OBJECTIVE To establish a predictive model for drug-induced liver injury (DILI) of tigecycline (TGC) to enable early recognition and management of high-risk patients. METHODS A retrospective study was performed on intensive care unit inpatients receiving TGC treatment at the first affiliated hospital of Zhengzhou university between January 2023 and March 2024. Demographics, medical history, admission characteristics, and treatment data were collected. Lasso-logistic regression analysis was used to identify risk factors for TGC-induced DILI. A nomogram was constructed based on these factors, and its predictive performance was assessed. RESULTS A total of 242 patients were enrolled, including 78 in the DILI group and 164 in the non-DILI group. The DILI group had higher proportions of females, age ≥60 years, alcohol consumption, acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) scores ≥21, TGC treatment durations ≥14 d, TGC overdosing, and concomitant use of ≥3 d compared with the non-DILI group (P<0.05). Logistic regression analysis indicated that female, age≥60 years, APACHE Ⅱ score ≥21, TGC treatment duration ≥14 d, TGC overdosing, and concomitant use of≥3 medications were independent risk factors for TGC-induced DILI (P<0.05). The area under the curve (AUC) of the nomogram was 0.870 (95%CI: 0.795-0.952). Calibration curve analysis suggested good agreement between model predictions and observations, and the decision curve showed that the patients could obtain clinical benefit within the threshold range of 10%-95%. CONCLUSION Gender, age, APACHE Ⅱ score, TGC duration, TGC overdose and concomitant medication are risk factors of TGC-induced DILI, and the nomogram based on these variables has good clinical performance.

OBJECTIVE Analyze the key control points and risk points of the process, propose the key points of the review and inspection, based on the continuous encapsulation process of lipid nanoparticles. METHODS On the basis of analyzing the lipid components and coating process of marketed lipid nanoparticles, the similarities and differences in the realization methods, fluid properties, equipment material form, advantages and challenges were analyzed. The key control points, challenge points and risk points, and propose the key technical points of the process were analyzed. RESULTS The challenge and risk points of continuous encapsulation of lipid nanoparticles mainly focus on five aspects: process control model, selection of equipment and hybrid device, application and development of PAT technology, identification and control of disturbance, and disposal of abnormal events. Accordingly, six technical points that should be paid special attention to in the official review and inspection: process research and control strategy, equipment confirmation and plant facilities, process verification and continuous process confirmation, process analysis and control, cleaning verification and cross-pollution prevention and control, and data integrity. CONCLUSION In order to promote the industrialization scale application of new continuous manufacturing technology, review and inspection technical guide is very important. Drug regulatory agency should do more early researches together with the industry.

OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry(LC-MS/MS) method for the simultaneous determination of the concentrations of verapamil and norverapamil in human breast milk and apply it in clinical practice. METHODS Milk samples(100 μL) were precipitated with 300 μL of methanol containing internal standard(5 ng·mL^-1 verapamil-d₃), and the supernatant was taken for analysis after vortexing and centrifugation. The chromatographic separation was performed on a Waters ACQUITY BEH C₁₈ column with gradient elution at 0.4 mL·min^-1, where mobile phases A and B were 0.1% formic acid-10 mmol·L^-1 ammonium acetate-water and methanol, respectively. The injection volume was 2 μL, and the analysis time was 4 min. The detection of the analytes was performed by electrospray ionization in positive mode by multiple reaction monitoring with the transition of m/z 455.3→165.2(verapamil), m/z 441.5→165.3(norverapamil) and m/z 458.3→165.0(verapamil-d₃). The established LC-MS/MS method was validated, and the method was used to determine the drug concentrations in breast milk of lactating patients. RESULTS The calibration curves for verapamil and norverapamil exhibited good linearity within the concentration range of 0.5 to 100 ng·mL^-1 (r=0.999). The intra-assay and inter-assay accuracies were both within ±15% of the labeled values, and the relative standard deviations were less than 15%. The extraction recovery, matrix effect, and stability all met the acceptance criteria for bioanalytical method validation. This analytical method was effectively employed to quantify drug concentrations in the breast milk of a lactating patient. The verapamil concentration in the breast milk of the patient ranged from 1.80 ng·mL^-1 to 10.73 ng·mL^-1, while norverapamil concentrations varied from 2.15 ng·mL^-1 to 5.15 ng·mL^-1. The relative infant dose of verapamil in this patient was approximately 0.15%. CONCLUSION The established method is simple, rapid, and sensitive. It is suitable for monitoring drug concentrations in clinical milk and can provide reference for safe drug use during lactation.

OBJECTIVE To explore the value of pharmaceutical care for patients with CKD3-5D by resident clinical pharmacists. METHODS Clinical pharmacists in the department of nephrology and three students formed a resident pharmacists team to develop standardized pharmaceutical care procedures(including admission medication reconciliation, doctor's order review, DRPs recognition, pharmaceutical care, medication education, discharge medication reconciliation, etc.) to provide pharmaceutical care for patients with 3-5D chronic kidney disease(CKD). The basic information, disease diagnosis and drug reorganization information of patients admitted to the department of nephrology of our hospital in 2024 were collected. The classification system based on the modified version of the European Foundation for Pharmaceutical Care Network(PCNE) was used to analyze the drug related problems(DRPs) of patients for assessment, intervention and statistical analysis. RESULTS A total of 141 patients were included in this study, and pharmacists found 54 DRPs, with an incidence of 38.3%. Among them, 36 cases(66.67%) were related to the effectiveness of treatment. Clinical pharmacists carried out 60 interventions, and the acceptance and complete implementation rate was 79.63%. The harmfulness grades of the 54 DRPs were as follows: 22 in grade E(40.74%), 16 in grade D(29.63%), 6 in grade C(11.11%), 6 in grade B(11.11%), and 4 in grade F(7.41%). CONCLUSION DRPs in patients with CKD3-5D are relatively common and harmful to some extent. Resident clinical pharmacists can identify and timely solve DRPs in patients with CKD3-5D through standardized pharmaceutical care, and assist physicians to ensure the safety, effectiveness and economy of drug use for patients.

OBJECTIVE To investigate the toxic mechanisms of Tripterygium wilfordii tablet(TWT) causing male mice reproductive damage and to identify detoxification targets. METHODS TWT was used to induce reproductive injury in mice. Metagenomic and metabolomics analysis were employed to perform differential analysis and functional analysis of gut microbiota and metabolites, aiming to identify the causative strains and metabolic pathways for reproductive injury, and to elucidate the mechanisms by which the microbiota and metabolites affect reproductive injury. RESULTS TWT significantly reduced the testicular index and sperm count in mice, leading to oxidative stress in testicular tissues. And TWT disrupted the gut microbiota and testicular metabolism. Supplementation with exogenous indole-3-lactic acid and Lactobacillus reuteri could regulate oxidative stress and improve testicular damage induced by TWT. CONCLUSION TWT cause reproductive damage by disrupting the gut microbiota and testicular metabolism. Lactobacillus reuteri and its metabolite, indole-3-lactic acid, improve male mice reproductive damage induced by TWHF tablets by regulating oxidative stress in testicular tissues.

OBJECTIVE To evaluate the safety of intra-articular injection of α2-macroglobulin(α2-M) derived from human plasma Cohn fraction Ⅳ. METHODS α2-M was prepared from human plasma Cohn fraction Ⅳ and its purity and activity were tested. A rabbit red blood cell hemolysis test was conducted using an in vitro test tube method. The local irritancy was evaluated by injecting α2-M into the knee joint cavity of rats. The abnormal toxicity test was conducted by injecting α2-M into the abdominal cavity of mice and guinea pigs. RESULTS The purity of fraction Ⅳ derived α2-M was 95%, with an activity of (6.835±0.104) μg·mL^-1. In the in vitro hemolysis test, no hemolysis or aggregation was observed macroscopically, but slight hemolysis was detected by spectrophotometry. The irritancy test showed no obvious abnormalities at the injection site of the rats after administration, with good general condition, appearance, behavior, and spirit, and no abnormal changes in routine blood and blood biochemistry indicators except for PCT and Bas. In the abnormal toxicity test, no abnormal reactions were observed within 30 min after intraperitoneal injection of the test article in mice and guinea pigs, and the average body weight of mice and guinea pigs increased by the end of the observation period. CONCLUSION α2-M derived from human plasma Cohn fraction Ⅳ is considered to be safe in vivo.

OBJECTIVE To prepare lutein microcapsules using yeast cells as the wall material and lutein as the core material by the freeze-drying method. METHODS One-way tests and response surface method optimization were employed to explore the effects of different temperatures, times and core ratios on the embedding rate of the microcapsules, thereby determining the optimal preparation process. Additionally, the microchemistry of the microcapsules, storage stability, and in vitro simulated digestion were analyzed to evaluate the impacts on the antioxidant activity of the microcapsules, in vitro digestive release behavior, and the digestive effect under a fluorescence microscope. RESULTS The results indicated that the optimal preparation process involved a temperature of 40 ℃, a time of 1.5 h, and a core material ratio of 1∶3(g∶g). Under these optimized conditions, the embedding rate of lutein microcapsules reached 81.77%. Scanning electron microscopy results demonstrated that the microcapsule particles were intact, with a smooth surface, dense structure and an excellent embedding effect. Compared with the control group, microencapsulation treatment could significantly enhance the physiological activity and storage stability of lutein. Under light conditions, it increased by 29.40%, showing good light resistance. Under acidic conditions, it increased by 14.70%-48.07%, and under neutral or weak alkaline conditions, it increased by 45.33%-58.44%, which improved the pH stability of lutein and enabled it to better resist the destruction of intestinal fluid. Investigations of the storage environment of lutein microcapsules revealed that the activity of lutein microcapsules increased by 7.06% under light-avoidance conditions. Lutein microcapsules stored under neutral or weak alkaline conditions had the best effect. They could be stored at room temperature for 28 d, during which the antioxidant activity decreased by 23.74%. Reducing the temperature could increase the antioxidant activity and significantly extend the shelf life. In the simulated gastrointestinal digestion test, the yellow-green fluorescence signal under the fluorescence microscope was first enhanced and then weakened, indicating that lutein was digested and utilized in the gastrointestinal tract. The microcapsules had favorable release properties, and exhibited the highest antioxidant activity and release rate during 2 h gastrointestinal digestion, which could effectively reduce the loss of lutein and improve its bioavailability. CONCLUSION This paper broadens new perspectives for the application of yeast cells and also provides a new reference basis for the development of the lutein industry.

OBJECTIVE To explore the efficacy of small/short interfering RNA- insulin-like growth factor 1 receptor(siRNA-IGF1R) in the treatment of sorafenib-resistant liver cancer. METHODS SiRNA-IGF1R was transfected into sorafenib-resistant hepatocellular carcinoma cells, and the effects of blank control, siRNA-NC(Lipo3000), siRNA-IGF1R, sorafenib, siRNA-IGF1R combined with sorafenib on the proliferation, migration and invasion of the drug-resistant cells were compared by CellTiter-Glo^® luminescent cell viability assay(CTG) detection and Transwell assay. In vivo, the mouse xenograft tumor model was constructed by drug-resistant cell line, and the tumor volume, mouse body weight, and IGF1R expression in blank control, siRNA-IGF1R, sorafenib, siRNA-IGF1R combined with sorafenib groups were compared. RESULTS In vitro, compared with the blank control group, siRNA-NC(Lipo3000) and sorafenib alone had no effect on the proliferation, migration and invasion of sorafenib-resistant HepG2 cells. SiRNA-IGF1R and siRNA-IGF1R combined with sorafenib treatment inhibited the proliferation, migration and invasion of HepG2-so cells; and the combined effect of the two drugs was superior to that of siRNA-IGF1R treatment alone. In vivo, the combination of siRNA-IGF1R and sorafenib significantly inhibited tumor growth in mice, outperforming the effect of siRNA-IGF1R alone, with no significant difference in mouse body weight; siRNA-IGF1R markedly reduced IGF1R expression in tumor tissues. CONCLUSION IGF1R is a target for the treatment of sorafenib resistance in liver cancer, and siRNA-IGF1R enhances the efficacy of sorafenib in the treatment of drug-resistant liver cancer by knocking down IGF1R.

OBJECTIVE To identify the composition of glyceryl mono-and distearate (GMD) from different sources using an LC-TOF-MS method and compare the composition and proportion of glycerides in samples. METHODS A Kinetex C₁₈ column (2.1 mm×100 mm, 2.6 μm) was used as analysis column. Methanol-acetonitrile-water(1∶1∶1, containing 5 mmol·L^-1 ammonium acetate) was used as mobile phase A, and isopropanol(containing 5 mmol·L^-1 ammonium acetate) was used as mobile phase B, gradient elution was performed at a flow rate of 0.3 mL·min^-1. The analysis was carried out in ESI positive and negative ion full scanning(TIC) mode and quantified by area normalization method. RESULTS The composition and proportion of 19 fatty acid glycerides in six different sources of GMD showed significant differences in the composition and proportion of glycerides. CONCLUSION This method can be used to determine the composition and proportion of glycerides from different sources, thus contributing to the revelation of the internal mechanism affecting the quality equivalence of GMD.

OBJECTIVE To optimized the extraction process of Ganoderma lucidum crude polysaccharide using Ganoderma lucidum fruiting body as experimental material, and discuss its antioxidant activity. METHODS In this study, the extraction conditions of crude polysaccharide from Ganoderma lucidum were optimized by single factor experiment and response surface methodology. The polysaccharide was extracted by hot water extraction method, protein was removed by Sevag method, and purified by anion exchange column chromatography and gel column chromatography. Its structure was preliminarily determined by UV spectrum, FT-IR spectrum and atomic force microscope. The antioxidant activity of Ganoderma lucidum polysaccharide was evaluated by detecting DPPH radical, ABTS radical, hydroxyl radical and superoxide anion scavenging ability. RESULTS The results showed that the best extraction conditions of Ganoderma lucidum crude polysaccharide was extraction temperature 92.4 ℃, extraction time 5 h 5 min, liquid-solid ratio 21∶1, and the yield was 2.967±0.228%. Ganoderma lucidum polysaccharide obtained by extraction and purification conform to the structural characteristics of polysaccharide, and did not contain nucleic acids and proteins. Atomic force microscopy showed that most of them presented a chain like conformation. Ganoderma lucidum polysaccharide can significantly scavenge DPPH radical, ABTS radical, hydroxyl radical and superoxide anion. CONCLUSION Ganoderma lucidum polysaccharide has good antioxidant ability, this study provides a basis for further development and application of Ganoderma lucidum.