ObjectiveTo compare the differences between the ultrafiltration method and the dextran gel filtration method during the purification of Tfn-modified PCL micelles by using purification efficiency and micelle purity as indicators. MethodsCoumarin-6 （C6） was used as a fluorescent probe and was loaded into HOOC-PEG-PCL to form PCL micelles by the film-dispersion method. Tfn was then conjugated to the surface of PCL micelles via an amidation reaction， resulting in two types of micelles： Tfn/PCL_H and Tfn/PCL_L. The pharmaceutical properties of the two types of micelles were characterized. The micelles were then purified through ultrafiltration method and dextran gel method respectively， and the efficiency of the two methods， along with the purity of the final micelles， was compared. The density of Tfn on the surface of PCL micelles was also calculated. ResultsThe hydrated diameter of PCL micelles was approximately 73 nm， and the C6 loading efficiency was around 0.046%. The size increased to 134 nm and 158 nm for Tfn/PCL_L and Tfn/PCL_H， respectively. The micelle population was monodisperse. The purification results showed that， for the ultrafiltration method， after two and one rounds of purification， the Tfn/C6 ratio stabilized at 23.6 and 3.4 for Tfn/PCL_H and Tfn/PCL_L， respectively. For the dextran gel filtration method， the Tfn/C6 ratio reached 23.7 for the Tfn/PCL_H group after two rounds of purification. However， for the Tfn/PCL_L group， the Tfn/C6 ratio increased during four rounds of dextran gel purification， and a significant difference （P = 0.042 4） was observed between the first and last filtrations. The density of Tfn in the final micelles were calculated. For the ultrafiltration method， the Tfn density of Tfn/PCL_H and Tfn/PCL_L were 94.9% and 13.8%， respectively. For the dextran gel filtration method， the density of the two micelles were 95.6% and 14.4%， respectively. For Tfn/PCL_L group， the density results revealing a statistically significant difference （P=0.000 2）. ConclusionThe purification efficiency of the two methods is comparable. However， the purity of the final micelles shows a significant difference， with the dextran gel filtration method resulting in higher purity， particularly for the Tfn/PCL_L micelles.

Objective: To develop a health literacy evaluation scale for Chinese high school students, providing a tool for dynamic monitoring of health literacy among high school students and evaluating the effectiveness of health school construction. Methods: Through theoretical research, an evaluation index system for health literacy of Chinese high school students was constructed. Two rounds of Delphi expert consultations were conducted to quantitatively screen the items, and the item pool was revised based on expert opinions to compile the health literacy evaluation scale for Chinese students. Two focus group interviews were held to collect suggestions from health educators, high school teachers, and high school students regarding optimized scale length, question types, difficulty and wording of the scale. The scale was revised accordingly. A pilot survey was conducted in Beijing and Tianjin in November 2024, and the reliability and validity of the scale were evaluated based on the pilot survey data. Results: The response rate in both rounds of Delphi expert consultations was over 80%, and the expert authority coefficient was over 0.70. The expert opinions were highly concentrated, and the dispersion was small. The revised item pool based on expert opinions contained 39 items. The revised scale based on the suggestions and opinions collected from the focus group interviews had a moderate number of questions and difficulty level. The pilot survey obtained 800 valid responses, with the response rate of 89.39%. The Cronbach α coefficient of the scale was 0.911, χ 2/df =3.321, the root mean square error of approximation was 0.054, the adjusted goodness-of-fit index was 0.991 , and the factor loadings of some items were less than 0.40. Conclusion The health literacy evaluation scale for Chinese high school students demonstrates scientific rigor and practical applicability, with good internal consistency and structural validity.

Objective: To develop and validate a health literacy assessment scale for junior high school students, providing an effective tool for evaluating and monitoring health literacy among Chinese adolescents. Methods: Based on school health education policy documents, a health literacy assessment framework was constructed, comprising five horizontal and four vertical dimensions. From May to June and August to September in 2024, the framework was refined through Delphi expert consultations and focus group discussions, leading to the development of the Health Literacy Assessment Scale for Junior High School Students. In September 2024, a convenience sample of 625 students from three junior high schools in Beijing and Tianjin completed the questionnaire. Item analysis, reliability, and validity tests were conducted to evaluate the scale. Results: The recovery rate for two rounds of expert consultation questionnaires was 100%. The expert authority coefficients ( Cr ) were 0.86 and 0.87 respectively (both >0.70), with Kendall W values of 0.34 and 0.27 ( P <0.05). The focus group discussions followed a rigorous structure, and after multiple rounds of item screening and revision, the version 3.0 of the junior high school students health literacy assessment scale was developed, comprising 57 items. Three items that failed to meet the comprehensive screening criteria were preliminarily removed, and the final scale contained 54 items. The scale demonstrated excellent reliability, with an overall Cronbach s α coefficient of 0.92 and split half reliability of 0.93. Confirmatory factor analysis [ χ 2/df =2.094, root mean square error of approximation ( RMSEA )=0.042, comparative fit index ( CFI )=0.911, Tucker Lewis index ( TLI )=0.907] indicated good model fit indices. Conclusions The preliminary development of the health literacy assessment scale for junior high school students follows a rigorous item screening process with well designed dimensions, demonstrating good reliability and validity, thus serving as an appropriate evaluation tool for adolescent health literacy.

Background::An evidence gap still exists regarding the efficacy and safety of tegoprazan in patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China. Methods::This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement. Results::A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: -1.7%, 95% confidence interval [CI]: -8.5%, 5.0%, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients' diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively. Conclusion::Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

Objective:To investigate the effect of brinzolamide-timolol maleate eye drops on the metabolism of intravitreally injected vancomycin hydrochloride (VH) in rabbit eyes.Methods:Nine healthy male New Zealand white rabbits were selected.Among them, three were used to extract blank aqueous humor and the right eyes of the remaining six were set as experimental eyes.The experimental eye was topically administered 30 μl of brinzolamide-timolol maleate eye drops twice a day.The fellow eyes were set as control eyes.The intraocular pressure of both eyes was measured before the initial application of the eye drops and 1 hour after application of the eye drops next day.Both eyes of each rabbit were intravitreally injected with 0.5 mg of VH (10 mg/ml) solution.The aqueous humor was drawn at 2 hours and 1, 2, 4, 6, 8, 10 and 12 days after intravitreal injection.VH concentrations in aqueous humor were measured by high performance liquid chromatography.The time of peak concentrations ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and the area under the concentration-time curve ( AUC) of VH in rabbit eyes were calculated by the average concentrations.This study was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-01). Results:The intraocular pressure after eye drop was significantly lower than that before eye drop in experimental eyes ( P<0.01).The tmax of VH in experimental eyes and control eyes were both 1 day.The Cmax of VH in experimental eyes and control eyes were (61.40±13.48) and (51.56±5.07)μg/ml, respectively.The VH aqueous concentrations in the experimental eyes on days 4, 6 and 8 after injection were all significantly higher than those in the control eye ( t=2.378, 3.150, 2.694; all P<0.05).The t1/2 of VH in the aqueous humor of the experimental eyes was 2.69 days, which was 31% longer than 2.05 days of the control eyes.The AUC0-10 d of experimental eyes increased by 24.3% relative to the control eyes. Conclusions:Brinzolamide-timolol maleate eye drops can significantly extend the ocular residence time of intravitreally injected VH.

Objective:To compare the effects of brinzolamide-timolol (B&T) eye drops and dipivefrine hydrochloride (DH) eye drops on the intraocular metabolism of ranibizumab after intravitreal injection in rabbit.Methods:Eighteen New Zealand white rabbits were randomly and equally divided into DH group, B&T group, and control group.The right eye was selected as the experimental eye.The B&T and DH groups received DH and B&T eye drops, respectively, twice daily, 30 μl each time.The control group did not receive any treatment.Intraocular pressure (IOP) was measured in both eyes before the first administration and 1 hour after the first administration on the second day.After IOP measurement, the experimental eye received an intravitreal injection of 0.25 mg ranibizumab (10 mg/ml).Aqueous humor samples were collected 1, 3, 7, 10, 14, 21 and 28 days after injection.Ranibizumab concentration in the aqueous humor was measured by ELISA kit.Pharmacokinetic parameters including time to peak concentration ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and area under the concentration-time curve (AUC) of ranibizumab were calculated.This experiment was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-03). Results:The tmax of ranibizumab in the aqueous humor was 1 day in all three groups.The Cmax values in the control, B&T and DH groups were (8.122±2.445), (13.079±3.140) and (8.299±0.899)μg/ml, respectively.Except for day 3 in the control group, the ranibizumab concentrations in aqueous humor of the B&T group were higher than that of the DH group and the control group at all time points after injection, with statistically significant significances (all P<0.05).The t1/2 of ranibizumab in aqueous humor in the control group, B&T group, and DH group were (2.90±0.29), (3.36±0.35) and (2.80±0.29) days, respectively, and the AUC0-t values were (52.697±10.178), (80.244±11.249) and (51.985±8.734)μg/ml·d, respectively.The t1/2 and AUC0-t of ranibizumab in aqueous humor of the B&T group were significantly higher than those of the DH group and the control group, and the differences were statistically significant (all P<0.05).The mean bioavailability in the B&T group was increased by 52.3% compared to the control group. Conclusions:B&T eye drops prolong the half-life and enhance the intraocular bioavailability of ranibizumab after intravitreal injection in rabbits, whereas DH has no significant effect on its intraocular metabolism.

The neuropsychiatric disorder course is among the most challenging subjects in medical education, currently facing the "three difficulties" of teaching, learning, and transition from theory to practice. This study attempts to carry out clinical thinking informatization technology-based teaching reform guided by clinical competence. A cognitive map for neuropsychiatric disorders was developed using a symptom-based framework. Leveraging this cognitive map and integrating artificial intelligence, a clinical thinking teaching application for neuropsychiatric disorders was designed and continuously refined. Reform initiatives were explored and summarized in areas such as theoretical teaching, practical teaching, standardized training for resident physicians, teaching assessment, and textbook reform. The reform improved the clinical thinking and clinical competence of students for neuropsychiatric disorders.

Objective:To investigate the effect of brinzolamide-timolol maleate eye drops on the metabolism of intravitreally injected vancomycin hydrochloride (VH) in rabbit eyes.Methods:Nine healthy male New Zealand white rabbits were selected.Among them, three were used to extract blank aqueous humor and the right eyes of the remaining six were set as experimental eyes.The experimental eye was topically administered 30 μl of brinzolamide-timolol maleate eye drops twice a day.The fellow eyes were set as control eyes.The intraocular pressure of both eyes was measured before the initial application of the eye drops and 1 hour after application of the eye drops next day.Both eyes of each rabbit were intravitreally injected with 0.5 mg of VH (10 mg/ml) solution.The aqueous humor was drawn at 2 hours and 1, 2, 4, 6, 8, 10 and 12 days after intravitreal injection.VH concentrations in aqueous humor were measured by high performance liquid chromatography.The time of peak concentrations ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and the area under the concentration-time curve ( AUC) of VH in rabbit eyes were calculated by the average concentrations.This study was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-01). Results:The intraocular pressure after eye drop was significantly lower than that before eye drop in experimental eyes ( P<0.01).The tmax of VH in experimental eyes and control eyes were both 1 day.The Cmax of VH in experimental eyes and control eyes were (61.40±13.48) and (51.56±5.07)μg/ml, respectively.The VH aqueous concentrations in the experimental eyes on days 4, 6 and 8 after injection were all significantly higher than those in the control eye ( t=2.378, 3.150, 2.694; all P<0.05).The t1/2 of VH in the aqueous humor of the experimental eyes was 2.69 days, which was 31% longer than 2.05 days of the control eyes.The AUC0-10 d of experimental eyes increased by 24.3% relative to the control eyes. Conclusions:Brinzolamide-timolol maleate eye drops can significantly extend the ocular residence time of intravitreally injected VH.

Objective:To compare the effects of brinzolamide-timolol (B&T) eye drops and dipivefrine hydrochloride (DH) eye drops on the intraocular metabolism of ranibizumab after intravitreal injection in rabbit.Methods:Eighteen New Zealand white rabbits were randomly and equally divided into DH group, B&T group, and control group.The right eye was selected as the experimental eye.The B&T and DH groups received DH and B&T eye drops, respectively, twice daily, 30 μl each time.The control group did not receive any treatment.Intraocular pressure (IOP) was measured in both eyes before the first administration and 1 hour after the first administration on the second day.After IOP measurement, the experimental eye received an intravitreal injection of 0.25 mg ranibizumab (10 mg/ml).Aqueous humor samples were collected 1, 3, 7, 10, 14, 21 and 28 days after injection.Ranibizumab concentration in the aqueous humor was measured by ELISA kit.Pharmacokinetic parameters including time to peak concentration ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and area under the concentration-time curve (AUC) of ranibizumab were calculated.This experiment was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-03). Results:The tmax of ranibizumab in the aqueous humor was 1 day in all three groups.The Cmax values in the control, B&T and DH groups were (8.122±2.445), (13.079±3.140) and (8.299±0.899)μg/ml, respectively.Except for day 3 in the control group, the ranibizumab concentrations in aqueous humor of the B&T group were higher than that of the DH group and the control group at all time points after injection, with statistically significant significances (all P<0.05).The t1/2 of ranibizumab in aqueous humor in the control group, B&T group, and DH group were (2.90±0.29), (3.36±0.35) and (2.80±0.29) days, respectively, and the AUC0-t values were (52.697±10.178), (80.244±11.249) and (51.985±8.734)μg/ml·d, respectively.The t1/2 and AUC0-t of ranibizumab in aqueous humor of the B&T group were significantly higher than those of the DH group and the control group, and the differences were statistically significant (all P<0.05).The mean bioavailability in the B&T group was increased by 52.3% compared to the control group. Conclusions:B&T eye drops prolong the half-life and enhance the intraocular bioavailability of ranibizumab after intravitreal injection in rabbits, whereas DH has no significant effect on its intraocular metabolism.

The neuropsychiatric disorder course is among the most challenging subjects in medical education, currently facing the "three difficulties" of teaching, learning, and transition from theory to practice. This study attempts to carry out clinical thinking informatization technology-based teaching reform guided by clinical competence. A cognitive map for neuropsychiatric disorders was developed using a symptom-based framework. Leveraging this cognitive map and integrating artificial intelligence, a clinical thinking teaching application for neuropsychiatric disorders was designed and continuously refined. Reform initiatives were explored and summarized in areas such as theoretical teaching, practical teaching, standardized training for resident physicians, teaching assessment, and textbook reform. The reform improved the clinical thinking and clinical competence of students for neuropsychiatric disorders.