Diabetic peripheral neuropathy is one of the most common complications of diabetes. Aldose reductase is a key enzyme in the pathogenesis of diabetic complications. This review systematically reviews the efficacy and safety of five kinds of aldose reductase inhibitors in the treatment of diabetic peripheral nerves. Epalrestat is the only aldose reductase inhibitor in clinical application so far. A number of clinical trials have shown that epalrestat has a certain therapeutic effect on diabetic peripheral neuropathy and has sufficient safety, but long-term studies have shown that its therapeutic effect is not better than mecobalamine. Torrestat, zoporestat, ponastat, and fedastat were all withheld from the market or withdrawn from the market due to efficacy or safety concerns, which was inferred to be related to the structural characteristics of the drugs. Development of more effective and safer aldose reductase inhibitors from the perspective of drug structure will become one of the future research focuses on diabetic peripheral neuropathy.

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 study the relationship between the spectral effect and the antibacterial effect of Rhizoma macrophylla L. based on grey correlation degree method and partial least square method. METHODS HPLC was used to establish the fingerprint of 13 batches of Moghania macrophylla (Willd.) Kuntze. The antibacterial activity of Moghania macrophylla (Willd.) Kuntze against 4 common pathogenic bacteria (Staphylococcus epidermidis, Escherichia coli, Staphylococcus aureus and Bacillus subtilis) was determined by microdilution method. Using the Similarity Evaluation System of Fingerprint of Traditional Chinese Medicine (TCM), the characteristic maps of 13 batches of Moghania macrophylla (Willd.) Kuntze were established, and the similarity evaluation and characteristic peak identification were carried out. The relative inhibition rate was used as the index of antibacterial activity, and the spectral effect relationship was established by using grey correlation analysis and partial least square method. RESULTS There were 29 common peaks in the fingerprints of 13 batches of samples, and the similarity was no less than 0.906. Peaks 12, 16, 17, 19 and 20 were identified as genistein, ononin, daidzein, genistein and chickpeas A. Staphylococcus epidermidis, Escherichia coli and Staphylococcus aureus had good bacteriostatic effect on 4 kinds of pathogenic bacteria. The results of spectral effect relationship analysis showed that peak 16 (ononin), peak 20 (chickpea A), peak 21 and peak 25 were the main active components of the antibacterial activity. CONCLUSION Through the study of the spectrum effect relationship, it is confirmed that the antibacterial effect of Moghania macrophylla (Willd.) Kuntze is the result of the combined action of many components, which could provide reference for the basic research and quality control of pharmacodynamic substances of Moghania macrophylla (Willd.) Kuntze.

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.

OBJECTIVE To screen the effective components and potent substances of Bletilla striata and to preliminarily predict its mechanism of action. METHODS Oxford cup and microdilution methods were used to evaluate the inhibition of Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus in different extracted parts of Bletilla striata. Subsequently, a mouse model of acne vulgaris was established to assess the effects of the different extracted components of Bletilla striata on auricular tissue lesions, histopathology, and inflammatory factors. Furthermore, the chemical compositions of the three extracts were analyzed using ultra high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-Q-TOF-MS). Network pharmacology was utilized to predict the relevant targets, pharmacodynamic components, and related pathways of Bletilla Striata in the treatment of acne. Additionally, molecular docking was performed on the key pharmacodynamic components and targets to further validate these pharmacodynamic substances. RESULTS The ethyl acetate extract of Bletilla striata could effectively inhibit three kinds of acne-causing bacteria, and its MIC was 2.34, 2.34, 4.59 mg·mL^-1, respectively, the ethyl acetate extract of Bletilla striata significantly improved the auricular tissue lesions in mice, while the remaining two extracts exhibited no anti-acne effect. A total of 51 components of Bletilla striata were identified, including 48 components in the ethyl acetate extract, 13 components in the butanol extract, and 15 components in the water extract, stilbenes were most enriched in the ethyl acetate extract. The results of network pharmacology and molecular docking validation indicated that constituents such as batatasin Ⅲ, 3-(4-hydroxybenzyl)-4-methoxy-2, 7-dihydroxy-9, 10-dihydrophenanthreneand, 3-O-methylbatatasin Ⅲ may serve as key active constituents of Bletilla striata in the treatment of acne. Additionally, MAPK1 and TNF among others may represent potential targets of Bletilla striata in anti-acne therapy. CONCLUSION This study shows that the ethyl acetate extracted parts of Bletilla striata have good anti-acne effects, in which the Stilbenes represented by batatasin Ⅲ may be the main medicinal components, which may provide important references for the in-depth study of the mechanism of Bletilla striata in treating acne.

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 prepare polymyxin B sulfate multivesicular liposomes (PMB-MVLs), optimize their formulation, and their quality, stability, release and investigate their antibacterial activity in vitro. METHODS The PMB-MVLs were prepared by the double-emulsion method. The response surface method of Box-Behnken design was used to optimize the initial prescription. High performance liquid chromatography method was established to quantitatively analyze PMB in PMB-MVLs. The physicochemical properties, the in vitro drug release behavior, in vitro antimicrobial activity and formulation safety of PMB-MVLs were investigated. RESULTS The appearance of PMB-MVLs prepared by optimal prescription were non-concentric spherical vesicles with uniform size. The encapsulation efficiency of PMB-MVLs were (69.521±1.531)%. The average particle size was (5.84±1.42) μm, and the average Zeta potential was (-26.77±0.55)mV. The PMB-MVLs showed good stability when stored at 4 ℃ for one month. The results showed that PMB-MVLs were released continuously for 72 h in vitro, and there was no sudden release effect. The in vitro antibacterial activities of PMB-MVLs on E.coli and P.aeruginosa were significantly stronger than those of the free PMB. And PMB-MVLs has no risk of hemolysis within its range of antimicrobial activity. CONCLUSION The slow-release PMB-MVLs are successfully prepared with uniform particle size, high encapsulation efficiency, and enhanced antibacterial activity.

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.