OBJECTIVE To optimize the spray drying process of Ejiao zaoqi water extract concentrate, and to measure the physical fingerprint of spray drying extract powder. METHODS The powder yield, calycosin-7-O-β-D-glucopyranoside transfer rate, hesperidin transfer rate and extract moisture content were used as evaluation indexes, and the AHP-entropy weight method was used to weight, and the spray drying process was optimized by Plackett-Burman test combined with Box-Behnken response surface method. Twelve secondary physical indexes of micromeritic properties, such as moisture content and bulk density of spray dried extract powder, were determined, and the physical fingerprints was determined for similarity analysis. RESULTS The optimal spray drying conditions were as follows: liquid concentration of 0.25 g·mL^-1, addition of dextrin 5.0 g·100 mL^-1, air inlet velocity of 0.41 m³·min^-1, air temperature of 140 ℃, injection speed of 10 mL·min^-1, temperature of liquid 60 ℃, and gun pressure of 0.4 MPa. The similarity of the physical fingerprints of the 10 batches of detection powder was greater than 0.9. CONCLUSION The spray drying process of the selected Ejiao zaoqi water extract concentrate is stable and feasible, which can provide a basis for the research and development of this preparation.

OBJECTIVE To isolate and identify the pathogen of enteritis in Whitmania pigra to provide basis for its scientific prevention and treatment. METHODS Illumina high-throughput sequencing technique was used to analyze and compare the diversity and difference of intestinal microbial community structure between enteritis and healthy leeches, and to identify the potential pathogens of enteritis in Whitmania pigra. The pathogenic strains were isolated and purified from the intestinal tract of diseased leeches by pure microbial culture, and the sequence of 16S rDNA gene was analyzed to determine its taxonomic status. Koch's back staining method and intestinal pathological section were used to verify the pathogenicity of the Isolated strains, and the drug sensitivity was evaluated by disk diffusion method (K-B method). RESULTS The results of the Illumina high-throughput sequencing showed that compared with healthy leeches, the intestinal microbial community diversity of diseased leeches decreased significantly, and the relative abundance of Aminobacter, Lactobacillus and Prevotella decreased significantly(P<0.05). The relative abundance of Citrobacter, a common aquatic pathogen, increased significantly, reaching 60.92%, while that in the healthy leeches was 0.01%, suggesting that Citrobacter may be a potential pathogen. A strain of Citrobacter freundii SZ01 was isolated and identified from the intestinal tract of diseased leeches under the culture conditions of Citrobacter. Regression infection showed that the infection of leechs by SZ01 strain was consistent with that of natural infection. Antimicrobial sensitivity test showed that SZ01 strain was resistant to 10 antibiotics including cefalexin and ampicillin, moderately sensitive to five antibiotics including tetracycline and minocycline, and sensitive to 12 antibiotics including gentamicin, cefoperazone, and kanamycin. CONCLUSION High-throughput sequencing technique can effectively identify the pathogen of enteritis in Whitmania pigra. This study provides a basis for the prevention and treatment of Whitmania pigra enteritis and has reference significance for the application of high-throughput sequencing technique in the rapid isolation and identification of intestinal pathogens in aquatic animals.

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 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 establish an LC-MS/MS method for determining the concentration of acteoside(the main component of Rehmannia glutinosa leaf total glycosides capsules) in the plasma of young rats and investigate the exposure levels and toxicokinetic characteristics of acteoside following repeated oral gavage administration of different doses of Rehmannia glutinosa leaf total glycosides capsules. METHODS Plasma samples were processed using protein precipitation with methanol-acetonitrile (1∶1). Chromatographic separation was performed on a Waters ACQUITY UPLC HSS T3 column (2.1 mm×100 mm, 1.7 μm), with mobile phase consisting of 0.1% formic acid in water and 0.1% formic acid in acetonitrile, at a flow rate of 0.5 mL·min^-1. The injection volume was 2 μL. Mass spectrometry detection was carried out using electrospray ionization in negative mode (ESI^-1) and multiple reaction monitoring (MRM). The ion transitions monitored were 623.1/160.9 for acteoside and 269.0/158.9 for genistein which served as the internal standard. The established LC-MS/MS method was applied to analyze the plasma concentrations of acteoside in young Wistar rats after the first and last administrations of Rehmannia glutinosa leaf total glycosides capsules during a toxicity study. Pharmacokinetic profiles were constructed and kinetic parameters were calculated. RESULTS An LC-MS/MS method was developed and validated for the accurate determination of acteoside in rat plasma within a concentration range of 2-500 ng·mL^-1. Young Wistar rats were repeatedly gavaged with suspensions of Rehmannia glutinosa leaf total glycosides capsules for 8 weeks at dose levels ranging from 30 to 750 mg·kg^-1. No accumulation of acteoside exposure was observed within this dose range, and the exposure did not exhibit linear kinetics with increasing dose. CONCLUSION The developed LC-MS/MS method is applicable for measuring the concentration of acteoside from Rehmannia glutinosa leaf total glycosides capsules in rat plasma and supports toxicokinetic studies in young rats.

OBJECTIVE To investigate the synthesis and characterization of moxifloxacin hydrochloride. METHODS Using ethyl 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylate and (S,S)-2,8-diazabicyclo[4.3.0] nonane as the starting materials, moxifloxacin hydrochloride was prepared through five steps: chelation, condensation, hydrolysis, salt formation, and refinement. RESULTS and CONCLUSION Compared with other routes, this route is of mild conditions, simple postprocessing, less impurities, high process safety, and less environmental pollution.The prominent advantage of this route is that it can effectively remove boric impurities from moxifloxacin. The chemical structures of the target moxifloxacin hydrochloride and its key intermediates were characterized by IR, HR-MS, XRD and NMR spectra, including ¹H-NMR,¹H-¹HCOSY, ¹³C-NMR, DEPT, HSQC, and HMBC spectra.

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.

OBJECTIVE To explore the effect and molecular mechanism of nalmefene on postoperative cognitive dysfunction (POCD) in aged rats. METHODS Seventeen-month-old SD rats were randomly divided into control group (Control), model group (Model), model + nalmefene group (Model+Nal), model+nalmefene+EX527 group (Model+Nal+EX527) with 8 rats in each group after one week of acclimatization. The POCD animal models (excluding the Control group) were established by sevoflurane anesthesia and exploratory laparotomy. The rats in Model+Nal group were subcutaneously injected with 0.1 mg·kg^-1 nalmefene hydrochloride 30 min before anesthesia induction. The rats in Model+Nal+EX527 group were injected subcutaneously with 0.1 mg·kg^-1 nalmefene hydrochloride and intraperitoneally with 10 mg·kg^-1 EX527 (Sirt1 inhibitor) 30 min before anesthesia induction. Morris water maze experiment was conducted to analyze the cognitive abilities of rats. Hippocampal tissues were collected 3 d after surgery. The pathological changes of the hippocampus were observed by HE staining. Neuron apoptosis was analyzed by Tunel staining. ELISA method was used to detect the contents of TNF-α and IL-6. The protein expression levels of Bax, Bcl-2, Sirt1, TLR4 and NF-κB p65 were determined by Western blot. RESULTS Compared with the Control group, the cognitive dysfunction was seen, neuronal damage and the proportion of apoptotic neurons in hippocampal DG region were increased, TNF-α and IL-6 contents as well as the expression of Bax, TLR4 and NF-κB p65 were elevated, while the expression of Bcl-2 and Sirt1 was decreased in the Model group (P<0.001). Compared with the Model group, the cognitive ability was enhanced, neuronal damage and the proportion of apoptotic neurons in hippocampal DG region were decreased, TNF-α and IL-6 contents as well as the expression of Bax, TLR4 and NF-κB p65 were reduced, whereas the expression of Bcl-2 and Sirt1 was elevated in the Model+Nal group (P<0.001). Compared with the Model+Nal group, the cognitive ability was suppressed, neuronal damage and the proportion of apoptotic neurons in hippocampal DG region were increased, TNF-α and IL-6 contents as well as the expression of Bax, TLR4 and NF-κB p65 were elevated, while the expression of Bcl-2 and Sirt1 was decreased in the Model+Nal+EX527 group (P<0.001). CONCLUSION Nalmefene can reduce neuroinflammation and neuronal damage, and improve cognitive dysfunction in aged POCD rats through regulating Sirt1/TLR4/NF-κB pathway.

OBJECTIVE To establish the UPLC fingerprint of wild Qingqiao from Hebei province, analyze the correlation between fingerprint and antioxidant effect, and preliminarily determine its antioxidant active substances, so as to provide a basis for controlling the quality of wild Qingqiao from Hebei province. METHODS The fingerprints of 29 batches of wild Qingqiao from Hebei province were established by UPLC, and the common peaks were identified by UPLC-Q-TOF-MS. The free radical scavenging rate of 1,1-diphenyl-2-picrylhydrazyl (DPPH) method and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) method was used as the antioxidant index to evaluate the antioxidant activity of wild Qingqiao from Hebei province. The spectrum-effect relationship between common peaks and antioxidant activity of wild Qingqiao from Hebei province was analyzed by grey correlation method and partial least squares regression. RESULTS The UPLC fingerprints of 29 batches of wild Qingqiao from Hebei province were established, and the similarity was between 0.950 and 0.999. A total of 20 common peaks were identified. The common peaks were identified by comparison of standards and UPLC-Q-TOF-MS analysis as citric acid, rengynic acid-1'-O-β-D-glucoside, rengynic acid, rengyol, forsythoside D, adoxosidic acid, forsythide, forsythenside B, 4-hydroxybenzaldehyde, (+)-epipinoresinol-4'-O-β-D-glucoside, forsythoside J, forsythoside A, calcelarioside A, rutin, isoquercetin, rhamnetin, ferulic acid, forsythin, pinoresinol and forsythigenin. By scavenging DPPH and ABTS free radicals, it was found that 29 batches of wild Qingqiao from Hebei province had antioxidant capacity. The results of spectrum-effect analysis showed that 9 components such as citric acid, rengynic acid-1'-O-β-D-glucoside and rengynic acid were positively correlated with antioxidant capacity. Based on the two statistical models, it can be inferred that forsythoside A, rhamnetin and ferulic acid are the main components of the antioxidant activity of wild Qingqiao from Hebei province. CONCLUSION In this study, a quality evaluation model based on chemical composition and antioxidant activity was established, which could provide reference for the antioxidant active ingredients and quality control of wild Forsythiae Fructus from Hebei.