To analyze the adverse drug reactions (ADRs) of 0.01% atropine sulfate eye drops in myopia control among children and adolescents, providing safety evidence for its clinical application.

Retrospective analysis of ADR data from pediatric and adolescent patients using the 0.01% atropine sulfate eye drops (hospital-prepared formulation) in our institution from January 2022 to December 2024.

A total of 51 ADR cases were collected, with an incidence rate of 0.29%. Visual disorders were the most frequent (54.71%), primarily manifesting as eye pain, blurred vision, and photophobia; followed by skin and subcutaneous tissue disorders (11.76%), mainly presenting as rash; and nervous system disorders (9.80%), including dizzinessand headache. Newly reported ADRs accounted for 35 cases (68.63% of total reports). All ADRs were mild or moderate, with no severe cases observed.

0.01% atropine sulfate eye drops show favorable short-term safety and a low incidence of adverse drug reactions in myopia control among children and adolescents. As a real-world pharmacovigilance data report, this study provides certain cautions for the clinical use of 0.01% atropine sulfate eye drops; however, its long-term safety requires further investigation and validation.

To explore the mechanism of action of catechin (CAT) on mice with a model of high altitude polycythemia through mediating the intestinal hypoxia-inducible factor-2α (HIF2α) iron metabolism pathway.

SPF-grade male Balb/cmice were randomly divided into control group (reared in a normal atmospheric pressure environment: northeastern Qinghai province, China, at an altitude of 2 260 m, 36°73′ north latitude, 101°75′ east longitude, without any treatment), model group (reared in a high-altitude hypoxic environment: a certain place in southwestern Qinghai province, China, at an altitude of 4 208 m, 32°90′ north latitude, 95°25′ east longitude, without any treatment), the experimental group (based on model group, intragastrically administered with 100 mg·kg^-1 CAT once a day from the 29th to the 35th day) and the oe-HIF2α group (based on experimental group, intravenously injected with lentivirus-coated oe-HIF2α plasmids by the tail vein once a day from the 34th to the 35th day). Real-time fluorescence quantitative polymerase chain reaction was used to detect the relative expression level of HIF2α mRNA in intestinal tissues; Western blot assay was used to detect the relative expression levels of HIF2α, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cleaved-cysteine-aspartic acid protease 3 (Cleaved-Caspase3), ferroportin (FPN), transferrin receptor (TFRC) in intestinal tissues, as well as the relative expression levels of GATA binding factor 1 (GATA-1) and erythropoietin receptor (EpoR) in bone marrow red blood cells; automatic hematology analyzer was used to detect the levels of hemoglobin, red blood cell count and hematocrit in peripheral blood; the spectrophotometric method was used to detect the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and content of malondialdehyde (MDA) in intestinal tissues; the immunofluorescence staining assay was used to detect the positive expression of ferritin (Ferritin) in intestinal tissues.

The relative expression levels of HIF2α mRNA in control group, model group and experimental group were 1.00±0.18, 1.61±0.16 and 1.21±0.13, respectively; the hemoglobin levels in control group, model group, experimental group and oe-HIF2α group were (132.91±11.44), (221.37±26.92), (178.65±19.32) and (206.33±21.37) g·L^-1, respectively; the red blood cell count levels were (4.79±0.75), (9.26±1.11), (6.08±1.03) and (7.74±0.96)×10¹²·L^-1, respectively; the hematocrit levels were (44.17±4.06)%, (63.58±6.38)%, (51.79±4.45)% and (58.24±5.07)%, respectively; the relative expression levels of GATA-1 protein were 1.00±0.17, 2.03±0.33, 1.52±0.19 and 1.80±0.23, respectively; the relative expression levels of EpoR were 1.00±0.11, 1.83±0.31, 1.29±0.20 and 1.62±0.24, respectively; the relative fluorescence intensities of Ferritin were 1.00±0.12, 7.86±0.97, 2.97±0.49 and 4.75±0.51, respectively; the relative expression levels of FPN protein were 1.00±0.14, 1.69±0.25, 1.31±0.18 and 1.52±0.19, respectively; the relative expression levels of TFRC protein were 1.00±0.10, 2.18±0.23, 1.67±0.15 and 1.86±0.15, respectively. There were statistically significant differences in the above-mentioned indicators between model group and control group, between experimental group and model group, and between oe-HIF2α group and experimental group (all P<0.05).

CAT can inhibit cell apoptosis, oxidative stress and excessive iron metabolism in the intestines of mice with high altitude polycythemia by mediating the expression of intestinal HIF2α, and play a role in the prevention and treatment of high altitude polycythemia.

Based on the previously established competency model for clinical investigators in drug clinical trials, this study aims to evaluate the effectiveness of a targeted training program, clarify the role of this model in improving investigators’ professional competence, operational skills, and ethical awareness, and provide evidence-based basis for the precise optimization of clinical trial training models.

Investigators from tertiary Grade A hospitals in Beijing who had participated in at least one clinical trial in the past three years were selected as the research subjects. The training content was designed based on the core elements of the competency model. A pre-training and post-training paired design was adopted to evaluate the improvement of knowledge and skills through standardized Good Clinical Practice (GCP) simulation tests; online questionnaire surveys were conducted to collect trainees’ satisfaction feedback on training content, teaching quality, organizational management and other dimensions. Wilcoxon signed-rank test was used to compare scores before and after training. Stratified by gender, the Mann-Whitney U test was used to compare the inter-group differences in post-training competency scores of investigators of different genders. Stratified by educational background, professional title and working years of clinical trial practice, the Kruskal-Wallis H test was adopted to analyze the inter-group differences in post-training scores among investigators with different educational levels, different professional titles, and different working years.

A total of 81 clinical investigators were included, with a median age of 34 (31.00, 44.00) years. The proportions of males and females were 27.16% and 72.84%, respectively. Among the participants, 62.96% held doctoral degrees, and 32.10% had senior professional titles. The median pre-training total score (Q1, Q3) was 35.00 (31.00, 39.00) scores, while the median post-training total score (Q1, Q3) was 43.00 (40.00, 46.00) scores, indicating a significant improvement in the trainees’ total scores (Z=-7.30, P<0.001). The scores for all competency sub-dimensions increased significantly compared to those before training. Among them, the differences in scores before and after training for ethical awareness and subject protection, GCP implementation capability, study design and protocol execution, and data quality control were all statistically significant (all P<0.001). Subgroup analysis showed that the total competency scores of investigators with different genders, professional titles, and years of experience in clinical trials significantly improved after training, with no statistically significant differences in the magnitude of improvement between groups. Participants with master’s or doctoral degrees showed significant improvements in post-training scores (all P<0.001), while those with bachelor’s degrees showed no significant difference between pre- and post-training scores (P>0.05). Furthermore, 85.19% of the trainees rated the overall performance of the training as very satisfied.

The training program designed based on the competency model could improve the GCP theoretical level and practical knowledge reserve of clinical investigators in clinical trials, and has good trainee acceptance and practicality. By accurately matching the core competency needs of clinical investigators, this training model provides a replicable practical path for the optimization of the clinical trial talent training system.

To observe the clinical efficacy and safety of low-dose mifepristone tablets combined with dienogest tablets in the treatment of ovarian chocolate cyst patients.

Patients with ovarian endometriomas were divided to control group, treated with dinoprost tablets at a dose of 2 mg once daily (qd), while the treatment group received additional low-dose mifepristone tablets at 5 mg qd in addition to the control regimen. Both groups were treated for 6 months. The clinical efficacy, dysmenorrhea symptom scores, hormone levels, carbohydrate antigen 125 (CA125) levels, endometrial thickness, uterine volume, inflammatory factor levels, and safety profiles before and after treatment were compared.

A total of 123 patients were enrolled, with 63 cases in the control group and 60 cases in the treatment group. The treatment group demonstrated a significantly higher overall response rate [91.67% (55 cases/60 cases) vs. 77.78% (49 cases/63 cases), P<0.05]. After treatment, the visual analog scale (VAS) scores of the control group and the treatment group were (2.13±0.67) and (1.78±0.55) points, respectively; the dysmenorrhea symptom scale (CMSS) scores were (21.78±4.19) and (19.86±4.54) points, respectively; the levels of FSH in the control group and the treatment group were (5.06±1.11) and (4.48±1.17) U·L^-1, respectively; the levels of estradiol (E₂) were (204.43±34.68) and (185.73±35.14) pmol·L^-1, respectively; the levels of progesterone (P) were (12.14±2.43) and (10.81±2.29) ng·mL^-1, respectively; the levels of CA125 were (37.31±4.34) and (33.12±4.49) U·mL^-1, respectively; endometrial thickness was (5.88±1.46) and (5.15±1.32) mm, respectively; the uterine volume was (106.15±13.62) and (98.89±11.57) cm³, respectively; the levels of interleukin-6 (IL-6) in the control group and treatment group were (14.38±2.19) and (13.44±2.05) ng·L^-1, respectively; the levels of IL-17 were (8.47±2.08) and (7.56±2.11) pg·mL^-1, respectively; the levels of amyloid A (SAA) were (18.62±2.17) and (17.59±2.13) mg·L^-1, respectively; the recurrence rate was 14.29% (9 cases/63 cases) and 5.00% (3 cases/60 cases), respectively; menstrual restoration time was (46.3±7.1) and (38.5±6.2) d, respectively; the differences of above indicators were all statistically significant compared betwwen two groups (P<0.05, P<0.01). The adverse drug reactions in the control group and the treatment group mainly included headache, breast discomfort, and mild irregular bleeding and the incidence was 9.52% (6 cases/63 cases) in the control group and 11.67% (7 cases/60 cases) in the treatment group (P>0.05).

For patients with ovarian chocolate cysts, low-dose mifepristone tablets combined with dienogest tablets represents a valuable therapeutic strategy, offering enhanced pain relief, hormonal control, and overall efficacy compared to dienogest monotherapy, alongside a comparable safety profile.

To develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for determining the concentration of posaconazole in dried blood spot (DBS) samples, providing a feasible reference for the application of the dried blood spot method and the clinical practice of posaconazole therapeutic drug monitoring (TDM).

DBS samples were obtained by dropping whole blood samples containing posaconazole onto Whatman 903^® cards and drying them. The sample processing procedure involved cutting out a round hole with a diameter of 3 mm to obtain the analytical sample. The sample was extracted by adding 0.2% formic acid-50% acetonitrile (containing an internal standard of 0.50 μg·ml^-1), followed by sonication and centrifugation. The supernatant was directly injected for detection. LC-MS/MS was used for determination. The Phonomenex Kinetex XB-C₁₈ column was selected as the chromatographic column, and gradient elution was used for separation. The mass spectrometry detection mode was positive ion multiple reaction monitoring. The monitored ion pairs for the analyte posaconazole and the internal standard D₅-posaconazole were 701.3→614.4 and 705.3→618.4, respectively. Full method validation was conducted in accordance with ICH Guideline M10 (Bioanalytical Method Validation and Study Sample Analysis), covering selectivity, specificity, linearity, carryover, accuracy, precision, extraction recovery, matrix effect, analyte stability, together with DBS-specific validation parameters including hematocrit (Hct) impact, spotting volume effect and spot homogeneity. In addition, the developed DBS method was applied to the detection of clinical TDM samples of posaconazole and compared with the plasma method, and the consistency of the two methods was evaluated.

The LC-MS/MS method for the determination of posaconazole in DBS had good selectivity and linearity (0.10-10.00 μg·ml^-1), without the influence of cross-talk and carry-over. The recovery rate of the analyte during the sample processing was in the range of 70.67%-75.66%. The intra-batch accuracy and precision were in the ranges of -12.18%--0.86% and 3.05%-8.75%, respectively, and the inter-batch accuracy and precision were in the ranges of -4.21%-3.49% and 8.57%-12.21%, respectively. For the matrix effect tested with six blank whole blood samples from different sources, the accuracy was within ±15% and the precision was all <15%. The stability results showed that posaconazole was stable for at least 3, 3, 14, 30, and 90 days at room temperature (20-25 ℃), 37 ℃, 4 ℃ -20 ℃, and -70 ℃ in DBS samples, respectively. The results of Bland-Altman and Passing-Bablok analyses of 78 clinically verified samples showed that there was a good correlation between the determination results of posaconazole in dried blood spots (DBS) and plasma. However, there was a significant deviation (P<0.001). The determination results in DBS were lower than those in plasma (average difference=0.33 μg·ml^-1), and this was more significant in cases with low hematocrit (Hct).

A straightforward and practical LC-MS/MS method was successfully developed and fully validated for posaconazole quantitation in DBS samples. This method requires a minimal blood volume (minimum 10 μL whole blood), features a short analytical runtime (2.00 min per injection) and facilitates streamlined laboratory operation with robust practicability, which can serve as a convenient alternative analytical strategy for routine clinical TDM of posaconazole.

To establish a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for simultaneous determination of calcitonin salmon in human plasma.

Precipitate plasma samples using organic reagents, then centrifuge and collect the supernatant, proceed with concentration, reconstitution, and sample injection, and a phenomenex Jupiter^® C4-300A column (2.1 mm×50.0 mm, 5.0 μm) was used for chromatographic separation. The mobile phase was 0.1% formic acid water (phase A) -0.1% formic acid acetonitrile (phase B); gradient elution with a flow rate of 0.50 mL·min^-1, column temperature 50 ℃, injection volume 20 μL. A custom-labeled isotopic compound was used as the internal standard, scanning was carried out by means of multi reaction monitoring (MRM) in the positive ionization mode with an electric spray ionization source(ESI). Examine the specificity, standard curve, lower limit of quantification (LLOQ), precision, accuracy, recovery rate, matrix effect, and stability of the method.

The method showed a good specificity results of the method, and there is no interference between the analyte and the internal standard. The linear range of the standard curves for the tested substances was 2.00、4.00、10.00、50.00、100.00、200.00、360.00、400.00 pg·mL^-1, The standard curve was y=2.98×10^-2x+5.30×10^-3 (R²=0.997 4) and the lower limit of quantification(LLOQ) is 2.00 pg·mL^-1. The intra-day and inter day relative standard deviation (RSD) were both less than 15%, extraction recovery rates ranging from 60.13% to 75.39% (RSD<15%), and matrix effects ranging from 97.45% to 109.72% (RSD<10%). The stability of the matrix samples was verified by placing them at room temperature for 24 hours, repeatedly freezing and thawing at -20 ℃ and -70 ℃ for 5 times, freezing at -20 ℃ and -70 ℃ for 49 days, and placing the processed samples in an automatic sampler for 333 hours, with accuracy ranging from 97.03% to 108.64%, all stable.

The established HPLC-MS/MS method is simple, rapid, highly sensitive, and specific, and can be used for the detection of plasma samples in pharmacokinetic studies.