Microwave-assisted synthesis of highly sulfated mannuronate glycans as potential inhibitors against SARS-CoV-2.

Algae-based marine carbohydrate drugs are typically decorated with negative ion groups such as carboxylate and sulfate groups. However, the precise synthesis of highly sulfated alginates is challenging, thus impeding their structure-activity relationship studies. Herein we achieve a microwave-assisted synthesis of a range of highly sulfated mannuronate glycans with up to 17 sulfation sites by overcoming the incomplete sulfation due to the electrostatic repulsion of crowded polyanionic groups. Although the partially sulfated tetrasaccharide had the highest affinity for the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, the fully sulfated octasaccharide showed the most potent interference with the binding of the RBD to angiotensin-converting enzyme 2 (ACE2) and Vero E6 cells, indicating that the sulfated oligosaccharides might inhibit the RBD binding to ACE2 in a length-dependent manner.

Machine learning and optical coherence tomography-derived radiomics analysis to predict persistent diabetic macular edema in patients undergoing anti-VEGF intravitreal therapy.

BACKGROUND: Diabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. This study aimed to develop and evaluate an OCT-omics prediction model for assessing anti-vascular endothelial growth factor (VEGF) treatment response in patients with DME. METHODS: A retrospective analysis of 113 eyes from 82 patients with DME was conducted. Comprehensive feature engineering was applied to clinical and optical coherence tomography (OCT) data. Logistic regression, support vector machine (SVM), and backpropagation neural network (BPNN) classifiers were trained using a training set of 79 eyes, and evaluated on a test set of 34 eyes. Clinical implications of the OCT-omics prediction model were assessed by decision curve analysis. Performance metrics (sensitivity, specificity, F1 score, and AUC) were calculated. RESULTS: The logistic, SVM, and BPNN classifiers demonstrated robust discriminative abilities in both the training and test sets. In the training set, the logistic classifier achieved a sensitivity of 0.904, specificity of 0.741, F1 score of 0.887, and AUC of 0.910. The SVM classifier showed a sensitivity of 0.923, specificity of 0.667, F1 score of 0.881, and AUC of 0.897. The BPNN classifier exhibited a sensitivity of 0.962, specificity of 0.926, F1 score of 0.962, and AUC of 0.982. Similar discriminative capabilities were maintained in the test set. The OCT-omics scores were significantly higher in the non-persistent DME group than in the persistent DME group (p < 0.001). OCT-omics scores were also positively correlated with the rate of decline in central subfield thickness after treatment (Pearson's R = 0.44, p < 0.001). CONCLUSION: The developed OCT-omics model accurately assesses anti-VEGF treatment response in DME patients. The model's robust performance and clinical implications highlight its utility as a non-invasive tool for personalized treatment prediction and retinal pathology assessment.

Preparation and characterization of amphiphilic chitosan/iodine composite film as antimicrobial material.

The composite film of amphiphilic chitosan/iodine, poly(aminoethyl) chitosan citronellal Schiff base iodine (PACSC-I), was prepared, and characterized by SEM, AFM, FTIR, 1H NMR and XRD. The physicochemical properties of the film including hydrophilicity, water absorption, mechanical, thermal degradation, iodine release and antibacterial properties were tested, and the cytocompatibility evaluation of the composite film was also performed. The results showed that PACSC-I was successfully prepared with good hydrophilicity (water contact angle 47.34°), water absorption capacity (water absorption ratio 229.55 %), elasticity (elongation at break 6.72 %) and thermal stability. The composite film had a controlled release effect on iodine, reaching a maximum released concentration of 8.84 × 10-4 mol/L. PACSC-I exerted a synergistic antibacterial effect with strong antibacterial activities. Cell viability and apoptosis assays showed that PACSC-I had good biocompatibility towards HaCaT cells. Therefore, the PACSC-I film had promising applications in the medical field as antibacterial material.

One-Month Outcomes of Intravitreal Anti-VEGF vs. Dexamethasone Implant in the Treatment of Diabetic Macular Edema in Vitrectomized Eyes.

Objectives: To compare short-term effect of intravitreal ranibizumab with dexamethasone implant for diabetic macular edema (DME) in vitrectomized eyes. Methods: Single-center, prospective, randomized study of vitrectomized eyes with DME. Study eyes were divided into two groups, receiving ranibizumab (IVV group, n = 35 eyes) or dexamethasone implant (IVD group, n = 35 eyes) respectively. Patients were evaluated at baseline, Week 1 and Month 1. The main outcome measures included best-corrected visual acuity (BCVA), central retinal thickness (CRT) and intraocular pressure (IOP). Results: BCVA and CRT were similar in the two groups at baseline. At Week 1, the CRT improvement was significant in two groups (P = 0.041 in IVV group, P = 0.030 in IVD group), but at Month 1, only IVD group had significant improvement in CRT (P < 0.001). And BCVA gains were significant at Week 1 (P = 0.029) and Month 1 (P = 0.001) in IVD group, whereas IVV group did not show significant BCVA gains (P = 0.056 at Week1, P = 0.166 at Month 1). The changes of BCVA and CRT were significantly higher in IVD group than IVV group at Month1, but the changes were not significant at Week1. Conclusions: Comparing to anti-VEGF therapy, DEX implant is more effect in improving BCVA and reducing CRT in vitrectomized eyes at 1 month, which indicated DEX implant is a better strategy.

Exploring the Immune Infiltration Landscape and M2 Macrophage-Related Biomarkers of Proliferative Diabetic Retinopathy.

Backgrounds: Diabetic retinopathy (DR), especially proliferative diabetic retinopathy (PDR), is the major cause of irreversible blindness in the working-age population. Increasing evidence indicates that immune cells and the inflammatory microenvironment play an important role during PDR development. Herein, we aim to explore the immune landscape of PDR and then identify potential biomarkers correlated with specific infiltrating immune cells. Methods: We mined and re-analyzed PDR-related datasets from the Gene Expression Omnibus (GEO) database. Using the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm, we investigated the infiltration of 22 types of immune cells in all selected samples; analyses of differences and correlations between infiltrating cells were used to reveal the immune landscape of PDR. Thereafter, weighted gene co-expression network analysis (WGCNA) and differential expression analysis were applied to identify the hub genes on M2 macrophages that may affect PDR progression. Results: Significant differences were found between infiltration levels of immune cells in fibrovascular membranes (FVMs) from PDR and normal retinas. The percentages of follicular helper T cells, M1 macrophages, and M2 macrophages were increased significantly in FVMs. Integrative analysis combining the differential expression and co-expression revealed the M2 macrophage-related hub genes in PDR. Among these, COL5A2, CALD1, COL6A3, CORO1C, and CALU showed increased expression in FVM and may be potential biomarkers for PDR. Conclusions: Our findings provide novel insights into the immune mechanisms involved in PDR. COL5A2, CALD1, COL6A3, CORO1C, and CALU are M2 macrophage-related biomarkers, further study of these genes could inform novel ideas and basis for the understanding of disease progression and targeted treatment of PDR.

A Systematic Strategy for the Characterization of 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-d-glucoside Metabolites In Vivo by Ultrahigh Performance Liquid Chromatography Coupled with a Q Exactive-Orbitrap Mass System.

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-d-glucoside (THSG), a polyphenol stilbene compound, is the main active constituent in Polygonum multiflorum. In this study, a comprehensive analytical strategy was developed for the characterization of THSG metabolites in vivo (rat plasma, bile, urine, heart, liver, spleen, lung, kidney, and stomach) utilizing ultrahigh performance liquid chromatography coupled with Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UHPLC-Q Exactive-Orbitrap MS) based on multiple data-processing techniques. As a result, a total of 75 metabolites were characterized in bio-samples, and calculated Clog P values were further employed to assign the chemical structures of some isomers. Glucoside hydrolysis, hydrogenation, hydroxylation, glucuronide conjugation, and sulfate conjugation would be the major metabolic pathways of THSG. It appeared that most metabolites would generally undergo phase I reactions followed by phase II reactions. These results provided valuable information for in-depth understanding of the safety and efficacy of THSG and showed a valuable methodology for metabolic characterization.

Preparation of norfloxacin-grafted chitosan antimicrobial sponge and its application in wound repair.

Trauma is one of the most common health issues in humans, and bacterial infection of the wound may result in many complications. In this paper, using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) as a coupling agent, chitosan (CS) was grafted with norfloxacin (NF), an antibacterial agent, to prepare a CS-NF sponge by freezing-induced phase separation. The CS-NF sponge was characterized by ultra violet-visible spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy. Its porosity and water absorption ratio were determined, the antimicrobial activity was evaluated by inhibition zone assay, and its wound repair effect was investigated in a full-thickness cutaneous excisional wound animal model. The results showed that NF was successfully grafted onto CS, and the obtained CS-NF sponge had both a high porosity and water absorption ratio. The CS-NF sponge displayed significant antimicrobial activities in the inhibition zone assay. In vivo the CS-NF sponge exhibited a strong wound healing effect, with a wound healing rate close to 100% by day 15. Therefore, the CS-NF sponge is a novel promising wound-healing dressing for clinical practice.

Iridoid Glycosides from Phlomis Medicinalis Diels: Optimized Extraction and Hemostasis Evaluation.

Phlomis medicinalis Diels, an important perennial herbal plant unique to the Qinghai-Tibet Plateau, is often used as Tibetan Materia Medicine Radix Phlomii for the treatment of cold, cough, and convergence trauma. In order to efficiently extract the iridoid glycosides from P. medicinalis, an ultrasound-assisted deep eutectic solvent extraction technique was employed. The main parameters influencing the extraction process were studied through single-factor tests and the extraction was optimized by using response surface methodology. The hemostasis activity of total iridoid glycosides (TIG) from P. medicinalis was evaluated in vitro and in mice. The optimization results revealed that the optimal process parameters were liquid-solid ratio 20 : 1, choline chloride-lactic acid concentration 79 %, and sonication time 34 min, under which a TIG extraction yield of 20.73 % was obtained. Meanwhile, high-performance liquid chromatography-photodiode array/mass spectrometry (HPLC-PDA/MS) was employed to characterize the optimized extract and indicated that TIG from P. medicinalis mainly consisted of sixteen reported iridoid glycosides with a total content of 91.22 %. The experimental results in vivo and in vitro indicated that TIG from P. medicinalis had strong hemostasis activities, which may be achieved by increasing the fibrinogen levels. Therefore, the ultrasound-assisted deep eutectic solvent extraction is an effective method to extract iridoid glycosides from P. medicinalis and they will be promising candidates to be developed for medical hemostasis agents.

PRRX1 Is a Novel Prognostic Biomarker and Facilitates Tumor Progression Through Epithelial-Mesenchymal Transition in Uveal Melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UM develops and is sustained by inflammation and immunosuppression from the tumor microenvironment (TME). This study sought to identify a reliable TME-related biomarker that could provide survival prediction and new insight into therapy for UM patients. Based on clinical characteristics and the RNA-seq transcriptome data of 80 samples from The Cancer Genome Atlas (TCGA) database, PRRX1 as a TME- and prognosis-related gene was identified using the ESTIMATE algorithm and the LASSO-Cox regression model. A prognostic model based on PRRX1 was constructed and validated with a Gene Expression Omnibus (GEO) dataset of 63 samples. High PRRX1 expression was associated with poorer overall survival (OS) and metastasis-free survival (MFS) in UM patients. Comprehensive results of the prognostic analysis showed that PRRX1 was an independent and reliable predictor of UM. Then the results of immunological characteristics demonstrated that higher expression of PRRX1 was accompanied by higher expression of immune checkpoint genes, lower tumor mutation burden (TMB), and greater tumor cell infiltration into the TME. Gene set enrichment analysis (GSEA) showed that high PRRX1 expression correlated with angiogenesis, epithelial-mesenchymal transition (EMT), and inflammation. Furthermore, downregulation of PRRX1 weakened the process of EMT, reduced cell invasion and migration of human UM cell line MuM-2B in vitro. Taken together, these findings indicated that increased PRRX1 expression is independently a prognostic factor of poorer OS and MFS in patients with UM, and that PRRX1 promotes malignant progression of UM by facilitating EMT, suggesting that PRRX1 may be a potential target for UM therapy.

Microvascular Structure Changes After Intravitreal Ranibizumab Injection in Retinal Vein Occlusion Patients With and Without Macular Ischemia.

Purpose: To investigate the changes in the macular microvascular structure after anti-vascular endothelial growth factor (anti-VEGF) treatment in retinal vein occlusion (RVO) patients with and without macular ischemia. Methods: A total of 39 patients were divided into the macular ischemia group (n = 22) and the nonischemia group (n = 17) at baseline. All the patients received an intravitreal injection of ranibizumab with a 3+ pro re nata (PRN) regimen. The foveal avascular zone (FAZ) areas, macular vessel density (VD), and macular ischemic index (ISI) were evaluated at baseline and 3 and 6 months after treatment. Results: After treatment, some patients in the macular ischemia group achieved obvious reperfusion in macular nonperfusion areas. The VD and macular ISI improved in RVO patients, but the changes in VD and macular ISI were different in the two groups. The improvement of best corrected visual acuity (BCVA) was positively correlated with the improvement of macular perfusion status. Macular perfusion remained stable in most patients in RVO and only one patient had macular ischemia aggravation. Conclusion: The macular microvascular structures were stable in most RVO patients after anti-VEGF treatment. At the same time, some patients with macular ischemia presented reperfusion in macular nonperfusion areas, and still a few patients presented aggravated macular ischemia. Macular ISI is a good way to evaluate macular perfusion status in RVO compared to VD.

Comparison of Inflammatory and Angiogenic Factors in the Aqueous Humor of Vitrectomized and Non-Vitrectomized Eyes in Diabetic Macular Edema Patients.

Objectives: To compare the aqueous concentrations of inflammatory and angiogenetic factors in vitrectomized vs. non-vitrectomized eyes with diabetic macular edema (DME). Methods: Aqueous samples were obtained from 107 eyes with DME before intravitreal injection of anti-VEGF, 36 eyes with previous pars plana vitrectomy (PPV) combined with pan-retinal endolaser photocoagulation (PRP), and 71 treatment-naïve. Interleukin (IL)-6, IL-8, interferon-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, and vascular endothelial growth factor (VEGF) were measured by cytometric bead array (CBA). Optical coherence tomography (OCT) was used for measuring central retinal thickness (CRT). Results: IL-6, IL-8, IP-10, and MCP-1 in aqueous humor of DME vitrectomized eyes were significantly higher than in non-vitrectomized DME eyes, while VEGF was lower than in non-vitrectomized DME eyes. VEGF in aqueous humor significantly correlated with CRT for DME in non-vitrectomized DME eyes. IL-6, IL-8, IP-10, and MCP-1 in aqueous humor were not significantly associated with VEGF for DME in vitrectomized eyes. Conclusions: Inflammation might play an important role in the pathogenesis of DME in vitrectomized eyes. Moreover, inflammation might play a central role in the development of DME via the VEGF-independent pathway. Thus, anti-inflammatory therapy might be a strategy for DME in vitrectomized eyes.

Screening of Quality Markers During the Processing of Reynoutria multiflora Based on the UHPLC-Q-Exactive Plus Orbitrap MS/MS Metabolomic Method.

The root of Reynoutria multiflora (Thunb.) Moldenke (syn: Polygonum multiflorum Thunb.) is a distinguished herb that has been popularly used in traditional Chinese medicine. The raw Reynoutria multiflora (RRM) should be processed by steaming before use, and the processing time is not specified in the processing specification. Our previous studies showed that the efficacy and toxicity of processed Reynoutria multiflora (PRM) at different processing times were inconsistent. A comprehensive identification method was established in this study to find a quality marker of raw Reynoutria multiflora (RRM) and processed Reynoutria multiflora (PRM) with different processing times. Metabolomics based on ultra-high-performance liquid chromatography tandem quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive plus orbitrap MS/MS) was used in this study. Using the CD.2 software processed database, multivariate statistical analysis methods coupled with cluster analysis and heatmap were implemented to distinguish between RRMs and PRMs with different processing times. The results showed that RRM and PRMs processed for 4, 8, 12, and 18 h cluster into group 1, and PRM processed for 24 and 32 h into group 2, indicating that it can effectively distinguish between the two groups and twenty potential markers, made the highest contributions to the observed chemical differences between two groups. Among them, tetrahydroxystilbene-O-hexoside-O-galloyl and sucrose can be used to identify PRM processed for 24 h. Therefore, the properties of RRM changed after 24 h of processing, and the quality markers were screened to distinguish RRM and PPM. It can also be used as an important control technology for the processing of RM, which has wide application prospects.

Clinical effect of conbercept on improving diabetic macular ischemia by OCT angiography.

BACKGROUND: Varying degrees of macular ischemia generally occur in diabetic retinopathy (DR). This study aims to evaluate the effect of conbercept with 3+ pro re nata (PRN) on macular perfusion status in patients with diabetic macular edema (DME) and quantitatively assess changes in foveal avascular zone (FAZ) areas and capillary density in macular regions by applying optical coherence tomography angiography (OCTA). METHODS: Fifty patients were divided into ischemic (n = 31) and non-ischemic (n = 19) groups according to the presence of ischemia on OCTA at baseline. All patients received intravitreal injections of 0.5 mg of conbercept with 3+ PRN principle. The FAZ areas and macular vessel density measured using OCTA were evaluated at baseline, 3 months, and 6 months after treatment in both groups. RESULTS: At months 3 and 6, the FAZ area in the ischemic group changed from 0.510 ± 0.171 mm2 to 0.441 ± 0.158 mm2 then to 0.427 ± 0.153 mm2 (p = 0.003, p = 0.296); in the non-ischemic group, it remained stable (p = 0.269, p = 0.926). The superficial vessel density changed from 41.1 ± 4.1 to 42.5% ± 4.7% then to 42.6% ± 4.6% (p = 0.043, p = 0.812), and the deep vessel density changed from 40.7 ± 4.4 to 42.3% ± 3.6% then to 42.3% ± 4.7% (p = 0.072, p = 0.961) in the ischemic group. In the non-ischemic group, the superficial vessel density changed from 44.8 ± 3.2 to 46.0% ± 3.5% then to 45.7% ± 3.3% (p = 0.108, p = 0.666), whereas the deep vessel density changed from 43.6 ± 3.6 to 43.8% ± 3.2% then to 43.5% ± 4.5% (p = 0.882, p = 0.736). Reperfusion in macular nonperfusion areas was observed. CONCLUSION: Anti-vascular endothelial growth factor treatment may have a positive effect on macular perfusion status. Furthermore, OCTA had advantages in quantifying and calculating blood flow index in the study of macular perfusion status.

Association between uveitis and psoriatic disease: a systematic review and Meta-analysis based on the evidence from cohort studies.

AIM: To conduct a systematic review and Meta-analysis to examine the association between uveitis and psoriatic disease, and to evaluate whether one condition predisposes individuals to the other. METHODS: We performed a comprehensive search of PubMed and EMBASE to identify cohort studies examining the association between uveitis and psoriatic disease [psoriasis and/or psoriatic arthritis (PsA)]. We used a random-effects model to calculate the pooled relative risks (RRs) adjusted for confounders, along with the 95% confidence intervals (CIs). RESULTS: This Meta-analysis included a total of 6 studies and a maximum of 80 178 648 participants. Compared with non-psoriatic controls, uveitis risk was significantly elevated in patients with psoriasis (RR=1.49; 95%CI: 1.08-2.07), and PsA (RR=3.16; 95%CI: 2.16-4.63). Furthermore, pre-existing uveitis was associated with a significantly increased risk of psoriasis (RR=1.62; 95%CI: 1.44-1.83), and PsA (RR=4.44; 95%CI: 3.52-5.60). CONCLUSION: The results of this systematic review and Meta-analysis suggest an overall positive bidirectional association between uveitis and psoriatic disease (psoriasis and PsA), warranting increased awareness among clinicians involved in the management of these two conditions. Therefore, there remains a need for more detailed studies of the possible common pathogenesis of psoriatic disease and uveitis.

Postoperative follow-up of a case of atypical morning glory syndrome associated with persistent fetal vasculature.

BACKGROUND: Morning glory syndrome is a relatively rare congenital optic disc anomaly that is often difficult to identify when associated with additional congenital ocular anomalies. This case report describes the diagnosis, treatment, and postoperative follow-up care of a young girl with morning glory syndrome accompanied by persistent fetal vasculature, retinal fold, and retinal detachment. Here, we also give a brief review of the relevant literature. CASE PRESENTATION: A 5-year-old girl was referred to our clinic for a complaint of decreased vision for 6 months in the right eye. The best corrected visual acuity was hand motion in her right eye and 0.8 in her left eye. A fundus examination indicated vitreous opacities and scattered hemorrhages, as well as striped folds in the temporal retina of the affected eye. B-ultrasound and magnetic resonance imaging scans suggested that it could be a congenital dysplasia of the right eye. Pars plana vitrectomy was performed in the right eye. Morning glory syndrome associated with persistent fetal vasculature was confirmed in subsequent follow-up observation according to the fundus appearance, optical coherence tomography, and fundus fluorescein angiography imaging. CONCLUSIONS: The patient was diagnosed as morning glory syndrome associated with persistent fetal vasculature and retinal fold. The morning glory disc with the presence of retinal folds did not seem quite typical and that made the diagnosis difficult. This report stresses the importance of considering concurrent morning glory syndrome and persistent fetal vasculature. Vitrectomy may be beneficial in the management of the morning glory syndrome and persistent fetal vasculature if accompanied by retinal detachment in similar cases.

A novel frameshift mutation in the PITX2 gene in a family with Axenfeld-Rieger syndrome using targeted exome sequencing.

BACKGROUND: Axenfeld-Rieger syndrome (ARS) is an autosomal dominant genetic disorder that is characterized by specific abnormalities of the anterior segment of the eye. Heterozygous mutations in two developmental transcription factor genes PITX2 and FOXC1 have been identified within ARS patients, accounting for 40 to 70% of cases. Our purpose is to describe clinical and genetic findings in a Chinese family with ARS. METHODS: An ARS family with three affected members was recruited. The patients underwent a series of complete ophthalmologic examinations, general physical examination and dental radiography. DNA samples of proband II-1 were used for targeted exome sequencing of the FOXC1 and PITX2 genes. Sanger sequencing was used to validate the variation in PITX2. Quantitative real-time PCR was carried out to detect the expression of PITX2 in patients and normal controls. RESULTS: All affected members showed iris atrophy, corectopia, shallow anterior chamber, complete or partial angle closure, and advanced glaucoma. In addition, they revealed systemic anomalies, including microdontia, hypodontia, and redundant periumbilical skin. A novel heterozygous frameshift variation, c.515delA, in PITX2 was found in the proband, which might lead to a truncated PITX2 protein (p.Gln172ArgfsX36). Sanger sequencing validated that the variation completely cosegregated with the ARS phenotype among this family, but was absent in 100 unrelated controls. Quantitative real-time PCR analysis revealed that the mRNA expression of PITX2 was significantly decreased in patients compared with that in unrelated normal controls. CONCLUSIONS: PITX2 c.515delA (p.Gln172ArgfsX36) was the genetic etiology of our pedigree. The mutation led to decreased PITX2 gene expression and a truncated mRNA transcript.

Clinical application of accommodating intraocular lens.

The present review describes recent advances in application of accommodating intraocular lenses (AIOLs). Standard monofocal intraocular lenses (MIOLs) only correct distance vision, while AIOLs are designed to allow both good distance vision and near vision, which is achieved through the contraction and relaxation of ciliary muscles by providing transformation of the axial movement or curvature of the lens. Thus, AIOLs may be a better choice for those patients who demand a higher level of visual performance. Since techniques to analyze the performance of AIOLs have not been standardized, and there is a variety of both subjective and objective methods, it is hard to measure the performance of these intraocular lenses. By evaluating advantages and disadvantages of various AIOLs, and introducing techniques for measurement the performance postoperative, this paper can provide some relative information on choosing the type of AIOLs in the clinic.

A Missense Mutation in GJA8 Encoding Connexin 50 in a Chinese Pedigree with Autosomal Dominant Congenital Cataract.

Congenital cataract is leading cause of visual impairment and blindness in children worldwide. Approximately one-third of congenital cataract cases are familial, whose genetic etiology can be distinguished by targeted exome sequencing. Here, a three-generation congenital cataract pedigree was recruited, and physical and ophthalmologic examinations were taken. Targeted exome sequencing of 139 cataract-related genes was performed on the proband III:1. Sanger sequencing was used to validate the presence of variation identified via exome sequencing in family members and 200 controls. Conservative and functional prediction was performed with bioinformatic tools. We, thus, found a heterozygous missense mutation c.10T>A (p.W4R) in gap junction protein alpha 8 (GJA8) in the patients. However, this mutation was not present in normal family members and 200 unrelated controls. The GJA8 gene encodes a gap junction protein, connexin 50 (Cx50), in lens fibers that provide channels for exchange of ions and small molecules between adjacent cells. Conservative and functional prediction suggests that the W-to-R substitution at codon 4 may impair the function of the human Cx50 protein. Accordingly, we analyzed the distribution of Flag-tagged mutant Cx50 protein in HeLa cervical cancer cells. Immunofluorescent staining showed that the W-to-R substitution impaired Cx50 trafficking to the plasma membrane to form the gap junction. In conclusion, c.10T>A (p.W4R) in GJA8 is the newly identified genetic cause of familial congenital cataract. The W-to-R substitution near the amino-terminus may alter the localization of mutant Cx50, thereby impairing gap junction formation, which is the molecular pathogenic mechanism of this mutation.

Prevalence of cerebral palsy in children aged 1 - 6 in Guangxi, China.

OBJECTIVE: To study the prevalence of cerebral palsy (here in after referred to CP) in children aged 1 - 6 in Guangxi, China, and its epidemiologic characteristics and relevant risk factors. METHODS: Investigations on the prevalence and etiology of CP in children at ages of 1 - 6 were conducted in Nanning, Hengxian and Qinzhou of Guangxi from June to December in 1998, with a cluster sampling. RESULTS: Totally, 150 806 children aged 1 - 6 were investigated in Nanning, Hengxian and Qinzhou of Guangxi, with 89 418 boys and 61 388 girls. Among them, 193 children were diagnosed as CP, with a prevalence rate of 1.28 per thousand, higher in boys (136 cases, 1.52 per thousand ) than in girls (57 cases, 0.93 per thousand ), with statistical significance (chi(2) = 9.536 7, P = 0.02). Logistic regression analysis showed that risk factors for CP were children who could not cry after birth (neonatal asphyxia), Apgar score less than eight, delivery at lower level of maternity hospital, number of mother's gravidity, no prenatal checks for mothers, and taking antipyretics and preserved food with salt during pregnancy. CONCLUSIONS: Prevalence of CP in children of Guangxi was at a lower level in comparison with that in other areas at home and abroad, which, maybe, was related with the lower neonatal survival and higher infant mortality.