OBJECTIVE To analyze and identify the metabolites of pirtobrutinib （PTN） in rats， and clarify the possible metabolic pathways of PTN in rats. METHODS Six rats were intragastrically administered with 10 mg/kg PTN suspension. Blood samples were collected from the rats 30 minutes before administration and at 0.25， 0.5， 1， 2， 4， 6， 8， 12， 24 hours after administration. Urine and feces samples were collected 12 hours before administration and 24 hours after administration. UHPLC- Orbitrap Exploris 240 system combined with Compound Discoverer 3.0 and Xcalibur 2.0 software were adopted for structural identification and metabolic pathway analysis of PTN metabolites in rat plasma， urine， and feces. RESULTS A total of 29 PTN metabolites were identified， including 17， 19 and 22 metabolites in plasma， urine and feces， respectively. The metabolic pathways of PTN mainly included oxidation， sulfation， glucuronidation， etc.， and its metabolites were mostly combination products of two or more different metabolic forms. In detail， a total of 26 metabolites were associated with phase Ⅰ metabolic reactions （14 oxidation metabolites， 9 reduction/dehydrogenation metabolites， 8 demethylation metabolites， and 5 hydrolysis metabolites）. Meanwhile， a total of 20 products were involved in phase Ⅱ metabolites （14 sulfation metabolites and 8 glucuronic acid binding metabolites）. CONCLUSIONS PTN exhibits a diverse range of metabolites in rat fecal samples， with the primary metabolic pathways being oxidation， sulfation， glucuronidation， and others.

Dome-shaped macula (DSM) mostly presents as an inward bulging of the macular area within the area of posterior staphyloma in highly myopic eyes.According to the optical coherence tomography results, DSM has been classified as vertical, horizontal and round type, but its formation mechanism is still controversial.The appearance of DSM was initially thought to be associated with low intraocular pressure and vitreous macular traction.There is growing support that DSM is an adaptive protective mechanism developed to resist the progression of myopia.However, recent studies suggest that the macular bulge may be the result of progressive asymmetric choroidal and scleral thinning in the surrounding area, rather than active inward bulging of the central macula.In addition, DSM in highly myopic eyes is often accompanied by a variety of myopic complications that lead to decreased visual acuity and visual impairment in the eye with DSM, such as serous retinal detachment, retinoschisis, choroidal neovascularization, macular hole and Bruch membrane defects.However, the causal relationship between DSM and myopic complications is unclear, and there are still no effective preventive measures or treatments for related complications.This article summarizes the mechanism of DSM formation in highly myopic eyes and its association with myopic complications to provide a theoretical basis for exploring the visual prognosis of patients with high myopia and the pathogenesis of DSM.

Objective:To compare the mydriatic effects of a combination of 1% tropicamide and 2.5% phenylephrine with a 0.5% tropicamide and 0.5% phenylephrine combination in patients with type 2 diabetes.Methods:A randomized, double-blind, controlled trial was conducted.Ninety Chinese patients (90 eyes) with dark irises and type 2 diabetes who needed mydriasis examination at the Fundus Disease Clinic of Tianjin Medical University Eye Hospital from June to September 2024 were included.The subjects were divided into control group (30 patients 30 eyes), high concentration group (30 patients 30 eyes) and half-dilution group (30 patients 30 eyes) using the random number table method, which received 2 drops of a mixture of 0.5% tropicamide and 0.5% phenylephrine, 2 drops of a mixture of 1% tropicamide and 2.5% phenylephrine, 1 drop of a mixture of 1% tropicamide and 2.5% phenylephrine+ 1 drop of saline respectively.The pupil diameter of the patients was measured with a pupillometer 40 minutes before and after instillation.The study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2024KY-16).Written informed consent was obtained from all participants.Results:The proportions of patients whose pupil diameters reached 7 mm 40 minutes after the initial administration in the control group, high-concentration group, and half-dilution group were 56.7%(17/30), 86.7%(26/30) and 66.7%(20/30), respectively, with a statistically significant overall difference ( χ2=6.667, P=0.036).The proportion of patients in the high-concentration group whose pupil diameter reached 7 mm 40 minutes after the initial administration was higher than that in the control group, and the difference was statistically significant ( P<0.05).The pupil diameters 40 minutes after the initial administration in the control group, the high-concentration group and the half-dilution group were (7.01±0.86), (7.64±0.61) and (7.49±1.15)mm, respectively, with a statistically significant overall difference ( F=4.019, P=0.021), and the pupil diameter of the high-concentration group was significantly higher than that of the control group ( P=0.024).Changes in pupil diameter 40 minutes after the initial administration in the control group, high-concentration group and half-dilution group were (3.23±0.81), (3.82±0.60) and (3.62±0.75)mm, respectively, with a statistically significant overall difference ( F=5.121, P=0.008), and the change in pupil diameter in the high-concentration group was higher than that in the control group ( P=0.007). Conclusions:The combination of 1% tropicamide and 2.5% phenylephrine has better pupil dilation than the combination of 0.5% tropicamide and 0.5% phenylephrine.It is recommended that pupil dilation be performed with a high-concentration mydriatic drug prior to outpatient fundus examination for diabetic patients.

Objective:To explore the association between sleep and myopia among students aged 6-15 years in Tianjin.Methods:A cross-sectional study was conducted.A total of 218 864 primary and secondary school students aged 6-15 years in Tianjin were recruited from January 2023 to May 2023.Basic information and responses to the Children's Sleep Habits Questionnaire (CSHQ) were collected.Logistic regression models were used to assess the association between myopia and sleep.The study followed the Declaration of Helsinki, and the research protocol was approved by the Medical Ethics Committee of Tianjin Medical University Eye Hospital (No.ChiCTR2200065710). All questionnaires and demographic information were collected with parental consent.Results:It was found that 68 121(31.12%) students were myopic and 178 514(81.56%) had sleep disorders.The prevalence of myopia among students with average daily sleep durations of ≤8 hours, >8-9 hours, >9-10 hours, and >10 hours was 52.17%(9 288/17 803), 35.35%(31 037/87 787), 25.18%(24 481/97 216), and 20.64% (3 315/16 058), respectively, and the difference was statistically significant ( χ2=6 835.649, P<0.001). After adjusting for sex, age, body mass index, and potential confounding factors, compared with students with average daily sleep duration of >10 hours, students with average daily sleep durations of ≤8 hours ( OR=1.496, 95% CI: 1.415-1.581, P<0.001), >8-9 hours ( OR=1.364, 95% CI: 1.383-1.447, P<0.001), and >9-10 hours ( OR=1.257, 95% CI: 1.202-1.316, P<0.001) had a higher risk of myopia.Students with sleep disorders, bedtime resistance, sleep-onset delay, irregular sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing, and daytime sleepiness were more likely to be myopic. Conclusions:Sleep is a key factor influencing myopia among schoolchildren aged 6-15 years in Tianjin.

Objective:To compare the changes in spherical equivalent (SE) and axial length (AL) between children with axial myopia and refractive myopia.Methods:A prospective cohort study was conducted.A total of 1 738 students from grades 1 to 6 were recruited from two consistent 9-year schools in the Binhai New Area of Tianjin using cluster random sampling.Visual acuity, refractive status, and ocular biological parameters were measured from February to May in 2018 and 2021.Participants were categorized into subgroups as follows: low, moderate, and high myopia based on SE; longer AL group and shorter AL groups based on AL; and steeper cornea and flatter cornea groups based on corneal curvature radius (CCR). Myopic children were further classified into the following groups: axial myopia (longer AL and flatter cornea), refractive myopia (shorter AL and steeper cornea), mixed myopia (longer AL and steeper cornea), and non-axial non-refractive myopia (shorter AL and flatter cornea). Changes in SE (ΔSE) and AL (ΔAL) at the end of the follow-up period were compared among the different classification groups.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY-39). Written informed consent was obtained from the guardians of all participants.Results:The ΔSE in the longer AL group was (-1.57±1.52)D, which was significantly greater than (-1.17±1.47)D in the shorter AL group ( t=3.99, P<0.01). The ΔAL in the steeper cornea group was (0.92±0.50)mm, which was significantly greater than (0.86±0.54)mm in the flatter cornea group ( t=-2.12, P=0.04). Among children aged 10-12 years, males, and the low myopia, SE progression was faster in those with longer AL compared to shorter AL, with statistically significant differences ( t=2.66, 3.31, 3.90; all P<0.05). In children aged 10-12 years, AL growth was faster in the longer AL group than in the shorter AL group, with a statistically significant difference ( t=-1.29, P=0.04). Among females and the low myopia, AL growth was faster in those with steeper corneas than in those with flatter corneas, with statistically significant differences ( t=-3.22, -2.43; both P<0.05). Refractive myopia had a smaller ΔSE than axial myopia and the difference was statistically significant ( P<0.05). Within the low myopia, SE progression was greater in axial myopia than in refractive myopia, with a statistically significant difference ( P<0.05). Conclusions:Among myopic children, those with longer axial lengths exhibit faster SE progression, while those with steeper corneas show faster axial elongation.Among children with low myopia, axial myopia is associated with a greater risk of SE progression than refractive myopia.

Objective To evaluate answers to typical clinical questions related to neuro-ophthalmology generated by Artificial Intelligence(AI)Large Language Models(LLM)and to explore the performance of neuro-ophthalmology-related questions on LLM in a multidimensional manner using objective and expert assessment.Methods Multicenter,random-ized,cross-sectional pilot study.Thirty typical questions related to neuro-ophthalmology were selected based on four per-spectives:definition,etiology,clinical manifestations and signs,and treatment and prognosis,and were analyzed quantita-tively using Deepseek,Wenxin Yiyin 4.0,Doubao,and Kimi 1.5,which are four open-source LLMs in China,and quantita-tively analyzed with objective assessment;and quantitatively rated by three ophthalmologists using expert assessment for 120 answer texts.Three ophthalmology experts quantitatively scored the 120 answer texts.Three ophthalmologists quantita-tively scored the 120 answer texts.Level 3,5,and 4 Likert scales were developed according to the completeness,accura-cy,professionalism,relevance,and criticality of the question texts,respectively.The best-performing LLM was selected,and its performance was observed across the four types of questions.Additionally,three other experts assessed whether the best-performing one could be evaluated as a substitute for real-world doctor-patient communication.Results In the objective Chinese text reading difficulty analysis,the differences in total word count among the four LLMs were statistically significant(all P＜0.001).Of the four LLMs,Kimi 1.5 performed the best,with frequencies of 61％,29％,and 41％for the highest scores in completeness(3),accuracy and professionalism(5),and relevance and usefulness(4),respective-ly.Kimi 1.5 performed more consistently on the questions on the four areas of neuro-ophthalmologic disorders:definition,etiology,clinical manifestations and signs,treatment,and prognosis,with no between-group differences(P＞0.05).Con-clusion Chinese language LLMs have great potential in the clinical application of neuro-ophthalmology.Kimi 1.5 outper-forms other LLMs in terms of completeness,accuracy,professionalism,relevance,and usefulness,but it still cannot re-place real-world doctor-patient communication.There is a need to explore new diagnostic and therapeutic model of AI+physician in the future.

Endovascular aneurysm repair(EVAR)is the most common treatment for abdominal aortic aneurysm.However,when the common iliac artery has expansion or aneurysm,there may be internal leakage at the distal end of the stent.In this case,the ideal endovascular repair should ensure the pelvic blood supply on the premise of complete exclu-sion of the aneurysm.It is feasible and safe to use iliac branch devices(IBD)to preserve unilateral or bilateral internal iliac arteries,and its technology and clinical results are equivalent to standard EVAR.But IBD has certain anatomical a-daptability.In this paper,the current status of preservation of internal iliac artery with IBD is systematically reviewed.

OBJECTIVE To study the mechanism of Wenshen Tongdu Recipe in promoting the recovery of motor function in rats with spinal cord injury.METHODS A total of 144 SD rats were randomly divided into sham operation group,model group,predni-sone group,low-dose Wenshen Tongdu Recipe group,medium-dose Wenshen Tongdu Recipe group,high-dose Wenshen Tongdu Recipe group,3BDO group,and 3BDO+Wenshen Tongdu Recipe group(medium dose).The rat spinal cord injury model was estab-lished by modified Allen's method.Intervention began 1 day after modeling,and the drug was administered continuously for 14 days.During the drug administration period,the motor function of the rats in each group was evaluated by Basso-Beattie-Bresnahan(BBB)score and inclined plane test.On the 3rd,7th and 14th days after modeling,the pathological changes of the spinal cord tissues of the rats in each group were observed by HE staining;the expression levels of inflammatory factors IL-1β,IL-6,IL-4 and IL-10 in the serum of the rats in each group were detected by ELISA;the expression of Beclin 1,LC3B and p62 proteins was detected by immu-nohistochemistry;the expression of CD16 and CD206 proteins was detected by immunofluorescence staining;the expression of autoph-agy-related molecules(Beclin 1,LC3B)and Akt/mTOR pathway-related proteins in the spinal cord tissues was detected by Western blot.RESULTS Compared with the model group,the BBB score and angle of the inclined board test of rats in the medium-dose Wenshen Tongdu Recipe group were increased,and the disordered arrangement of spinal cord tissue,spinal cord vacuoles and inflam-matory infiltration were significantly improved,especially on the 14th day.Compared with the sham operation group,the expression levels of serum IL-1β and IL-6 in the model group increased(P<0.01),and the expression levels of IL-4 and IL-10 decreased(P<0.05,P<0.01);compared with the model group,the levels of IL-1β and IL-6 in the Wenshen Tongdu Recipe group were signifi-cantly decreased(P<0.01),and the levels of IL-4 and IL-10 were significantly increased(P<0.05,P<0.01);compared with the Wenshen Tongdu Recipe group,the serum IL-1β and IL-6 concentrations of mice in the 3BDO group increased(P<0.01),and the level of IL-10 decreased(P<0.05).Compared with the sham operation group,the M1/M2 ratio,P62 protein expression,p-Akt/Akt and p-mTOR/mTOR ratios in the spinal cord tissue of the rats in the model group were significantly increased(P<0.05,P<0.01),and the relative protein expression of Beclin1 was decreased(P<0.01);compared with the model group,the M1/M2 ratio,p-Akt/Akt and p-p70S6K/p70S6K ratios in the Wenshen Tongdu Recipe group were significantly decreased(P<0.01).Compared with the model group,the Beclin1 protein level in the 3BDO group was decreased,and the p-Akt/Akt and p-mTOR/mTOR ratios were increased(P<0.05,P<0.01).Compared with the Wenshen Tongdu Recipe group,the M1/M2 ratio in the 3BDO group and the 3BDO+Wen-shen Tongdu Recipe group increased(P<0.01),the positive rates of Beclin1 and LC3B proteins in the 3BDO group decreased signifi-cantly(P<0.01),and the p-p70S6K/p70S6K ratio in the 3BDO+Wenshen Tongdu Recipe group increased significantly(P<0.01).CONCLUSION Wenshen Tongdu Recipe may regulate microglial polarization through Akt/mTOR signaling pathway to acti-vate autophagy,promote the secretion of anti-inflammatory factors,reduce the release of pro-inflammatory factors,alleviate neuroin-flammatory response,and thus promote spinal cord injury repair.

Dome-shaped macula (DSM) mostly presents as an inward bulging of the macular area within the area of posterior staphyloma in highly myopic eyes.According to the optical coherence tomography results, DSM has been classified as vertical, horizontal and round type, but its formation mechanism is still controversial.The appearance of DSM was initially thought to be associated with low intraocular pressure and vitreous macular traction.There is growing support that DSM is an adaptive protective mechanism developed to resist the progression of myopia.However, recent studies suggest that the macular bulge may be the result of progressive asymmetric choroidal and scleral thinning in the surrounding area, rather than active inward bulging of the central macula.In addition, DSM in highly myopic eyes is often accompanied by a variety of myopic complications that lead to decreased visual acuity and visual impairment in the eye with DSM, such as serous retinal detachment, retinoschisis, choroidal neovascularization, macular hole and Bruch membrane defects.However, the causal relationship between DSM and myopic complications is unclear, and there are still no effective preventive measures or treatments for related complications.This article summarizes the mechanism of DSM formation in highly myopic eyes and its association with myopic complications to provide a theoretical basis for exploring the visual prognosis of patients with high myopia and the pathogenesis of DSM.

Objective:To compare the mydriatic effects of a combination of 1% tropicamide and 2.5% phenylephrine with a 0.5% tropicamide and 0.5% phenylephrine combination in patients with type 2 diabetes.Methods:A randomized, double-blind, controlled trial was conducted.Ninety Chinese patients (90 eyes) with dark irises and type 2 diabetes who needed mydriasis examination at the Fundus Disease Clinic of Tianjin Medical University Eye Hospital from June to September 2024 were included.The subjects were divided into control group (30 patients 30 eyes), high concentration group (30 patients 30 eyes) and half-dilution group (30 patients 30 eyes) using the random number table method, which received 2 drops of a mixture of 0.5% tropicamide and 0.5% phenylephrine, 2 drops of a mixture of 1% tropicamide and 2.5% phenylephrine, 1 drop of a mixture of 1% tropicamide and 2.5% phenylephrine+ 1 drop of saline respectively.The pupil diameter of the patients was measured with a pupillometer 40 minutes before and after instillation.The study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2024KY-16).Written informed consent was obtained from all participants.Results:The proportions of patients whose pupil diameters reached 7 mm 40 minutes after the initial administration in the control group, high-concentration group, and half-dilution group were 56.7%(17/30), 86.7%(26/30) and 66.7%(20/30), respectively, with a statistically significant overall difference ( χ2=6.667, P=0.036).The proportion of patients in the high-concentration group whose pupil diameter reached 7 mm 40 minutes after the initial administration was higher than that in the control group, and the difference was statistically significant ( P<0.05).The pupil diameters 40 minutes after the initial administration in the control group, the high-concentration group and the half-dilution group were (7.01±0.86), (7.64±0.61) and (7.49±1.15)mm, respectively, with a statistically significant overall difference ( F=4.019, P=0.021), and the pupil diameter of the high-concentration group was significantly higher than that of the control group ( P=0.024).Changes in pupil diameter 40 minutes after the initial administration in the control group, high-concentration group and half-dilution group were (3.23±0.81), (3.82±0.60) and (3.62±0.75)mm, respectively, with a statistically significant overall difference ( F=5.121, P=0.008), and the change in pupil diameter in the high-concentration group was higher than that in the control group ( P=0.007). Conclusions:The combination of 1% tropicamide and 2.5% phenylephrine has better pupil dilation than the combination of 0.5% tropicamide and 0.5% phenylephrine.It is recommended that pupil dilation be performed with a high-concentration mydriatic drug prior to outpatient fundus examination for diabetic patients.