A Wolfram-like syndrome family: Case report.

BACKGROUND: Wolfram-like syndrome (WFLS) is an autosomal dominant inherited disease characterized by a single heterozygous pathogenic variant in the WFS1 gene. Its clinical presentation is similar to autosomal recessive Wolfram syndrome. CASE PRESENTATION: We reported a case of a 10-year-old boy and his family members who initially experienced hearing impairment (HI), followed by optic atrophy. Genetic testing revealed the presence of a WFS1 variant (chr4-6302385 exon8 NM_006005.3: c.2590G > A, p. Glu864Lys). CONCLUSION: Wolfram-like syndrome, a rare neurodegenerative genetic disorder, manifested as deafness, optic atrophy, and diabetes mellitus. There hasn't been a definite treatment yet. Early identification of the variant in the WFS1 gene is beneficial for genetic counseling.

Global research hotspots and trends on robotic surgery in obstetrics and gynecology: a bibliometric analysis based on VOSviewer.

Objective: Over the last two decades, the quantity of papers published in relation to robotic surgery in obstetrics and gynecology has continued to grow globally. However, no bibliometric analysis based on VOSviewer has been performed to evaluate the past and present of global research in the field. In this study, we aimed to analyze the bibliometric characteristics of papers on robotic surgery in obstetrics and gynecology to reveal research hotspots and trends in this field. Methods: The Web of Science Core Collection was searched for scientific papers on robotic surgery in obstetrics and gynecology published between January 1, 1998 and December 31, 2023. Bibliometric metadata of each selected paper was extracted for analysis. The results were visualized by VOSviewer (version 1.6.18). Results: A total of 1,430 papers met the inclusion criteria. The United States had the highest total link strengths and contributed the most papers (n = 793). The Mayo Clinic produced the largest number of papers (n = 85), and Professor Pedro T Ramirez contributed the most papers (n = 36). The number of citations ranged from 0 to 295 with a total sum of 29,103. The Journal of Minimally Invasive Gynecology published the most relevant papers (n = 252). Keywords were classified into six clusters based on co-occurrence data, of which cluster 1, cluster 4 and cluster 6 had more main keywords with the largest average publication year. Conclusions: This is the first VOSviewer-based bibliometric analysis of robotic surgery research in obstetrics and gynecology. The United States was the leading country, and the Journal of Minimally Invasive Gynecology was the most productive journal in the field. Scientists and institutions from around the world should push their boundaries to bring about deep collaboration. The main research topic has always been the use of robotic surgery in the treatment of gynecologic malignancies. More randomized controlled trials need to be conducted to compare surgical outcomes of robotic surgery with other surgical approaches. Robotic sacrocolpopexy for pelvic organ prolapse has become a new research hotspot, and robotic surgery for sentinel lymph node detection in gynecologic malignancies are more potential directions for future research.

Role of microRNA-4739 in enhancing cisplatin chemosensitivity by negative regulation of RHBDD2 in human cervical cancer cells.

BACKGROUND: Cisplatin (DDP) is a widely used chemotherapy drug for advanced cervical cancer (CC), but resistance poses a significant challenge. While miR-4739 has been implicated in tumor development, its specific role in regulating DDP resistance in CC remains unclear. METHODS: We analyzed the expression levels of miR-4739 and RHBDD2 in DDP-resistant and DDP-sensitive CC tissues using quantitative real-time polymerase chain reaction (PCR) and assessed their correlation through Spearman's correlation analysis. DDP-resistant CC cell lines (HeLa/DDP and SiHa/DDP) were established by gradually increasing DDP concentrations, followed by transfection with miR-4739 mimics, si-RHBDD2, or a RHBDD2 overexpression vector. A series of functional assays, including CCK-8 assay, colony formation, flow cytometry, and transwell assay were performed. The interaction between miR-4739 and RHBDD2 was confirmed by luciferase reporter assay. We examined the protein levels of RHBDD2, P-gP, MRP1, cleaved caspase-3, and E-cadherin through western blot analysis. Moreover, we generated xenograft tumors by injecting stably transfected HeLa/DDP cells into mice to compare their tumorigenesis capacity. RESULTS: We observed downregulation of miR-4739 and upregulation of RHBDD2 in DDP-resistant CC tissues and cell lines. MiR-4739 was shown to directly bind to RHBDD2 gene sequences to repress RHBDD2 expression in HeLa/DDP and SiHa/DDP cells. Our in vitro and in vivo experiments demonstrated that overexpressing miR-4739 overcame DDP resistance in CC cells by targeting RHBDD2. Furthermore, RHBDD2 overexpression reversed the effects of miR-4739 mimics on drug-resistance-related proteins (P-gP and MRP1) and the expression of cleaved caspase-3 and E-cadherin in HeLa/DDP cells. CONCLUSIONS: In summary, our study revealed that miR-4739 can reverse DDP resistance by modulating RHBDD2 in CC cells.

Identification of potential inhibitors against Staphylococcus aureus shikimate dehydrogenase through virtual screening and susceptibility test.

Staphylococcus aureus shikimate dehydrogenase (SaSDH) plays a crucial role in the growth of Staphylococcus aureus (S. aureus), but absent in mammals and therefore a potential target for antibacterial drugs to treat drug-resistant S. aureus infection. In this study, a 3D model of SaSDH was constructed by homology modelling and inhibitors of SaSDH were screened through virtual screening. (-)-Gallocatechin gallate and rhodiosin were identified as inhibitors with Kis of 2.47 µM and 73.38 µM, respectively. Molecular docking and isothermal titration calorimetry showed that both inhibitors interact with SaSDH with a KD of 44.65 µM for (-)-gallocatechin gallate and 16.45 µM for rhodiosin. Both inhibitors had antibacterial activity, showing MICs of 50 µg/mL for (-)-gallocatechin gallate and 250 µg/mL for rhodiosin against S. aureus. The current findings have the potential for identification of drugs to treat S. aureus infections by targeting SaSDH.

Acute Macular Neuroretinopathy after SARS-CoV-2 Infection: An Analysis of Clinical and Multimodal Imaging Characteristics.

BACKGROUND: This study aimed to analyze clinical and multimodal imaging characteristics of acute macular neuroretinopathy (AMN) post-recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Retrospective observational study. Medical records and multimodal imaging of 12 AMN eyes of eight patients (six female and two male) with recent SARS-CoV-2 infection were retrospectively analyzed. RESULTS: Four patients (50%) presented with bilateral AMN. Fundus ophthalmoscopy revealed a reddish-brown lesion around the macula, and two eyes had cotton-wool spots at the posterior pole. Three eyes showed mild hypo-autofluorescence. All FFA images (7 eyes) showed no abnormal signs. On OCT scans, all eyes showed outer nuclear layer (ONL) thinning, 8 eyes (66.7%) showed ONL hyperreflectivity, 5 eyes (41.7%) showed outer plexiform layer (OPL) hyperreflectivity, 8 eyes (66.7%) showed interdigitation zone (IZ) disruption, 11 eyes (91.6%) showed ellipsoid zone (EZ) disruption, 2 eyes (16.7%) showed cotton-wool spots and inner plexiform layer (IPL) hyperreflectivity, 1 eye (8.3%) had intraretinal cyst and 1 eye (8.3%) had inner nuclear layer (INL) thinning. Persistent scotoma, ONL hyperreflectivity and IZ/EZ disruption as well as recovery of OPL hyperreflectivity were reported after follow-up in three cases. CONCLUSIONS: AMN post-SARS-CoV-2 mostly affected young females and could present unilaterally or bilaterally. Dark lesions on IR reflectance and outer retinal hyperreflectivity on OCT are useful in diagnosing AMN. OPL/ONL hyperreflectivity on OCT could disappear after follow-up, but ONL thinning and IZ/EZ could persist.

Intraoperative slow-release dexamethasone intravitreal implant (Ozurdex) in epiretinal membrane peeling surgery: a prospective randomized controlled trial.

Purpose: This study aimed to determine the efficacy of the dexamethasone (DEX) intravitreal implant for the regression of macular edema and the improvement of best-corrected visual acuity (BCVA) after the removal of idiopathic epiretinal membrane (ERM). Methods: This prospective randomized controlled trial recruited 81 patients with idiopathic ERM. These patients all underwent 25-gauge pars plana vitrectomy combined with ERM and internal limiting membrane peeling surgery. Among them, 41 eyes in the DEX group received additional DEX implants and 40 in the non-DEX group did not. Outcomes including central retinal thickness (CRT), BCVA, and intraocular pressure were measured 1 and 3 months after surgery. Results: The DEX group had thinner CRTs compared to the non-DEX group at 1 month postoperatively (p <0.05), but did not differ significantly at the 1-week and 3-month follow-up visits (p = 0.109 and p = 0.417, respectively). There were no statistical differences with respect to BCVA (p = 0.499, 0.309, 0.246, and 0.517, respectively) and intraocular pressure (p = 0.556, 0.639, 0.741, and 0.517, respectively) between the two groups at each point of follow-up visits. Conclusion: DEX accelerated the reduction of CRT at 1 month after surgery. However, no evidence of further anatomical (CRT) or functional (BCVA) benefits using DEX was observed at 3 months. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT05416827.

Vitrectomy with sulfur hexafluoride versus air tamponade for idiopathic macular hole: a retrospective study.

BACKGROUND: To evaluate the effect of room air and sulfur hexafluoride (SF6) gas in idiopathic macular hole(MH)surgery. METHODS: Retrospective, interventional, and comparative study. 238 eyes with the idiopathic macular hole that underwent pars plana vitrectomy, internal limiting membrane peeling, fluid-air exchange, and 20% SF6 (SF6 group:125 eyes) or room air tamponade (air group: 113 eyes) were reviewed. The primary outcome measure was the closure rate of primary surgery. RESULTS: The baseline characteristics of the SF6 group and air group were comparable except for the hole size (479.90 ± 204.48 vs. 429.38 ± 174.63 µm, P = 0.043). The anatomical closure rate was 92.8% (116 / 125) with the SF6 group and 76.1% (86 / 113) with the air group (P < 0.001). A cut-off value of MH size to predict primary anatomical closure was 520 µm, which is based on the lower limit of 95% confidential interval of the MH size among the unclosed patients in the air group. There was no significant difference in anatomical closure rates between SF6 and air group (98.7% vs. 91.9%, P = 0.051) for MH ≤ 520 µm, whereas a significantly lower anatomical closure rate was shown in the air group than SF6 group (46.2% vs. 84.0%, P < 0.001) for MH > 520 µm. CONCLUSION: SF6 exhibited more effectiveness than air to achieve a good anatomical outcome for its longer tamponade when MH > 520 µm.

Optical coherence tomography angiography-guided vs indocyanine green angiography-guided half-dose photodynamic therapy for acute central serous chorioretinopathy: 6-month randomized trial results.

PURPOSE: This study aimed to compare the anatomic and functional results of optical coherence tomography angiography (OCTA)-guided half-dose photodynamic therapy (PDT) versus indocyanine green angiography (ICGA)-guided PDT in eyes with acute central serous chorioretinopathy (CSC). METHODS: One hundred and thirty-one eyes of 131 patients with acute central serous chorioretinopathy (CSC) were recruited, and randomly assigned to the OCTA-guided group and ICGA-guided group. The primary outcome measures were the rates of complete subretinal fluid (SRF) resolution at 1 month, 3 months, and 6 months. The secondary outcomes included best-corrected visual acuity (BCVA), central retinal thickness (CRT), choroidal capillary flow deficit density at each scheduled visit, and recurrence rate of SRF at 3 months and 6 months. RESULTS: There were 110 eyes that finished the follow-up, with 56 eyes in the OCTA-guided group and 54 eyes in the ICGA guided group. OCTA-guided PDT was demonstrated to be noninferior to ICGA-guided PDT for SRF resolution rate at 1 months and 6 months (P = 0.021 and P = 0.037), but not at 3 months for acute CSC (P = 0.247). The average CRT of the ICGA-guided group was significantly lower than that of the OCTA-guided group at 3-month visit (P = 0.046), but no significant difference was found between them at the 1-month and 6-month visits (P = 0.891 and 0.527). There was no significant difference between the two groups for BCVA (P = 0.359, 0.700, and 0.143, respectively) and the deficit area on CC (P = 0.537, 0.744,and 0.604, respectively) at 1, 3, and 6 months. CONCLUSION: OCTA may replace ICGA to guide PDT for the treatment of acute CSC and their follow-up.

Elevated number and density of macrophage-like cell as a novel inflammation biomarker in diabetic macular edema.

To quantitatively analyze the number and density of macrophage-like cells (MLCs) at the vitreoretinal interface at macular region in diabetic retinopathy (DR) with and without diabetic macular edema (DME). This cross-sectional study involved 240 eyes of 146 treatment-naïve DR patients, including 151 eyes with DME. The number and density of MLCs were analyzed quantitatively using optical coherence tomography angiography (OCTA) and were compared between DME and non-DME eyes as well as proliferative DR (PDR) and non-PDR (NPDR) eyes. Correlation between MLCs density and vessel density of macular superficial capillary plexus (SCP) at macular region was evaluated. The number and density of macular MLCs were both elevated in DME group compared to non-DME group (all p < 0.001). The morphology of MLCs in DME eyes appeared larger and fuller. NPDR eyes had higher number and density of MLCs (p = 0.027 and 0.026), greater central macular thickness (CMT) (p = 0.002) and vessel density than PDR eyes in non-DME group but comparable to PDR eyes in DME group. The number and density of MLCs at macular region were significantly higher with larger and fuller morphology in DR patients with DME than those without DME. PDR eyes had fewer MLCs than NPDR eyes for DR eyes without DME.

Troponin T1 Promotes the Proliferation of Ovarian Cancer by Regulating Cell Cycle and Apoptosis.

Background: Troponin T1 (TNNT1) is implicated in human carcinogenesis. However, the role of TNNT1 in ovarian cancer (OC) remains unclear. Objectives: To investigate the effect of TNNT1 on the progression of ovarian cancer. Materials and Methods: The level of TNNT1 was evaluated in OC patients based on The Cancer Genome Atlas (TCGA). Knockdown or overexpression of TNNT1 using siRNA targeting TNNT1 or plasmid carrying TNNT1 was performed in the ovarian cancer SKOV3 cell, respectively. RT-qPCR was performed to detect mRNA expression. Western blotting was used to examine protein expression. Cell Counting Kit-8, colony formation, cell cycle, and transwell assays were performed to analyze the role of TNNT1 on the proliferation and migration of ovarian cancer. Besides, xenograft model was carried out to evaluate the in vivo effect of TNNT1 on OC progression. Results: Based on available bioinformatics data in TCGA, we found that TNNT1 was overexpressed in ovarian cancer samples comparing to normal samples. Knocking down TNNT1 repressed the migration as well as the proliferation of SKOV3 cells, while overexpression of TNNT1 exhibited opposite effect. In addition, down-regulation of TNNT1 hampered the xenografted tumor growth of SKOV3 cells. Up-regulation of TNNT1 in SKOV3 cells induced the expression of Cyclin E1 and Cyclin D1, promoted cell cycle progression, and also suppressed the activity of Cas-3/Cas-7. Conclusions: In conclusion, TNNT1 overexpression promotes SKOV3 cell growth and tumorigenesis by inhibiting cell apoptosis and accelerating cell-cycle progression. TNNT1 might be a potent biomarker for the treatment of ovarian cancer.

DeepFundus: A flow-cytometry-like image quality classifier for boosting the whole life cycle of medical artificial intelligence.

Medical artificial intelligence (AI) has been moving from the research phase to clinical implementation. However, most AI-based models are mainly built using high-quality images preprocessed in the laboratory, which is not representative of real-world settings. This dataset bias proves a major driver of AI system dysfunction. Inspired by the design of flow cytometry, DeepFundus, a deep-learning-based fundus image classifier, is developed to provide automated and multidimensional image sorting to address this data quality gap. DeepFundus achieves areas under the receiver operating characteristic curves (AUCs) over 0.9 in image classification concerning overall quality, clinical quality factors, and structural quality analysis on both the internal test and national validation datasets. Additionally, DeepFundus can be integrated into both model development and clinical application of AI diagnostics to significantly enhance model performance for detecting multiple retinopathies. DeepFundus can be used to construct a data-driven paradigm for improving the entire life cycle of medical AI practice.

Semaphorin 3A Inhibits Endoplasmic Reticulum Stress Induced by High Glucose in Müller Cells.

PURPOSE: This study aimed to explore the effect of the Semaphorin3A (Sema3A)/Neuropilin-1 (Nrp-1) pathway on Müller cell activities and endoplasmic reticulum (ER) stress induced by high glucose (HG) in vitro. METHODS: The primary Müller cells of C57BL/6J mice were isolated and cultured in normal or high glucose medium. The expression of endogenous Sema3A and its coreceptor Nrp-1 was measured by Western blot. Müller cells were incubated with exogenous recombinant Sema3A protein or transfected with lentiviral vectors expressing small hairpin RNA (shRNA) to knock down the expression of endogenous Sema3A. The proliferation of Müller cells was detected by CCK-8 assay and EdU staining. The migratory ability was detected by the Transwell migration assay. The level of endoplasmic reticulum (ER) stress was analyzed through the detection of GRP78/BiP, IRE1α, phosphorylated IRE1αS724 (p-IRE1αS724), and the splicing rate of XBP1 (XBP1s/XBP1) by using immunofluorescence, Western blot or quantitative polymerase chain reaction (qPCR). RESULTS: HG induced the upregulation of endogenous Sema3A and Nrp-1 receptors in Müller cells. The expression of GRP78/BiP and IRE1α was upregulated by HG, with an increased splicing rate of XBP1. Exogenous Sema3A inhibited HG-induced Müller cell proliferation, migration, and GRP78/BiP-IRE1α-XBP1 axis activation. Knockdown of Sema3A promoted proliferation, migration, and ER stress induced by high glucose in Müller cells. CONCLUSION: Sema3A inhibited the increased proliferative and migratory activities induced by high glucose by attenuating ER stress in Müller cells.

The comparison of two different strategies of intravitreal conbercept for polypoidal choroidal vasculopathy in Chinese patients results from a 48-week randomized phase 4 study: STAR study.

PURPOSE: To compare a treat-and-extend (TAE) strategy with a fixed dosing regimen of intravitreal conbercept (IVC) for the management of treatment-naïve polypoidal choroidal vasculopathy (PCV) patients. METHODS: 249 patients with treatment-naïve PCV were randomized 1:1 to fixed dosing regimen with injections every 12 weeks (3 + Q12W) group or treat-and-extend regimen(3 + TAE) group. Patients received 3 monthly intravitreal injections of 0.5 mg conbercept as loading dose in both groups. The 3 + Q12W patients were monitored monthly and received mandated injections every 12 weeks; the 3 + TAE patients were monitored and treated monthly until the resolution of exudative disease activity; the interval between visits was then individualized according to study protocol. Visual and anatomical outcomes were compared between the two groups. RESULTS: At 48 weeks, there was no significant difference between the 3 + Q12W group and 3 + TAE group in mean BCVA improvement (p = 0.421), mean changes in central retinal thickness (CRT) (p = 0.818), maximum retinal thickness (MRT) (p = 0.448), pigment epithelial detachment (PED) height (p = 0.221), PED volume (p = 0.076), branching vascular network (BVN) area (p = 0.615), polypoidal lesion number (p = 0.701), polypoidal lesion area (p = 0.424), rates of patients who avoided vision loss of ≥15 ETDRS letters (p = 0.397) or complete polypoidal lesion regression rate (43.8% vs. 41.8%, p = 0.814). The 3 + Q12W group had more decreased retinal haemorrhage area (p = 0.014) and fewer mean numbers of injections comparing with 3 + TAE group (6.6 vs. 9.4, p < 0.001). Mean maximum extension interval between injections after loading injections was 9.6 ± 2.0 weeks for 3 + TAE group, with 27.8% of patients achieving an extension interval of 12 weeks and 61.1% patients 8 weeks or more. CONCLUSIONS: Both 3 + Q12W and 3 + TAE regimens of IVC could result in improvement in visual and anatomical outcomes in PCV patients.

Comparison of efficacy and safety of intravitreal ranibizumab and conbercept before vitrectomy in Chinese proliferative diabetic retinopathy patients: a prospective randomized controlled trial.

BACKGROUND: To compare the efficacy and safety of preoperative intravitreal injections of ranibizumab and conbercept in Chinese proliferative diabetic retinopathy (PDR) patients. METHODS: This prospective randomized controlled trial enrolled 90 eyes of 80 patients with PDR. Forty-four eyes of 40 patients that received intravitreal ranibizumab (IVR) injections (0.5 mg/0.05 mL) before vitreous surgeries were assigned to the IVR group. Forty-six eyes of 40 patients that received intravitreal conbercept (IVC) injections (0.5 mg/0.05 mL) before vitreous surgeries were assigned to the IVC group. Intraoperative and postoperative indices were assessed for further comparison between the two groups. RESULTS: There were no statistically significant differences in all surgery indices, including intraoperative indices (surgery time, P = 0.225; intraoperative bleeding, P = 0.808; endodiathermy use, P = 0.693; incidence of iatrogenic retinal breaks, P = 0.740; relaxing retinotomy, P = 0.682; retinal reattachment, P = 0.682 and silicone oil tamponade, P = 0.814) and postoperative indices (postoperative vitreous hemorrhage (VH), P = 0.808; neovascular glaucoma (NVG), P = 0.964; recurrent retinal detachment, P = 0.531; postoperative fibrovascular proliferation progression, P = 0.682 and reoperation, P = 0.955) between the two groups. There were no statistically significant differences in best-corrected visual acuity (BCVA) at each follow-up visit (P = 0.939, 0.669, 0.741 and 0.717, respectively) or in central retinal thickness (CRT) (P = 0.976, 0.699, 0.551 and 0.686, respectively). As for safety profile, both groups had no ocular or system adverse events during the observation period. CONCLUSIONS: IVR and IVC as a pretreatment of vitrectomy had similar efficacy and safety profile for Chinese PDR patients. TRIAL REGISTRATION: Registered at ClinicalTrials.gov ( NCT05414149 ).

Correlation of photoreceptor damage with anti-retina antibodies level in aqueous humor in macular edema patients.

This study aimed to investigate the correlation between the severity of photoreceptor damage and the level of anti-retina antibodies (ARAs) in aqueous humor, including recoverin, CA II and enolase-α IgG antibody of macular edema patients. Aqueous humor samples were collected from macular edema patients and from cataract patients. Patients were divided into three groups according to the severity of discontinuity of ellipsoid zone (EZ) shown on optical coherence tomography (OCT) imaging: cataract patients with intact EZ, macular edema patients with mild EZ damage, and macular edema patients with severe EZ damage. The level of ARAs was determined with enzyme-linked immunosorbent assay (ELISA). The correlation between the level of ARAs and the degree of photoreceptor damage was analyzed. The level of ARAs of the intact EZ group was significantly lower than that in the severely damaged group (P < 0.05). The level of recoverin IgG of the intact EZ group was significantly lower than mildly damaged group (P = 0.030). In a subgroup analysis, the level of recoverin IgG of DME patients was correlated with their central retinal thickness (CRT) (r = 0.462, P = 0.035). The level of ARAs in aqueous humor of patients with DME and RVO-ME was correlated with the degree of photoreceptor damage.

Comparison of 24×20 mm2 swept-source OCTA and fluorescein angiography for the evaluation of lesions in diabetic retinopathy.

AIM: To compare ultra-widefield (24×20 mm2) swept-source optical coherence tomography angiography (SS-OCTA) and fluorescein angiography (FA) in the evaluation of diabetic retinopathy (DR) lesions. METHODS: Forty-six eyes of 23 patients with treatment-naïve DR were included at Peking University People's Hospital from September 1, 2021, until December 31, 2021, as well as 23 age and gender matched healthy controls. Quantitative assessments of DR lesions on FA and SS-OCTA (superficial capillary plexus, SCP, 24×20 mm2) were performed. RESULTS: Area of fovea avascular zone (FAZ) was larger in DR cases than controls (0.34±0.069 mm2 vs 0.287±0.108 mm2, P=0.006). In DR eyes, the mean FAZ area was 0.34±0.069 and 0.334±0.087 mm2 on SS-OCTA and FA, respectively (P=0.428), while the median FAZ perimeter was 2.382 (IQR, 2.201-2.59) and 2.333 (IQR, 2.138-2.6) mm on SS-OCTA and FA images (P=0.733). There was no significant difference in the size of the non-perfusion area (NPA) between the images on SS-OCTA and FA (12.389, IQR 4.96-28.3 and 11.125, IQR 5-28.31 mm2, P=0.197). The median total microaneurysm (MA) count was 35 (IQR, 19-46) and 73 (IQR, 43-93) on SS-OCTA and FA (P<0.001), respectively. No significant difference in intra-retinal microvascular abnormality (IRMA) and neovascularization (NV) count was found between the two techniques. The intraclass coefficient (ICCs) of all the parameters above indicated stable repeatability. CONCLUSION: Ultra-widefield SS-OCTA represents a reliable, noninvasive, and quantitative imaging technique in the assessment of microvasculature in DR, which offers a potential substitute for FA in DR evaluation.

Metabolomic comparison followed by cross-validation of enzyme-linked immunosorbent assay to reveal potential biomarkers of diabetic retinopathy in Chinese with type 2 diabetes.

Purpose: To identify the biomarkers in the critical period of development in diabetic retinopathy (DR) in Chinese with type 2 diabetes using targeted and untargeted metabolomics, and to explore the feasibility of their clinical application. Methods: This case-control study described the differential metabolites between 83 Chinese type 2 diabetes mellitus (T2DM) samples with disease duration ≥ 10 years and 27 controls matched cases. Targeted metabolomics using high-resolution mass spectrometry with liquid chromatography was performed on plasma samples of subjects. The results were compared to our previous untargeted metabolomics study and ELISA was performed to validate the mutual differential metabolites of targeted and untargeted metabolomics on plasma. Multiple linear regression analyses were performed to adjust for the significance of different metabolites between groups. Result: Mean age of the subjects was 66.3 years and mean T2DM duration was 16.5 years. By cross-validating with results from previous untargeted metabolomic assays, we found that L-Citrulline (Cit), indoleacetic acid (IAA), 1-methylhistidine (1-MH), phosphatidylcholines (PCs), hexanoylcarnitine, chenodeoxycholic acid (CDCA) and eicosapentaenoic acid (EPA) were the most distinctive metabolites biomarkers to distinguish the severity of DR for two different metabolomic approaches in our study. We mainly found that samples in the DR stage showed lower serum level of Cit and higher serum level of IAA compared with samples in the T2DM stage, while during the progression of diabetic retinopathy, the serum levels of CDCA and EPA in PDR stage were significantly lower than NPDR stage. Among them, 4 differential key metabolites including Cit, IAA, CDCA and EPA were confirmed with ELISA. Conclusion: This is the first study to compare the results of targeted and untargeted metabolomics via liquid chromatography-mass spectrometry to find the serum biomarkers which could reflect the metabolic variations among different stages of DR in Chinese. The progression of DR in Chinese at different critical stages was related to the serum levels of specific differential metabolites, of which there is a significant correlation between DR progression and increased IAA and decreased Cit, hexanoylcarnitine, CDCA, and EPA. However, larger studies are needed to confirm our results. Based on this study, it could be inferred that the accuracy of targeted metabolomics for metabolite expression in serum is to some extent higher than that of untargeted metabolomics.

Comparison of swept-source OCTA and indocyanine green angiography in central serous chorioretinopathy.

BACKGROUND: To compare swept-source optical coherence tomography angiography (SS-OCTA) and indocyanine green angiography (ICGA) in patients with central serous chorioretinopathy (CSC). METHODS: SS-OCTA and ICGA images of 39 eyes with symptomatic CSC were collected and aligned. Spatial overlap of the annotations of the coarse granulated high reflective area on choriocapillary OCTA and the hyperfluorescence area on mid-phase ICGA was calculated according to the Jaccard index (JI). SS-OCTA findings of fellow eyes and changes in SS-OCTA abnormalities during the follow-up were also analyzed. RESULTS: Three main types of abnormalities in choriocapillaris SS-OCTA images were found: type A, coarse granulated high reflective area (39 eyes [100%]); type B, roundish dark halo around Type A (32 eyes [82.1%]); and type C, coarse granulated low reflective area (39 eyes [100%]). The mean JI of type A on SS-OCTA and the hyperfluorescence area on ICGA were 0.55 ± 0.15 for grader 1 and 0.49 ± 0.15 for grader 2. The mean area of type A abnormalities on SS-OCTA and hyperfluorescence on ICGA was 3.976 (IQR, 2.139-8.168) and 3.043 (IQR, 1.408-4.909) mm2 (P = 0.199). The areas of type A, B and C abnormalities on SS-OCTA after laser treatment or observation were 3.36mm2 (IQR, 2.399-9.312), 2.9mm2 (IQR, 2.15-3.7), and 0.19mm2 (IQR, 0.08-0.23), respectively, which was smaller than those in the baseline (7.311mm2 (IQR 3.788-11.209), P < 0.001; 4.3mm2 (IQR, 2.8-9.8), P = 0.002;0.33mm2 (IQR, 0.23-0.38), P < 0.001). The change in the type A, B or C area was not significantly different between the two groups (P = 0.679, 0.732, and 0.892). CONCLUSION: The coarse granulated high reflective area in SS-OCTA corresponded well with the hyperpermeability area in ICGA. SS-OCTA promotes noninvasive visualization and follow-up quantifications of the choroidal vasculature in CSC patients.

Diurnal changes of retinal microvascular circulation and RNFL thickness measured by optical coherence tomography angiography in patients with obstructive sleep apnea-hypopnea.

Purpose: To evaluate capillaries perfusion and retinal nerve fiber layer (RNFL) thickness diurnal changes of macular/optic disc regions among participants with or without obstructive sleep apnea-hypopnea (OSA) using spectral-domain optical coherence tomography angiography (OCTA). Methods: In this study, we enrolled a cohort of 35 participants including 14 patients with mild-to-moderate OSA, 12 patients with severe OSA, and 9 healthy individuals. All participants had Berlin questionnaire filled. At 20:00 and 6:30, right before and after the polysomnography examination, a comprehensive ocular examination was conducted. The systemic and ocular clinical characteristics were collected, and OCTA scans were performed repeatedly. Blood flow and RNFL thickness parameters were then exported using built-in software and analyzed accordingly. Results: After sleep, the overall vessel density (VD) variables, especially macular and choriocapillaris VDs, were relatively comparative and stable. One exception was the RPC vessel density at the inside-disc region with a decreasing trend in the mild-to-moderate group (p=0.023). RNFL changes before and after sleep in the nasal-inferior and peripapillary region were statistically significant (p=0.003; p=0.043) among three groups. And multiple testing correction verified the significant difference in diurnal changes between the mild-to-moderate group and the control group in pairwise comparisons (p=0.006; p=0.02). Conclusions: The changes of imperceptible blood flow and RNFL thickness overnight around optic disc areas could be observed in OSA patients. Despite physiological fluctuations, aberrant diurnal changes might be useful for identifying a decrease in micro-environmental stability associated with the development of various ocular diseases such as glaucoma. Other VD variables, especially macular and choriocapillaris VDs, are relatively stable in eyes of patients having OSA with different severity.

Apogossypolone Inhibits Cell Proliferation and Epithelial-Mesenchymal Transition in Cervical Cancer via Activating DKK3.

Apogossypolone (ApoG2), a novel derivative of gossypol lacking of two aldehyde groups, exhibits anti-tumor effects. However, the mechanisms by which ApoG2 regulates cervical cancer (CC) cells remain unclear. In this study, we treated two CC cell lines (CaSki and HeLa) with an increasing concentration of ApoG2 for 24 h. Cell Counting Kit-8 (CCK-8) assay, colony formation assay, flow cytometry and transwell invasion assay were utilized to detect cell proliferation, apoptosis and invasion in vitro. We first observed that ApoG2 inhibited cell proliferation, invasion and epithelial-to-mesenchymal transition (EMT) process in CC cells, along with upregulation of Dickkopf Wnt signaling pathway inhibitor 3 (DKK3) in a dose-dependent manner. The immunohistochemistry confirmed the downregulation of DKK3 in tumor tissues. Moreover, DKK3 was correlated with FIGO stage and lymph node metastasis. Functionally, DKK3 overexpression significantly suppressed cell viability, colony formation and invasion, but promoted apoptosis in CaSki and HeLa cells. Overexpression of DKK3 upregulated the protein levels of cleaved caspase-3 and E-cadherin, but downregulated the protein levels of Bcl-2, N-cadherin and Vimentin. Furthermore, DKK3 knockdown reversed the suppressive effects of ApoG2 on CaSki cell proliferation, invasion and EMT markers, while DKK3 overexpression enhanced these effects. In addition, ApoG2 treatment inhibited CC xenograft tumor growth and upregulated the protein levels of DKK3, cleaved caspase-3 and E-cadherin. In conclusions, these findings suggested that ApoG2 could effectively inhibit the growth and invasion of CC cells at least partly by activating DKK3.