ArchiveTo 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.
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 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 expression of methyltransferase-like 3 (METTL3) in cerebrospinal fluids (CSF) and its correlation with the prognosis of children with medulloblastoma (MB).
Cerebrospinal fluids were collected from MB children. METTL3 protein levels were quantified using the Enzyme-Linked ImmunoSorbent Assay (ELISA) and its correlations with clinicopathological features were analyzed. The prognostic significance was evaluated via the Kaplan-Meier survival curve and Cox proportional hazards regression. Bioinformatics analysis was conducted to assess the association of METTL3 with chemotherapeutic drug sensitivities and functional enrichment of METTL3 in brain tumors.
Ki-67 index was the only clinicopathological factor significantly correlated with CSF METTL3 levels (P<0.05). METTL3 high expression group showed superior progression-free survival (PFS) (HR=0.376, 95% CI:0.133-1.064, P<0.05). Cox analysis identified METTL3 expression as an independent prognostic factor for PFS (P<0.05). Significant negative correlations between METTL3 expression and 50% inhibitory concentrations (IC50) of methotrexate/vinblastine/etoposide (P<0.001). Gene enrichment revealed METTL3′s involvement in neural development and Notch signaling pathways.
METTL3 might serve as a prognostic biomarker for MB pediatric patients. Further validation with expanded cohorts and mechanistic studies (in vivo/in vitro) is warranted.
To investigate the clinical efficacy and safety of atorvastatin tablets combined with bivalirudin injection in patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI).
Patients with acute STEMI were divided into control group and treatment group according to whether combined medication was used. The control group was given an intravenous continuous bolus of bivalirudin for injection at a dose of 0.75 mg·kg-1 during the operation, and after the operation, intravenous pumping of bivalirudin was continued at a dose of 1.75 mg·(kg·h)-1 until 6 hours postoperatively. The treatment group was treated with atorvastatin combined with bivalirudin, where the administration method of bivalirudin was the same as that in the control group, and atorvastatin calcium tablets were administered orally at a dose of 20 mg each time, bid. Both groups received a 30-day treatment course, and relevant reexaminations were conducted after the course. The efficacy, myocardial function indicators, blood coagulation indicators, blood lipid indicators, and inflammatory factor indicators were compared between the two groups.
The trial recruited 118 patients, with 54 assigned to the control group and 64 to the treatment group. At 30 days postoperatively, the efficacy rates of the control group and the treatment group were 74.07% and 89.06%, respectively. At 30 days after surgery, the cardiac troponin T levels in the control group and the treatment group were (7.58±1.27) and (7.01±1.38) μg·L-1, respectively; the global longitudinal strain values were (16.87±1.05)% and (16.34±1.01)%, respectively; the fibrinogen degradation product levels were (4.09±0.80) and (3.82±0.51) μg·mL-1 , respectively; the D-dimer levels were (0.97±0.42) and (0.82±0.33) mg·L-1, respectively; the low-density lipoprotein cholesterol levels were (2.26±0.77) and (1.97±0.61) mmol·L-1, respectively; the β2-microglobulin levels were (2.45±0.12) and (2.36±0.14) mg·L-1, respectively; and the macrophage inflammatory protein-1α levels were (26.22±3.90) and (24.20±4.33) pg·mL-1, respectively. The differences in the above indicators between the treatment group and the control group were all statistically significant (all P<0.05). The incidence of adverse reactions was 7.41% (4 cases/54cases) in the control group and 4.69% (3 cases/64cases) in the treatment group, and the incidence of major adverse cardiovascular events was 5.56% (3 cases/54 cases) and 1.56% (1 case/64 cases), respectively, with no statistically significant differences (all P>0.05).
Atorvastatin tablets combined with bivalirudin injection have a significant efficacy in STEMI patients after PCI. It can achieve the goals of improving myocardial function and coagulation function, effectively controlling the patient′s blood lipid level, reducing the inflammatory response, and exhibit good safety.
To reveal the association between the vanM gene and different glycopeptide resistance phenotypes in Enterococcus faecium, drug susceptibility testing and sequencing analysis were conducted on four E. faecium strains carrying the vanM gene.
The broth microdilution method was employed to determine the susceptibility of four E. faecium strains to glycopeptide antibiotics. Polymerase chain reaction (PCR) was performed to detect the vancomycin-resistant genotypes, while population analysis profiling (PAP) was used to identify the presence of heteroresistant strains among vancomycin-susceptible isolates. Quantitative real-time PCR (qRT-PCR) was conducted to analyze the relative expression level of the vanM gene in E. faecium, and genomic sequencing was carried out for alignment of the resistance gene cluster.
All four E. faecium strains carried the vanM gene. Strain SZD1 was susceptible to vancomycin, whereas SZD2 was identified as a vancomycin-heteroresistant strain. Strain SZD3 exhibited a high relative expression level of the vanM gene and showed resistance to vancomycin. In addition, strain SZD4 harbored both vanA and vanM genotypes, conferring high-level resistance to vancomycin.
E. faecium strains harboring the vanM gene can exhibit diverse glycopeptide resistance phenotypes, and such variations may be associated with the structure, copy number, and expression level of the vanM gene cluster, as well as the coexistence of other resistance genes.
To explore the effects and mechanism of resveratrol on the proliferation, migration and glycolysis of breast cancer cells by regulating the liver kinase B1 (LKB1)/AMP activated protein kinase (AMPK) pathway.
Human breast cancer MDA-MB-231 cells were divided into four groups: control group, low-concentration experimental group (25 μmol·L-1 resveratrol), high-concentration experimental group (50 μmol·L-1 resveratrol) and inhibitor group (50 μmol·L-1 resveratrol + 4 μmol·L-1 AMPK inhibitor BML-275). The cell proliferation of each group was detected by thiazolyl blue (MTT) assay and Edu staining; the cell migration was detected by scratch test; the cell apoptosis was detected by flow cytometry; the glucose consumption and lactic acid production of cells in each group were measured by glucose content kit and lactic acid content kit, respectively; the protein expressions of glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), hexokinase 2 (HK2), LKB1 and AMPK in each group were detected by Western blot.
The cell proliferation inhibition rates of control group, low-concentration experimental group, high-concentration experimental group and inhibitor group were (0±0)%, (32.27±3.68)%, (56.75±5.82)% and (24.41±3.06)%, respectively; the Edu-positive rates were (52.64±6.95)%, (30.72±4.21)%, (18.86±2.54)% and (41.37±4.88)%, respectively; the scratch healing rates were (34.24±3.82)%, (23.67±2.74)%, (14.85±2.03)% and (29.74±3.42)%, respectively; the cell apoptosis rates were (3.04±0.32)%, (21.81±2.64)%, (34.43±3.86)% and (12.67±1.93)%, respectively; the glucose consumption levels were (31.74±3.52), (23.18±2.64), (14.33±1.67) and (28.27±3.12) μmol·L-1, respectively; the lactic acid production levels were (48.12±4.43), (31.27±3.75), (18.85±2.14) and (42.36±4.19) μmol·L-1, respectively; the relative expression levels of GLUT1 were 1.14±0.12, 0.76±0.08, 0.41±0.04 and 0.94±0.09, respectively; the relative expression levels of LDHA were 1.32±0.14, 0.89±0.09, 0.47±0.05 and 1.13±0.12, respectively; the relative expression levels of HK2 were 0.97±0.09, 0.61±0.06, 0.34±0.04 and 0.86±0.09, respectively; the relative expression levels of LKB1 were 0.93±0.10, 1.38±0.14, 1.75±0.17 and 1.12±0.11, respectively; the relative expression levels of AMPK were 1.02±0.11, 1.56±0.16, 2.04±0.23 and 1.18±0.13, respectively. Compared with control group, the above indicators in the low- and high-concentration experimental groups were statistically significantly different (all P<0.05); compared with the high-concentration experimental group, the above indicators in the inhibitor group were statistically significantly different (all P<0.05).
Resveratrol may inhibit the proliferation, migration and glycolysis of breast cancer cells by activating the LKB1/AMPK pathway.
To investigate the effects of abatacept (ABT)-mediated micro ribonucleic acid-16-5p (miR-16-5p) in rats with acute myocardial infarction (AMI) based on the neurogenic locus notch homolog protein 1 (Notch1)/hypoxia inducible factor 1α (HIF-1α) signaling pathway.
AMI rat model was established using the left anterior descending coronary artery ligation method. A total of 50 rats were randomly divided into the sham-operation group (thoracotomy without ligation), model group, experimental group (5 mg·kg-1 ABT), Ad-scramble group (tail vein injection of adenovirus-coated NC-mimic) and Ad-miR-16-5p group (tail vein injection of adenovirus-coated miR-16-5p mimic), with 10 rats in each group. Cardiac function indicators in each group were detected by echocardiography. Fluorescence in situ hybridization was used to detect miR-16-5p relative expression levels in rat myocardial tissue. Enzyme-linked immunosorbent assay was used to detect serum lactate dehydrogenase and creatine phosphohykinase levels, as well as inflammatory factor and oxidative stress factor levels in myocardial tissue. Immunofluorescence was used to detect Notch1 and HIF-1α protein expression in rat myocardial tissue.
The left ventricular ejection fractions (EF) in the sham-operation group, model group and experimental group were (64.72±6.15)%, (42.70±5.26)% and (59.51±6.61)%, respectively; the relative fluorescence intensities of miR-16-5p were 1.00±0.11, 2.53±0.33 and 1.37±0.19, respectively; the lactate dehydrogenase (LDH) levels in the sham-operation group, model group, experimental group, Ad-scramble group and Ad-miR-16-5p group were (154.64±27.48), (347.14±48.67), (173.42±28.45), (179.75±29.83) and (336.47±41.35) IU·L-1, respectively; the creatine phosphohykinase (CPK) levels were (161.37±29.14), (425.43±52.34), (201.67±31.23), (197.74±30.48) and (413.46±49.78) IU·L-1, respectively; the interleukin-1β (IL-1β) levels in myocardial tissue were (35.48±6.93), (129.64±19.51), (52.52±8.48), (51.62±7.32) and (118.42±19.51) pg·mg-1 prot, respectively; the superoxide dismutase levels in myocardial tissue were (83.45±13.42), (34.54±5.61), (76.63±15.63), (75.87±14.23) and (41.75±5.92) U·mg-1 prot, respectively; the relative fluorescence intensities of Notch1 were 1.00±0.16, 1.86±0.22, 1.36±0.19, 1.29±0.25 and 1.71±0.28, respectively; the relative fluorescence intensities of HIF-1α were 1.00±0.13, 2.41±0.37, 1.64±0.24, 1.57±0.29 and 2.10±0.38, respectively; the above indicators showed statistically significant differences between the sham-operation group and the model group, between the model group and the experimental group, and between the Ad-scramble group and the Ad-miR-16-5p group (P<0.01, P<0.001).
ABT may protect cardiac function in AMI rats, improve myocardial tissue pathological damage and fibrosis, and reduce oxidative stress and inflammatory responses by mediating miR-16-5p expression to regulate the Notch1/HIF-1α signaling pathway.
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 establish a population pharmacokinetic model of amoxicillin and clavulanate potassium tablets in healthy Chinese subjects under fasting condition.
Based on the previously confirmed bioequivalence results, this study retrospectively collected the plasma concentration data of 18 subjects who received the test preparation and 17 subjects who received the reference preparation. The population pharmacokinetic model of amoxicillin was constructed using Phoenix NLME software. The effects of covariates such as gender, age, albumin, serum creatinine, creatine kinase, fasting blood glucose, and total cholesterol on pharmacokinetics were evaluated by forward inclusion and backward elimination methods. Model validation included goodness-of-fit plots, bootstrap method, and visual predictive check (VPC).
The population pharmacokinetic model of amoxicillin in healthy subjects conformed to a two-compartment model with first-order elimination kinetics and lag time, which could well describe the data. Serum creatinine and body mass index (BMI) were significant covariates. The parameters of the final model were as follows: central volume of distribution (V)=51.56 L, peripheral volume of distribution (V2)=7.65 L; clearance (CL)=39.99 L·h-1, intercompartmental clearance (CL2)=1.78 L·h-1, absorption rate constant (Ka)=1.45 h-1. Serum creatinine had an impact on CL2 and Ka, while BMI affected V.
The two-compartment model with first-order elimination kinetics and lag time can better describe the in vivo absorption characteristics of amoxicillin after oral administration of amoxicillin and clavulanate potassium tablets in healthy subjects.
This study used 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) as a derivatization reagent to establish an LC-MS/MS analytical method for the quantitative detection of a class of amine drugs, mesalazine(5-ASA) and two thiol drugs, methimazole (MMI) and captopril (CAP).
Plasma samples were processed using derivatization and protein precipitation methods. Optimal derivatization conditions (derivatization reagent concentration, reaction temperature, and derivatization time) were investigated for different drugs. The analytical columns used were Thermo AccucoreTM C18 (2.4 μm, 30 mm×4.6 mm), Agilent Poroshell 120 EC-C18 (4 μm, 50 mm×4.6 mm) as analytical columns, with 0.1% formic acid-acetonitrile, 0.1% formic acid-methanol, and 5 mM ammonium acetate-methanol: acetonitrile (V∶V=50∶50) as the gradient mobile phase, with flow rates of 0.5 mL·min-1 and 0.6 mL·min-1, respectively, using an ESI source for positive/negative ion detection in multiple reaction monitoring (MRM) mode.
5-ASA, MMI, and CAP all undergo nucleophilic substitution reactions with NBD-Cl, reacting rapidly and completely under suitable derivatization conditions. The established MMI analytical method has a linear range of 1.00-500 ng·mL-1, with good linearity (r=0.998 9). The linear ranges of the CAP and 5-ASA analytical methods are both 2.00-1 000 ng·mL-1, with good linear relationships (CAP: r=0.999 3, 5-ASA: r=0.999 6). The intra- and inter-batch precision (CV) and accuracy (RE) were both less than 15%, making the methods suitable for the analysis of actual samples of the corresponding drug formulations and successfully applied to the pharmacokinetic studies of MMI.
The established NBD-Cl derivatization LC-MS/MS analytical methods for the three drugs exhibit advantages such as high sensitivity, strong specificity, and low background noise, and successfully address the issues of low mass spectrometry response, poor spectral retention, and the tendency of CAP to oxidize. The methods require minimal plasma sample volume and have short analysis times, providing a feasible solution for the analysis of biological samples of the three drugs. They also demonstrate the applicability of NBD-Cl derivatization technology in the analysis of amine- and thiol-containing drugs.
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 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.
A 20-month-old male infant was admitted to the department of infectious diseases of our hospital due to infectious fever and left cervical lymphadenitis. He received treatment with piperacillin sodium and tazobactam sodium for injection. After 7 consecutive days of medication (a total of 23 administrations) without adverse reactions, the infant suddenly developed symptoms of anaphylactic shock during the 24th administration, including irritability, incessant crying, pale complexion, cyanosis of the lips, cold extremities, and unmeasurable blood pressure. Medical staff immediately discontinued the infusion of piperacillin sodium and tazobactam sodium for injection and initiated rescue measures such as intramuscular injection of epinephrine. Eventually, the infant was successfully resuscitated. This case reminds medical personnel that the sensitization period of β-lactam antibiotics can last for several days or even months, which is concealed throughout the entire treatment course. The absence of adverse reactions during initial medication does not rule out subsequent risks. It is necessary to strengthen medical staff’s attention to medication monitoring during each administration to ensure the safety of pediatric medication.
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 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.
As an antimalarial drug, hydroxychloroquine has anti-inflammatory and immunomodulatory effects, and can treat rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and other diseases. Because of its potential to inhibit virus therapy, it is widely used during the period of novel coronavirus pneumonia. Hydroxychloroquine also has drug side effects, which can cause damage to multiple systems such as the nervous system, cardiovascular system, retina, digestive system, skin, and blood system. Its toxic mechanism is related to Cytochrome P450 3A4 (CYP3A4) enzyme metabolism, blocking inward rectifier K+current(IK1), interfering with photoreceptors and retinal pigment epithelial (RPE) cells, and other effects. This study provides a review of the toxic side effects and molecular mechanisms caused by the application of hydroxychloroquine, providing theoretical support for the study of its toxic effects and rational clinical use.
To investigate the trends of the disease burden attributable to high body mass index (BMI) globally and in China from 1990 to 2021, to provide evidence for obesity prevention and control strategies.
Based on the Global Burden of Disease (GBD) 2021 database, data on high BMI-related deaths, disability-adjusted life years (DALYs), age-standardized mortality rates, and age-standardized DALYs rates globally and in China from 1990 to 2021 were extracted. The Joinpoint software was used to calculate the average annual percentage change (AAPC) of age-standardized mortality rates and DALYs. Disease burden ranking were performed using the GBD Compare tool.
Globally, deaths attributable to high BMI increased from 1.4595 million to 3.7091 million (increase of 154.13%, AAPC=0.29%, P<0.001); in China, from 0.1420 million to 0.5756 million (increase of 305.23%, AAPC=1.12%, P<0.001). Males showed higher increases than in females in both. Globally, the number of DALYs increased from 48.0421 million person-years to 128.5201 million person-years (increase of 167.52%), while in China, it increased from 5.4339 million person-years to 20.8652 million person-years (increase of 283.9%). For China, the top five diseases for mortality rates and DALYs rates attributable to high BMI were ischemic heart disease, hypertensive heart disease, diabetes, stroke, and chronic kidney disease. Alzheimer's disease showed an AAPC of 9.87% (P<0.001) for age-standardized mortality rate, rising from the 17th to the 6th place.
From 1990 to 2021, disease burden attributable to high BMI significantly increased globally and in China, with China’s growth rate far exceeding the global average. Comprehensive life-cycle obesity prevention and control should be strengthened, with special focus on high-burden diseases such as cardiovascular diseases, diabetes, and cancers. New directions for prevention and control of stroke and Alzheimer’s disease should be emphasized.
To analyze the developmental status and core characteristics of new drug registration clinical trials in China, and to forecast future trends, thereby providing references for the research and development (R&D) layout of the pharmaceutical industry and the optimization of relevant policies.
Based on public data from the Annual Drug Evaluation Report and the Annual Report on the Progress of Clinical Trials for New Drug Registration in China published by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) from 2020 to 2024, a comprehensive analysis was conducted on the growth in the number of clinical trials, drug types, distribution of indications, implementation efficiency, and progress in key areas.
In 2024, the total number of registered clinical trials reached 4 900, a record high. The proportion of Phase Ⅱ and Phase Ⅲ trials increased steadily, indicating continuous optimization of R&D efficiency. Clinical trials for chemical drugs and biological products were concentrated in the anti-tumor field, while trials for traditional Chinese medicine focused primarily on respiratory and digestive system diseases. Trials in key areas such as cell and gene therapy, drugs for rare diseases, and pediatric medications showed significant growth.
New drug clinical trials in China are demonstrating trends towards greater efficiency, innovation, and internationalization. Future efforts should focus on policy guidance and technological innovation to further optimize resource allocation, overcome homogeneous competition, and promote the high-quality development of the pharmaceutical industry.
Metabolic dysfunction-associated steatohepatitis (MASH) has become a research hotspot for new drug development in the field of liver diseases. Given the complex pathogenesis of MASH, coupled with constraints in disease understanding and therapeutic options, clinical trials are required to involve liver biopsies and prolonged monitoring of clinical outcomes, thereby contributing to the difficulties in drug development. To accelerate the R&D process, an increasing number of new methods and technologies are being developed and explored for application in clinical development of MASH therapeutic drugs. This paper introduces the progress of new methods such as non-invasive tests, optimized clinical trial designs, and artificial intelligence technologies in MASH clinical development, and discusses the challenges encountered in their application to clinical trials.
To develop a clinical trial management system (CTMS) to realize full-process review and management of clinical trial projects, research team management, document management, subject management, drug sample management, free medical order management and quality management.
Within the framework of the existing hospital information system, we collaborated with the hospital information center and a commercial software company to design and develop a full-process intelligent information system for clinical trials. Based on WebService, the system was connected to the hospital information system through standardized application programming interfaces (APIs), with the establishment of standard data dictionaries and governance rules to achieve secure data exchange between heterogeneous systems.
The system balanced development costs and functionality, and achieved good application effects. It integrated functions including project process, document management, drug sample management, subject management, free inspection and testing, and quality management, formed a medical database covering the entire project cycle of subjects, and ensured the authenticity and traceability of data.
This system fully leverages the advantages of joint development and informatization, improves the enrollment efficiency and implementation quality of clinical trials, and provides reference experience for other hospitals to implement integrated clinical trial management systems.
To address issues such as low efficiency and poor consistency in the submission of bioequivalence trial data under the Clinical Data Interchange Standards Consortium standards, this study aimed to develop a set of reusable standardized core data sets to improve data preparation efficiency and regulatory submission quality.
A systematic review of multiple approved BE trial projects was conducted, covering different trial designs, dosage forms, and study types. Common data structures and mapping rules were extracted through business analysis, and standardized data set templates covering both SDTM and ADaM layers were developed in strict accordance with CDISC standards.
This study summarized 274 SDTM and 338 ADaM data element-specific attributes applicable to bioequivalence trials. A set of standardized core data sets suitable for most BE trial scenarios was established and successfully applied in a two-formulation, two-period, two-sequence crossover BE study evaluating a gel patch.
The standardized dataset constructed in this study provides a preliminary framework for the standardization of BE trial data, which requires further validation through large-scale applications to clarify its applicability and robustness in enhancing the standardization level and work efficiency of BE trial data processing. It holds significant practical value for ensuring data quality and improving the success rate of submissions, while also serving as a referenceable example for the development of foundational datasets within the industry.
Currently, there are no approved adolescent weight management drugs in China, and there is a significant unmet medical need for adolescent weight management. With glucagon like peptide-1 receptor agonists (GLP-1 RA) design becoming a hot topic in the research and development of adolescent obesity, the number of communication and applications for clinical application in China has gradually increased. Combined with relevant problems encountered in the evaluation, we discussed the design and evaluation consideration for clinical trials of adolescent weight management, so as to improve the research and development and provide references for researchers.