Unmasking of molecular players: proteomic profiling of vitreous humor in pathologic myopia.

BACKGROUND: This study aimed to identify the differentially expressed proteins in the vitreous humor (VH) of eyes with and without pathologic myopia (PM), providing insights into the molecular pathogenesis. METHODS: A cross-sectional, observational study was conducted. VH samples were collected from patients undergoing vitrectomy for idiopathic epiretinal membrane (ERM), macular hole (MH), or myopic retinoschisis (MRS). Label-free quantitative proteomic analysis identified differential protein expression, with validation using ELISA. RESULTS: The proteomic profiling revealed significantly higher expressions of tubulin alpha 1a (TUBA1A) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) in PM groups (MH-PM, MRS-PM) compared to controls (MH, ERM). Conversely, xylosyltransferase 1 (XYLT1), versican core protein (VCAN), and testican-2 (SPOCK2) expressions were lower in PM. ELISA validation confirmed these findings. CONCLUSIONS: Our study provides novel insights into the molecular mechanisms of PM. The differentially expressed proteins EEF1A1, TUBA1A, XYLT1, VCAN, and SPOCK2 may play crucial roles in chorioretinal cell apoptosis, scleral extracellular matrix (ECM) synthesis, and scleral remodeling in PM. These proteins represent potential new targets for therapeutic intervention in PM, highlighting the importance of further investigations to elucidate their functions and underlying mechanisms in disease pathogenesis.

Research on Automated Modeling Technology of Sluice Gate Project Based on BIM Technology.

In order to improve the efficiency and accuracy of the modeling and design work of the sluice gate project, this paper proposes an automatic generation template of the sluice gate project with customized semantics and project layout scheme, aiming at realizing the rapid assembling of all kinds of components of the sluice gate project. In the construction process, this paper first starts from basic parametric modeling and proposes constraints as the basis of modeling. Subsequently, a template library framework is developed based on the constraints to ensure that the generated templates have a high degree of standardization and consistency. Finally, an efficient and flexible template library is successfully constructed by using the customized classes and functions of Revit API, which provides powerful technical support for the modeling and design work of sluice gate engineering. This achievement helps to promote the informationization and intelligent development of the water conservancy engineering industry, and its versatility and scalability also make it have a wide range of application prospects in other water conservancy engineering fields.

SERUM LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR BEFORE AND AFTER INTRAVITREAL INJECTION OF RANIBIZUMAB OR CONBERCEPT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

OBJECTIVE: To investigate the serum levels of vascular endothelial growth factor (VEGF) before and after intravitreal injection of conbercept or ranibizumab for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy patients. METHODS: This study is a prospective, interventional case series and involved 28 patients, 18 treated with 0.5 mg of conbercept and 10 treated with 0.5 mg of ranibizumab. Serum concentrations of VEGF were determined by enzyme-linked immunosorbent assay before the injection and at 1 day, 1 week, and 1 month after anti-VEGF treatments. RESULTS: The baseline serum VEGF level of the ranibizumab group was 367.11 ± 311.87 pg/mL, whereas that of the conbercept group was 315.06 ± 170.88 pg/mL (P = 0.653). In the conbercept group, VEGF level significantly decreased to 36.32 ± 72.11 pg/mL at 1 day (P = 0.03) and returned to 136.55 ± 144.62 pg/mL at 1 week (P = 0.03). At 1 month, the concentration increased to 334.48 ± 197.41 pg/mL and showed no significant difference compared with the baseline. In the ranibizumab group, the serum VEGF levels were 292.42 ± 239.80 pg/mL, 282.60 ± 201.36 pg/mL, and 308.83 ± 266.89 pg/mL at 1 day, 1 week, and 1 month after intravitreal injection, respectively. There was no significant difference in the ranibizumab group at each detection time point (P = 0.45). CONCLUSION: Conbercept significantly decreased serum VEGF level 1 day and 1 week after injection, but this effect was not sustained for 1 month. In contrast, ranibizumab had no significant effect on serum VEGF concentration changes. The reduction in serum VEGF by conbercept may affect its systemic safety profile.

A comparison between the therapeutic effects of Conbercept combined with panretinal photocoagulation and panretinal photocoagulation monotherapy for high-risk proliferative diabetic retinopathy.

Objective: To compare the therapeutic effects of the administration of intravitreal Conbercept (IVC) plus panretinal photocoagulation (PRP) to that of PRP monotherapy in patients with high-risk proliferative diabetic retinopathy (PDR). Methods: In this retrospective consecutive case series, we analyzed the data on high-risk PDR patients followed up for 12 months. Patients were divided into two groups: the IVC+PRP group and the PRP monotherapy group. Patients in the IVC+PRP group were initially administered 3 IVC injections and PRP, while patients in the PRP monotherapy group received PRP only. Depending on the grouping criteria, patients in both groups were administered either IVC+PRP or PRP only if the neovascularization (NV) did not regress. From the initiation to month 12 of treatment, we recorded and compared the data on the NV regression rate, improvement in best-corrected visual acuity (BCVA), laser spots, changes in central macular thickness (CMT), complications, and the need for vitrectomy for all patients. Results: In this study, 79 eyes of 58 patients in the IVC+PRP group and 86 eyes of 60 patients in the PRP monotherapy group were included. During the follow-up of 12 months, the number of eyes with complete regression, partial regression, and no regression or increase in NV were 56 (70.88%), 23 (29.12%), and 0 (0%) in the IVC+PRP group and 13 (15.12%), 50 (58.14%), and 23 (26.74%) in the PRP group (p < 0.001). The BCVA was significantly higher and CMT was lower in the patients of the IVC+PRP group than in the PRP monotherapy group at 3, 6, and 12 months of follow-up (p < 0.05). The mean number of laser spots was lower in the patients of the IVC+PRP group than in the PRP group (1,453 ± 87 spots vs. 2,267 ± 94 spots, p < 0.05). A significantly lower percentage of patients in the IVC+PRP group underwent vitrectomy than that in the PRP group (7 (8.86%) vs. 27 (31.40%), p < 0.001). Conclusion: High-risk PDR patients treated with IVC + PRP showed a higher rate of NV regression, more effective improvement in the BCVA, and lower vitrectomy rate compared to those who were administered PRP monotherapy.

Serum Untargeted Metabolomics Reveal Potential Biomarkers of Progression of Diabetic Retinopathy in Asians.

Purpose: To reveal molecular mechanisms of diabetic retinopathy (DR) in Asians and facilitate the identification of new therapeutic targets through untargeted metabolomics. To determine the differences in serum metabolites and metabolic pathways between different stages of diabetic retinopathy in patients with type 2 diabetic mellitus (T2DM) and proliferative DR (PDR) and non-proliferative DR (NPDR) and identify differential metabolites between T2DM and DR (NPDR and PDR) patients. Methods: This prospective observational registration study described the differential metabolites between 45 T2DM patients and 15 control cases with no significant differences in clinical characteristics. Their biospecimens and clinical information were collected and recorded in their medical reports. DR phenotypes of the subjects were verified by retina specialists. Serum metabolites were analyzed using high-resolution mass spectrometry with liquid chromatography. Untargeted metabolomics was performed on serum samples from 15 T2DM patients, 15 non-proliferative diabetic retinopathy patients, 15 proliferative diabetic retinopathy patients, and 15 diabetic controls. Discriminatory metabolic features were identified through partial least squares discriminant analysis (PLS-DA), hierarchical clustering analysis (HCA), and generalized linear regression models. Result: Through untargeted metabolomics, 931 features (523 in positive and 408 in negative modes) with 102 common metabolites highly relevant to the presence of DR were detected. In the adjusted analysis, 67 metabolic features differed significantly between T2DM and NPDR patients. Pathway analysis revealed alterations in metabolisms of amino acids and fatty acids. Glutamate, phosphatidylcholine, and 13-hydroperoxyoctadeca-9,11-dienoic acid (13-PHODE) were key contributors to these pathway differences. A total of 171 features distinguished PDR patients from T2DM patients, and pathway analysis revealed alterations in amino acid metabolism, fatty acid metabolism, nitrogen metabolism, and tricarboxylic acid cycle. Aspartate, glutamate, glutamine, ornithine, N-acetyl-l-glutamate, N-acetyl-l-aspartate, citrate, succinate, N-(L-arginino)succinate, 2-oxoglutarate, 13-hydroperoxyoctadeca-9,11-dienoic acid, methionine, lysine, threonine, phenylalanine, N(pi)-methyl-l-histidine, phosphatidylcholine, and linoleate were major contributors to the pathway differences. Between NPDR patients and PDR patients, there were 79 significant differential metabolites. Enrichment pathway analysis showed changes in amino acid metabolism, fatty acid metabolism, pantothenate, and CoA biosynthesis. Aspartate, glutamine, N-acetyl-l-glutamate, N-acetyl-l-aspartate, pantothenate, dihomo-gamma-linolenate, docosahexaenoic acid, and icosapentaenoic acid were key factors for the differences of these pathways. Conclusion: This study demonstrated that the pathways of arginine biosynthesis metabolism, linoleic acid metabolism, alanine, aspartate, and glutamate metabolism, as well as d-glutamine and d-glutamate metabolism, were dysregulated in DR patients of the Asian population. Increased levels of glutamate, aspartate, glutamine, N-acetyl-l-glutamate, and N-acetyl-l-aspartate and decreased levels of dihomo-gamma-linolenate, docosahexaenoic, and icosapentaenoic were considered as the metabolic profile that could distinguish PDR from NPDR in Asians. Phosphatidylcholine and 13-PHODE were identified as two major novel metabolite markers in advanced stages of DR in our study.

Effect of a Template Case Report Based on Cognitive Task Analysis on Emergency Thinking Ability of Resident Doctors in Standardized Training.

OBJECTIVE: To explore the effect of a template case report based on cognitive task analysis on the emergency thinking ability of resident doctors in standardized training. METHODS: The doctors were split into two groups, according to the date they joined the emergency department (n = 40, each group): the observation and control groups. In the observation group, the resident doctors' teachers in standardized training adopted the cognitive task analysis method to determine the primary links of emergency thinking, made case templates, and carried out training based on the case template report. In the control group, traditional teaching methods were used by the teachers. RESULTS: In the observation and control groups, the scores at departure were 88.10 ± 3.88 and 75.23 ± 7.19, respectively (P < 0.05), and the student's ability improvement rates were 92.5% and 75.0% (P < 0.01). In addition, the awareness rate of "know how to study" and "know how to work in emergency" in the observation group was 90% and 90%, respectively. The rate of doctors that considered "missed diagnosis and misdiagnosis can be reduced" was 85%, and the rate of doctors that considered "help to learn in other departments in the future" was 80%. CONCLUSION: Template case reports based on the cognitive task analysis for emergency thinking training can help resident doctors in standardized training improve their emergency thinking ability.

Expression of fractalkine (CX3CL1) and its receptor in endotoxin-induced uveitis.

BACKGROUND/AIMS: Chemokines play a critical role in inflammation and neurodegenerative disease in the central nervous system. In this study, endotoxin-induced uveitis (EIU) was induced to test the expression of fractalkine, a special neuronal chemokine, and its receptor CX3CR1 in acute inflammation of the retina. METHODS: EIU was induced by footpad injections of lipopolysaccharide (LPS). Eight rats were sacrificed at each time point (0, 8, 16, 24, 48, and 72 h) after LPS injection. Sections were made for histopathological tests. Immunohistochemistry was performed using antibodies specific to fractalkine and CX3CR1. Retinas were collected, and total protein and mRNA from both the induced and control rats were extracted. mRNA and protein expression of fractalkine and CX3CR1 in the retina were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blots, respectively. RESULTS: The EIU model was successfully induced. In control rats, both fractalkine and its receptor CX3CR1 were detected in the retina. LPS injection induced a transient upregulation of both proteins at 24 h as determined by the increased number of positively stained cells as well as increased levels of mRNA and protein (p < 0.05). CONCLUSION: A transitory increased expression of fractalkine and its receptor CX3CR1 occurred at the crest time of EIU, and this change in expression may play a role in the turnover of LPS-induced acute retina inflammation.

One-year outcomes of intravitreal conbercept combined rescue therapy for polypoidal choroidal vasculopathy in a Chinese population: a real-life clinical data.

AIM: To evaluate the real-life clinical outcomes of intravitreal injection of conbercept combined rescue therapy for polypoidal choroidal vasculopathy (PCV). METHODS: This was an open label, single center, and interventional study. All enrolled patients were treated initially with three consecutive monthly intravitreal conbercept injections (0.5 mg). Additional conbercept injections were administered upon substantial polyp regression with improved visual acuity (VA). Eyes with partial or no polyp regression and poor VA were rescue treated with photodynamic therapy (PDT) for subfoveal polyps or thermal laser photocoagulation for extrafoveal polyps. Best-corrected visual acuity (BCVA), central foveal thickness (CFT) and polyp regression were observed as primary outcomes. Side effects were also collected during the follow-up period. RESULTS: A total of 56 eyes (56 patients) with PCV were included. BCVA increased significantly from the baseline of 43.52±24.21 letters to 55.88±21.94 letters (P<0.001) at 12mo, while CFT decreased significantly from 457.41±207.86 µm to 247.98±127.08 µm (P<0.001). All patients showed polyp regression. Twenty-three eyes achieved complete polyp regression after the three initial injections, which increased to 44 eyes at 12mo. Seventeen eyes underwent rescue therapy, among which 2 eyes treated with PDT and 15 eyes treated with laser photocoagulation. A mean of 4.30±1.43 injections were given per eye. No intraocular inflammation, retinal or vitreous hemorrhage, or systemic complication occurred. CONCLUSION: Conbercept is an effective and safe option for the treatment of PCV in Chinese population. The treatment regimen of three initial conbercept injections followed by additional injections or rescue therapies is efficacious for treating PCV.

Efficacy and safety of ranibizumab for wet age-related macular degeneration in Chinese patients.

AIM: To evaluate the clinical efficacy and safety of ranibizumab for wet age-related macular degeneration (wAMD) in Chinese patients and to determine the mean number of injections administered over one year of follow-up. METHODS: This single centre, retrospective observational case series study included data from 121 patients with wAMD (121 eyes) who were diagnosed by indirect ophthalmoscopy, fluorescence fundus angiography (FFA), indocyanine green angiography, and optical coherence tomography. Ranibizumab was injected into the vitreous cavities once per month for 3mo and as needed afterwards. Changes in visual acuity and central foveal thickness (CFT) during the follow-up period were compared, and the mean number of injections over the year was calculated. Patients with one or more adverse events related to the drugs and injections were recorded for further adverse events analysis. RESULTS: The study population included 70 males and 51 females aged between 50 and 87y (mean: 71.32±9.41y). The mean number of injections over the first year was 5±1 (range: 3-9). The mean best-corrected visual acuity by Early Treatment Diabetic Retinopathy Study increased from 43.2±19.3 (95%CI: 39.8-46.7) at baseline to 51.7±20.1 (95%CI: 48.1-55.3), and central foveal thickness (CFT) decreased from 526.5±277.0 µm (95%CI: 476.6-576.4) to 258.2±161.6 µm (95%CI: 229.2-287.3) at 12mo. The differences were statistically significant (P<0.001). Visual acuity significantly improved in 34.1% of the patients (38 eyes), stabilized in 66.1% of the patients (80 eyes), and significantly decreased in 2.5% of the patients (3 eyes). CFT at baseline was an independent risk factor of decreased CFT and increased visual acuity. None of the patients had severe adverse events during the follow-up period. CONCLUSION: Ranibizumab can effectively control disease progression and improve visual acuity in patients with wAMD. The disease conditions of most patients stabilized after a one-year treatment with an average of 5 injections.

Prevalence of neutralizing factors against adeno-associated virus types 2 in age-related macular degeneration and polypoidal choroidal vasculopathy.

Adeno-associated virus type 2 (AAV2) mediated gene therapy providing a potential treatment in the eye. However, immune responses can limit virally mediated gene transfer and therapy. To assess preexisting AAV2 neutralizing factors (NF) titers in peripheral blood and the vitreous in patients with age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). 130 subjects were enrolled: 50 with neovascular AMD, 30 with PCV, and 50 controls. The serum and the vitreous were obtained for AAV2 NF assay. We found AAV2 NF are present in all of AMD, PCV patients and controls we tested. There were no significant differences in prevalence of NAb in serum between AMD, PCV and controls (P=0.999). There was no correlation between NF in serum and in vitreous (P>0.05), and NF in vitreous was significantly less than in serum. Our results for the first time showed in Chinese population, NF against AAV2 was present in serum of all the patients with AMD or PCV and controls, and there were no significant differences among these groups. Therefore, it demonstrated there were no correlations between AAV2 NF titer and these diseases. We found NF in vitreous was considerably less than in serum in all groups. We also found no direct correlation between NF in vitreous and in serum suggesting serum antibody levels may not be used to predict their counterparts in the vitreous. Our results will provide crucial information for future clinical studies in the development of new therapies based on AAV2 mediated gene delivery in the eye.

Outcome of intravitreal bevacizumab for idiopathic choroidal neovascularization in the Chinese population.

OBJECTIVE: To assess the long-term visual and anatomical outcomes and safety of intravitreal injection of bevacizumab for idiopathic choroidal neovascularization (ICNV) in Chinese patients. DESIGN: Retrospective interventional case series. PARTICIPANTS: Seventy-seven eyes of 77 patients with ICNV. METHODS: Patients were given intravitreal injection of bevacizumab (1.25 mg/0.05 mL) for ICNV between March 2006 and May 2008. Main outcome measures were changes in best-corrected visual acuity (BCVA), central foveal thickness, which was measured by optical coherence tomography, and fluorescein angiography findings. RESULTS: Mean follow-up was 14.3 (SD 2.4, range 10-20) months. Mean BCVA improved from 0.66 (SD 0.36) logMAR at baseline to 0.25 (SD 0.28) logMAR at final follow-up (p < 0.001). Sixty-one patients (79%) gained BCVA of > or = 2 Snellen lines, and 1 eye (1%) lost BCVA of > or = 2 Snellen lines. Mean central foveal thickness decreased from 365 (SD 124) microm at baseline to 211 (SD 94) microm at final visit (p < 0.001). Sixty-two eyes (81%) needed reinjection. Both BCVA improvement and the change in central foveal thickness between the 1- time injection group and the multi-injections group were not statistically significant (p = 0.45 and p = 0.19, respectively). No significant ocular or systemic adverse effects were observed. CONCLUSIONS: The long-term results suggest an encouraging efficacy and safety of intravitreal bevacizumab for ICNV in Chinese patients.

Association of c3 gene polymorphisms with neovascular age-related macular degeneration in a chinese population.

PURPOSE: The purpose of this study was to determine whether the genetic polymorphisms of complement factor 3 (C3) are associated with neovascular age-related macular degeneration (AMD) in the Chinese population. METHODS: A total of 123 unrelated Chinese Han patients with neovascular AMD and 130 control subjects were recruited. Their six single-nucleotide polymorphisms (SNPs) in the C3 gene, one in the complement factor H (CFH) gene and two in the complement factor B (CFB) gene were characterized. Their genotypes, allele frequencies, and odds ratios were analyzed. RESULTS: The G allele of the C3 IVS2 rs2250656, but not other tested C3 SNPs of rs2230205, rs10411506, rs2230199, rs339392, and rs163913, was significantly associated with a reduced risk for AMD in the Chinese population (OR 0.605, 95% CI 0.39-0.93, p = 0.023), even after adjusting for age, gender, smoking status, CFH rs1061170, CFB rs4151667, and CFB rs641153 allele status (OR 0.58, 95% CI 0.35-0.96, p = 0.033). However, the C3 haplotype of A-A-C-A-T-T was identified as a statistically significant risk factor for neovascular AMD (OR 1.41, 95% CI 1.02-1.94). Furthermore, the C allele of the CFH rs1061170, but not the CFB rs4151667 and rs641153, was significnatly associated with increased risk for AMD (OR 3.09, 95% CI 1.55-6.15, p < 0.001). CONCLUSION: The G allele of C3 IVS2 rs2250656 may be a significantly protective factor for neovascular AMD in the Chinese population. This, together with low MAF of C3 R102G, may be partially responsible for the low prevalence of AMD in the Chinese population.