OBJECTIVE To establish a UPLC-MS/MS method for simultaneous determination of 14 components in Shenmai granules, and analyze the quality differences of red ginseng feed from different manufacturers. METHODS Shimadzu Shim-pack gist C₁₈(2.1 mm×100 mm,2 μm) chromatographic column with acetonitrile-water as the mobile phase were used to determine the contents of 14 saponin components in 71 batches of Shenmai Granules. And then analyzed the main material basis affecting the difference in red ginseng feeding in Shenmai granules combined with chemometrics and evaluated the quality of red ginseng feeding in Shenmai granules from different manufacturers combined with EW-TOPSIS. RESULTS The concentrations of 14 components had a good linear relationship (r≥0.998 5); and the average recovery rate was 95.6%-105.0%(RSD<4.7%). According to the analysis of chemometrics and EW-TOPSIS, the samples produced by the three manufacturers were grouped into three categories, among which the quality of red ginseng feeding by manufacturer B was generally good, and the red ginseng feeding by manufacturer C was adulterated. CONCLUSION This method is specific, sensitive, efficient, and reliable, and can be used for the quality control of Shenmai granules.

OBJECTIVE To study the pharmacokinetics of polymyxin B (PB) in sepsis patients and to provide evidence for its rational clinical use. METHODS Sepsis patients were given intravenous PB, every 12 h (q12 h), 4 consecutive doses. Blood samples were collected before each dose and 0.5, 1, 2, 3, 6, 9, 12 h after the fifth dose. The plasma concentrations of PB were determined by UHPLC-MS/MS method. The main pharmacokinetic parameters were calculated by non-compartment model, and a limited sampling model was established with sparse blood concentration data points. RESULTS A total of 18 patients were included. The main pharmacokinetic parameters of PB were as follows: area under the concentration-time curve for the 24 h exposure after the fifth dose(AUC_{0-24 h}) was (63.33±30.88) mg·h·L^-1, plasma concentrations prior to the fifth dose(ρ₀) was (2.01±1.54) mg·L^-1, post the fifth dose peak plasma concentration(ρ_max) was (6.90±4.22) mg·L^-1, plasma concentrations of 12 h after the fifth dose(ρ₁₂) was (1.64±1.04) mg·L^-1, average steady-state plasma concentration(ρ_ss,av) was (2.64±1.29) mg·L^-1, trough concentrations after the first, second and third doses were (3.35±2.50) (2.74±1.60) and (1.76±1.10) mg·L^-1, respectively. The recommended two-point regression equation is AUC_{0-12 h}=2.08+1.22ρ₁+9.41ρ₆. CONCLUSIONS There are individual variabilities in the pharmacokinetic parameters of PB in patients with sepsis. The loading dose of the first dose can reach the steady-state concentration as soon as possible, and the PB concentration point 1,6 h after administration can be used to estimate AUC_{0-24 h}. It is suggested to monitor PB-AUC_{0-24 h} to guide the adjustment of PB dosage in adult patients with sepsis.

OBJECTIVE To establish the HPLC fingerprint of Forsythiae Fructus and develop a multi-component quantitative analysis method based on quantitative analysis of multi-components by single-marker(QAMS). METHODS The fingerprints of 47 Forsythiae Fructus samples from four provinces, including Henan, Shandong, Shanxi and Shaanxi, were established by high performance liquid chromatography (HPLC), while their similarity was evaluated. Chemical pattern recognition of Forsythiae Fructus was studied by hierarchical cluster analysis (HCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The content of forsythoside B, forsythoside A, hyperin, arctiin, phillyrin and phillygenin were determined by using QAMS, and the differences of samples from different producing areas were analyzed. RESULTS The fingerprints of 47 Forsythiae Fructus samples were established with similarities ranged from 0.785 to 0.989, and a total of 30 common peaks were identified. According to HCA, the samples were divided into three groups. OPLS-DA analysis can effectively distinguish Forsythiae Fructus from several producing areas (Q²>0.5). There was no significant difference in the content of 6 components in 47 batches of samples by QAMS and external standard method (ESM) (P>0.05), but there was significant difference in the content of active components in samples from different origin (P<0.01). The average contents of forsythoside B, forsythoside A, hyperin, arctiin, phillyrin and phillygenin in samples from different provinces were, Henan(4.50、20.58、0.52、2.39、7.46、1.76 mg·g^-1), Shandong(0.90, 9.26、0.36、1.39、3.84、3.87 mg·g^-1), Shanxi(0.82、8.74、0.29、1.16、2.64、1.75 mg·g^-1), Shaanxi(5.18、55.10、0.88、3.36、13.11、9.25 mg·g^-1). CONCLUSION The chemical composition of Forsythiae Fructus samples from different locations was similar, but the origin factors had a significant effect on the content of active ingredients, and the samples from Shaanxi province had the highest content. The HPLC fingerprint combined with the simultaneous determination of multi-component content analysis method established in this study is stable and reliable. The fingerprint combined with the chemical pattern recognition can provide a basis for the identification of origins and quality evaluation of Forsythiae Fructus.

OBJECTIVE To establish a method for simultaneous determination of 8 aminoglycoside antibiotics (AGs) including kanamycin, gentamycin C1, gentamycin C2, gentamycin C1a, tobramycin, neomycin, isepamicin and etimicin by LC-MS/MS with instant library searching. METHODS Eight AGs were separated by Shiseido PC HILIC (2.0 mm×100 mm, 3 μm) column, with 0.5% formic acid aqueous solution-0.1% formic acid acetonitrile solution as mobile phase and 0.4 mL·min^-1 of flow rate,and procedure of the gradient elution was performed. The screening method of 8 AGs was established by the scanning mode of multiple reaction monitoring (MRM). Typical mass spectrograms of 8 AGs were collected by collision energy expansion (CES) function and enhanced ion (EPI) scanning mode, and added them to the already established mass spectralibrary of antibiotics searching. RESULTS The established method has the advantages of short analysis time, strong specificity and high sensitivity. The screening and qualitative analysis of 8 AGs can be realized within 10 min. Three batches of the INSA insulin product were detected by this method, and kanamycin that was less than the detection limit of 0.05 ng·mg^-1 were not detected in above samples. CONCLUSION In this study, the detection method of 8 AGs established by LC-MS/MS with instant library searching can quickly screen and accurately determine trace AGs.

Thrombocytopenia is a disorder characterized by a decreased platelet count in the peripheral blood, which can be caused by various congenital and acquired diseases. Currently, thrombopoiesis-promoting drugs used for thrombocytopenia primarily include recombinant human interleukin-11 (rhIL-11), recombinant human thrombopoietin (rhTPO), and thrombopoietin receptor agonist (TPO-RA). Hetrombopag is an innovative oral non-peptide TPO-RA that has been approved for treating chronic adult primary immune thrombocytopenia (ITP) with inadequate response to glucocorticoids and immunoglobulin, as well as severe aplastic anemia (SAA) with poor response to immunosuppressive therapy in China. Clinical studies have demonstrated that hetrombopag is safe and well-tolerated in ITP and SAA patients. Currently, there is an ongoing phase Ⅲ clinical trial investigating the efficacy of hetrombopag in managing chemotherapy-induced thrombocytopenia (CIT). This article provides a review on the research progress of hetrombopag in treating thrombocytopenia, aiming to offer valuable insights for clinical practice.

OBJECTIVE To construct molecularidentification of Fritillaria taipaiensis and its relatives based on Indel marker. METHODS One hundred and three chloroplast genomes of 13 Fritillaria species were downloaded from GenBank and were subsequently used to screen Indel marker based on sequence alignment. Then, in accordance with the conserved upstream and downstream of Indel marker, a pair of specific primers was designed accordingly, by which a method including routine PCR and electrophoresis was constructed. Furthermore, the specificity, sensitivity, and optimal reaction temperature of the method were assessed. RESULTS One deletion of 137 bp was found in the accD-psaI spacer region of F. taipaiensis chloroplast genome according to the multiple sequence alignments, which was defined as the Indel marker for F. taipaiensis. The constructed method exhibited high specificity due to the fact that only F. taipaiensis exhibited a band of 302 bp after routine PCR and electrophoresis. The limit of detection for F. taipaiensis DNA template was 0.239 ng·μL^-1, and the optimal melting temperature (T_m) value was 58 ℃. CONCLUSION This accurate, quick and cost-affordable method provides not only identification of F. taipaiensis and its related species, but also technical reference for identification of other traditional medicines.

OBJECTIVE To study the in vitro release behavior and anti-tumor effect of paclitaxel-loaded rhein conjugate (PTX/TPGS-CR) micelles. METHODS The in vitro drug release behavior of PTX/TPGS-CR micelles in different release media was investigated by dialysis method with Taxol^® as the control. The cytotoxicity of PTX/TPGS-CR micelles on mouse breast cancer 4T1 cells was evaluated by MTT assay with Taxol^® as a control. The effect of PTX/TPGS-CR micelles on the cell cycle and apoptosis of human cervical carcinoma HeLa cells was detected by flow cytometry. The effect of PTX/TPGS-CR micelles on the migration of HeLa and 4T1 cells was investigated by scratch experiments. RESULTS The results of in vitro release assay showed that 50.84% and 71.38% of PTX in PTX/TPGS-CR micelles were released in pH 7.4 phosphate buffer (PBS) within 12 and 72 h, respectively, 79.19% of PTX in PTX/TPGS-CR micelles were released in pH 5.8 PBS which simulated the tumor microenvironment within 12 h, and almost all of PTX in the micelles was released within 72 h. The results of the cytotoxicity assay showed that PTX/TPGS-CR micelles had a strong inhibitory effect on the proliferation of 4T1 cells and displayed a time-and-concentration-dependent characteristic, with IC₅₀ of 0.321 9 nmol·mL^-1 at 72 h. PTX/TPGS-CR micelles could induce early apoptosis and late apoptosis in HeLa and 4T1 cells. PTX/TPGS-CR micelles can induce HeLa cells arrest in G2/M phase (arrested by PTX) and G0/G1 phase, which inhibited cell division and proliferation. PTX/TPGS-CR micelles can inhibit the migration of HeLa and 4T1 cells and reduce tumor metastasis. CONCLUSION PTX/TPGS-CR micelles have good pH-responsive drug release characteristics, which can release drugs slowly in the blood environment and rapidly in the tumor microenvironment. PTX/TPGS-CR micelles could inhibit tumor cells proliferation and migration and promote cell apoptosis. PTX/TPGS-CR micelles have a good tumor treatment potential.

OBJECTIVE To investigate the nebulization characteristics of Houning inhalation solution (HNIS)in vitro and to provide the reference for the clinical administration. METHODS The delivery rate (DR),delivered amount (DA) and aerodynamic particle size distribution (APSD) in vitro of HNIS were determined by means of respiratory simulator and the next generation impactor(NGI)with the syringin as the indication component and compared among the different types of nebulizers, compressors, atomization modes and breathing patterns. RESULTS In the same atomization condition and under the adult breathing pattern,the DR were between 23.3-52.2 μg·min^-1, the DA were between 178.8-353.2 μg and the deposition fraction in simulated throat (DFST) was about 2.1% for the jet nebulizers, the DR were between 3.2-21.2 μg·min^-1, the DA were between 12.9-82.7 μg and the DFST were about 0.7% for the ultrasonic nebulizers, the DR were between 7.2-16.5 μg·min^-1, the DA were between 93.5-217.2 μg and the DFST were about 0.1% for the mesh nebulizers, the mass median aerodynamic diameter (MMAD ) were between 2.2-3.6 μm. In the same atomization condition and under the child breathing simulation,the DR were between 1.5-24.3 μg·min^-1, the DA were between 26.3-215.4 μg. CONCLUSION The nebulization characteristics of HNIS are significant affected by the patterns and brands of the atomiztion equipment, suggesting that the atomization system should be selected according to the requirement in the clinical. Under the child breathing pattern, with the DA and DR reduced, the dosage and atomization time should be adjusted according to the age and pulmonary function of the patients to ensure the safety and efficiency of clinical medication.

Quercetin, a natural polyphenol, is one of the most abundant flavonoids found in many plant foods. Quercetin is a natural antioxidant, which can protect cells from damage caused by free radicals. Quercetin is a lipophilic compound that can pass through the cell membrane and regulate many intracellular and extracellular signal pathways related to disease progression and chemoprevention. Quercetin has a wide range of pharmacological activities, anti-inflammatory, antibacterial, anti-cancer and prevention of cardiovascular and cerebrovascular diseases, but its low solubility and bioavailability limit its clinical application. In order to improve these drawbacks, people have carried out structural modifications on quercetin, such as modifying hydroxyl groups to generate esters or ethers, modifying carbonyl groups to generate hydrazone or carbonyl oxygen substituted products, 8-substituted products, and forming complexes with metal ions. Quercetin derivatives with good solubility, high bioavailability, improved activity and enhanced anti-cancer activity were obtained by optimizing the structure of quercetin. The research progress of quercetin derivatives in recent years is reviewed to provide reference for the further development of quercetin derivatives.

OBJECTIVE To explore the occurrence and characteristics of remdesivir-related bradyarrhythmia and provide references for clinical safe drug use. METHODS The case reports of remdesivir-related bradyarrhythmia published in PubMed, Embase, CNKI, Wanfang and VIP were searched from the establishment of each database to October 2023, and statistical analysis was conducted on relevant information and data. RESULTS A total of 32 cases from 23 articles were identified and included in the analysis. There were 16 males (50.0%) and 14 females (43.8%), aged from 3 months to 80 years, with an average age of (43.1±23.5) years. Twenty-seven patients (84.4%) experienced bradyarrhythmia within 3 days after medication. When bradyarrhythmia occurred, the heart rate decreased by 25.0% to 76.0% from baseline, and 20 patients (62.5%) presented with severe bradyarrhythmia. After withdrawal or continuation of treatment and symptomatic management such as atropine or cardiac pacing, all patients had a good outcome except for 2 cases (6.3%) who eventually died from exacerbation of the primary disease. CONCLUSIONS Clinical monitoring of the patient's heart rate should be strengthened during the use of remdesivir, especially in the first 3 days after medication. Once bradyarrhythmia is found, the patient's condition should be comprehensively considered to decide whether to stop remdesivir, and atropine or cardiac pacing can be inserted if necessary.