A Modified Single-Armed Suture Technique for Traumatic Cyclodialysis Cleft with Vitreoretinal Injury.

Our aim was to assess the therapeutic efficacy of a modified single-arm suture technique on traumatic cyclodialysis cleft with vitreoretinal injury. The procedure involved fixing a detached ciliary body using a single-armed 10-0 polypropylene suture under the assistance of a 29-gauge needle. Patients with a traumatic cyclodialysis cleft combined with an anterior and posterior segment injury who underwent modified internal cyclopexy together with vitreoretinal surgery were enrolled in this study. Ultrasound biomicroscopy (UBM) was used to diagnose and evaluate the cyclodialysis and anterior segment injury. B-scan ultrasonography was performed to assess the condition of the vitreous, retina and choroid. The surgical time and successful rate for repairing the cyclodialysis cleft were recorded. Preoperative and postoperative best-corrected visual acuity (BCVA), and intraocular pressure (IOP) were documented for assessment. The study included 20 eyes. The extent of the cyclodialysis cleft was from 30° to 360°. Besides a traumatic cyclodialysis cleft, the included cases also combined this with vitreous hemorrhages, retinal detachment, macular holes, choroid avulsion, and suprachoroidal hemorrhage. All the clefts were anatomically closed in one surgery. The average surgical time for fixing the cyclodialysis cleft was 2.68 ± 0.54 min/30° cleft. A significant improvement in LogMAR BCVA was observed from 2.94 ± 0.93 preoperatively to 1.81 ± 1.11 at the 6-month follow-up. IOP was elevated from 10.90 ± 6.18 mmHg preoperatively to 14.45 ± 2.35 mmHg at the 6-month follow-up. The modified single-armed suture technique was proved to be an effective method to fix the traumatic cyclodialysis cleft, which could facilitate the use of the procedure to repair chorioretinal disorders. It improved the BCVA and maintained the IOP with less postoperative complications.

New insight of metabolomics in ocular diseases in the context of 3P medicine.

Metabolomics refers to the high-through untargeted or targeted screening of metabolites in biofluids, cells, and tissues. Metabolome reflects the functional states of cells and organs of an individual, influenced by genes, RNA, proteins, and environment. Metabolomic analyses help to understand the interaction between metabolism and phenotype and reveal biomarkers for diseases. Advanced ocular diseases can lead to vision loss and blindness, reducing patients' quality of life and aggravating socio-economic burden. Contextually, the transition from reactive medicine to the predictive, preventive, and personalized (PPPM / 3P) medicine is needed. Clinicians and researchers dedicate a lot of efforts to explore effective ways for disease prevention, biomarkers for disease prediction, and personalized treatments, by taking advantages of metabolomics. In this way, metabolomics has great clinical utility in the primary and secondary care. In this review, we summarized much progress achieved by applying metabolomics to ocular diseases and pointed out potential biomarkers and metabolic pathways involved to promote 3P medicine approach in healthcare.

Molecular investigation of candidate genes for pyroptosis-induced inflammation in diabetic retinopathy.

Background: Diabetic retinopathy is a diabetic microvascular complication. Pyroptosis, as a way of inflammatory death, plays an important role in the occurrence and development of diabetic retinopathy, but its underlying mechanism has not been fully elucidated. The purpose of this study is to identify the potential pyroptosis-related genes in diabetic retinopathy by bioinformatics analysis and validation in a diabetic retinopathy model and predict the microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) interacting with them. Subsequently, the competing endogenous RNA (ceRNA) regulatory network is structured to explore their potential molecular mechanism. Methods: We obtained mRNA expression profile dataset GSE60436 from the Gene Expression Omnibus (GEO) database and collected 51 pyroptosis-related genes from the PubMmed database. The differentially expressed pyroptosis-related genes were obtained by bioinformatics analysis with R software, and then eight key genes of interest were identified by correlation analysis, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network analysis. Then, the expression levels of these key pyroptosis-related genes were validated with quantitative real-time polymerase chain reaction (qRT-PCR) in human retinal endothelial cells with high glucose incubation, which was used as an in vitro model of diabetic retinopathy. Western blot was performed to measure the protein levels of gasdermin D (GSDMD), dasdermin E (GSDME) and cleaved caspase-3 in the cells. Moreover, the aforementioned genes were further confirmed with the validation set. Finally, the ceRNA regulatory network was structured, and the miRNAs and lncRNAs which interacted with CASP3, TLR4, and GBP2 were predicted. Results: A total of 13 differentially expressed pyroptosis-related genes were screened from six proliferative diabetic retinopathy patients and three RNA samples from human retinas, including one downregulated gene and 12 upregulated genes. A correlation analysis showed that there was a correlation among these genes. Then, KEGG pathway and GO enrichment analyses were performed to explore the functional roles of these genes. The results showed that the mRNA of these genes was mainly related to inflammasome complex, interleukin-1 beta production, and NOD-like receptor signaling pathway. In addition, eight hub genes-CASP3, TLR4, NLRP3, GBP2, CASP1, CASP4, PYCARD, and GBP1-were identified by PPI network analysis using Cytoscape software. High glucose increased the protein level of GSDMD and GSDME, as critical effectors of pyroptosis, in retinal vascular endothelial cells. Verified by qRT-PCR, the expression of all these eight hub genes in the in vitro model of diabetic retinopathy was consistent with the results of the bioinformatics analysis of mRNA chip. Among them, CASP4, GBP1, CASP3, TLR4, and GBP2 were further validated in the GSE179568 dataset. Finally, 20 miRNAs were predicted to target three key genes-CASP3, GBP2, and TLR4, and 22 lncRNAs were predicted to potentially bind to these 20 miRNAs. Then, we constructed a key ceRNA network that is expected to mediate cellular pyroptosis in diabetic retinopathy. Conclusion: Through the data analysis of the GEO database by R software and verification by qRT-PCR and validation set, we successfully identified potential pyroptosis-related genes involved in the occurrence of diabetic retinopathy. The key ceRNA regulatory network associated with these genes was structured. These findings might improve the understanding of molecular mechanisms underlying pyroptosis in diabetic retinopathy.

Identification and Validation of Autophagy-Related Genes in Diabetic Retinopathy.

Background: Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, which is associated with damage of blood-retinal barrier and ischemia of retinal vasculature. It devastates visual acuity due to leakage of retinal vessels and aberrant pathological angiogenesis in diabetic patients. The etiology of DR is complex, accumulated studies have shown that autophagy plays an important role in the pathogenesis of DR, but its specific mechanism needs to be further studied. Methods: This study chose the online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE146615 to carry on the research. Autophagy-related genes that were potentially differentially expressed in DR were screened by R software. Then, the differentially expressed autophagy-related genes were analyzed by correlation analysis, tissue-specific gene expression, gene-ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) network analysis. Finally, retinal pigment epithelial cell line (ARPE-19) incubated with high glucose (HG) was used to mimic the DR model, and the mRNA level of key genes was verified by quantitative real-time polymerase chain reaction (qRT-PCR) in vitro. Results: A total of 23 differentially expressed autophagy-related genes (9 up-regulated genes and 14 down-regulated genes) were identified by differential expression analysis. The analysis of tissue-specific gene expression showed that these differentially expressed autophagy-related genes were enriched in the retina. GO and KEGG enrichment analysis showed that differentially expressed autophagy-related genes were significantly enriched in autophagy-related pathways such as regulation of autophagy and macroautophagy. Then 10 hub genes were identified by PPI network analysis and construction of key modules. Finally, qRT-PCR confirmed that the expression of MAPK3 in the DR model was consistent with the results of bioinformatics analysis of mRNA chip. Conclusion: Through bioinformatics analysis, we identified 23 potential DR autophagy-related genes, among which the down-regulated expression of MAPK3 may affect the occurrence and development of DR by regulating autophagy. It provides a novel insight into the pathogenesis of DR.

Investigation of a Hypoxia-Immune-Related Microenvironment Gene Signature and Prediction Model for Idiopathic Pulmonary Fibrosis.

Background: There is growing evidence found that the role of hypoxia and immune status in idiopathic pulmonary fibrosis (IPF). However, there are few studies about the role of hypoxia and immune status in the lung milieu in the prognosis of IPF. This study aimed to develop a hypoxia-immune-related prediction model for the prognosis of IPF. Methods: Hypoxia and immune status were estimated with microarray data of a discovery cohort from the GEO database using UMAP and ESTIMATE algorithms respectively. The Cox regression model with the LASSO method was used for identifying prognostic genes and developing hypoxia-immune-related genes. Cibersort was used to evaluate the difference of 22 kinds of immune cell infiltration. Three independent validation cohorts from GEO database were used for external validation. Peripheral blood mononuclear cell (PBMC) and bronchoalveolar lavage fluid (BALF) were collected to be tested by Quantitative reverse transcriptase-PCR (qRT-PCR) and flow cytometry from 22 clinical samples, including 13 healthy controls, six patients with non-fibrotic pneumonia and three patients with pulmonary fibrosis. Results: Hypoxia and immune status were significantly associated with the prognosis of IPF patients. High hypoxia and high immune status were identified as risk factors for overall survival. CD8+ T cell, activated CD4+ memory T cell, NK cell, activated mast cell, M1 and M0 macrophages were identified as key immune cells in hypoxia-immune-related microenvironment. A prediction model for IPF prognosis was established based on the hypoxia-immune-related one protective and nine risk DEGs. In the independent validation cohorts, the prognostic prediction model performed the significant applicability in peripheral whole blood, peripheral blood mononuclear cell, and lung tissue of IPF patients. The preliminary clinical specimen validation suggested the reliability of most conclusions. Conclusions: The hypoxia-immune-based prediction model for the prognosis of IPF provides a new idea for prognosis and treatment.

Immune and Metabolic Alterations in Liver Fibrosis: A Disruption of Oxygen Homeostasis?

According to the WHO, "cirrhosis of the liver" was the 11th leading cause of death globally in 2019. Many kinds of liver diseases can develop into liver cirrhosis, and liver fibrosis is the main pathological presentation of different aetiologies, including toxic damage, viral infection, and metabolic and genetic diseases. It is characterized by excessive synthesis and decreased decomposition of extracellular matrix (ECM). Hepatocyte cell death, hepatic stellate cell (HSC) activation, and inflammation are crucial incidences of liver fibrosis. The process of fibrosis is also closely related to metabolic and immune disorders, which are usually induced by the destruction of oxygen homeostasis, including mitochondrial dysfunction, oxidative stress, and hypoxia pathway activation. Mitochondria are important organelles in energy generation and metabolism. Hypoxia-inducible factors (HIFs) are key factors activated when hypoxia occurs. Both are considered essential factors of liver fibrosis. In this review, the authors highlight the impact of oxygen imbalance on metabolism and immunity in liver fibrosis as well as potential novel targets for antifibrotic therapies.

Effect of Parenting Training on Neurobehavioral Development of Infants.

BACKGROUND Early interventions have been believed to have a positive influence on the neurodevelopment of infants. Our Child Health Center has carried out parenting training for parents of infants for several years to promote the neurobehavioral development of infants at an early stage. MATERIAL AND METHODS We enrolled 117 families with term infants age 0-3 months who had completed a parenting training class at the Child Health Center of the Department of Pediatrics, the Third Xiangya Hospital. Parenting training included 4 parts: nursing, intelligence, social contact, and physical ability. A nurse practitioner demonstrated procedures to parents, who then performed them at home for 1 month. The Neonatal Behavioral Neurological Assessment (NBNA) was used to evaluate infants before and 1 month after parenting training. RESULTS In the comparative analysis before and after parenting training, there was a significant increase in the NBNA scores. For the infants whose parents received parenting training, the NBNA scores in total score (33.74±0.19 before parenting training vs. 36.69±0.20 after 1 month), neonatal behavioral capacity (10.19±0.14 before parenting training vs. 11.26±0.10 after 1 month), passive muscle tension (7.28±0.07 before parenting training vs. 7.82±0.04 after 1 month), and initiative muscle tension (4.29±0.08 before the parenting training vs. 5.61±0.13 after 1 month) were significantly higher one month before (P<0.01). CONCLUSIONS Term infant neurobehavior was associated with participation in parenting training, suggesting that these practices of parenting training support better early neurobehavioral development of infants.

Oxygen homeostasis and cardiovascular disease: A role for HIF?

Hypoxia, the decline of tissue oxygen stress, plays a role in mediating cellular processes. Cardiovascular disease, relatively widespread with increased mortality, is closely correlated with oxygen homeostasis regulation. Besides, hypoxia-inducible factor-1(HIF-1) is reported to be a crucial component in regulating systemic hypoxia-induced physiological and pathological modifications like oxidative stress, damage, angiogenesis, vascular remodeling, inflammatory reaction, and metabolic remodeling. In addition, HIF1 controls the movement, proliferation, apoptosis, differentiation and activity of numerous core cells, such as cardiomyocytes, endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages. Here we review the molecular regulation of HIF-1 in cardiovascular diseases, intended to improve therapeutic approaches for clinical diagnoses. Better knowledge of the oxygen balance control and the signal mechanisms involved is important to advance the development of hypoxia-related diseases.

Intracranial hemorrhage associated with late-onset group B streptococcus disease-a case report and a review of literature.

To report a case of intracranial hemorrhage in an 86-day-old boy with late-onset group B streptococcus (GBS) disease and review the literature of GBS disease. Physical and auxiliary examinations and PubMed search with keywords of "GBS disease" and "intracranial hemorrhage". The 86-day-old boy was admitted to hospital for respiratory arrest. High tension in bregma indicated intracranial infection. Laboratory examination showed low red blood cell account, low white blood cell account and high C-reactive protein account. Also, GBS was positive in cerebrospinal fluid (CSF) and blood culture. Computed tomography (CT) indicated intracranial hemorrhage. Meropenem and other supportive treatment started immediately. Because of the patient's poor condition, the patient's parents abandoned the treatment. As for literature review, intracranial hemorrhage is rarely seen in late-onset disease (LOD). The case contributes to further exploration on the syndromes of GBS disease. Clinical workers should notice the complexity of bacterial infection. The relationship between polluted breast milk and infection remains to be explored.