Objective:To observe the effects of RasGRP4 gene deletion on the structure and function of the retina in diabetic mice, and to explore the mechanism of RasGRP4 in diabetic retinopathy (DR) by transcriptome sequencing in conjunction with bioinformatics analysis. Methods:A total of 12 male C57BL/6J mice were divided into normal group, diabetic group (DM group), with 6 mice in each group. Six male RasGRP4 knockout mice were uesd as RasGRP4 knockout diabetic group (DM-KO group). Mice in the DM group and DM-KO group were fed with high-fat diet combined with intraperitoneal injection of streptozotocin to establish diabetic model and body weight and blood glucose were monitored regularly. Three months after modeling, optical coherence tomography was used to detect the retinal thickness and ganglion cell layer thickness. Electroretinography was used to detect the function of the retina in mice under dark-adapted conditions. Total RNA was extracted from the retinas of mice in DM group and DM-KO group, and transcriptomic sequencing was performed to screen differentially expressed genes (DEG). Core genes were screened using MCODE and Cytohubba plug-ins of Cytoscape v3.8.2 software. At the same time, the functional enrichment analysis of gene samples (GO) of the selected DEG was performed. The mRNA relative expression levels of interleukin-8, transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), NOd-like receptor thermal protein domain protein 3 (NLRP3), Caspase-1 and IL-1β in each group were detected by real-time quantitative polymerase chain reaction. t test was used to compare the two groups. One-way analysis of variance was used to compare the three groups. Results:Compared with the DM group, there was no significant difference in blood glucose and body weight in the DM-KO group with the extension of high-fat diet ( t=0.12, 2.02, 0.22, 0.10, 0.59, 0.41, 1.35, 0.31, 1.12, 1.58, 1.47, 1.20, 1.24, 0.39, 0.66, 0.14; P>0.05). The retinal thickness and ganglion cell layer thickness of mice in the three groups were significantly reduced in the DM group compared with the normal group, while DM-KO was significantly increased compared with the DM group, and the differences were statistically significant ( F=30.43, 7.81; P<0.000 1, 0.01). Comparison of a-wave and b-wave amplitudes among the three groups showed that the DM group was significantly lower than the normal group, while the DM-KO was significantly higher than the DM group, and the differences were statistically significant ( F=16.46, 35.58; P<0.001, 0.000 1). Compared with the DM group, 184 differential genes (DEG) were screened in the DM-KO group, among which 39 up-regulated and 145 down-regulated genes were detected, respectively. The results of the MCODE plug-in analysis showed that Col1a2, Fbln1, Fbn1, Col6a3, Fmod, Ogn, Tgfb, Mfap4, Vcan, Nid2, and Col18a1 were core genes in the DEG. Cytohubba plug-in analysis showed that Col1a2, Mrc1, Cd47, Fbn1, Cybb, Cd163, Fbln1, Fmod, Adgre1, and Col6a3 were the core genes in DEG. The results of the GO functional enrichment analysis showed that DEG was mainly involved in hemoglobin complexes, MHC class Ⅱ protein complex, apical plasma membrane, inflammasome complex, immunological synapse, response to bacterium, inflammatory response, immune system processe, response to hypoxia, and cell adhesion were significantly enriched. Comparison of mRNA relative expression levels of IL-8, TGF-β, IFN-γ, NLRP3, Caspase-1 and IL-1β in the three groups showed that the DM group was significantly higher than the normal group, while the DM-KO was significantly lower than the DM group, with statistical significance ( F=12.43, 15.41, 70.09, 29.04, 11.79, 41.28; P<0.01). Conclusion:RasGRP4 deficiency plays a therapeutic role in the development of DR through inhibition of inflammatory factor secretion and NLRP 3 inflammasome pathway activation.

Objective:To observe the effects of RasGRP4 gene deletion on the structure and function of the retina in diabetic mice, and to explore the mechanism of RasGRP4 in diabetic retinopathy (DR) by transcriptome sequencing in conjunction with bioinformatics analysis. Methods:A total of 12 male C57BL/6J mice were divided into normal group, diabetic group (DM group), with 6 mice in each group. Six male RasGRP4 knockout mice were uesd as RasGRP4 knockout diabetic group (DM-KO group). Mice in the DM group and DM-KO group were fed with high-fat diet combined with intraperitoneal injection of streptozotocin to establish diabetic model and body weight and blood glucose were monitored regularly. Three months after modeling, optical coherence tomography was used to detect the retinal thickness and ganglion cell layer thickness. Electroretinography was used to detect the function of the retina in mice under dark-adapted conditions. Total RNA was extracted from the retinas of mice in DM group and DM-KO group, and transcriptomic sequencing was performed to screen differentially expressed genes (DEG). Core genes were screened using MCODE and Cytohubba plug-ins of Cytoscape v3.8.2 software. At the same time, the functional enrichment analysis of gene samples (GO) of the selected DEG was performed. The mRNA relative expression levels of interleukin-8, transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), NOd-like receptor thermal protein domain protein 3 (NLRP3), Caspase-1 and IL-1β in each group were detected by real-time quantitative polymerase chain reaction. t test was used to compare the two groups. One-way analysis of variance was used to compare the three groups. Results:Compared with the DM group, there was no significant difference in blood glucose and body weight in the DM-KO group with the extension of high-fat diet ( t=0.12, 2.02, 0.22, 0.10, 0.59, 0.41, 1.35, 0.31, 1.12, 1.58, 1.47, 1.20, 1.24, 0.39, 0.66, 0.14; P>0.05). The retinal thickness and ganglion cell layer thickness of mice in the three groups were significantly reduced in the DM group compared with the normal group, while DM-KO was significantly increased compared with the DM group, and the differences were statistically significant ( F=30.43, 7.81; P<0.000 1, 0.01). Comparison of a-wave and b-wave amplitudes among the three groups showed that the DM group was significantly lower than the normal group, while the DM-KO was significantly higher than the DM group, and the differences were statistically significant ( F=16.46, 35.58; P<0.001, 0.000 1). Compared with the DM group, 184 differential genes (DEG) were screened in the DM-KO group, among which 39 up-regulated and 145 down-regulated genes were detected, respectively. The results of the MCODE plug-in analysis showed that Col1a2, Fbln1, Fbn1, Col6a3, Fmod, Ogn, Tgfb, Mfap4, Vcan, Nid2, and Col18a1 were core genes in the DEG. Cytohubba plug-in analysis showed that Col1a2, Mrc1, Cd47, Fbn1, Cybb, Cd163, Fbln1, Fmod, Adgre1, and Col6a3 were the core genes in DEG. The results of the GO functional enrichment analysis showed that DEG was mainly involved in hemoglobin complexes, MHC class Ⅱ protein complex, apical plasma membrane, inflammasome complex, immunological synapse, response to bacterium, inflammatory response, immune system processe, response to hypoxia, and cell adhesion were significantly enriched. Comparison of mRNA relative expression levels of IL-8, TGF-β, IFN-γ, NLRP3, Caspase-1 and IL-1β in the three groups showed that the DM group was significantly higher than the normal group, while the DM-KO was significantly lower than the DM group, with statistical significance ( F=12.43, 15.41, 70.09, 29.04, 11.79, 41.28; P<0.01). Conclusion:RasGRP4 deficiency plays a therapeutic role in the development of DR through inhibition of inflammatory factor secretion and NLRP 3 inflammasome pathway activation.

Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

Objective:To evaluate the accuracy, completeness, and reproducibility of domestic open-source large language models (LLM) in diabetic retinopathy (DR) patient education, and to explore their potential as intelligent virtual assistants for DR patient education.Methods:A total of 41 questions and answers related to the diagnosis and treatment of DR in five categories, namely risk factors, screening and examination, symptoms and staging, diagnosis, treatment and prognosis.All questions were repeated twice as a " new dialogue" in the LLM, and all the answers were recorded.Three senior fundus physicians independently evaluated the answers on a 6-point Likert scale for accuracy and a 3-point Likert scale for completeness and repeatability, and for each answer, the evaluator was asked to make a recommendation between the LLM and the manual answers.Five questions were randomly selected to evaluate the three open source LLM, ERNIE Bot 3.5, Qwen and Kimi chat, and the LLM with the best overall performance was selected for further evaluation in the full question bank.Results:Among the three LLM, Kimi chat had the best overall performance, Kimi chat performed best, with percentages of 6 for accuracy, 3 for completeness, and 3 for repeatability among the 5 questions at 90%, 90%, and 100%, respectively.For all questions answered, the number of words in manual replies was 106 (70, 202), which was significantly lower than 505 (386, 600) in Kimi chat ( Z=-7.866, P<0.001).There was no significant correlation between the number of Kimi chat replies and the accuracy score ( rs=-0.044, P=0.492), but it was positively correlated with the integrity score ( rs=0.239, P<0.001).The interclass correlation coefficient for accuracy and completeness scores were above 0.700 among three evaluators, with the highest agreement for repeatability at 0.853, followed by completeness of the first response at 0.771.The proportion of responses ≥5 points for accuracy was 87.0%(214/246), the proportion ≥2 points for completeness was 98.0%(241/246), and the proportion higher than 70% for repeatability was 78.5%(193/246).Kimi chat excelled in answering basic questions about the disease such as disease definition, staging, frequency of screening, and common risk factors, but performed poorly on questions involving treatment choices that require a doctor's professional judgment.The proportion of evaluators choosing Kimi chat responses as superior was 69.5% (171/246), and the reasons for non-selection included lack of characteristic answers, inclusion of too much irrelevant information, and lack of responses to questions requiring a high degree of medical expertise. Conclusions:Kimi chat answers DR-related diagnostic questions in a detailed and well-organized manner, with a high degree of accuracy, completeness and reproducibility.

Objective:To evaluate changes in operational effectiveness after the implementation of ambulatory surgical management in pars plana vitrectomy (PPV).Methods:A retrospective clinical study. 17 528 surgeries in 10 895 eyes of 10 895 patients who underwent minimally invasive PPV on an ambulatory and/or inpatient basis at Tianjin Medical University Eye Hospital from August 2015 to June 2023 were included in this study. Among them, 5 346 eyes in 5 346 cases were male; 5 549 eyes in 5 549 cases were female. The age ranged from 0 to 95 years, with the mean age of (57.74±13.15) years. 6 381 surgeries in 3 615 eyes from August 2015 to December 2018 (the initial period of day surgery) were used as the control group; 11 147 surgeries in 7 280 eyes from January 2019 to June 2023 (the expanded period of day surgery) were used as the observation group. According to the management mode of ambulatory surgery, the observation group was subdivided into the decentralized management group (January 2019 to December 2020) and the centralized management group (January 2021 to June 2023), with 2 905 and 4 375 eyes and 4 646 and 6 501 surgeries, respectively. Changes in the percentage of day surgery, average hospitalization days, and average unplanned reoperation rate were compared. The Mann-Whitney U test was used to compare numerical variables between groups; the chi-square test or Fisher's exact test was used to compare categorical variables. Results:The number of cases of daytime PPV performed in the observation group and control group was 7 852 (70.44%, 7 852/11 147) and 24 (0.38%, 24/6 381) cases, respectively, and the average hospitalization days were 1 (1) and 5 (3) d. Compared with the control group, the observation group had a significantly higher percentage of day surgery ( χ2=8 051.01) and a considerably lower mean hospitalization day ( Z=4 536 844.50), and the differences were statistically significant ( P<0.000 1). The mean hospitalization days in the decentralized and centralized management groups were 2 (3) and 1 (0) d, respectively, and unplanned reoperations were 34 (0.73%, 34/4 646) and 171 (2.63%, 171/6 501) eyes, respectively. Compared with the decentralized management group, average hospitalization days was significantly lower ( Z=1 436.94) and unplanned reoperation rate was significantly higher ( χ2=54.10) were significantly lower in the centralized management group, both of which were statistically significant ( P<0.000 1). Conclusion:PPV ambulatory management model can significantly reduce the average hospitalization day, but also results in higher rates of unplanned reoperations.

Objective:To investigate the prevalence and risk factors of tessellation fundus (TF) among Tianjin Medical University students with different refractive statuses.Methods:A cross-sectional study. From September to December 2019, 346 students from Tianjin Medical University were randomly selected and underwent slit-lamp examination, non-cycloplegic auto-refraction, subjective refraction, best-corrected visual acuity, ocular biometric measurement, and non-dilation fundus photography. The differences in the prevalence of TF in basic characteristics and ocular biometric parameters were compared. Based on the equivalent spherical (SE), refractive status was divided into the non-myopia group (SE>-0.50 D) and the myopia group (SE≤-0.50 D). The myopia group was further divided into mild myopia group (-3.00 D26 mm group. The logistic regression was used to analyze the risk factors affecting TF. Trend tests were performed for each risk factor and TF.Results:Of the 346 subjects, 324 (93.6%, 324/346) were myopia, of whom 73 (21.1%, 73/346), 167 (48.3%, 167/346), and 84 (24.3%, 84/346) were mild myopia, moderate myopia, and high myopia, respectively; 22 (6.4%, 22/346) were non-myopia. There were 294 (85.0%, 294/346) students with TF in the macula, including 9 (40.91%, 9/22), 58 (79.45%, 58/73), 145 (86.83%, 145/167), and 82 (97.62%, 82/84) in non-myopia, low myopia, moderate myopia, and high myopia group, respectively; 52 (15.0%, 52/346) students were without TF in the macula. There were statistically significant gender differences ( χ2=4.47), SE ( t=6.29), AL ( t=-8.29), anterior chamber depth ( Z=-2.62), lens thickness ( Z=-2.23), and average corneal radius ( Z=-3.58) between students with and without TF in the macula ( P<0.05). Spherical equivalent and axial length were independent risk factors for TF and its severity ( P≤0.001). With an increasing degree of myopia, and increasing axial length, the risk of TF increased ( P for trend<0.001). Conclusions:The prevalence of TF is 85.0% among Tianjin Medical University students. TF is detected in the fundus of no myopia, mild myopia, moderate myopia and high myopia. The degree of myopia is higher, the AL is longer, the possibility of TF is higher.

Objective To report and analyze the renal function improvement in a case with ad-vanced bilateral renal cell carcinoma after targeted therapy. Methods The patient was a 60-year-old man who complained of lower back pain for 1 month. Ultrasound and CT scan detected bilateral renal masses, left lesion was 11.0 cm×9.4 cm×8.5 cm, and the right one was 3.5 cm×4.3 cm×4.1 cm. X-ray examination showed metastatic lesions in liver and lower right lung. GFR was 20.39 ml/min of left kidney, 25.40 ml/min of right kidney. The renal biopsy confirmed renal clear cell carcinoma. Sorafenib was administrated 400 mg twice or once daily for 12 weeks. Results After the targeted therapy, the decreased bilateral kidney tumor sizes were identified by CT scan. There was liquid nec-rosis in the tumor, and no new metastatic lesion detected. The kidney function was improved as well. The total GFR increased to 71.38 ml/min. Left kidney GFR increased to 31.57 ml/min, right kidney GFR increased to 39.81 ml/min, respectively. Conclusion Targeted therapy could improve renal function in advanced renal cell carcinoma cases by controlling tumor development.

Objective To investigate the relationship between the polymorphism of human multidrug resistance 1 gene(MDR1)polymorphism and early MMF pharmacokinetics.Methods Twenty-eight Chinese primary renal transplant recipients were emrolled.On day 14 post-transplant,patients took the MMF orally on fast.Whole blood samples(2 ml)were obtained at the following time points:predose(G0)and 0.5,1,1.5,2,4,6,8,10 and 12 h(C0.5,C1,C1.5,G2,C4,C6,C8,C10,C12,respectively)postdose during the dosing interval.The MPA plasrna concentration was assayed by high performance liquid chromatography (HPLC).Pharmacokinetie parameters were determined by WINNOLIN 3.1.Three major single nucleotide polymorphisrrls(SNP),C1236 T,G2677 T/A,C3435 T of MDR1 were analyzed by PCR-RFLP.Pharmacokinetie parameters of MPA were compared between different MDR1 genotype and haplotype groups.Ailele frenqueneis were also compared in high(MPA area under concentratation-time curve 0～12 h,frequencies of 1236 TT,2677 TT/AA,3435 TT in three major MDR1 SNP positions,exons 12,21 and 26,were 0.368,0.184 and 0.211,respectively.MPA AUC was significantly higher in 1236 TT group than in 1236 CC/CT group(65.36±11.51 vs 53.33±13.77,P=0.032).On C1236 T SNP,TT genotype frequency showed significant difference between MPA high and low exposure groups(66.7%vs 15.4%,P=0.013,OR=2.526).T allele frequency was marginally higher in MPA high exposure group than that in low exposure group(83.3%vs 53.3%,P=0.072).Conclusion TT genotype on 1236 of MDR1 indicates a risk of early high exposure to MPA in Chinese renal transplant patients given by oral MMF,