OBJECTIVE To prepare, characterize, and investigate the transdermal behavior of methotrexate phospholipid complex organogel (MTX-PC/OG). METHODS The solubility of MTX-PC in the oil phase, lowest gelling concentration, phase transition temperature, and stability were evaluated as criteria. Preliminary screening of oil phase types, gelling agents, and types and amounts of cogelators for MTX-PC/OG was carried out. The effects of oil phase type, cogelator type and dosage on the transdermal behavior of MTX-PC in vitro were investigated by modified Franz diffusion cell method. The appearance, viscosity, phase transition temperature, content and rheological properties of MTX-PC/OG were characterized. RESULTS Medium chain triglyceride (MCT), isopropyl myristate (IPM) and ethyl oleate (EO) exhibited favorable solubility for MTX-PC. Glycerin monostearate (GMS) demonstrated the most robust gelling capacity as a gelling agent, with optimal gel spreading at a 12.5% concentration. In vitro transdermal permeation results indicated that using MCT as the oil phase and Span 20 as the cogelator significantly enhanced MTX permeation and retention. MTX-PC/OG appeared as a light yellow semisolid state with a uniform texture, viscosity of (85.9±0.5) Pa·s, and a phase transition temperature of (50.4±0.5) ℃. Rheological assessments revealed that MTX-PC/OG is a pseudoplastic fluid with shear-thinning effects, suitable for transdermal drug delivery. Rheological assessments revealed that MTX-PC/OG is a pseudoplastic fluid with shear-thinning effects that facilitate its easy spread. CONCLUSION MTX-PC/OG prescription process is reasonable, with good transdermal and rheological behavior, making it well-suited for skin topical drug delivery.

OBJECTIVE To explore the development of maximum residue limit standards for pesticides in Atractylodis Macrocephalae Rhizoma that conform to the characteristics of traditional Chinese medicine use. METHODS The samples were processed by QuEChERS method, and a combination of GC-MS/MS and LC-MS/MS was used to screen and determine 99 pesticide indicators in Atractylodis Macrocephalae Rhizoma. At the same time, the sensitivity, recovery rate, reproducibility, and precision of the method were verified. A risk assessment model and transformation principle that conforms to the characteristics of traditional Chinese medicine were adopted to determine the indicators and limits of the pesticide limit standards for Atractylodis Macrocephalae Rhizoma. RESULTS The established method for determining 99 pesticides in Atractylodis Macrocephalae Rhizoma meets the methodological requirements. A total of 12 pesticides were detected in 53 batches of Atractylodis Macrocephalae Rhizoma samples, including: tebuconazole, benzofenapyr, cypermethrin and S-cypermethrin, pyraclostrobin, thiamethoxam, enoxymorpholine, diazinon, propiconazole, fipronil, and methoxam. According to the GB2763 conversion guidelines, the limit standard for diazinon in Atractylodis Macrocephalae Rhizoma was converted into a drug standard. CONCLUSION This study helps to understand the risk of pesticide residues in Atractylodis Macrocephalae Rhizoma and provides ideas for the formulation of pesticide residue limit standards for traditional Chinese medicine.

OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of tobramycin and dexamethasone in artificial tears, and detect drug use concentration in human tears and in vitro release. METHODS Zorbax Eclipse plus-C₈ column was used with 2 mmol·L^-1 ammonium acetate aqueous solution as mobile phase A and 90% methanol aqueous solution as mobile phase B for gradient elution. The flow rate was 0.5 mL·min^-1, the column temperature was maintained at 40 ℃, and the injection volume was 2 μL. A mass spectrometer was used with ESI ionization mode, MRM mode, and positive ion mode. RESULTS Tobramycin and dexamethasone showed good linearity in the concentration range of 200-5 000 ng·mL^-1, and the lower limit of quantification was 200 ng·mL^-1. CONCLUSION The established method is rapid, efficient, accurate and sensitive, and can be used for the detection of drug concentration in tears and in vitro release test of tobramycin and dexamethasone eye drops.

OBJECTIVE To investigate the occurrence and clinical characteristics of cutaneous squamous cell carcinoma (SCC) induced by voriconazole in order to provide references for clinical safe use of the drug. METHODS The case reports of cutaneous SCC induced by voriconazole were retrieved from PubMed, Embase, Web of science, CNKI, Wanfang and VIP database from establishment of each database to June 2024. The relevant data were collected and analyzed. RESULTS A total of 36 cases from 22 articles were identified and included in the analysis. There were 29 males (80.6%) and 7 females (19.4%), and the patients were aged from 6 to 69 years with an average age of (36.7±19.6) years. Voriconazole was used for antifungal treatment in 21 cases (58.3%) and prevention of fungal infection in 15 cases (41.7%), with a dose of 50-800 mg·d^-1 and a course of 35 d-168 months. Fourteen cases (38.9%) of cutaneous SCC occurred at 36 months and above, and 23 cases (63.9%) occurred in the head and neck, 97.2% of the patients had a history of immune function abnormalities, 75.0% had a history of sun exposure, 72.2% had a history of using immunosuppressive drugs, and 61.1% had a history of hematopoietic stem cell transplantation or organ transplantation. Approximately 70% of the patients received surgical treatment, especially Mohs surgery. After surgery, chemoradiotherapy and other treatment, 13 patients (36.1%) had a good outcome, 7 patients (19.4%) had cancer metastasis or death, 16 patients (44.4%) did not have description on the outcome. The recovery time was 14 days to 2 years. CONCLUSION Voriconazole can cause cutaneous SCC, especially in male patients, and most occur at 36 months and above after start of medication. In the clinical use of voriconazole, clinicians should pay attention to the cutaneous lesions of the patients, and assess the risk as early as possible and actively take preventive measures.For patients who need to be treated with voriconazole for a long time, regular follow-up or regular skin examination is recommended, and combined treatment with traditional Chinese medicine can also be considered to shorten the course of the disease, improve the efficacy and reduce the toxic side effects. There are many potential factors in the current study, and further prospective studies are required to determine the rationality of the appropriate dosage and duration of voriconazole administration.

OBJECTIVE To investigate the key factors and directions for construction of a standard system for microbial control of pharmaceutical excipients. METHODS The contents related to pharmaceutical excipient microbial control including general requirements and monographs of standards in Chinese Pharmacopeia, United States Pharmacopeia and European Pharmacopeia were extracted and analyzed in combination with the current industrial status. RESULTS The included pharmacopoeias exhibit considerable differences in the coverage of pharmaceutical excipients and requirement for microbial control and there is still a lack of scientific and systematic guiding standards. The industrial requirements are yet to be met in terms of testing methodology, standardization, and instruction. CONCLUSION Attention should be paid to the methodological research and risk management of microbial control of pharmaceutical excipients. Instructive standards for microbial control of pharmaceutical excipients should be developed based on comprehensive consideration of excipient features and intended use with formulation as a core, to improve the quality standard system of pharmaceutical excipients and ensure drug safety.

Sleep disorders are increasingly prevalent within the population, and optimal sleep is essential for overall health. The sleep-wake cycle is a multifaceted process influenced by a variety of factors, including several neurotransmitters such as acetylcholine, norepinephrine, serotonin, histamine, dopamine, orexin, and gamma-aminobutyric acid (GABA). The activity of these neurotransmitters is further modulated by numerous nutrients involved in their metabolic pathways. In recent years, GABA has garnered significant attention due to its critical role in sleep regulation. This review aims to examine the mechanisms through which GABA affects sleep, its clinical implications, as well as recent advancements in research and future directions in this field.

OBJECTIVE To investigate the biosynthetic pathway of C₂₁ steroidal compounds in Cynanchum otophyllum Schneid. METHODS Metabolomics and transcriptomics were used to compare and analyze the relative contents of C₂₁ steroids in the roots, stems and leaves of C. otophyllum. Then, the genes related to C₂₁ steroid biosynthesis in C. otophyllum were screened through Kyoto Encyclopedia of Genes and Genomes(KEGG) database annotation. Finally, some differentially expressed genes (DEGs) were verified by quantitative real-time PCR. RESULTS The qingyangshengenin content in the roots was significantly up-regulated, with the relative qingyangshengenin content in the roots being approximately 73.10 times higher than that in the leaves and 19.05 times higher than that in the stems. Transcriptomic analysis revealed that 269 DEGs annotated C₂₁ steroidal biosynthetic pathways. By analyzing the DEGs annotated between the comparison groups, 18 key enzymes were screened out in the C₂₁ steroidal synthesis pathway, which were encoded by 87 genes, among which AACT and other enzymes were the key enzymes in the upstream stage of the biosynthesis pathway. Quantitative real-time PCR was performed to verify the expression trend of eight DEGs, which was consistent with the corresponding transcriptome data. CONCLUSION The biosynthetic pathway of C₂₁ steroidal compounds is systematically analyzed in this study, and several key enzymes and coding genes are screened, which enrich the omics data of C. otophyllum. These findings lay a foundation for further study on the biosynthesis mechanism of C₂₁ steroid compounds of C. otophyllum.

OBJECTIVE To examine the herbal evidence of “Agaru” Tibetan medicines,conduct biopharcological studies and proveide a basis for the corrent origin and quality control. METHODS Through literature research, combined with field visits and expert consultations, variety classification, origins, characteristics and effects, compound preparation,and quality standards of “Agaru” type Tibetan medicines were compiled and summarized. The morphological and microscopic characteristics of “Aerma” medicinal materials were observed. Physicochemical identification was carried out based on thin-layer chromatography and determination of volatile oil components and content using GC-MS technology. RESULTS The name “Agaru” has evolved from Sanskrit loanwords and is a typical Tibetan medicine characterized by “multiple varieties and multiple origins”. Tibetan medicine often classifies it based on color into three categories: white (transliterated as “A Er Jia” or “A Jia Ga Bu”), black (transliterated as “A Er Na” or “A Ga Na Bao”), and red (transliterated as “A Er Ma” or “A Ga Ku Ao”). There is a significant difference in the varieties and origins of “Agaru” type Tibetan medicines used by Tibetan doctors in different regions, involving about 15 species (including varieties and forms) of plants from 5 families and 7 genera. Among them, “Alma” is widely used clinically, and its mainstream base is the heartwood of Camphora glandulifera (Wall.) Nees. Biopharmacological research was carried out on “Aerma” [C. glandulifera (Wall.) Nees], a clinically used variety of the “Agaru” group of Tibetan medicines, providing basic data for the establishment of its quality standards. CONCLUSION This study completes the botanical verification of the Tibetan medicine “Agaru” and the pharmacognostical research on “Aerma” [C. glandulifera (Wall.) Nees]. This will provide an important basis for the scientific evaluation of quality and in-depth development of “Agaru”.

OBJECTIVE To prepare methotrexate (MTX)-nicotinamide (NIC) coamorphous (MTX-NIC CA), evaluate its pharmacokinetic behavior in rats, and explore its solubilization mechanism. METHODS The coamorphous complex was prepared by melting method and characterized by powder X-ray diffraction and other techniques; the physical stability and thermodynamic stability of MTX-NIC CA were examined. The solubilization mechanism was studied by solubility profile method. The concentration of MTX in rat plasma was determined by high-performance liquid chromatography and the pharmacokinetic curve was drawn. RESULTS The physical stability of MTX-NIC CA was good; the reaction of MTX with NIC was a spontaneous enthalpy-driven reaction, and the mechanism of NIC for enhancing the solubility of MTX was that a soluble A_L-type complex with a ligand-to-metal ratio of 1∶1 was formed in solution. Compared with the raw drug MTX, the t_max of MTX-NIC CA was prolonged, and the c_max, AUC_0-t, AUC_0-∞ and F were significantly increased (P<0.05). CONCLUSION The MTX-NIC CA is successfully prepared by melting method with good stability, and the formation of co-amorphous complex improves the bioavailability of poorly soluble drugs.

OBJECTIVE To evaluate the safety characteristics of Rehmannia glutinosa leaf total glycosides capsules in juvenile Wistar rats, and provide reference for the use of Rehmannia glutinosa leaf total glycosides capsules in child and adolescent patients. METHODS Twenty-seven-day-old Wistar rats were randomly divided into control and low-, medium-, and high-dosage groups. Each dosage group was given the Rehmannia glutinosa leaf total glycosides by gavage repeatedly for 8 weeks, followed by a 4 week recovery. The clinical symptoms, body weight, food consumption, hematological and serum biochemical indexes, central nervous system function, learning and memory ability, skeletal development, reproductive function, organ weight and histopathological changes of the rats was observed. RESULTS Rehmannia glutinosa leaf total glycosides capsules did not show significant effects on the clinical symptoms, body weight, food consumption, hematological and serum biochemical indexes, main organ weights, central nervous system function, bones, sexual cycle, sperm counts, vitality and form of the rats. No histopathological changes were observed associated with Rehmannia glutinosa leaf total glycosides capsules. CONCLUSION The no-observed-adverse-effect-level (NOAEL) for Rehmannia glutinosa leaf total glycosides capsules in juvenile rats is determined to be 750 mg·kg^-1 in the 8 week feeding study. The data provides reference for the use of Rehmannia glutinosa leaf total glycosides capsules in child and adolescent patients.