reaction related to drug administration was found, and no pathological changes were found in organs. CONCLUSION The tetravalent influenza vaccine adjuvanted with PEG6000 and cationic (DOTAP∶DOPC mole ratio 4∶1)-modified liposome has good safety.

OBJECTIVE To design and synthesize novel CDK9 inhibitors 1-(2-adamantan-1-yl-1H-indole-5-yl)-3-substituted thiourea derivatives and study their anti-gastric cancer activities. METHODS A series of target compounds 7a-7m were synthesized from adamantan formyl chloride by 6-step reactions. The structures of the target compounds were identified by ¹H-NMR, ¹³C-NMR, and HRMS. MTT assay was used to detect the inhibitory effect of synthetic compounds on the growth of gastric cancer cells, ADP-Glo kinase assay was used to detect the effect of synthetic compounds on CDK9 kinase activity and Western blot assay was used to detect the regulatory effect of hit compound on downstream signaling pathways. RESULTS The target compounds had certain inhibitory activity on the growth of gastric cancer cells, among which compound 7l had the best activity on the gastric cancer cell line (SGC-7901) with IC₅₀ value of (2.26±0.04) μmol·L^-1, and 7l had little toxicity on normal gastric epithelial cells (IC₅₀ >100 μmol·L^-1). In addition, 7l showed specific inhibitory effect on CDK9 kinase activity in vitro. Upon 1 μmol·L^-1 7l treatment, CDK9 kinase activity was only (21.67±1.47)%, and in gastric cancer cells 7l inhibited CDK9 downstream protein p-ser2 expression in a concentration-dependent manner. Finally, molecular docking study showed that 7l could stably bind to the active site of CDK9 and had a high binding affinity. CONCLUSION This series of compounds have good anti-gastric cancer activity and are worth of further study.

OBJECTIVE To analyze the difference of chemical components of different processed products of Polygonati Rhizoma produced in Shaanxi Province. METHODS Ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) was developed to determine the chemical components of different processed products of Polygonati Rhizoma produced in Shaanxi Province. The data was analyzed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The structures of chemical markers of different processed products of the plants were identified based on accurate primary mass spectrometry and secondary mass spectrometry fragment ion, combined with the reference map, software database searching and related literature. RESULTS A total of 45 components were identified, there were 23 chemical components with significant differences distinguished by the method of OPLS-DA, including 13 amino acids, 5 alkaloids, 2 saccharides, 1 coumarin, 1 saponin, 1 organic acids. CONCLUSION There are some chemical differences among the three products. This study can provide material basis for the quality control and pharmacodynamic research of processed products of Polygonati Rhizoma.

OBJECTIVE To establish an origin classification model of Angelica dahurica with unbalanced sample size based on near-infrared spectroscopy combined with data-enhanced convolutional neural network(CNN) algorithm. METHODS In this study, 95 samples of Angelica dahurica were collected, and near-infrared spectroscopy was performed on different samples within the wavelength range of 12 500 to 4 000 cm^-1. The near-infrared spectroscopy dataset of Angelica dahurica used in this study faces issues such as small sample size and uneven distribution of sample origins. To enhance the generalizability of the model, three data augmentation algorithms were proposed, including spectral shifting, spectral noise addition, and spectral combination. Additionally, to address the problem of sample imbalance, Focal Loss was used as the loss function for training the CNN model. RESULTS The three data enhancement algorithms were applied to the SVM model. Adding Gaussian noise with a signal-to-noise ratio of 20 to the spectral data had the best effect, which could increase the accuracy of the model to 84.2%. Aiming at the problem of sample imbalance, Focal Loss is used as the loss function to train the CNN model, and the accuracy rate can reach 94.7%. CONCLUSION The infrared spectroscopy combined with data-enhanced CNN algorithm provides a rapid and non-destructive detection method and reliable data analysis method for the origin traceability of Radix Angelicae Dahuricae, and provides a new method reference for the origin traceability of Chinese medicinal materials.

OBJECTIVE To screen the quality markers (Q-marker) of Rhododendron molle based on HPLC-ELSD and network pharmacology, compare the contents of quality markers in different parts, different flowering periods and different producing areas of R. molle, and explore the potential medicinal value of R.molle and speculate its possible mechanism of action. METHODS HPLC-ELSD was used to establish the fingerprint of R. molle, and hierarchical clustering analysis (HCA), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were carried out. The network diagram of ' component-target-pathway-pharmacological effect-efficacy ' was constructed by network pharmacology method, and the disease prediction was carried out. The quality markers of R. molle were screened and quantitatively analyzed. RESULTS In this study, the fingerprints of 11 batches of Rhododendron molle were established, and total of 10 common peaks were calibrated. Four differential components were obtained after analysis. It was predicted that rhodojaponin-Ⅲ, rhodojaponin-Ⅱ, hyperoside and quercitrin were candidate components of quality markers of R. molle and network pharmacology analysis was performed. It involved 84 target proteins, including ATK1, TNF, INS, etc., acting on 159 signaling pathways, and had potential therapeutic effects on tumors, autoimmune diseases, and cardiovascular diseases. The results of component content determination showed that the flowering of Rhododendron molle might have better curative effect, and the S10 origin was the best. CONCLUSION The quality markers of R. molle are predicted by chemical pattern recognition, fingerprint and network pharmacology. It is proved that R. molle could treat diseases through multiple targets and multiple pathways, which provides a reference for improving the establishment of quality control standards of R. molle and further exploring the mechanism of disease treatment.

OBJECTIVE To express recombinant protein PBP-ApoA1 by fusion of P-selectin banding peptide (PBP) and apolipoprotein (ApoA1) by Escherichia coli, and PBP-ApoA1 was applied to further prepare a recombinant high-density lipoprotein (HDL) loading with curcumin (Cur), named PA-rHDL-Cur, for the effective treatment of atherosclerosis (AS) by targeting to activated platelets. METHODS The soluble expression of PBP-ApoA1 was achieved using a co-expression strategy with glutathione S-transferase (GST) tag. The purified PBP-ApoA1, phospholipid and cholesterol were encapsulated with Cur to prepare PA-rHDL-Cur by thin-film hydration method. The physicochemical properties of PA-rHDL-Cur were characterized by particle size analyzer and UV spectrophotometer, while the release stability was evaluated using dialysis method. Cell viability and cellular uptake efficiency of PA-rHDL-Cur were assessed in vitro. Platelet adhesion experiments were conducted to confirm the targeting ability of PA-rHDL towards activated platelets. Furthermore, the antioxidant activity, cholesterol efflux effect, and reduction in oxidized high-density lipoprotein uptake capacity of RAW264.7 macrophages treated with PA-rHDL-Cur were investigated. RESULTS The yield of PBP-ApoA1 obtained by shake flask fermentation and purification was 1.3 g·L^-1. The resulting PA-rHDL-Cur exhibited uniform particle size with an average diameter of (165.3±29.6) nm and the Zeta potential of (-2.19±1.28) mV. The biocompatibility of this drug delivey system was satisfactory. In vitro cell experiments demonstrated that PA-rHDL-Cur effectively targeted atherosclerotic lesions, releasing curcumin to reduce oxidative stress within foam cells at the lesion site, significantly enhancing the bioavailability of Cur. Additionally, the presence of ApoA1 in PA-rHDL facilitated cholesterol efflux, thereby delaying the progression of atherosclerosis. CONCLUSION This design of biomimetic recombinant high-density lipoprotein nano-drug delivery system provides a new approach and theoretical basis for the development of novel nanocarriers against atherosclerosis.

OBJECTIVE To study the betulinic acid nanovesicle delivery system, and determine the distribution of the preparation in mice. METHODS A physical characterization method of nanovesicles was established, focusing on the aspects of morphology, particle size, Zeta potential, etc.In the study of tissue distribution of betulinic acid nanovesicles in vivo, mice were injected through the tail vein, and the concentrations of betulinic acid in various tissues and plasma at different time points were determined by HPLC, and the targeting parameters were calculated. RESULTS Betulinic acid nanovesicles shape is spherical and uniformly dispersed. The particle size is 140.51 nm, polymer dispersity index(PDI) is 22.58%, Zeta potential is -28.8 mV, encapsulation efficiency is 90.52%, drug loading is 8.30%. Compared with the injection group, the concentration of betulinic acid nanovesicles in the tissues and plasma of mice in the injection group was higher, the total area under the curre(AUC) increase 1.81 times, and the target evaluation index concentration ratio(Ce) of liver tissue is 3.51, relative tissue exposure(re) is 2.87, targeting efficiency(te) is 1.07. CONCLUSION The results show that the betulinic acid nanovesicles have small particle size, good stability, high encapsulation efficiency and drug loading, and meet the design requirements.The betulinic acid nanovesicle delivery system shows that the preparation of nanovesicles from betulinic acid can significantly improve the bioavailability of drugs and have obvious targeting to liver.

OBJECTIVE To study the pharmacokinetics and nasal residence time of nicorandil (NIC) thermosensitive nasal gel in rats. METHODS The concentration of NIC in rat plasma was determined by HPLC method. Rats were randomly divided into nasal and intragastric groups of 6 animals each. NIC thermosensitive nasal gel was nasally administered to the test group at a dose of 2.5 mg·kg^-1 and NIC suspension was given intragastricaly to the control group at a dose of 5.0 mg·kg^-1. The drug plasma concentrations at different times following administration were determined and the main pharmacokinetic parameters of NIC for the two groups such as t_max, ρ_max, t_1/2, AUC_0-t, AUC_0-∞ and relative bioavailability (F_r) for the NIC nasal gel were estimated. Furthermore, with dye method, the nasal residence time of the NIC nasal gel was investigated by using rats as test model and 0.9% NS as reference. RESULTS The t_max of the in group and ig group were 0.08 and 0.33 h, ρ_max were 19.63 and 12.55 μg·mL^-1, t_1/2 were 2.63 and 2.27 h, AUC_0-t were 22.04 and 28.93 μg·h·mL^-1, AUC_0-∞ were 24.54 and 30.42 μg·h·mL^-1, respectively. The relative bioavailability (F_r) of the NIC nasal gel was found to be 161.34%. The nasal residence time of the NIC nasal gel and 0.9% NS were observed to be 13.4 and 2.2 min, respectively. CONCLUSION NIC thermosensitive nasal gel may be a new dosage form for treating angina pectoris with good clinical application prospect due to its rapid in vivo absorption, high bioavailability, longer nasal residence time and convenient administration.

OBJECTIVE To establish a quality evaluation method for Mailuoshutong Pills by combining fingerprints and multi indicator quantification combined with chemometrics. METHODS Agilent ZORBAX SB-Aq C₁₈ chromatography column (4.6 mm×250 mm, 5 μm) was used, and the column temperature was maintained at 30 ℃. The mobile phase was acetonitrile-0.1% phosphoric acid aqueous solution. Gradient elution was carried out at a flow rate of 1.0 mL·min^-1, and the detection wavelengths were 216, 230, 280, 248, 327, 280 and 254 nm. The fingerprints of Mailuoshutong Pills(MLSTP) were established, the common peaks were determined combined with chemometric analysis, and the contents of 11 indicator components were determined. RESULTS A total of 30 common peaks were labeled in the fingerprints, and 12 components were identified through comparison with reference materials. The similarity of fingerprints of 16 batches of MLSTP were more than 0.990. Through cluster analysis, principal component analysis, and partial least squares discriminant analysis, it was found that gallic acid, neochlorogenic acid, cryptochlorogenic acid, chlorogenic acid, paeoniflorin, berberine hydrochloride, calycosin-7-glucoside, isochlorogenic acid A, isochlorogenic acid C, hapargoside, and berberine hydrochloride were the main factors affecting the quality of MLSTP, and the variation ranges of the content determination of the 11 components mentioned above were 0.62-0.84, 1.45-2.50, 1.30-2.78, 3.35-5.28, 2.44-4.02, 0.54-0.88, 0.16-0.23, 0.61-0.76, 1.39-1.76, 0.41-0.54 and 2.28-3.34 mg·g^-1, respectively. CONCLUSION The established multi-wavelength switching fingerprint spectrum combined with chemometric analysis and multi index content determination method is stable and reliable, which can provide scientific basis for the quality control and comprehensive evaluation of MLSTP.

OBJECTIVE To establish a UHPLC-Q-Exactive-Orbitrap-MS method to determine the contents of six sesquiterpenes in Nardostachys jatamansi DC. based on the ‘spider web' model. METHODS The extraction methods of six sesquiterpenes in Nardostachys jatamansi DC. were studied and determined by cobweb mode. Waters CORTECS^TM C₁₈ chromatographic column (4.6 mm×150 mm, 2.7 μm) was used. Acetonitrile was used as mobile phase A, and 0.05% formic acid solution containing 5 mmol·L^-1 ammonium formate was used as mobile phase B. Gradient elution was conducted at a flow rate of 0.5 mL·min^-1. The column temperature was maintained at 35 ℃. Detection was carried out in electrospray positive ion mode. RESULTS The results of spider web showed that the optimum extraction conditions were methanol extraction∶solid-liquid=1∶12.5, heating reflux for 30 min. Deoxyeugenol A, nardosinonediol, nardosinone A, axinysone B, nardosinone and nardosinone H had good linear relationship with the peak area integral value in the range of 0.386 4-1.425 6, 0.366 3-2.424 5, 0.462 1-1.458 8, 0.639 7-1.783 2, 3.542 5-14.657 6 and 0.432 7-1.439 3 μg·mL^-1, respectively, and the correlation coefficients (r) were not less than 0.999 3. The average recoveries of the six components were 98.39%, 100.05%, 100.35%, 97.13%, 102.84% and 97.15%, respectively. The results were analyzed and evaluated by clustering and partial least squares (PLS-DA). The results showed that the potential differential markers of Nardostachys jatamansi DC were nardosinone, nardosinone A and nardosinone H. CONCLUSION The method established in this study can realize the rapid and accurate quantitative analysis of six sesquiterpenes in Nardostachys jatamansi DC, which can provide reference for the quality evaluation of Nardostachys jatamansi DC.

OBJECTIVE To develop a supercritical fluid chromatography method for separation of brivaracetam and its three stereoisomers. METHODS Brivaracetam and its three isomers were separated on a silica gel column coated with amylose-tris (3,5-dimethyl phenylcarbamate) (CHIRALPAK AD, 4.6 mm×250 mm, 10 μm) and maitained at 40 ℃. The mobile phase consisted of a mixture of CO₂ and methanol (90∶10). The flow rate was at 2.0 mL min^-1 , and the detection wavelength was set at 205 nm. The back pressure of SF-CO₂ was set at 18 MPa, and the injection volume was 6 μL. RESULTS Brivaracetam and its three isomers were separated successfully in 10 min with a resolution factor of 2.8, 2.8 and 4.0, respectively. Brivaracetam exhibited a good linear relationship with peak area within the concentration range of 0.01-0.5 mg·mL^-1(r=0.999 8, n=8). Isomer A, B, and C also exhibited a good linear relationship with peak area within the concentration range of 0.005-0.5 mg·mL^-1 (r=0.999 9, n=9). The detection limits of brivaracetam and its three isomers(S/N=3) were all 2 μg·mL^-1, and the quantitation limits(S/N=10) were all 5 μg·mL^-1. The average spiked recoveries of three isomers at three different concentration levels were 102.1%, 105.8% and 102.6%, respectively(n=9). CONCLUSION Compared with conventional liquid chromatography, supercritical fluid chromatography can significantly improve the separation efficiency, shorten the separation time, and greatly reduce the amount of alkane organic solvents, which can be effectively used for the quality control of the isomer impurities in brivaracetam tablets.

OBJECTIVE To provide historical evidence for the safety usage of Fermentum Rubrum (red yeast rice) by textural study. METHODS Based on sorting and collating of historical literatures, this article reviewed name, production area, sourcing, fermentation processing, function and contraindication of red yeast rice. RESULTS The mainstream name of red yeast rice had not changed since ancient times, with Fujian, Jiangxi and Zhejiang as the main production area; japonica rice and indica rice were the main raw materials, fermented with red yeast rice mother; the ancient production process of red yeast rice mainly involved soaking rice, steaming rice, mixing red yeast rice mother, fermentation and drying as the key processes. Now, the manufacturing method of red yeast rice have still been used since the Ming Dynasty. Red yeast rice had remarkable medicinal effects and diverse edible functions, and no adverse reactions had been reported in its widespread use for thousands of years. The selected fungi, fermentation process and other aspects of Japanese red yeast rice were different from Chinese red yeast rice, and there might be infection by miscellaneous bacteria, which might cause adverse reactions. CONCLUSION This study provides systematically review on the medicinal history of red yeast rice, which can give historical base and references for the safe and reasonable application, rational development and utilization of red yeast and its products in China.