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Abstract Purpose Prostate cancer (PCa) is a common malignancy in men, with an escalating mortality rate attributed to Recurrence and metastasis. Recent studies have illuminated collagen’s critical regulatory role within the tumor microenvironment, significantly influencing tumor progression. Accordingly, this investigation is dedicated to examining the relationship between genes linked to collagen and the prognosis of PCa, with the objective of uncovering any possible associations between them. Methods Gene expression data for individuals with prostate cancer were obtained from the TCGA repository. Collagen-related genes were identified, leading to the development of a risk score model associated with biochemical recurrence-free survival (BRFS). A prognostic nomogram integrating the risk score with essential clinical factors was crafted and evaluated for efficacy. The influence of key collagen-related genes on cellular behavior was confirmed through various assays, including CCK8, invasion, migration, cell cloning, and wound healing. Immunohistochemical detection was used to evaluate PLOD3 expression in prostate cancer tissue samples. Results Our study identified four key collagen-associated genes (PLOD3, COL1A1, MMP11, FMOD) as significant. Survival analysis revealed that low-risk groups, based on the risk scoring model, had significantly improved prognoses. The risk score was strongly associated with prostate cancer prognosis. Researchers then created a nomogram, which demonstrated robust predictive efficacy and substantial clinical applicability.Remarkably, the suppression of PLOD3 expression notably impeded the proliferation, invasion, migration, and colony formation capabilities of PCa cells. Conclusion The risk score, derived from four collagen-associated genes, could potentially act as a precise prognostic indicator for BRFS of patients. Simultaneously, our research has identified potential therapeutic targets related to collagen. Notably, PLOD3 was differentially expressed in cancer and para-cancer tissues in clinical specimens and it also was validated through in vitro studies and shown to suppress PCa tumorigenesis following its silencing.

Retinal ischemia is a common clinical event leading to retinal ganglion cell (RGC) death, resulting in irreversible vision loss. In the retina, glia-neuron communication is crucial for multiple functions and homeostasis. Extracellular vesicles, notably exosomes, play a critical role. The functions and mechanisms of retinal astrocyte-secreted exosomes remain unclear. Here, we isolated astrocyte-derived exosomes under hypoxia or normoxia and explored their role in an in vivo retinal ischemia-reperfusion (RIR) model. We found that hypoxia triggered astrocytes to produce a significantly increased number of exosomes, which could be internalized by RGCs in vivo or in vitro. Also, in the RIR model, the hypoxia-induced exosomes ameliorated the RIR injury and suppressed the RGC apoptosis. Furthermore, microRNA sequencing of retinal astrocyte-secreted exosomes revealed different patterns of exosomal miRNAs under hypoxia, particularly enriched with miR-329-5p. We verified that miR-329-5p was specifically bound to mitogen-activated protein kinase 8 mRNA, and subsequent JNK-pathway molecules were downregulated. We anticipated that the miR-329-5p/JNK pathway is a key to suppressing RGC apoptosis and preventing RIR injury. Such findings provided insights into the therapeutic potential of hypoxia-induced astrocyte-secreted exosomes and the miR-329-5p for treating retina ischemic diseases.

Abstract Purpose Prostate cancer (PCa) is one of the major tumor diseases that threaten men’s health globally, and biochemical recurrence significantly impacts its prognosis. Disulfidptosis, a recently discovered cell death mechanism triggered by intracellular disulfide accumulation leading to membrane rupture, is a new area of research in the context of PCa. Currently, its impact on PCa remains largely unexplored. This study aims to investigate the correlation between long non-coding RNAs (lncRNAs) associated with disulfidptosis and the prognosis of PCa, seeking potential connections between the two. Methods Transcriptomic data for a PCa cohort were obtained from the Cancer Genome Atlas database. Disulfidptosis-related lncRNAs (DDRLs) were identified through differential expression and Pearson correlation analysis. DDRLs associated with biochemical recurrence-free survival (BRFS) were precisely identified using univariate Cox and LASSO regression, resulting in the development of a risk score model. Clinical factors linked to BRFS were determined through both univariate and multivariate Cox analyses. A prognostic nomogram combined the risk score with key clinical variables. Model performance was assessed using Receiver Operating Characteristic (ROC) curves, Decision Curve Analysis (DCA), and calibration curves. The functional impact of a critical DDRL was substantiated through assays involving CCK8, invasion, migration, and cell cloning. Additionally, immunohistochemical (IHC) staining for the disulfidptosis-related protein SLC7A11 was conducted. Results The prognostic signature included AC026401.3, SNHG4, SNHG25, and U73166.1 as key components. The derived risk score from these signatures stood as one of the independent prognostic factor for PCa patients, correlating with poorer BRFS in the high-risk group. By combining the risk score with clinical variables, a practical nomogram was created, accurately predicting BRFS of PCa patients. Notably, silencing AC026401.3 significantly hindered PCa cell proliferation, invasion, migration, and colony formation. IHC staining revealed elevated expression of the dithiosulfatide-related protein SLC7A11 in tumor tissue. Conclusions A novel prognostic signature for PCa DDRLs, possessing commendable predictive power, has been constructed, simultaneously providing potential therapeutic targets associated with disulfidptosis, among which AC026401.3 has been validated in vitro and demonstrated inhibition of PCa tumorigenesis after its silencing.

Abstract Objective The primary aim of this study was to create a nomogram for predicting survival outcomes in penile cancer patients, utilizing data from the Surveillance, Epidemiology, and End Results (SEER) and a Chinese organization. Methods Our study involved a cohort of 5744 patients diagnosed with penile cancer from the SEER database, spanning from 2004 to 2019. In addition, 103 patients with penile cancer from Sun Yat‐sen Memorial Hospital of Sun Yat‐sen University were included during the same period. Based on the results of regression analysis, a nomogram is constructed and validated internally and externally. The predictive performance of the model was evaluated by concordance index (c‐index), area under the curve, decision curve analysis, and calibration curve, in internal and external datasets. Finally, the prediction efficiency is compared with the TNM staging model. Results A total of 3154 penile patients were randomly divided into the training group and the internal validation group at a ratio of 2:1. Nine independent risk factors were identified, including age, race, marital status, tumor grade, histology, TNM stage, and the surgical approach. Based on these factors, a nomogram was constructed to predict OS. The nomogram demonstrated relatively better consistency, predictive accuracy, and clinical relevance, with a c‐index over 0.73 (in the training cohort, the validation cohort, and externally validation cohort.) These evaluation indexes are far better than the TNM staging system. Conclusion Penile cancer, often overlooked in research, has lacked detailed investigative focus and guidelines. This study stands as the first to validate penile cancer prognosis using extensive data from the SEER database, supplemented by data from our own institution. Our findings equip surgeons with an essential tool to predict the prognosis of penile cancer better suited than TNM, thereby enhancing clinical decision‐making processes.

Abstract Background The university years are a developmentally crucial phase and a peak period for the onset of mental disorders. The beliefs about the changeability of negative emotion may play an important role in help-seeking. The brief digital growth mindset intervention is potentially scalable and acceptable to enhance adaptive coping and help-seeking for mental health needs in university students. We adapted the Single-session Intervention on Growth Mindset for adolescents (SIGMA) to be applied in university students (U-SIGMA). This protocol introduces a two-armed waitlist randomized controlled trial study to examine the effectiveness and acceptability of U-SIGMA in promoting help-seeking among university students in the Greater Bay Area. Methods University students (N = 250, ages 18–25) from universities in the Greater Bay Area will be randomized to either the brief digital growth mindset intervention group or the waitlist control group. Participants will report on the mindsets of negative emotions, perceived control over anxiety, attitude toward help-seeking, physical activity, hopelessness, psychological well-being, depression, anxiety, and perceived stress at baseline and the 2-week and 8-week follow-ups through web-based surveys. A 30-min digital intervention will be implemented in the intervention group, with a pre- and post-intervention survey collecting intervention feedback, while the control group will receive the link for intervention after 8 weeks. Discussion This protocol introduces the implementation plan of U-SIMGA in multi-cities of the Greater Bay Area. The findings are expected to help provide pioneer evidence for the effectiveness and acceptability of the brief digital intervention for university students in the Chinese context and beyond and contribute to the development of accessible and effective prevention and early intervention for university students’ mental health. Trial registration HKU Clinical Trials Registry: HKUCTR-3012; Registered 14 April 2023. http://www.hkuctr.com/Study/Show/7a3ffbc0e03f4d1eac0525450fc5187e .

Abstract Background SPOCK3 is a secreted extracellular matrix proteoglycan. This study aimed to investigate the effect of SPOCK3 on the malignant progression of prostate cancer and to construct a prognostic model to predict DFS of patients with prostate cancer. Methods Clinical and transcriptome sequencing data for prostate cancer were download from the TCGA and GEO databases. The survival curve showed that SPOCK3 has prognostic significance. GO, KEGG, and GSEA enrichment analysis were used to investigate how SPOCK3 affects the malignant progression of prostate cancer. Based on ESTIMATE and ssGSEA, the relationship between SPOCK3 and immune cell infiltration in prostate cancer tissue was clarified. Univariate and multivariate COX regression analysis was used to identify the independent prognostic factors of prostate cancer OS and to construct a nomogram. The calibration curve and ROC curves were drawn to assess the nomogram's predictive power. Results The survival curve revealed that patients in the low-expression group of SPOCK3 had a poor prognosis. According to enrichment analysis, SOPCK3-related genes were enriched in collagen-containing extracellular matrix, PI3K-Akt, and MAPK signaling pathway. ESTIMATE analysis revealed that SPOCK3 expression was positively correlated with the interstitial score, immune score, and ESTIMATE score. The results of ssGSEA analysis revealed that the infiltration levels of Mast cells, NK cells, and B cells were higher in the SPOCK3 high expression group. Cox regression analysis showed that SPOCK3 expression level, T and Gleason score were independent risk factors of patient prognosis, and a nomogram was constructed. The ROC curve showed the AUCs of DFS at 2, 3, and 5 years. Conclusion SPOCK3 is a protective factor for DFS in prostate cancer patients. SPOCK3 is significantly associated with immune cell infiltration. The prognostic model constructed based on SPOCK3 has excellent predictive performance.

We forecast realized volatilities by developing a time-varying heterogeneous autoregressive (HAR) latent factor model with dynamic model average (DMA) and dynamic model selection (DMS) approaches. The number of latent factors is determined using Chan and Grant's (2016) deviation information criteria. The predictors in our model include lagged daily, weekly, and monthly volatility variables, the corresponding volatility factors, and a speculation variable. In addition, the time-varying properties of the best-performing DMA(DMS)-HAR-2FX models, including size, inclusion probabilities, and coefficients, are examined. We find that the proposed DMA(DMS)-HAR-2FX model outperforms the competing models for both in-sample and out-of-sample forecasts. Furthermore, the speculation variable displays strong predictability for forecasting the realized volatility of financial futures in China.

Background: This study presents the initial case of phlegmonous enteritis following endoscopic submucosal dissection (ESD), a rare and potentially fatal complication. Additionally, a comprehensive review of relevant literature is provided. Case report: A 66-year-old female patient, diagnosed with Hashimoto's thyroiditis and thrombocytopenia, underwent ESD to address a laterally spreading tumor located in the ascending colon. After the procedure, the patient manifested abdominal pain and a high fever, was diagnosed with peritonitis, necessitating an emergency exploratory laparotomy and right hemicolectomy. Subsequent histological examination indicated a significant presence of neutrophil infiltration across all layers of the intestines. The ascites culture yielded the growth of Escherichia coli. Literature review: A search was conducted in the PubMed database to identify case reports conforming to the definition of phlegmonous enteritis proposed by Rokitansky et al. We retrieved about 30 studies regarding phlegmonous enteritis from 1951 to 2022, with around 39 cases. Among these, only 28 patients had comprehensive medical data available. Subsequently, an examination of the literature was undertaken to explore the pathogenesis, prevention, and treatment of phlegmonous enteritis. Conclusion: The possibility of phlegmonous enteritis should be taken into consideration in cases of unexplained acute abdomen, particularly in patients with compromised immunity, in order to provide active surgical and antibiotic interventions.

BackgroundPositive surgical margin (PSM) or apical positive surgical margin (APSM) is an established predictive factor of biochemical recurrence or disease progression in prostate cancer (PCa) patients after radical prostatectomy. Since there are limited usable magnetic resonance imaging (MRI)-based models, we sought to explore the role of three-dimensional (3D) visualization for preoperative MRI in the prediction of PSM or APSM.MethodsFrom December 2016 to April 2022, 149 consecutive PCa patients who underwent radical prostatectomy were retrospectively selected from the Second Affiliated Hospital of Dalian Medical University. According to the presence of PSM or APSM, patients were divided into a PSM group (n=41) and a without PSM group (n=108) and into an APSM group (n=33) and a without APSM group (n=116). Twenty-one parameters, including prostate apical shape, PCa distance to the membranous urethra, and pubic angle, were measured on 3D visualization of MRI. The development of the nomogram models was built by the findings of multivariate logistic regression analysis for significant factors.ResultsTo predict the probability of PSM, a longer PCa distance to the membranous urethra (OR=0.136, p=0.019) and the distance from the anterior peritoneum to the anterior border of the coccyx (work space AP, OR=0.240, p=0.030) were independent protective factors, while a type 3 prostate apical shape (OR=8.262, p=0.025) and larger pubic angle 2 (OR=5.303, p=0.029) were identified as independent risk factors. The nomogram model presented an area under the curve (AUC) of the receiver operating characteristic curve (ROC) of PSM of 0.777. In evaluating the incidence of APSM, we found that the distance to the membranous urethra (OR=0.135, p=0.014) was associated with a low risk of APSM, while larger pubic angle 1 (OR=4.666, p=0.043) was connected to a higher risk of APSM. The nomogram model showed that the AUC of APSM was 0.755.ConclusionAs 3D visualization for preoperative MRI showed good performance in predicting PSM or APSM, the tool might be potentially valuable, which also needs to be validated by multicenter, large-scale, prospective studies.

Abstract Although dysregulated HMMR is linked to prostate cancer (PCa) prognosis, the precise mechanisms remain unclear. Here, we sought to elucidate the role of HMMR in PCa progression as well as underlying mechanism. Herein, we found that upregulation of HMMR frequently observed in PCa samples and was associated with poor prognosis. Additionally, HMMR significantly promoted PCa proliferation and metastasis through gain- and loss-of function approaches in vitro and in vivo. Mechanistically, HMMR may interact with AURKA and elevated AURKA protein level through inhibiting ubiquitination-mediated degradation, which subsequently activated mTORC2/AKT pathway to ensure the reinforcement of PCa progression. Moreover, upregulated E2F1 caused from sustained activation of mTORC2/AKT pathway in turn function as transcription factor to promote HMMR transcription, thereby forming a positive feedback loop to trigger PCa progression. Importantly, administration of the mTOR inhibitor partially antagonised HMMR-mediated PCa progression in vivo. In summary, we not only reveal a novel possible post-translation mechanism mediated by HMMR involved in AURKA regulation, but also describe a positive feedback loop that contributes to PCa deterioration, suggesting HMMR may serve as a potential promising therapeutic target in PCa.

BackgroundStroke is a common cerebrovascular disease. The purpose of this study was to explore the association between LIPC single nucleotide polymorphisms (SNPs) and the risk of stroke in the Chinese population.MethodsThis study recruited 710 stroke patients and 701 healthy controls. The four SNPs (rs690, rs6083, rs3829461, and rs6074) in LIPC were genotyped by the Agena MassARRAY. The correlation between LIPC polymorphisms and stroke risk was measured by odds ratio (OR) and 95% confidence interval (CI). In addition, multifactor dimensionality reduction (MDR) analysis was used to evaluate the impact of SNP–SNP interaction on stroke risk.ResultsOverall analysis showed that rs690 was associated with an increased risk of stroke (T vs. G: OR = 1.19, 95% CI: 1.01–1.40, p = 0.041; additive: OR = 1.20, 95% CI: 1.01–1.42, p = 0.036). The stratified analysis revealed that rs690 was associated with an increased risk of stroke in subjects aged ≤ 64 years, male patients, and smokers, and rs6074 was associated with an increased risk of stroke in subjects aged > 64 years, male patients, drinkers, and non-smokers (p < 0.05). The results of the MDR analysis suggested the four-locus model as the most favorable model for assessing the risk of stroke. The analysis of clinical parameters of stroke patients showed that rs690 was correlated with platelet distribution width (PDW) (p = 0.014) and hematocrit levels (p = 0.004), and rs6074 was correlated with low-density lipoprotein cholesterol (LDL-C) level (p = 0.033). Furthermore, bioinformatics analysis results demonstrated that the expression levels of LIPC and its related genes (APOB, CETP, PNPLA2, and LMF1) were significantly different between the control and stroke groups (p < 0.05), and LIPC-related proteins were mainly related to lipid metabolism.ConclusionThis study indicated that rs690 and rs6074 in LIPC were significantly associated with increased risk of stroke in the Chinese population, possibly by regulating the levels of PDW, HCT, and LDL-C.

BackgroundTo observe whether anti-angiogenesis therapy can induce changes in size and enhancement characteristics of hepatic hemangioma.Method133 patients with hepatic hemangioma lesions were analyzed and classified into a Bevacizumab group (n=65) and the control group (n=68). The parameters (Volume, CT enhancement ratio, enhancement patterns) of pre-and post-treatment in the bevacizumab and control groups independently calculated and compared by two radiologists. Correlation among the systolic blood pressure, diastolic blood pressure, heart rate with the hemangioma volume was evaluated using Pearson’s correlation analysis.ResultsThe hepatic hemangioma volume was significantly decreased after treatment in the Bevacizumab group (8.6 ± 18.7mL vs.7.3 ± 16.3mL, P0.05).The Pearson correlation results showed that blood pressure, heart rate, and hemangioma volume were unrelated or weakly related before and after bevacizumab treatment under the control of factors including weight, contrast injection scheme and CT scanning scheme.ConclusionsAnti-angiogenesis therapy can cause changes in enhancement pattern and volume of hepatic hemangioma. Radiologists should pay more attention to the reexamination of tumor patients treated with anti-angiogenesis therapy.

Veronicastrum axillare (Sieb. et Zucc.) Yamazaki is a traditional medical plant with versatile biological activities. Here, we reported the complete chloroplast genome sequence of V. axillare with a total length of 152,691 bp, containing two IR regions of 25,765 bp each, an LSC region of 83,559 bp, and an SSC region of 17,602 bp. The genome encodes 131 genes, including 85 protein-coding genes, 37 tRNAs, eight rRNAs, and one pseudogene (ycf1). The overall GC content is 38.3%, with the highest content of 43.31% in IR region. Comparative analysis revealed 4 potential hotspots among V. axillare and other Veroniceae plants, providing potential markers for population investigations in the tribe Veroniceae. A total of 56 simple sequence repeats were identified in V. axillare. Phylogenetic analysis indicated a sister relationship between V. axillare and V. sibiricum, suggesting a close genetic relationship between the two Veronicastrum species. Our results provide basic genetic resources for investigating the evolutionary status of V. axillare within the tribe Veroniceae.

Abstract Multiple small- to middle-scale cities, mostly located in northern China, became epidemic hotspots during the second wave of the spread of COVID-19 in early 2021. Despite qualitative discussions of potential social-economic causes, it remains unclear how this unordinary pattern could be substantiated with quantitative explanations. Through the development of an urban epidemic hazard index (EpiRank) for Chinese prefectural districts, we came up with a mathematical explanation for this phenomenon. The index is constructed via epidemic simulations on a multi-layer transportation network interconnecting local SEIR transmission dynamics, which characterizes intra- and inter-city population flow with a granular mathematical description. Essentially, we argue that these highlighted small towns possess greater epidemic hazards due to the combined effect of large local population and small inter-city transportation. The ratio of total population to population outflow could serve as an alternative city-specific indicator of such hazards, but its effectiveness is not as good as EpiRank, where contributions from other cities in determining a specific city’s epidemic hazard are captured via the network approach. Population alone and city GDP are not valid signals for this indication. The proposed index is applicable to different epidemic settings and can be useful for the risk assessment and response planning of urban epidemic hazards in China. The model framework is modularized and the analysis can be extended to other nations.

Abstract Background Acute glaucoma, characterized by a sudden elevation in intraocular pressure (IOP) and retinal ganglion cells (RGCs) death, is a major cause of irreversible blindness worldwide that lacks approved effective therapies, validated treatment targets and clear molecular mechanisms. We sought to explore the potential molecular mechanisms underlying the causal link between high IOP and glaucomatous RGCs death. Methods A murine retinal ischemia/ reperfusion (RIR) model and an in vitro oxygen and glucose deprivation/reoxygenation (OGDR) model were used to investigate the pathogenic mechanisms of acute glaucoma. Results Our findings reveal a novel mechanism of microglia-induced pyroptosis-mediated RGCs death associated with glaucomatous vision loss. Genetic deletion of gasdermin D (GSDMD), the effector of pyroptosis, markedly ameliorated the RGCs death and retinal tissue damage in acute glaucoma. Moreover, GSDMD cleavage of microglial cells was dependent on caspase-8 (CASP8)-hypoxia-inducible factor-1α (HIF-1α) signaling. Mechanistically, the newly identified nucleotide-binding leucine-rich repeat-containing receptor (NLR) family pyrin domain-containing 12 (NLRP12) collaborated with NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing protein 4 (NLRC4) downstream of the CASP8-HIF-1α axis, to elicit pyroptotic processes and interleukin-1β (IL-1β) maturation through caspase-1 activation, facilitating pyroptosis and neuroinflammation in acute glaucoma. Interestingly, processing of IL-1β in turn magnified the CASP8-HIF-1α-NLRP12/NLRP3/NLRC4-pyroptosis circuit to accelerate inflammatory cascades. Conclusions These data not only indicate that the collaborative effects of NLRP12, NLRP3 and NLRC4 on pyroptosis are responsible for RGCs death, but also shed novel mechanistic insights into microglial pyroptosis, paving novel therapeutic avenues for the treatment of glaucoma-induced irreversible vision loss through simultaneously targeting of pyroptosis.

Anti-VEGF drugs are first-line treatments for retinal neovascular diseases, but these anti-angiogenic agents may also aggravate retinal damage by inducing hypoxia. Mitophagy can protect against hypoxia by maintaining mitochondrial quality, thereby sustaining metabolic homeostasis and reducing reactive oxygen species (ROS) generation. Here we report that the anti-VEGF agent bevacizumab upregulated the hypoxic cell marker HIF-1α in photoreceptors, Müller cells, and vascular endothelial cells of oxygen-induced retinopathy (OIR) model mice, as well as in hypoxic cultured 661W photoreceptors, MIO-MI Müller cells, and human vascular endothelial cells. Bevacizumab also increased expression of mitophagy-related proteins, and mitophagosome formation both in vivo and in vitro, but did not influence cellular ROS production or apoptosis rate. The HIF-1α inhibitor LW6 blocked mitophagy, augmented ROS production, and triggered apoptosis. Induction of HIF-1α and mitophagy were associated with upregulation of BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3) and FUN14 domain containing 1 (FUNDC1), and overexpression of these proteins in culture reversed the effects of HIF-1α inhibition. These findings suggest that bevacizumab does induce retinal hypoxia, but that concomitant activation of the HIF-1α-BNIP3/FUNDC1 signaling pathway also induces mitophagy, which can mitigate the deleterious effects by reducing oxidative stress secondary. Promoting HIF-1α-BNIP3/FUNDC1-mediated mitophagy may enhance the safety of anti-VEGF therapy for retinal neovascular diseases and indicate new explanation and possible new target of the anti-VEGF therapy with suboptimal effect.

Background: Vogt-Koyanagi-Harada (VKH) disease is a multisystem autoimmune disorder which could induce bilateral panuveitis involving the posterior pole and peripheral fundus. Optical coherence tomography angiography (OCTA) provides several advantages over traditional fluorescence angiography for revealing pathological abnormalities of the retinal vasculature. Until recently, however, the OCTA field of view (FOV) was limited to 6 × 6 mm2 scans.Purpose: This study examined retinal vasculature and choriocapillaris abnormalities across multiple regions of the retina (15 × 9 mm2 wide field, macular, peripapillary regions) among acute and convalescent VKH patients using a novel widefield swept-source OCTA (WSS-OCTA) device and assessed correlations between imaging features and best-corrected visual acuity (BCVA).Methods: Twenty eyes of 13 VHK disease patients in the acute phase, 30 eyes of 17 patients in the convalescent phase, and 30 eyes of 15 healthy controls (HCs) were included in this study. Vascular length density (VLD) in superficial and deep vascular plexuses (SVP, DVP), vascular perfusion density (VPD) in SVP, DVP, and choriocapillaris (CC), and flow voids (FV) in CC were measured across multiple retinal regions via WSS-OCTA (PLEX Elite 9000, Carl Zeiss Meditec Inc., USA) using the 15 × 9 mm2 scan pattern centered on the fovea and quantified by ImageJ.Results: Compared to HCs, acute phase VKH patients exhibited significantly reduced SVP-VLD, SVP-VPD, and CC-VPD across multiple retinal regions (all p < 0.01). Notably, the FV area was more extensive in VKH patients, especially those in the acute phase (p < 0.01). These changes were reversed in the convalescent phase. Stepwise multiple linear regression analysis demonstrated that macular DVP-VLD and macular CC-VPD were the best predictive factors for BCVA in the acute and convalescent VKH groups.Conclusion: The wider field of SS-OCAT provides more comprehensive and detailed images of the microvasculature abnormalities characterizing VKH disease. The quantifiable and layer-specific information from OCTA allows for the identification of sensitive and specific imaging markers for prognosis and treatment guidance, highlighting WSS-OCTA as a promising modality for the clinical management of VKH disease.

Purpose: To investigate the involvement of peripapillary zone vascular abnormalities in Behcet's uveitis (BU) and associated visual dysfunction. We evaluated the retinal and choroidal microvascular features in both macular and peripapillary areas of BU patients to identify vascular abnormalities contributing to reduced best-corrected visual acuity (BCVA) using optical coherence tomography angiography (OCTA).Methods: A prospective, observational study was conducted in 24 eyes of 13 patients with BU and 24 eyes of 15 healthy participants as controls. They received a standard eye examination and were recorded by OCTA measurements of macular and peripapillary areas. The vascular densities of superficial capillary plexus (SCP) and deep capillary plexus (DCP), choroidal flow area, radial peripapillary capillary network (RPCN) density, foveal avascular zone (FAZ) area and perimeter, full retinal thickness (FRT), and peripapillary retinal nerve fiber layer thickness (pRNFLT) were measured.Correlations among microvascular, structural, and functional changes were assessed.Results: Our findings uncovered that the vascular density was significantly reduced in the peripapillary zone of BU eyes compared to healthy eyes, especially in the inferior subfield of the RPCN. The vascular densities of SCP and DCP quadrants within the macular zone had no significant difference between BU and control groups except for DCP density of the nasal parafoveal quadrant. Both FAZ area and perimeter were greater but without statistical significance in the BU group. Compared to healthy eyes, the choriocapillaris flow area was smaller while the FRT and pRNFLT were greater in the BU group. Notably, there was a significant correlation between the reduction in RPCN vascular density and decreased BCVA in BU patients.Conclusion: Based on OCTA, vascular changes associated with BU are more prominent in the peripapillary zone than those in the macular zone. The vascular density of the RPCN could serve as a sensitive indicator to monitoring BU pathogenic progression and treatment response using a non-invasively method of OCTA.

Retinal ischemia is a common pathological event that can result in retinal ganglion cell (RGC) death and irreversible vision loss. The pathogenic mechanisms linking retinal ischemia to RGC loss and visual deficits are uncertain, which has greatly hampered the development of effective treatments. It is increasingly recognized that pyroptosis of microglia contributes to the indirect inflammatory death of RGCs. In this study, we report a regulatory NOD-like receptor, NOD-, LRR- and CARD-containing 5 (NLRC5), as a key regulator on microglial pyroptosis and the retinal ischemia process. Through an in-depth analysis of our recently published transcriptome data, we found that NLRC5 was significantly up-regulated in retina during ischemia–reperfusion injury, which were further confirmed by subsequent detection of mRNA and protein level. We further found that NLRC5 was upregulated in retinal microglia during ischemia, while NLRC5 knockdown significantly ameliorated retinal ischemic damage and RGC death. Mechanistically, we revealed that knockdown of NLRC5 markedly suppressed gasdermin D (GSDMD) cleavage and activation of interleukin-1β (IL-1β) and caspase-3, indicating that NLRC5 promotes both microglial pyroptosis and apoptosis. Notably, we found that NLRC5 directly bound to NLRP3 and NLRC4 in inflammasomes to cooperatively drive microglial pyroptosis and apoptosis mediating retinal ischemic damage. Overall, these findings reveal a previously unidentified key contribution of NLRC5 signaling to microglial pyroptosis under ischemia or hypoxia conditions. This NLRC5-dependent pathway may be a novel therapeutic target for treatment of ischemic retinopathy.