Insights into "Yin Rhyme": Analysis of nonvolatile components in Tieguanyin oolong tea during the manufacturing process.

Tieguanyin (TGY) is renowned for its distinctive "Yin Rhyme" flavor. To elucidate the underlying formation mechanism, we conducted sensory evaluations, electronic tongue analysis, and widely-targeted metabolomics. Our sensory evaluations and electronic tongue results indicated that TGY exhibits a thick and mellow taste profile, contributing to the "Yin Rhyme" flavor. Metabolomics analysis of tea products revealed that TGY shows significantly higher concentrations of umami substances (L-glutamate, L-theanine) and bitter substances (valine, catechins) compared to Jinguanyin (JGY). Additionally, metabolomic analysis during different oolong tea processing stages revealed significant differences in 21 substances, including L-glutamate, L-theanine, valine, and catechins, between fresh leaves of both varieties. These substances exhibited distinct fluctuation patterns during processing, indicating that the cultivar plays a crucial role in developing the "Yin Rhyme" flavor, which was enhanced throughout processing. This study provides a theoretical foundation for understanding the formation of the unique "Yin Rhyme" flavor of TGY.

Co-Infection with Nocardia Terpene and Pneumocystis Jirovecii in a Patient with Anti-Synthetase Syndrome: A Case Report.

Background: Pulmonary infection is a common clinical complication associated with glucocorticoid. There have been no reported cases of mixed infections involving Nocardia and Pneumocystis jirovecii combined with anti-synthetase syndrome (ASS) activity. Methods: This study conducted a retrospective analysis of the clinical data from a patient with active ASS, treated for a pulmonary coinfection. Results: The patient exhibited fever, asthma, and cough as initial symptoms. Chest CT scan revealed multiple infiltration shadows, consolidation shadows, nodules, mass shadows, and internal cavities in both lungs. BALF mNGS detected Nocardia terpene and Pneumocystis jiroveci. Treatment with sulfamethoxazole/trimethoprim and corticosteroids led to an improvement. However, the patient experienced recurrent fever and a new rash with the reduction of the glucocorticoid dosage. Further investigation identified positive anti-Jo-1 and anti-Ro-52 antibodies and myogenic lesions on electromyography, which confirmed the diagnosis of ASS. Following treatment with immunoglobulin, methylprednisolone, and cyclosporine, the patient's condition significantly improved. Conclusion: Immunodeficiency patients are susceptible to opportunistic infections. mNGS is valuable for diagnosis and treatment. Although the image of Nocardia terpene and Pneumocystis jiroveci infections lack specificity, they exhibit distinctive features. Should fever and skin lesions reoccur post-effective anti-infective therapy, it is imperative to explore non-infectious causes and expedite autoantibody testing.

Genome-wide epigenetic dynamics of tea leaves under mechanical wounding stress during oolong tea postharvest processing.

Understanding the epigenetic responses to mechanical wounding stress during the postharvest processing of oolong tea provides insight into the reprogramming of the tea genome and its impact on tea quality. Here, we characterized the 5mC DNA methylation and chromatin accessibility landscapes of tea leaves subjected to mechanical wounding stress during the postharvest processing of oolong tea. Analysis of the differentially methylated regions and preferentially accessible promoters revealed many overrepresented TF-binding motifs, highlighting sets of TFs that are likely important for the quality of oolong tea. Within these sets, we constructed a chromatin accessibility-mediated gene regulatory network specific to mechanical wounding stress. In combination with the results of the TF-centred yeast one-hybrid assay, we identified potential binding sites of CsMYC2 and constructed a gene regulatory network centred on CsMYC2, clarifying the potential regulatory role of CsMYC2 in the postharvest processing of oolong tea. Interestingly, highly accessible chromatin and hypomethylated cytosine were found to coexist in the promoter region of the indole biosynthesis gene (tryptophan synthase ß-subunit, CsTSB) under wounding stress, which indicates that these two important epigenetic regulatory mechanisms are jointly involved in regulating the synthesis of indole during the postharvest processing of oolong tea. These findings improve our understanding of the epigenetic regulatory mechanisms involved in quality formation during the postharvest processing of oolong tea.

Intravitreal Dexamethasone Implant (Ozurdex) for Ocular Toxocariasis.

This study aimed to evaluate the efficacy and safety of intravitreal dexamethasone implants in the treatment of ocular toxocariasis (OT). A retrospective analysis was performed on 6 cases in which laboratory tests diagnosed OT. All patients were administered with intravitreal dexamethasone implants with or without vitrectomy. The average follow-up time was 19.7 months. All operated eyes achieved anatomic success, and all patients' visual acuity was improved. Five of these six had a visual acuity of 20/100, and three had final acuity of 20/40 or even better. Intravitreal dexamethasone implants can be used to treat different types of OT, which not only effectively control inflammation and improve the patient's vision but also reduce the use of systemic glucocorticoids.

Causal role of immune cells in uveitis: Mendelian randomization study.

Background: Uveitis, characterized by inflammation of the iris, ciliary body, and choroid, presents a significant global clinical challenge, contributing substantially to visual impairment. Risk factors include autoimmune diseases and immune cell dysfunctions, yet many remain unidentified. Immune cells, notably T cells, B cells, and monocytes, play pivotal roles in uveitis pathogenesis. While biologic agents show promise, comprehensive studies on immune cell types in ocular diseases are lacking. Genome-wide association studies (GWAS) and Mendelian randomization (MR) present promising avenues to elucidate genetic susceptibilities and causal relationships between immune cell traits and uveitis risk. Methods: Two-sample MR analysis was used to evaluate the causal relationship between 731 immune cells and uveitis, and genome-wide significance analysis was performed for genetic variation in 731 immune cells traits (P < 5 × 10-8). Immune characteristics include median fluorescence intensity (MFI), relative cell counts (RC), absolute cell counts (AC), and morphological parameters (MP), which were determined by published GWAS, and public data from the IEU Open GWAS database. The main analysis method of MR is inverse variance weighting (IVW). Heterogeneity and horizontal pleiotropy were also assessed. Results: 5 immunophenotypes, including CD62L-DC %DC, IgD+ CD38dim %B cell, CD3 on CM CD4+T cell, CD3 on CD45RA-CD4 +T cell, and CD3 on CD39+ CD4+ Treg may increase the risk of uveitis. 5 immunophenotypes, including CD11b on CD33dim HLA DR-Myeloid cell, HLA DR on CD33dim HLA DR+ CD11b-myeloid cell, CD14-CD16 + %monocyte, HLA DR on CD14-CD16 + monocyte and PDL-1 on CD14-CD16 + monocyte was negatively associated with the risk of uveitis. Among them, HLA DR on CD14-CD16 + monocyte (OR=0.921, 95%CI =0.875-0.970, P=0.001) and HLA DR on CD33dim HLA DR+ CD11b- (OR=0.879, 95%CI = 0.833-0.927, P=0.00) were negatively associated with the risk of uveitis in bi-direction. Conclusion: These results indicate that 10 immune cells traits are significantly associated with the risk of developing uveitis and 2 of them were strongly associated with uveitis bi-directionally, after excluding the effects of confounding factors such as some immune diseases, which provided new ideas and therapeutic targets for the study of immune mechanism of uveitis.

Impairment of Gal-9 and Tim-3 crosstalk between Tregs and Th17 cells drives tobacco smoke-induced airway inflammation.

Overexpression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on T cells has been observed in smokers. However, whether and how galectin-9 (Gal-9)/TIM-3 signal between T-regulatory cells (Tregs) and type 17 helper (Th17) cells contributes to tobacco smoke-induced airway inflammation remains unclear. Here, we aimed to explore the role of the Gal-9/TIM-3 signal between Tregs and Th17 cells during chronic tobacco smoke exposure. Tregs phenotype and the expression of TIM-3 on CD4+ T cells were detected in a mouse model of experimental emphysema. The role of TIM-3 in CD4+ T cells was explored in a HAVCR2-/- mouse model and in mice that received recombinant anti-TIM3. The crosstalk between Gal-9 and Tim-3 was evaluated by coculture Tregs with effector CD4+ T cells. We also invested the expression of Gal-9 in Tregs in patients with COPD. Our study revealed that chronic tobacco smoke exposure significantly reduces the frequency of Tregs in the lungs of mice and remarkably shapes the heterogeneity of Tregs by downregulating the expression of Gal-9. We observed a pro-inflammatory but restrained phenotypic transition of CD4+ T cells after tobacco smoke exposure, which was maintained by TIM-3. The restrained phenotype of CD4+ T cells was perturbed when TIM-3 was deleted or neutralised. Tregs from the lungs of mice with emphysema displayed a blunt ability to inhibit the differentiation and proliferation of Th17 cells. The inhibitory function of Tregs was partially restored by using recombinant Gal-9. The interaction between Gal-9 and TIM-3 inhibits the differentiation of Th17 cells and promotes apoptosis of CD4+ T cells, possibly by interfering with the expression of retinoic acid receptor-related orphan receptor gamma t. The expression of Gal-9 in Tregs was reduced in patients with COPD, which was associated with Th17 response and lung function. These findings present a new paradigm that impairment of Gal-9/Tim-3 crosstalk between Tregs and Th17 cells during chronic tobacco smoke exposure promotes tobacco smoke-induced airway/lung inflammation.

Knockdown H19 Accelerated iPSCs Reprogramming through Epigenetic Modifications and Mesenchymal-to-Epithelial Transition.

H19 is an essential imprinted gene that is expressed to govern normal embryonic development. During reprogramming, the parental pronuclei have asymmetric reprogramming capacities and the critical reprogramming factors predominantly reside in the male pronucleus. After inhibiting the expression of H19 and Gtl2, androgenetic haploid ESCs (AG-haESCs) can efficiently and stably support the generation of healthy SC pups at a rate of ~20%, and double-knockout parthenogenetic haESCs can also produce efficiently. Induced pluripotent stem (iPS) cell reprogramming is thought to have a characteristic epigenetic pattern that is the reverse of its developmental potential; however, it is unclear how H19 participates in iPS cell reprogramming. Here, we showed that the expression of H19 was transiently increased during iPSC reprogramming. H19 knockdown resulted in greater reprogramming efficiency. The genes associated with pluripotency showed enhanced expression during the early reprogramming process, and the Oct4 promoter was demethylated by bisulfite genomic sequencing analysis. Moreover, expression analysis revealed that the mesenchymal master regulators associated with epithelial-to-mesenchymal transition (EMT) were downregulated during reprogramming in H19 knockdown. These findings provide functional insight into the role of H19 as a barrier to the early reprogramming process.

Management after cataract surgery for patients with diabetic retinopathy: a systematic review and meta-analysis.

PURPOSE: To evaluate the safety and effectiveness of various treatment modalities in patients with diabetic retinopathy (DR) who underwent cataract surgery. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted using the PubMed, Embase, Cochrane Library, and CNKI databases up to December 22, 2021. The safety and efficacy of treatment modalities were assessed using the risk ratio (RR) to compare the progression of DR and the mean difference to evaluate the best corrected visual acuity (BCVA) and macular thickness (MT). RESULTS: The meta-analysis of the RCTs revealed that anti-VEGF (anti-vascular endothelial growth factor) drugs significantly reduced the progression of DR [RR: 0.37 (95%CI 0.19, 0.70), P = 0.002] and improved BCVA [mean difference = - 0.06 (- 0.12, - 0.01), P = 0.03] in patients with pre-existing DR who underwent cataract surgery. Steroid drugs also showed a significant reduction in macular thickness [mean difference = - 55.63 (- 90.73, - 20.53), I2 = 56%, P = 0.002] in DR patients two weeks after cataract surgery compared to the control group. The safety profiles of different management options did not differ significantly. CONCLUSION: The present meta-analysis suggests that anti-VEGF drugs can effectively slow down the progression of diabetic retinopathy, improve BCVA, and reduce MT in DR patients who underwent cataract surgery. Steroid drugs also show promise in reducing MT. However, further studies with larger sample sizes are required to compare the efficacy and safety of different management options in a multi-center clinical setting.

Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.

INTRODUCTION: This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. RESULTS: A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changes was - 1.1 letters (95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. CONCLUSIONS: QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

Association of variants in GJA8 with familial acorea-microphthalmia-cataract syndrome.

Congenital acorea is a rare disease with the absence of a pupil in the eye. To date, only one family and two isolated cases with congenital acorea have been reported. The gene associated with acorea has not been identified. In this study, we recruited a Chinese family acorea-microphthalmia-cataract syndrome. By analyzing the whole-exome sequencing (WES) data of this Chinese family, we revealed the association of a novel heterozygous variant, NM_005267.5:c.137G>A (p.G46E) in the gap junction protein alpha 8 (GJA8) gene encoding connexin 50 or CX50, with familial acorea-microphthalmia-cataract syndrome. Additionally, another variant, NM_005267.5:c.151G>A (p.D51N) in GJA8, was identified to co-segregate with this syndrome in an unrelated Japanese family. Ectopic expression of p.G46E and p.D51N mutant GJA8 genes in cultured cells caused protein mislocalization, suggesting that the p.G46E and p.D51N mutations in GJA8 impaired the function of the gap junction channels. These results established GJA8 as the first gene associated with familial acorea-microphthalmia-cataract syndrome.

PATHOLOGIC STUDY OF UNTREATED INTRARETINAL GLIOSIS SURGICALLY EXCISED VIA PARS PLANA VITRECTOMY.

PURPOSE: To evaluate the pathologic process of intraretinal glioses by investigating mass tissues resected from untreated eyes with intraretinal glioses. METHODS: Five patients with intraretinal gliosis without previous conservative treatment were included. All patients underwent pars plana vitrectomy. The mass tissues were excised and processed for the pathologic study. RESULTS: During surgery, it was observed that the intraretinal gliosis mainly affected the neuroretina and the retinal pigment epithelium was not affected. Pathologic examination revealed that all intraretinal glioses consisted of different proportions of hyaline vessels and hyperplastic spindle-shaped glial cells. In one case, the intraretinal gliosis was mainly composed of hyaline vascular components. In another case, the intraretinal gliosis showed a predominance of glial cells. The intraretinal glioses in the other three cases had vascular and glial components. The proliferated vessels showed different amounts of collagen deposits against different backgrounds. Vascularized epiretinal membrane was found in some intraretinal glioses. CONCLUSION: Intraretinal glioses affected the inner retinal layer. Hyaline vessels were the most characteristic pathologic changes; the proportion of proliferative glial cells varied in different intraretinal glioses. The natural course of intraretinal gliosis may involve the proliferation of abnormal vessels in the early stage, which then gradually become scarred and are replaced by glial cells.

Cytotoxicity and Antimicrobial Resistance of Salmonella enterica Subspecies Isolated from Raised Reptiles in Beijing, China.

BACKGROUND: Reptiles are asymptomatic carriers of Salmonella spp. Reptile-associated Salmonella infections have been noticed as a significant contributor to overall human salmonellosis. However, it remains unclear regarding the prevalence of reptile-associated Salmonella in China. METHODS: Fecal and gastrointestinal mucosal samples were taken from 104 snakes, 21 lizards, and 52 chelonians and cultured on selective medium. The positive clones were validated and annotated by biochemical screening and multiplex PCR verification. In addition, the antibiotic resistance of identified Salmonella isolates was detected and followed by cytotoxic activity detection on human colon cells via co-culturation. RESULTS: The overall prevalence of Salmonella in reptiles was 25.99%, with rates of 30.77%, 47.62%, and 7.69% in snakes, lizards, and chelonians, respectively. Further, all isolates showed variable drug-resistant activity to 18 antibiotics, of which 14 strains (30.43%) were resistant to more than eight kinds of antibiotics. More than half of isolated Salmonella strains were more toxic to host cells than the standard strain, SL1344. Whole genome sequencing (WGS) results showed that all lizard-associated strains belong to 4 serovar types, and 7 of them fall into the highly pathogenic serovars "Carmel" and "Pomona." CONCLUSIONS: Our results highlight the potential threat of zoonotic salmonellosis from captive reptiles in the Beijing area of China.

TGF-ß from the Porcine Intestinal Cell Line IPEC-J2 Induced by Porcine Circovirus 2 Increases the Frequency of Treg Cells via the Activation of ERK (in CD4+ T Cells) and NF-κB (in IPEC-J2).

Porcine circovirus 2 (PCV2) causes immunosuppression. Piglets infected with PCV2 can develop enteritis. Given that the gut is the largest immune organ, however, the response of the gut's immune system to PCV2 is still unclear. Here, IPEC-J2 cells with different treatments were co-cultured with PBMC or CD4+ T cells (Transwell). Flow cytometry and Western blotting revealed that PCV2-infected IPEC-J2 increased the frequency of CD4+ T cells among piglets' peripheral blood mononuclear cells (PBMCs) and caused CD4+ T cells to undergo a transformation into Foxp3+ regulatory T cells (Treg cells) via activating CD4+ T ERK. Cytokines production and an inhibitor assay showed that the induction of Tregs by PCV2-infected IPEC-J2 was dependent on TGF-ß induced by PCV2 in IPEC-J2, which was associated with the activation of NF-κB. Taken together, PCV2-infected IPEC-J2 activated NF-κB to stimulate the synthesis of TGF-ß, which enhanced the differentiation of CD4+ T cells into Treg cells through the activation of ERK in CD4+ T cells. This information sheds light on PCV2's function in the intestinal immune system and suggests a potential immunosuppressive mechanism for PCV2 infection.

Identification of microRNAs related with neural germ layer lineage-specific progenitors during reprogramming.

Differentiated cells can be reprogrammed to embryonic stem cell-like cells called induced pluripotent stem cells (iPSCs), in which the natural developmental differentiation process is reversed. It is unclear whether the multi-lineage cells can be isolated and identified during reprogramming. In the current study, we detected the expression of lineage markers, isolated neural lineages, and identified the related microRNAs during iPSC formation. Our results demonstrated that a neuroectoderm appeared earlier than mesoderm and definitive endoderm before forming colonies when mouse embryonic fibroblasts were subjected to iPSC formation using transcription factors (TFs). On day 3, the cells expressed Sox1 and Nestin and had ultrastructure consistent with the transition to identity neural germ layer lineage. Fluorescence-activated cell sorting analysis revealed a peak (40%) in neural progenitor marker-positive cells. When subsequently cultured in a neural precursor cell medium, these cells proliferated slowly, became round and aggregated, generating into neurons and glia. Genome-wide microRNA (miRNA) analysis identified 45 differentially regulated miRNAs. Molecular network analysis demonstrated that these miRNAs validated 6,047 experimental mRNA targets. The GO functional annotation analysis of mRNA targets revealed that most genes were related to neurogenesis, such as growth cone, neuronal cell body, neuron projection, and cell junction synapse. The network of protein-protein interactions was observed, which demonstrated that key nodes of neural lineage reprogramming-associated targets were Sall1, Foxa2, Nf2, Ctnnb1, Shh, and Bmpr1a. Therefore, these data suggested that TFs can drive the reprogramming of somatic cells towards a pluripotent state via neuroectoderm. Moreover, the neural lineage reprogramming system can address how miRNAs influence their target sites.

Altered Homotopic Connectivity in the Cerebellum Predicts Stereopsis Dysfunction in Patients With Comitant Exotropia.

Purpose: Comitant exotropia (CE) is a common eye disorder characterized by impaired stereoscopic vision and eye deviation. Previous neuroimaging studies demonstrated that patients with CE were accompanied by specific functional and structural abnormalities of the brain. However, the effect of impaired stereoscopic vision and eye deviation on interhemispheric homotopic connectivity remains unknown. Methods: A total of thirty-six patients with CE (25 males and 11 females) and 36 well-matched healthy controls underwent magnetic resonance imaging scanning. The voxel-mirrored homotopic connectivity (VMHC) method was applied to assess the interhemispheric homotopic connectivity changes in patients with CE. Furthermore, the support vector machine method was applied to assess to differentiate patients with CE from healthy controls (HCs) with the VMHC maps as a feature. Results: Compared with HCs, patients with CE showed significantly increased VMHC values in the bilateral cerebelum_ 8 and cerebelum_4_5. Moreover, we found that the VMHC maps showed an accuracy of 81.94% and an area under the curve of 0.87 for distinguishing the patients with CE from HCs. Conclusion: Our study demonstrates that patients with CE showed interhemispheric homotopic connectivity changes in the cerebellum, which might reflect the neurological mechanisms of impaired stereoscopic vision and eye deviation in patients with CE.

A Study on Mobile Resources for Language Education of Preschool Children Based on Wireless Network Technology in Artificial Intelligence Context.

Preschool language education is a requirement of basic education reform as well as a requirement for children's growth in all aspects of body and mind. It is extremely important and valuable in encouraging the entire growth of preschool education as well as children's general harmonious development. The degree of informatization is changing day by day, and many information technology concepts and tools have entered the preschool education field. The Internet, electronic school bags, ECE whiteboards, terminal devices, and rich digital resources and tools have been introduced into kindergarten classrooms. The continuous advancement and application of information technology have provided the feasibility of building a smart learning environment for kindergartens. To this end, this paper starts from the core concepts and theoretical foundations of preschool education and sorts out the concepts of learning resources, smart learning, and smart learning environments. Learning theory, teaching theory, and activity theory provide the theoretical foundation for the creation of language learning tools in preschool education. The technologies of campus network, Internet of Things, artificial intelligence, and rich media are examined under the role and inspiration of smart learning environment to provide theoretical support for scientific design of smart language learning environment in preschool education.

Changes of Optical Coherence Tomography Biomarkers in Macular Edema Secondary to Retinal Vein Occlusion After Anti-VEGF and Anti-Inflammatory Therapies.

Purpose: This study aimed to assess the short-term changes of macular microstructures following anti-VEGF and anti-inflammatory therapies in patients with macular edema secondary to retinal vein occlusion (RVO-ME). Patients and Methods: In this retrospective study, 70 eyes of 70 patients with RVO-ME were divided into the anti-VEGF (Group A, 35 eyes) and anti-inflammatory (Group B, 35 eyes) treatment groups. All patients underwent best-corrected visual acuity (BCVA) assessment, intraocular pressure (IOP) assessment, slit lamp, fundus fluorescein angiography (FA), scanning laser ophthalmoscopy (SLO), and spectral-domain optical coherence tomography (SD-OCT). Group A received intravitreal injection of 0.05 mL anti-VEGF antibodies (Lucentis® or Aflibercept®) monthly for 3 consecutive months, while Group B received 0.7 mg dexamethasone (Ozurdex®) single intravitreal injection. BCVA and SD-OCT biomarkers were recorded at baseline and 3 months after the first injection. Changes of BCVA and SD-OCT biomarkers following these treatments were compared between the two groups. Results: BCVA and SD-OCT biomarkers, except choroidal thickness, in both groups were significantly improved after treatment (all P < 0.01). At 3 months, the height of serous retinal detachment (SRD) was markedly lower (P = 0.006), with significantly less hyperreflective dots (HRD, P = 0.037) in Group B compared with Group A. Other SD-OCT biomarkers and BCVA were not significantly different between the two groups (all P > 0.05). Conclusion: Anti-VEGF and anti-inflammatory therapies are both effective in RVO-ME, with improvement in BCVA and SD-OCT biomarkers. Anti-inflammatory therapy may be more effective than anti-VEGF therapy in SRD and HRD resolution.

A retrospective analysis on comparison of optical coherence tomography manifestations among AMD, CEC, PM and ICN and its relationship with vision.

Background: Both macular choroidal neovascularization (MCN) and visual changes can occur in age-related macular degeneration (AMD), central exudative chorioretinopathy (CEC), pathological myopia (PM) and idiopathic choroidal neovascularization (ICN), but whether the optical coherence tomography (OCT) manifestations of the four diseases are different and their relationships with vision are not clear. This study clarifies this problem and can guide clinicians to prevent vision changes of patients according to OCT performance. Methods: 76 patients with MCN, included 25 AMD, 21 CEC, 18 PM and 12 ICN [refer to Chinese Ophthalmology (3rd Edition)], detected by OCT instrument, were enrolled in this study from June 2020 to June 2022. The OCT manifestations and indexes were observed. A comprehensive refractometer was used for detection of best corrected visual acuity (BCVA) and axial length (AL). Pearson chi squared and 1 way analysis of variance were used for enumeration data and continuous data test, and Pearson correlation coefficient was used for relationship analysis. Results: (I) Macular edema proportions in the MCN eyes among AMD, CEC, PM and ICN groups were 96.00% and 94.12%, 14.29% and 14.29%, 44.44% and 32.00%, 33.33% and 28.57%, with statistical differences (both P<0.001). (II) Patients with macular edema had a significantly higher loose and thickened tissue reflex of the neuroepithelial layer (100.00% vs. 4.26%) and limited non-reflective dark area (100.00% vs. 4.26%) (both P<0.001). (III) PM had the lowest width, height and central fovea thickness (CFT) [(1,403.43±114.41), (210.74±21.22) and (250.70±41.36) µm], and the highest distance to the fovea, BCVA and AL [(234.44±288.69) µm, (0.30±0.08) Log minimal angle of resolution (MAR), (28.48±5.72) mm] (all P<0.001). (IV) The width and height of patients with macular edema were lower than those of patients without macular edema [(1,738.43±348.71) vs. (2,493.95±771.53) µm, P<0.001; (305.71±81.22) vs. (367.29±107.91) µm, P=0.002] (P<0.05). (V) The width and height, CFT were negatively correlated to BCVA (r=-0.635, -0.712, -0.724, all P<0.001), and height, CFT were negatively correlated to AL (r=-0.244, -0.275, P=0.018, 0.007). The distance to the fovea was positively correlated to BCVA and AL (r=0.241, P=0.019; r=0.267, P=0.007). Conclusions: Most of the OCT indexes were related to the BCVA and AL in MCN patients, and MCN patients with OCT changes should be reminded to protect their vision.

Long Non-coding RNA GAS5 Knockdown Attenuates H2O2-Induced Human Trabecular Meshwork Cell Apoptosis and Promotes Extracellular Matrix Deposition by Suppressing miR-29b-3p and Upregulating STAT3.

The long non-coding RNA GAS5 (GAS5) is reportedly implicated in glaucoma. However, its significance in human trabecular meshwork cells (HTMCs) remains largely unclear. Here, we investigated the effect of GAS5 on the function of HTMCs and its interaction with miR-29b-3p in HTMCs. We established an H2O2-induced oxidative injury model using HTMCs. RT-qPCR or western blotting was performed to examine the expression of the indicated genes. Luciferase reporter assay was used to determine the interaction between GAS5, miR-29b-3p, miR-29b-3p, and STAT3. CCK8 assay was used to assess the proliferative rate of HTMCs. Exposure to H2O2 increased the expression of Bax, cleaved caspase-3, and extracellular matrix (ECM) proteins, accompanied by reduced Bcl-2 expression. These H2O2-induced changes were effectively alleviated by GAS5 knockdown with sh-GAS5. MiR-29b-3p was directly regulated by GAS5. The effect of sh-GAS5 on ECM protein expression was also observed with the miR-29b-3p mimic. STAT3 was directly regulated by miR-29b-3p. MiR-29b-3p silencing alleviated STAT3 inhibition, followed by the restoration of cell vitality, Bax, Bcl-2, and cleaved caspase-3 expression, and ECM deposition. Our study is the first experimental investigation to shed light on a novel molecular mechanism of the GAS5/miR-29b-3p/STAT3 axis in an H2O2-induced oxidative injury model using HTMCs, which may offer a promising therapeutic approach against glaucoma.

Exosomal miR-4488 and miR-1273g-5p inhibit the epithelial-mesenchymal transition of transforming growth factor ß2-mediated retinal pigment epithelial cells by targeting ATP-binding cassette A4.

Exosomal microRNAs (miRNAs) have been shown to be involved in the regulation of many disease progression, including proliferative vitreoretinopathy (PVR). However, the roles of exosomal miR-4488 and miR-1273 g-5p in PVR progression have not been demonstrated. Transforming growth factor ß2 (TGF-ß2)-induced ARPE-19 cells were used to stimulate the epithelial-mesenchymal transition (EMT) of cells. Exosomes derived from TGF-ß2-induced ARPE-19 cells were identified by transmission electron microscopy and nanoparticle tracking analysis. The expression levels of miR-4488, miR-1273 g-5p and ATP-binding cassette A4 (ABCA4) were measured by quantitative real-time PCR. The promotion levels of exosomes markers, EMT markers, apoptosis markers and ABCA4 were determined by western blot analysis. The migration, invasion and apoptosis of cells were determined by transwell assay, wound healing assay and flow cytometry. Our data showed that miR-4488 and miR-1273 g-5p were lowly expressed in TGF-ß2-induced ARPE-19 cells. Overexpressed exosomal miR-4488 and miR-1273 g-5p could inhibit the EMT, migration, invasion, and promote apoptosis in TGF-ß2-induced ARPE-19 cells. In addition, ABCA4 was a target of miR-4488 and miR-1273 g-5p. Overexpressed ABCA4 also could reverse the negatively regulation of exosomal miR-4488 and miR-1273 g-5p on the EMT, migration, and invasion of TGF-ß2-induced ARPE-19 cells. In conclusion, our data showed that exosomal miR-4488 and miR-1273 g-5p could inhibit TGF-ß2-stimulated EMT in ARPE-19 cells through targeting ABCA4.