Ligustilide (LIG) is a phthalide compound found in Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort, which has a wide range of pharmacological activities in clinical practice, including anti-inflammatory, antioxidant, analgesic, anti-tumor, neuroprotective, and vascular protective effects. However, LIG has poor stability and is easily affected by factors such as temperature, light, oxygen, pH value, and solvent type, leading to conformational changes. In addition, the low water solubility and low bioavailability of LIG limit its development and application in new drugs. The article reviews the research progress on natural sources, structural characteristics and structural modifications, degradation and transformation mechanisms, main degradation influencing factors, stabilization methods and bioactivity of LIG in recent years, in order to provide reference for the further development and applications of LIG.

Infectious diseases are always a hot topic in global public health, and their transmission routes and mechanisms have attracted much attention. From the perspective of transmission routes, mucosal infection routes account for a large proportion, and pathogens can enter human body through the surface mucosa of different organs to cause disease, making the mucosa become the front line of human immune defense. In the structure of human body, the respiratory tract and intestine are the key contact interfaces between the human internal environment and the outside world, and their mucosal immune system plays a crucial role in protecting the body from pathogens. Therefore, the activation of the respiratory tract which is directly exposed to the external environment, and the mucosal immune system of the gastrointestinal tract which is the largest immune organ, can effectively cut off the route of infection, which is of great significance. In this paper, the complex interaction between epithelial cells and immune cells was analyzed from the structural and cellular components of respiratory tract and gastrointestinal tract, and the mechanism of antigen activation of mucosal immune response was described. By collecting relevant information on respiratory and intestinal mucosal vaccines and summarizing their advantages, the current challenges in this area are faced, with the intention that new ideas for further exploration and research on the development of effective mucosal vaccines will be hoped for.

OBJECTIVE To isolate and identify the chemical constituents of the ethnic medicinal plant Illigera celebica and their cytotoxic activities. METHODS The ethyl acetate extracts of I. celebica were isolate and purified by silica gel, Rp-18, Sephadex LH-20 gel column chromatographies and preparative HPLC method. The chemical structures of the isolates were illustrated by comparison their physicochemical properties and spectroscopic data with those reported. The cytotoxicity was evaluated by MTT method. RESULTS Fourteen compounds were isolated and identified as actinodaphnine (1), norisoboldine (2), atheroline (3), pityriacitrin (4), 3, 3', 4'-tri-O-methylellagic acid (5), (+)-syringaresinol (6), (+)-pinoresinol (7), cleomiscosin A (8), stigmasta-4, 6, 8(14), 22-tetraen-3-one (9), liquiritigenin (10), scopoletin (11), isofraxidin (12), physcion (13) and chrysophamol (14). The tested compounds showed no significant cytotoxic activity against the MGC-803, T-47D and T-24 cell lines. CONCLUSION All the isolates are obtained from this medicinal plant for the first time, and compounds 11-13 are obtained from Illigera genus for the first time.

OBJECTIVE To use fingerprint combined with hierarchical clustering analysis (HCA), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) to identify chemical patterns. METHODS Chrom Core 120 C₁₈ (4.6 mm×250 mm, 5 μm) chromatographic column, 0.1% phosphoric acid aqueous solution (A)-acetonitrile (B) as mobile phase for gradient elution, volume flow rate of 0.8 mL·min^-1, detection wavelength of 280 nm, column temperature of 30 ℃ injection volume of 10 μL, HPLC method was used to establish the fingerprints of 30 batches of medicinal herbs from 12 origins, and similarity analysis, HCA, PCA and PLS-DA were used and other chemical pattern recognition technologies were used to screen and quantitatively analyze the differentially characteristic components. RESULTS The fingerprinting method established by the established fingerprint method met the methodological requirements, and 17 common peaks were indexed by HPLC fingerprint of 30 batches of Pterospermum chinensis, with a similarity of 0.863-0.975. HCA, PCA and PLS-DA were used to distinguish the PH from different origins, and combined with the previous experiments, three components, protocatechuic acid, proanthocyanidins B₂ and epicatechins, were comprehensively analyzed and screened as the active ingredients of the PH, and the content ranges were 0.103-1.676, 0.141-5.556 and 0.144-3.381 mg·g^-1, respectively. CONCLUSION The fingerprint of the medicinal materials and the determination of the contents of the three active ingredients established in this study are stable, reliable and reproducible, which provides a certain scientific basis for evaluating the quality of Pterospermum heterophyllum.

OBJECTIVE To explore the effect and possible mechanism of Xiaoyao San in chronic stress depression mice. METHODS The antidepressant effects of Xiaoyao San (XYS, low-dose 1.40 g·kg^-1, high-dose 2.79 g·kg^-1), mifepristone (1.73 mg·kg^-1) and fluoxetine (2.9 mg·kg^-1) were assessed in chronic unpredictable mild stress (CUMS)-exposed male mice. After the intervention, the depressive-like behaviors of mice were evaluated by open-field test (OFT), sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST). Hematoxylin eosin (HE) staining experiment was used to observe the pathological changes of the hippocampal tissue. Enzyme linked immunosorbent assay (ELISA) was used to detect the level of corticosterone (CORT) in serum of mice. Western blot (WB) experiment was used to detect the protein expression of nuclear and cytoplasmic glucocorticoid receptor (GR), phosphorylation GR, FK506 binding protein 51 (FKBP51), brain-derived neurotrophic factor (BDNF) in hippocampal tissue. RESULTS Compared with the control group, mice in the model group showed it was significantly deteriorated behavioral performance (P<0.01) and pathological changes in the hippocampal tissue, indicating the successful establishment of the CUMS model. After XYS treatment, the behavioral performance (P<0.05) of mice and pathologic manifestation of the hippocampal tissue were significantly improved, and the serum CORT level was significantly reduced (P<0.05). In addition, WB examination demonstrated that XYS treatment significantly increased the expression of GR, BDNF, pGR-S211, and nuclear GR in hippocampal tissue (P<0.05), while significantly decreased the expression of FKBP51 and pGR-S226 (P<0.05). CONCLUSION XYS may exert its anti-depressant effects by regulating the expression of FKBP51, phosphorylation GR and BDNF, improving the function of GR and regulating the homeostasis of the hypothalamic-pituitary-adrenal (HPA) axis.

OBJECTIVE To investigate the effect of stachydrine (STA) on hypoxia inducible factor-1α (HIF-1α)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathway in hypoxia/reoxygenation (H/R) induced cardiomyocyte pyroptosis model. METHODS H9C2 cardiomyocytes were separated into control group (Control group), model group (H/R group), H/R+low concentration STA group (H/R+STA-L group, 5 μmol·L^-1), H/R+medium concentration STA group (H/R+STA-M group, 10 μmol·L^-1), H/R+high concentration STA group (H/R+STA-H group, 20 μmol·L^-1), H/R+high concentration STA (20 μmol·L^-1)+HIF-1α activator group [H/R+STA-H+dimethyloxaloglycine(DMOG) group, 20 μmol·L^-1 STA+10 μmol·L^-1 DMOG]. H9C2 cell viability was tested by cell counting kit-8(CCK-8) assay. H9C2 cell apoptosis was measured by flow cytometry. The levels of IL-1β, IL-18, and LDH in cells were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of IL-1β, IL-18, Caspase-1, HIF-1α, and NLRP3 were quantified using Western blot. RESULTS Compared with the control group, the cell survival rate of the H/R group decreased (P<0.05), the positive expression rate of Caspase-1, levels of IL-1β, IL-18, LDH, and protein expression of Caspase-1, IL-1β, IL-18, HIF-1α, and NLRP3 increased (P<0.05). Compared with the H/R group, the cell survival rates of the H/R+STA-L group, H/R+STA-M group and H/R+STA-H group increased, the positive expression rate of Caspase-1, levels of IL-1β, IL-18, LDH, and protein expression of Caspase-1, IL-1β, IL-18, HIF-1α, and NLRP3 reduced (P<0.05). Compared with the H/R+STA-H group, the cell survival rate of the H/R+STA-H+DMOG group obviously reduced (P<0.05), the positive expression rate of Caspase-1, levels of IL-1β, IL-18, LDH, and protein expression of Caspase-1, IL-1β, IL-18, HIF-1α, and NLRP3 obviously increased (P<0.05). CONCLUSION STA can inhibit H/R induced cardiomyocyte pyroptosis, and its mechanism may be related to the HIF-1α/NLRP3 signaling pathway.

OBJECTIVE In order to improve the solubility and dissolution of the insoluble drug fenofibrate (FNB) optimize, the prescription of the self-microemulsifying drug delivery system (SMEDDS) was optimized and its quality was evaluated. METHODS The prescription composition and proportion range of SMEDDS were determined by the solubility experiment, compatibility test and pseudoternary phase diagram. Star point design-response surface methodology was used to further optimize the formulation of fenofibrate self-microemulsifying drug delivery system (FNB-SMEDDS) by using solubility, average particle size and polydispersity index (PDI) as evaluation indicators. The physical and chemical properties, and preliminary stability of FNB-SMEDDS were evaluated. RESULTS The optimal prescription of FNB-SMEDDS was ethyl oleate (EO) 22.86% as oil phase, polyoxyethylene (40) hydrogenated castor oil (cremophor RH40) 51.07% as surfactant, diethylene glycol monoethyl ether (transcutol HP) 26.07% as co-surfactant. The obtained FNB-SMEDDS was uniform and transparent. The FNB-SMEDDS was self-emulsified in water with average particle size of (39.29±0.45) nm, PDI of (0.11±0.01), Zeta potential of (-7.7±0.9) mV, drug loading rate of 15 mg·g^-1, encapsulation rate of (95.11±0.26)%, and emulsification time of (56.03±1.65) s. Stability experiments showed that after being stored at room temperature in the dark for 30 days, there was no significant change in its index components and appearance properties, indicating good stability. Compared with FNB API, FNB-SMEDDS significantly improved the in vitro dissolution of FNB. The cumulative release rates in water, pH 1.2 hydrochloric acid solution and pH 6.8 phosphate buffer solution for 120 min were (97.68±0.61)%, (92.23±4.07)% and (93.65±2.25)%, respectively. CONCLUSION FNB-SMEDDS has good appearance, high emulsification efficiency. It can significantly improve in vitro dissolution of the drug, and is expected to improve the in vivo bioavailability of FNB.

OBJECTIVE To design and release dihydroartemisinic(DHA) prodrug with long circulation ability in vivo by the stimulation of tumor cell microenvironment and improve drug accumulation in tumor site. METHODS DHA was covalently bonded to cetylamine (C16) carriers via disulfide (^-SS^-) and carbon-carbon bonds (^-CC^-) to synthesize two DHA/C16 coupled prodrugs of DHA-SS-C16 and DHA-CC-C16, which were formulated as self-assembled nanoparticles (DHA-SS-C16 NPs and DHA-CC-C16 NPs) by nanoprecipitation method. In vitro cellular studies were performed to assess the NPs' capacity in inhibiting the proliferation of 4T1 cells. Additionally, the pharmacokinetic behaviors in rats and the anti-tumor activity in 4T1 tumor bearing mice of NPs were also studied. RESULTS DHA-SS-C16 and DHA-CC-C16 were successfully synthesized. The particle size and Zeta potential of DHA-SS-C16 and DHA-CC-C16 NPs were (115.7±3.0) and (106.6±1.0) nm, (-34.5±0.4) and (-21.3±0.5 )mV, respectively. The average encapsulation efficiency and drug loading capacity of the two DHA/C16 coupled prodrugs were greater than 95% and 79% respectively, demonstrating good stability. NPs could inhibit the proliferation of 4T1 cells and reduce their migration ability. The pharmacokinetic studies showed that NPs prolonged the average retention time of DHA and enhanced the AUC of DHA to certain extent. The anti-tumor effect of DHA-SS-C16 NPs was better than that of DHA solution and DHA-CC-C16 NPs. CONCLUSION The self-assembled nano-drug delivery system designed in this paper, which utilizes disulfide bonds as connecting arm for DHA/C16-coupled prodrug, is capable of prolonging the retention time of drugs in the body, enhancing the accumulation of drugs at the tumor site, achieving responsive drug release in the tumor microenvironment, and improving anti-tumor effect. Furthermore, it also enhances the quality of life of mice. In conclusion, the nano-drug delivery system presents a promising long-acting and intelligent approach in drug delivery.

OBJECTIVE To establish the limit standard of common pesticides in Lilii Bulbus, based on the “GB2763-2021 National Standard for Food Safety Maximum Residue Limit of Pesticides in food” and the multiple residue detection method of banned pesticides in Chinese medicinal materials and Chinese herbal decoction pieces (plants) in Chinese Pharmacopoeia. METHODS In accordance with the conversion tenet of the maximum residue limit(MRL) of pesticides in food established by the research group under the National Standard for Food Safety GB2763-2021, the converted types of agricultural residue limit of Lilii Bulbus were ascertained. The risk assessment of the MRL value was accomplished, and the detection methodologies for the agricultural residue of Lilii Bulbus were established to appraise the residue status of 50 batches of samples. RESULTS The QuEChERS procedure was adopted for extracting Lilii Bulbus, the gas chromatography-tandem mass spectrometry (GC-MS/MS) approach was utilized to determine six categories of pesticides, and the liquid chromatography-mass spectrometry (LC-MS/MS) method was implemented to determine nine sorts of pesticide residues. Meanwhile, the current prohibited pesticide multi-residue determination approach of the pharmacopoeia was taken into account. Comprehensive risk assessment and actual sample residue data were leveraged to establish the limits for ten kinds of pesticide residues in Lilii Bulbus. CONCLUSION The established method is precise and efficient and can be exploited for the determination of the residues of ten commonly utilized pesticides in Lilii Bulbus. The limited conversion principle of traditional Chinese medicine variety limit standard is applied to effectuate the conversion of ten pesticides of Lilii Bulbusin GB2763-2021, providing support for the safety assessment of Lilii Bulbus.

OBJECTIVE To establish the HPLC fingerprints and content determination method of five index components of Dashanzha pills(DSZP), and evaluate the quality combined with chemical pattern recognition. METHODS The analysis was performed on an Eclipse plus C₁₈ column (4.6 mm×250 mm, 5 μm) at 30 ℃. Acetonitrile-0.1% formic acid aqueous solution was used as the mobile phase for gradient elution at flow rate of 1.0 mL·min^-1. The detection wavelength was set at 250 nm, and the injection volume was 10 μL. Based on 51 batches of DSZP samples, the fingerprint was established, and five index components were identified and quantitatively determined.Cluster analysis, principal component analysis and orthogonal partial least squares discriminant analysis were used to comprehensively analyze 51 batches of samples. RESULTS The fingerprints of DSZP were established, sixteen peaks were identified, and five chemical components were identified. They were chlorogenic acid (peak 5), vanillic acid (peak 6), hyperoside (peak 7), isochlorogenic acid B (peak 9), and isochlorogenic acid A (peak 10).The linear relationship of the five index components was good (r>0.998), and the recovery rate was 96.27%-109.35%, and the RSD was 2.83%-4.07%. The contents of chlorogenic acid, vanillicacid, hyperoside, isochlorogenic acid B, and isochlorogenic acid A were 0.047 2-0.227 0, 0.009 7-0.036 2, 0.023 0-0.370 2, 0.006 4-0.063 2 and 0.021 7-0.064 5 mg·g^-1, respectively. Except for manufacturer Q2, the contents of the products from the other manufacturers samples were maintained at (100±30)% of their respective average values, and the contents of the five components of manufacturer Q2 were mostly higher than 30% of the average value of all samples, indicating that there were great differences in product quality among different enterprises. The results of chemical pattern recognition showed that all samples could be roughly divided into two categories, indicating that the preparation process was relatively stable within the enterprise, but there were some differences between enterprises. The difference markers of the screened samples included the target components chlorogenic acid, hyperoside, and isochlorogenic acid B. CONCLUSION The quantitative method is accurate, rapid and feasible. Combined with chemical pattern recognition method, it can be used to evaluate the quality of DSZP.

OBJECTIVE To thoroughly interpret the newly introduced requirements set forth in the 2024 edition of the “Emergency Response Plan Management Measures” for the management of drug safety emergency plans. Furthermore, to delve into the methods for constructing a robust and comprehensive drug safety emergency management system tailored to the current circumstances, ultimately enhancing our emergency management capabilities. METHODS A detailed analysis of the new edition of the “Measures” was conducted. Based on this analysis, several key strategies were proposed. Firstly, the strengthening of the risk assessment system was emphasized, advocating for a more precise and forward-looking approach to identifying potential risks of the drug. Secondly, cross-regional collaboration was highlighted as essential for efficient resource allocation were swift response during emergencies. This involved breaking down barriers between regions and fostering seamless cooperation among different stakeholders. Thirdly, the standardization and dynamic refinement of plan formulation and implementation were emphasized. This ensured that emergency plans remained relevant and effective in the face of evolving challenges. Lastly, the development of an intelligent emergency response plan management platform was proposed, leveraging modern information technology to streamline processes, enhance data analysis, and improve overall efficiency. RESULTS The anticipated outcomes of implementing these strategies were multifaceted. The risk assessment system would be significantly enhanced, providing a more accurate picture of potential threats and enabling proactive measures to be taken. Cross-regional collaboration would lead to the establishment of efficient linkages, ensuring that resources could be quickly mobilized where they were needed most. The standardization and dynamic refinement of plans would guarantee that they were not only well-structured but also adaptable to new situations. Moreover, the introduction of an intelligent management platform would revolutionize the way emergency plans were managed, making the entire process more efficient, transparent, and data-driven. CONCLUSION The implementation of the 2024 edition of the “Emergency Response Plan Management Measures” represents a significant step forward in the field of drug safety emergency management. By adopting the proposed strategies, we can expect to witness a paradigm shift in the way these emergencies are handled. The resulting innovations and improvements will undoubtedly bolster our response capabilities, minimize the impact of drug safety incidents, and ultimately safeguard the public's well-being.

OBJECTIVE To analyze the intervention effect of prescription pre-review and Six Sigma management model on the qualified rate of outpatient prescriptions to improve the quality of pharmaceutical care and ensure the safety, rationality, and effectiveness of medication in patients. METHODS The qualified rates of outpatient prescriptions in Beijing Hospital from April 2020 to March 2024 were collected. The multi-stage model of interrupted time series analysis (ITSA) was used to analyze the changes in the qualified rate of outpatient prescriptions in three stages: before and after the pre-review system was implemented in the whole department, as well as the implementation of Six Sigma management method based on the pre-review. RESULTS The ITSA showed that the qualified rate of outpatient prescriptions in our hospital was stable around 86.56% before the pre-review was carried out in all departments. After the implementation of pre-review, the qualified rate of prescriptions in that month increased by 9.81%. In November 2021, after the implementation of define measure analyze improve control (DMAIC) management based on prescription pre-review, the qualified rate of prescriptions in the month increased to 98.07%, reaching the target value, and the qualified rate of prescriptions continued to increase with a monthly trend of 0.05%. CONCLUSION The implementation of prescription pre-review and Six Sigma management is conducive to the formation of a closed-loop management model of pre-review, in-process intervention, post-comment, result publicity, and timely communication and feedback, which significantly improves the level of rational drug use in the outpatient department, better standardizes the prescribing behavior of doctors, promotes the communication and cooperation between pharmacists and physicians, and ensures the medication safety of drug use for patients.

OBJECTIVE In the digital era, the digital transformation of traditional Chinese medicine standards has become an inevitable trend to improve the quality control of traditional Chinese medicine and promote the high-quality development of the industry. METHODS The research team has leveraged AI technology's advantages in image recognition and analysis, data mining and processing, model prediction, and decision support to carry out the digital transformation of traditional Chinese medicine standards. RESULTS AND CONCLUSION They aim to construct a new form of traditional Chinese medicine digital standards that is machine-readable, executable, interpretable, and decision-capable without human intervention. This effort actively promotes the digitalization, networking, and intelligent development of traditional Chinese medicine standards, contributing to the national strategic goal of continuously improving the level of standard digitization.