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 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.

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 establish a quality control method of human chain-activated immune cell preparations. METHODS The ability to secrete cytokines and in vitro cytotoxicity were detected by co-culture and flow cytometry analysis. Purity was determined by flow cytometry. The concentration of live cells and cell viability were determined by AO/PI dual fluorescence cell counter. The residual cytokines were determined by enzyme-linked immunosorbent assay. Mycoplasma nucleic acid was detected by probe real-time PCR.Other detection items were carried out according to the provisions of the 3rd part of Chinese Pharmacopoeia 2020. RESULTS The detection of human chain-activated immune cell preparations was carried out using the established method,and the results of biological activity research, physical and chemical characteristics research, and cytokine residual detection were normally distributed. The detection results were valid,and the coefficient of variation(CV) was less than 20%. All other indicators met the requirements of the Chinese Pharmacopoeia 2020. CONCLUSION A preliminary quality control method of human chain-activated immune cell preparations are established, which has the characteristics of ensuring the quality control lability, safety, and effectiveness of the cell preparations. It can be used for the quality control of the human chain-activated immune preparations.

OBJECTIVE To establish a population pharmacokinetic (PK) model for rosuvastatin and investigate the effects of demographic data, clinical characteristics, and genetic polymorphisms (ABCG2, SLCO1B1, SLCO1B3, SLCO10A1, ABCB1, CYP2C9) on its PK parameters in Chinese population. METHODS A total of 944 steady-state concentration data were collected from 944 patients with hyperlipidemia. UPLC-MS/MS was used to determine the plasma concentration of rosuvastatin. DNA was extracted and measured for concentration, and the Sequenom MassArray technology platform was utilized for genetic typing. Eventually a population PK model was established with non-linear mixed-effects modeling software (NONMEM). RESULTS The population estimates for the apparent clearance, apparent volume of distribution and absorption rate constant were 253 L·h^-1, 1 810 L and 0.318 h^-1, respectively. The datasets were best described by a one-compartment model with first-order elimination. The steady-state concentration of rosuvastatin increased as estimated glomerular filtration rate(eGFR) decreased and the variant allele for rs2199936 increased, under the same dosage regimen. Carrying one or two variant alleles for the ABCG2 rs2199936 showed a decrease of 32.6% and 53.2% in apparent clearance relative to the value in individuals without the variant allele. CONCLUSION Both ABCG2 rs2199936 and the eGFR were found to be significant covariates for apparent clearance. The results suggest that Chinese individuals with renal impairment and one or two variant alleles for the rs21999336 polymorphism (ABCG2) who are undergoing coronary angiography (CAG) should avoid high doses of rosuvastatin.

OBJECTIVE To prepare berberine hydrochloride microemulsion gel patch to improve the in vitro transdermal penetration and relative bioavailability in vivo. METHODS Firstly, through the screening of microemulsion dressing materials, and using the central point design response surface optimization method to optimize the microemulsion prescription, the best microemulsion prescription was obtained. The morphology and particle size of microemulsion were investigated by laser particle size analyzer and transmission electron microscope. Secondly, the matrix was selected for the gel paste, and then the optimal design of the gel paste was obtained by using the star design response surface optimization method. Finally, the microemulsion was added to the gel paste to prepare the berberine hydrochloride microemulsion gel paste, and the prescription process was verified. Through the in vitro transdermal test of mice, by comparing the permeation promoting effect of different concentrations of zzone, draw the cumulative permeation amount time curve of azone with different concentrations, and select the best amount of Azone. Finally, pharmacokinetic studies in rats and pharmacodynamic studies in mice were conducted. RESULTS Berberine hydrochloride microemulsion gel paste was successfully prepared. The best formulation of microemulsion was oil phase-emulsifier-co-emulsifier=0.11∶0.6∶0.3. The morphology and particle size of microemulsion were investigated by laser particle size analyzer and transmission electron microscope. The results showed that most microemulsion morphology was round, regular spherical, no aggregation, and the particle size was appropriate. The best prescription of gel paste NP700∶glycerol-dihydroxyaluminum aminoacetate=2.3∶17.5∶0.1 aluminum glycinate. The results of in vitro skin penetration test showed that azone with a mass fraction of 3% had the best penetration promoting effect. Pharmacokinetics showed that berberine hydrochloride microemulsion gel patch could prolong the action time in vivo. Preliminary pharmacodynamics shows that the drug can effectively improve the skin lesions, obviously inhibit the increase of inflammatory factors and improve the pathological tissue. CONCLUSION Microemulsion combined with gel patches can be used to prepare microemulsion gel patch with high drug loading and good therapeutic effect. The preparation of berberine hydrochloride microemulsion gel patch can effectively improve the bioavailability of berberine hydrochloride through percutaneous absorption.

OBJECTIVE To explore the characteristics of the inhibitory effect of low concentrations of deguelin on the proliferation of activated T cells. METHODS Human peripheral blood mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation, human T cells were purified using immunomagnetic beads, and T cells were activated with Anti-CD3/CD28 antibodies. Flow cytometry was used to detect T cell survival rate, proliferation index, apoptosis progression, CD25 expression level, and cell division ratio; ELISA was used to detect cytokines IL-2, IL-4, IL-6, IL-17, and IFN-γ secretion levels. RESULTS Low concentrations of deguelin inhibit T cell proliferation activated by anti-human CD3/CD28 antibodies, with an IC₅₀ of (73±12) nmol·L^-1, and a concentration of 400 nmol·L^-1 has no cytotoxicity. Low concentrations of deguelin do not affect the expression of CD25 and secretion of IL-2 in activated T cells but increases the proportion of G₀/G₁ phase cells. Low concentrations of deguelin promote the secretion of anti-inflammatory cytokine IL-4 and inhibit the production of pro-inflammatory cytokines IL-6, IL-17, and IFN-γ in T cells. CONCLUSION Low concentrations of deguelin significantly inhibit T cell proliferation in the G₀/G₁ phase and effectively suppress the secretion of pro-inflammatory cytokines, suggesting its potential role in the treatment of autoimmune diseases.