OBJECTIVE To explore investigator-initiated trial(IIT) approval management with a focus on risk prevention and control in the absence of guidelines for IIT approval management. METHODS Through a combination of literature review and practical experiences, this study analyzed the challenges encountered in the approval process and explored its potential risks, outlined the approval process following the promulgation of the management regulations, summarized its key aspects, and assessed the significance of the approval process with a focus on risk prevention and control.RESULTS There exist inherent risks in areas such as research design, participant protection, research team dynamics, and research funding. The authors advocate for the implementation of compliance review, peer expert evaluation, and a hierarchical approval review by expert technical committee, emphasizing scrutiny of scientific validity, feasibility, and funding adequacy. CONCLUSION The proactive identification and prevention of potential risks are highlighted as crucial benefits of the approval management. Centralized management of IIT projects, development of data management platforms, and diversification of funding channels to enhance risk mitigation should be further explored.

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.