To establish a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for analyzing the concentrations of methotrexate (MTX) and its metabolite 7-hydroxymethotrexate (7-OH-MTX) in human plasma, and to use it for clinical drug monitoring, in order to explore the relationship between their concentrations and liver and kidney toxicity.

Acetonitrile precipitation protein method was used to preprocess the samples, combined with HPLC-MS/MS detection. 369 blood samples from pediatric and adult patients who received high-dose methotrexate (HDMTX) chemotherapy were collected for methodological validation, and Spearman correlation analysis between concentration and hepatotoxicity and nephrotoxicity was performed using statistical software SPSS 27.

The linear relationship of MTX in human plasma was good within the concentration range of 0.005-2 μmol·L^-1 (r=0.998 8), and the linear relationship of 7-OH-MTX was good within the concentration range of 0.05-20 μmol·L^-1 (r=0.997 4). The intra batch and inter batch precision were all less than 10%, the extraction recovery rate reached 87.0-106.1%, and the coefficient of variation of matrix effect was less than 7%. The analysis of blood concentration measurements at 42 hours, 72 hours, and after HDMTX infusion showed that the concentration ratio of 7-OH-MTX/MTX was significantly negatively correlated with liver function indicators alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P<0.01), while there was no significant correlation with renal function indicators creatinine (CR) and creatinine clearance rate (CCR) (P>0.05).

The established method is simple, accurate, and sensitive, and is suitable for clinical drug therapy monitoring. By monitoring 7-OH-MTX/MTX, the occurrence of liver toxicity can be effectively predicted for timely clinical drug rescue.

To analyze the blood-absorbing components of Penthorum chinense Pursh using high-resolution ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and to systematically investigate the material basis and mechanism of its therapeutic effect on primary sclerosing cholangitis (PSC) by integrating network pharmacology and molecular docking.

High-resolution UPLC-MS/MS was employed to identify the blood-absorbing components of Penthorum chinense Pursh. Potential target proteins of these components were predicted using the Swiss Target Prediction database. Disease-related targets of PSC were retrieved from the Gene Expression Omnibus (GEO) database using the keyword "Primary sclerosing cholangitis." The intersection of component targets and disease targets was identified to obtain common targets. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to screen for core targets. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Metascape platform. Finally, molecular docking validation of key components with core targets was conducted using AutoDock Vina software.

A total of 174 blood-absorbing components were identified from Penthorum chinense Pursh, corresponding to 661 predicted component targets. 2 878 PSC-related disease targets were obtained, and 105 intersection targets were screened. PPI network analysis revealed core targets including RAC-alpha serine/threonine-protein kinase (AKT1), heat shock protein HSP 90-alpha (HSP90AA1), C-X-C chemokine receptor type 4 (CXCR4), tyrosine-protein kinase Lyn (LYN), and androgen receptor (AR). GO analysis indicated that Penthorum chinense Pursh may participate in inflammatory response and other processes by regulating molecular functions such as phosphotransferase activity on membrane rafts. KEGG enrichment analysis demonstrated that the intersecting targets were significantly enriched in pathways associated with the pathological mechanisms of PSC, including T helper 17 (Th17) cell differentiation and bile secretion. Molecular docking results demonstrated favorable binding stability between key components and core targets.

This study identified the blood-absorbing components of Penthorum chinense Pursh and preliminarily revealed its potential mechanism in treating PSC through a "multi component, multi target, multi pathway" synergistic approach, providing a scientific basis for the clinical application of Penthorum chinense Pursh in PSC treatment.

To establish a method for determination of zonisamide in plasma of epileptic children by micro-detection technology combined with high performance liquid chromatography-mass spectrometry (HPLC-MS/MS).

10 μL of plasma samples were pre-treated by precipitation protein method with organic solvent. Reversed-phase chromatographic columns were adopted. Flow phase: 0.075% formic acid-2 mmol·L^-1 ammonium acetate-water (A) and methanol (B), gradient elution; flow speed: 0.45 mL·min^-1; injection volume: 1 μL. The quantitative method adopted the internal standard method, and the isotope internal standard was zonisamide -¹⁵N-D₄. Ion source was electric spray ion (ESI) source, multireaction monitoring (MRM) mode for quantitative analysis, using positive ion monitoring mode. The specificity, standard curve, lower limit of quantitation (LLOQ), residual effect, precision, matrix effects, extraction recovery and stability were investigated.

The retention times of zonisamide and its internal standard were both 1.25 min, and there was no interference from endogenous substances within the retention time. The linear range of zonisamide was 1-62.5 μg·mL^-1 (r=0.999 7), and LLOQ was 1 μg·mL^-1. The intra-day and inter-day precision RSD was equal or less than 4.84%, and the accuracy ranges from 97.75%-107.95%, with good stability, and this method was not affected by common matrix.

This method involves micro-blood collection, which is simple to operate, highly efficient and rapid, and can be used for the monitoring of daily therapeutic drugs in children with epilepsy in clinical practice.

To explore the efficacy of ceftazidime/avibactam (CAZ/AVI) combined with polymyxin in the treatment of carbapenem-resistant Gram-negative bacteria (CRO) pulmonary infections.

A total of 80 patients with CRO pulmonary infections admitted to our hospital from December 2019 to December 2024 were selected and divided into a control group (n=37) and a CAZ/AVI group (n=43) based on treatment methods. The control group received colistimethate sodium combined with meropenem, while the CAZ/AVI group received CAZ/AVI combined with colistimethate sodium. The clinical efficacy, bacterial clearance rate, and prognosis were compared between the two groups. Based on treatment efficacy, patients were classified into an effective group and an ineffective group, and logistic analysis was performed to identify factors influencing treatment outcomes in CRO pulmonary infections.

The clinical efficacy and bacterial clearance rate in the CAZ/AVI group were higher than those in the control group (P<0.05); there was no statistically significant difference in 28-day mortality between the two groups (P>0.05). The levels of WBC, CRP, PCT, TNF-α, IL-6, and IL-10 in the CAZ/AVI group were lower than those in the control group (P<0.05). In the effective group, age, APACHE Ⅱ score, SOFA score, and the proportion of patients receiving continuous renal replacement therapy (CRRT) were lower than those in the ineffective group, while treatment duration and the proportion receiving CAZ/AVI combined with polymyxin were higher (P<0.05). Logistic analysis indicated that APACHE Ⅱ score, SOFA score, CRRT, treatment duration, and CAZ/AVI combined with polymyxin were influencing factors for treatment outcomes in CRO pulmonary infections (P<0.05).

CAZ/AVI combined with polymyxin shows significant efficacy in the treatment of CRO pulmonary infections.

To observe the clinical efficacy and safety of alirocumab injection combined with ticagrelor tablets in treating patients with moderate coronary artery stenosis accompanied by angina pectoris.

Patients exhibiting moderate coronary artery stenosis and angina pectoris were categorized into two groups according to their treatment methods: treatment group and control group. Both groups received basic treatment. The control group received additional ticagrelor tablets, starting with a dose of 180 mg, followed by 90 mg twice daily. The treatment group added alirocumab injection at an initial dose of 75 mg, subcutaneously injected every two weeks, with dose adjustments made from weeks 4-8 based on lipid levels. Both groups continued treatment for 12 weeks. The clinical efficacy, angina attack frequency, use of nitroglycerin tablets, echocardiographic parameters, lipid levels, coagulation and myocardial injury markers, Seattle Angina Questionnaire scores, 6-minute walk distances and safety evaluation were compared between the two groups. Safety was also evaluated.

A total of 92 patients were enrolled in this study, with 45 and 47 patients assigned to the control group and the treatment group, respectively. After treatment, the total effective rates were 75.56% (34 cases/45 cases) for the control group and 91.49% (43 cases/47 cases) for the treatment group. The corrected QTc intervals were (387.38±18.62) and (379.29±17.54) ms, respectively; QRS durations were (98.38±7.27) and (97.45±6.74) ms; cardiac outputs were (4.82±0.63) and (5.17±0.68) L·min^-1; cardiac indexes were (3.17±0.42) and (3.39±0.48) L·(min·m²)^-1; total cholesterol levels were (4.11±0.82) and (3.58±0.71) mmol·L^-1; triglyceride levels were (3.42±0.63) and (3.05±0.57) mmol·L^-1; low-density lipoprotein cholesterol levels were (3.42±0.54) and (2.95±0.40) mmol·L^-1; free fatty acid levels were (0.54±0.07) and (0.48±0.08) mmol·L^-1. The differences in the above indicators between the treatment group and the control group were all statistically significant (all P<0.05). The incidence rates of adverse reactions in control group and treatment group were 11.11% (5 cases/45 cases) and 14.89% (7 cases/47 cases), with no statistically significant difference (P>0.05).

Both alirocumab injection combined with ticagrelor tablets and ticagrelor tablets alone can treat moderate coronary artery stenosis associated with angina pectoris, however, the combination therapy more significantly improves efficacy, reduces the frequency of angina attacks and blood lipid levels, enhances overall cardiac function and quality of life, with good safety.

To evaluate the practice of pharmaceutical care in oncology clinical pharmacists after the implementation of the charging policy for pharmaceutical service.

The clinical data of patients who received paid pharmaceutical care in the oncology department of a tertiary hospital in Beijing from November 2024 to July 2025 were retrospectively analyzed, including monitoring content, monitoring drugs, monitoring type and intervention.

A total of 131 patients were enrolled, and the average number of monitored patients was 14.55 per month. A total of 361 pharmaceutical care suggestions were put forward, of which 154 (42.66%) were intervention suggestions, of which 207 (57.34%) were pharmaceutical evaluation recommendations. The main suggestions for intervention were: 42 suggestions for the treatment of adverse drug reactions (27.27%), 42 suggestions for the formulation/adjustment of medication regimens (27.27%), etc. The main recommendations included risk monitoring of adverse drug reactions (103 recommendations, 49.76%), medication education (67 recommendations, 32.37%), etc.

This study describes the initial practice after the implementation of the policy, which can provide a baseline for subsequent controlled studies and also provide a new idea for the implementation of the model of inpatient pharmaceutical care.

To investigate the effect and mechanism of quercetin on the recovery of pelvic floor function in a rat model of stress urinary incontinence (SUI) by regulating the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway.

Female SD rats were selected and assigned into the control (NC) group, SUI group, low-, medium-, and high-dose quercetin (L, M, H-quercetin) groups, and H-quercetin+JAK2-STAT3 activator RO8191 (H-quercetin+RO8191) group according to the criteria of 12 rats in each group. Each administration group was administered daily according to the dose, for 5 consecutive weeks. Subsequently, the urodynamics, intravesical pressure, pelvic floor function-related parameters of rats and the surface electrical signals of pelvic floor muscles were detected. The oxidative stress indexes were detected by ELISA and DCFH-DA fluorescent probe. HE staining was used to observe the pathological changes of urethral tissue. Moreover, protein expression was detected by Western blot.

In the SUI group, the density of cells and cell nuclei in the rat urethral tissue decreased, the cells atrophied and were arranged in a disordered manner with uneven staining, the muscular layer became thinner, the interstitial spaces widened, and intracellular vacuolation was observed. The urinary leakage point pressure, maximum volume, abdominal pressure, urinary leakage point pressure when abdominal pressing, urination time interval, urination efficiency, vaginal systolic pressure, vaginal resting pressure, type Ⅰ and type Ⅱ pelvic floor muscle fiber potentials, supeioxide dismucase (SOD) and glutathione peroxidase (GSH-Px) in the SUI group were lower than those in the NC group, while the residual urine volume, urine output, bladder neck range of motion, urethral rotation angle, malondialdhyde(MDA), reactive oxygen species (ROS) fluorescence intensities, p-JAK2/JAK2, and p-STAT3/STAT3 were higher (P<0.05). The urinary leakage point pressure, maximum volume, abdominal pressure, urinary leakage point pressure when abdominal pressing, urination time interval, urination efficiency, vaginal systolic pressure, vaginal resting pressure, type Ⅰ and type Ⅱ pelvic floor muscle fiber potentials, SOD and GSH-Px in the L, M, and H-quercetin groups were higher than those in the SUI group, while the residual urine volume, urine output, bladder neck range of motion, urethral rotation angle, MDA, ROS fluorescence intensities, p-JAK2/JAK2, and p-STAT3/STAT3 were lower (P<0.05). The urinary leakage point pressure, maximum volume, abdominal pressure, urinary leakage point pressure when abdominal pressing, urination time interval, urination efficiency, vaginal systolic pressure, vaginal resting pressure, type Ⅰ and type Ⅱ pelvic floor muscle fiber potentials, SOD and GSH-Px in the H-quercetin+RO8191 group were lower than those in the H-quercetin group, while the residual urine volume, urine output, bladder neck range of motion, urethral rotation angle, MDA, ROS fluorescence intensities, p-JAK2/JAK2, and p-STAT3/STAT3 were higher (P<0.05).

Quercetin may restore pelvic floor function in SUI rats by inhibiting the JAK2-STAT3 pathway.

To explore the effect of hyperoside on insulin resistance in polycystic ovary syndrome rats by regulating adenosine monophosphate activated protein kinase (AMPK)/glycogen synthase kinase 3β (GSK3β) signaling pathway.

Nine female SD rats were randomly selected from 45 as the normal (NC) group (equal amount of distilled water), while the rest were used to construct a polycystic ovary syndrome model and grouped into model group (equal amount of distilled water), experimental-L group (0.7 mg·kg^-1·d^-1 hyperoside), experimental-H group (1.5 mg·kg^-1·d^-1 hyperoside), and inhibitor group (1.5 mg·kg^-1·d^-1 hyperoside and 0.2 mg·kg^-1·d^-1 Compound C), with nine rats in each group. The blood glucose meter was used to measure fasting blood glucose (FBG) in rats. Enzyme linked immunosorbent assay (ELISA) method was used to measure fasting insulin (FINS), testosterone (T), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), triglycerides (TG), cholesterol (CHO), low-density lipoprotein (LDL), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Hematoxylin-eosin (HE) staining was used to detect pathological changes in ovarian tissue. Western blot was used to measure AMPK/GSK3β signaling pathway proteins in ovarian tissue.

The serum FBG levels in NC group, model group, experimental-L group, experimental-H group and inhibitor group were (5.54±0.69), (7.32±0.91), (6.65±0.82), (5.97±0.72) and (6.98±0.85) mmol·L^-1, respectively; the serum FINS levels were (9.58±1.39), (15.87±1.96), (13.65±1.62), (11.42±1.57) and (15.04±1.85) mU·L^-1, respectively; HOMA-IR indexes were 2.36±0.43, 5.16±0.71, 4.03±0.47, 3.03±0.52 and 4.67±0.68, respectively; the serum TG levels were (0.68±0.09), (1.58±0.18), (1.27±0.17), (0.98±0.13) and (1.46±0.18) mmol·L^-1, respectively; the serum CHO levels were (0.76±0.09), (1.52±0.18), (1.24±0.16), (1.01±0.14) and (1.41±0.17) mmol·L^-1, respectively; serum LDL levels were (1.62±0.23), (3.59±0.46), (3.06±0.42), (2.54±0.31) and (3.38±0.44) mmol·L^-1, respectively; serum LH levels were (4.21±0.57), (9.48±1.39), (7.86±0.96), (6.25±0.74) and (8.87±1.18) ng·mL^-1, respectively; serum FSH levels were (19.38±2.52), (8.27±1.05), (11.36±1.42), (14.65±1.76) and (9.57±1.48) ng·mL^-1, respectively; the serum T levels were (6.82±0.95), (13.86±1.62), (11.39±1.48), (8.98±1.14) and (12.64±1.53) ng·mL^-1, respectively; serum E2 levels were (1.02±0.14), (0.48±0.07), (0.72±0.09), (0.95±0.13) and (0.61±0.08) ng·mL^-1, respectively; the serum IL-6 levels were (53.46±7.69), (123.58±18.32), (98.39±13.58), (74.58±9.37) and (114.27±14.72) pg·mg^-1, respectively; serum TNF-α levels were (43.74±6.82), (82.19±10.46), (66.39±8.27), (51.72±7.24) and (73.54±1.02) pg·mg^-1, respectively; the relative protein expression levels of p-AMPK/AMPK in ovarian tissues were 0.79±0.11, 0.27±0.04, 0.49±0.07, 0.71±0.09 and 0.38±0.06, respectively; the relative protein expression levels of p-GSK3β/GSK3β were 0.19±0.04, 0.68±0.09, 0.47±0.07, 0.28±0.04 and 0.59±0.08, respectively. Among the above indexes, there were all statistically significant differences between NC group and modell group, model group and experimental-L group, experimental-L group and experimental-H group, experimental-H group and inhibitor group (all P<0.05).

Hyperoside improves insulin resistance in polycystic ovary syndrome rats by regulating AMPK/GSK3β signaling pathway.

To investigate the effect of daratumumab on the levels of serum micro ribonucleic acid (miR) miR-140-5p, miR-17-3p and miR-29c in patients with relapsed and refractory multiple myeloma (RRMM).

In this study, 92 RRMM patients included in the study were divided into control and study groups by random number table method, 46 cases in each group. All cases were admitted to the Affiliated Hospital of Nantong University from January 2022 to January 2025. The control group was treated with VRD regimen (bortezomib, dexamethasone, lenalidomide), and the study group was treated with DVD regimen (daratumumab, bortezomib, dexamethasone). Both groups were treated for 21 d as a course of treatment, a total of 4 courses of treatment. The efficacy after 4 course of treatment, T lymphocyte subsets, inflammation-related indicators, serum miR-140-5p, miR-17-3p, miR-29c levels before and after 4 course of treatment, and safety were compared between the two groups.

Compared with the control group (65.22%), the total remission rate (84.78%) of the study group after 4 course of treatment was higher (P<0.05). Compared with before treatment, the levels of peripheral blood CD3⁺, CD4⁺, CD4⁺/CD8⁺ and serum interferon-γ (IFN-γ), miR-140-5p and miR-29c increased after 4 course of treatment in the two groups, and the study group were higher; the levels of peripheral blood CD8⁺, serum C-reactive protein (CRP), transforming growth factor-β (TGF-β) and miR-17-3p decreased, and the study group were lower (all P<0.05). No significant difference was observed between the two groups in terms of safety (P>0.05).

Daratumumab could effectively regulate T lymphocyte subsets, inflammation-related indicators and serum levels of miR-140-5p, miR-17-3p and miR-29c in RRMM patients, improve the immune function of the body, reduce the inflammatory response of the body. The curative effect was significant and the safety was good.