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Objective: This study aimed to explore the potential causal relationship between intraocular pressure (IOP) and myopia. Methods: The study included 3,459 patients who underwent corneal refractive surgery at our institution between 2021 and 2023. Preoperative data on IOP, spherical equivalent (SE), axial length (AL), and corneal thickness (CCT) were collected. The association between IOP and myopia was investigated through rank correlation analysis, and causal inference was examined using Mendelian randomization (MR) methods, including MR-Egger, weighted median, mode-based estimation, simple mode, and inverse variance weighted (IVW) approaches. Utilizing summary statistics from genome-wide association studies (GWAS), IOP was considered as the exposure, with myopia as the outcome variable. IVW method was employed for the primary analysis, supplemented by sensitivity analyses. Results: Cross-sectional analysis revealed a non-significant association between corrected IOP (cIOP) and myopia (r = -0.019, P = 0.12). MR analysis indicated a non-significant genetic causal relationship between cIOP and myopia under the IVW method (OR = 1.001; 95 % CI [0.999–1.003], P = 0.22), a finding corroborated in replication samples (OR = 0.98; 95 % CI [0.96–1.00], P = 0.099). Conclusion: This study did not find a direct causal link between IOP and the development of myopia. These findings challenge the traditional role attributed to IOP in the progression of myopia and highlight the complex, multifactorial process of myopia development. This provides a new perspective on understanding the intricate mechanisms behind myopia progression.

BackgroundThe interplay between gut microbiota and metabolites in the early stages of sepsis-induced acute kidney injury (SA-AKI) is not yet clearly understood. This study explores the characteristics and interactions of gut microbiota, and blood and urinary metabolites in patients with SA-AKI.MethodsUtilizing a prospective observational approach, we conducted comparative analyses of gut microbiota and metabolites via metabolomics and metagenomics in individuals diagnosed with SA-AKI compared to those without AKI (NCT06197828). Pearson correlations were used to identify associations between microbiota, metabolites, and clinical indicators. The Comprehensive Antibiotic Resistance Database was employed to detect antibiotic resistance genes (ARGs), while Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways informed on metabolic processes and microbial resistance patterns.ResultsOur study included analysis of four patients with SA-AKI and five without AKI. Significant disparities in bacterial composition were observed, illustrated by diversity indices (Shannon index: 2.0 ± 0.4 vs. 1.4 ± 0.6, P = 0.230; Simpson index: 0.8 ± 0.1 vs. 0.6 ± 0.2, P = 0.494) between the SA-AKI group and the non-AKI group. N6, N6, N6-Trimethyl-L-lysine was detected in both blood and urine metabolites, and also showed significant correlations with specific gut microbiota (Campylobacter hominis and Bacteroides caccae, R > 0, P < 0.05). Both blood and urine metabolites were enriched in the lysine degradation pathway. We also identified the citrate cycle (TCA cycle) as a KEGG pathway enriched in sets of differentially expressed ARGs in the gut microbiota, which exhibits an association with lysine degradation.ConclusionsSignificant differences in gut microbiota and metabolites were observed between the SA-AKI and non-AKI groups, uncovering potential biomarkers and metabolic changes linked to SA-AKI. The lysine degradation pathway may serve as a crucial link connecting gut microbiota and metabolites.

Purpose: The aim of this study was to evaluate the effectiveness and safety of repeated low-level red light (RLRL) therapy in controlling myopia progression in children through a meta-analysis. Methods: We searched several databases including PubMed, Embase, The Cochrane Library, Web of Science, CNKI, WANFANG, CBM, and VIP with languages restricted to both Chinese and English. The search was conducted from the establishment of the databases to March 23, 2023. We collected randomized controlled trials and controlled experiments to evaluate changes in axial length (AL) and spherical equivalent (SE) before and after RLRL intervention. Two researchers performed literature screening and data extraction, and RevMan software (Ver 5.3) and StataMP 17.0 were used for meta-analysis. Results: A total of 141 articles were retrieved, and finally, six randomized controlled trials met the inclusion and exclusion criteria, including 820 eyes (RLRL group: 411 eyes, control group: 409 eyes). The meta-analysis results showed that the RLRL group was significantly better than the control group in controlling AL, and the difference between the two groups was statistically significant (mean difference [MD] = −0.22, 95% confidence interval [CI] [ - 0.28, −0.16]; P < 0.001). The RLRL group was also better than the control group in terms of SE, and the difference between the two groups was statistically significant (MD = 0.46, 95% CI [0.32, 0.6]; P < 0.001). Five studies reported adverse reactions in the RLRL group, and two cases stopped treatment due to the feeling of too bright light, while the others had no significant side effects in the short term. Conclusion: RLRL therapy is a safe and effective method for controlling myopia, which can inhibit the growth of AL and slow down the progression of myopia. However, further research and validation are needed to determine its treatment efficacy and course.

IntroductionCommon critical illnesses are a growing economic burden on healthcare worldwide. However, therapies targeting the gut microbiota for critical illnesses have not been developed on a large scale. This study aimed to investigate the changes in the characteristics of the gut microbiota in critically ill children after short-term pediatric intensive care unit (PICU) treatments.MethodsAnal swab samples were prospectively collected from March 2021 to March 2022 from children admitted to the PICU of Xinhua Hospital who received broad-spectrum antibiotics on days 1 (the D1 group) and 7 (the D7 group) of the PICU treatment. The structural and functional characteristics of the gut microbiota of critically ill children were explored using metagenomic next-generation sequencing (mNGS) technology, and a comparative analysis of samples from D1 and D7 was conducted.ResultsAfter 7 days of PICU admission, a significant decrease was noted in the richness of the gut microbiota in critically ill children, while the bacterial diversity and the community structure between groups remained stable to some extent. The relative abundance of Bacilli and Lactobacillales was significantly higher, and that of Campylobacter hominis was significantly lower in the D7 group than in the D1 group. The random forest model revealed that Prevotella coporis and Enterobacter cloacae were bacterial biomarkers between groups. LEfSe revealed that two Gene Ontology entries, GO:0071555 (cell wall organization) and GO:005508 (transmembrane transport), changed significantly after the short-term treatment in the PICU. In addition, 30 KEGG pathways were mainly related to the activity of enzymes and proteins during the processes of metabolism, DNA catabolism and repair, and substance transport. Finally, 31 antimicrobial resistance genes had significantly different levels between the D7 and D1 groups. The top 10 up-regulated genes were Erm(A), ErmX, LptD, eptB, SAT-4, tetO, adeJ, adeF, APH(3′)-IIIa, and tetM.ConclusionThe composition, gene function, and resistance genes of gut microbiota of critically ill children can change significantly after short PICU treatments. Our findings provide a substantial basis for a better understanding of the structure and function of gut microbiota and their role in critical illnesses.

IntroductionThe aim of this study is to demonstrate the relevance of primary acute angle closure (APAC) and COVID-19 infection, compare the demographic features and manifestations between COVID-19 positive and negative patients with APAC, and infer the underlying mechanism.MethodsThis study is based on all patients diagnosed with APAC at the glaucoma center of Eye, Ear, Nose and Throat Hospital of Fudan University (Fenyang road center) from 15th December 2022 to 11th January 2023. Totally 171 APAC cases were categorized into COVID-19 positive and negative group. Demographic features and final treatment level of the patients were compared between the two groups. Clinical manifestations, intraocular pressure, and anterior chamber configuration were also compared between the two groups.ResultsIn the COVID-19 positive group, the number of cases with APAC onset spiked in 22nd December 2022, which coincided with the spike of COVID-19 antigen positive people. Compared to the COVID-19 negative group, COVID-19 positive APAC patients were younger with a lower percentage of APAC history. Additionally, more eyes of COVID-19 positive APAC patients showed keratic precipitates. COVID-19 positive eyes had significantly larger anterior chamber depth with a more dilated pupil. Therefore, COVID-19 infection could probably act as a triggering factor of APACDiscussionThe onset of APAC might be accelerated by COVID-19 infection for patients with younger age and milder anatomical configuration. Additionally, COVID-19 related APAC cases might have a more abrupt and fierce onset. Ophthalmic emergent services should not be neglected during the epidemic period.

Abstract Background We aimed to analyze the clinical characteristics of secondary glaucoma related to cytomegalovirus (CMV)- and varicella zoster virus (VZV)-positive uveitis. Methods In this retrospective study, we enrolled patients with anterior uveitic secondary glaucoma. All the patients underwent aqueous and serum analyses for viral antibody through enzyme-linked immunosorbent assay. Among the 60 included patients, 22 had CMV-negative Posner-Schlossman syndrome (CMV-negative PSS), 25 had CMV-positive PSS, and 13 had VZV-positive anterior uveitis secondary glaucoma (VZV-AUSG). We evaluated the following main indicators: age, disease duration, intraocular pressure (IOP), cup-to-disc ratio, best corrected visual acuity (BCVA), corneal endothelial cell (CEC) count, ocular morphological changes, and medical treatments. Results We found that 53.2% (25/47) patients with PSS were CMV-positive. Patients with CMV-positive PSS had a larger cup-to-disc ratio (p = .043), lower CEC density (p = .017), more severe CEC loss (p

IntroductionThis retrospective study aims to present the characteristics of Posner-Schlossman syndrome (PSS) relapse following inactivated COVID-19 vaccination.MethodsFrom 2020 to 2022, 12 out of 106 PSS patients undergoing relapses after any dose of inactivated COVID-19 vaccines were enrolled. Medical histories, information on the vaccination and systemic adverse events were collected. Patients were treated with corticosteroids, intraocular pressure (IOP)-lowering drugs and systemic immunosuppressive agents (if needed). Daily regimen and release course were noted.ResultsThe recurrence rate after vaccination was 11.32% (12/106, 95% CI: 5.29%–17.35%) among 106 PSS patients we surveyed. All the 12 patients were inoculated with inactivated COVID-19 vaccines developed by Sinopharm, China. The mean time of relapse was 5.27 ± 3.72 days (range: 1–13 days, median: 4 days). Higher IOP and more keratic precipitates (KPs) were seen in the relapse following vaccination (33.55 ± 12.99 mmHg, 91.67% had KPs compared to 25.38 ± 3.80 mmHg, 33.33% had KPs in previous relapse, P = 0.009). The mean release course was 30.71 ± 34.74 days for the relapse following vaccination and 7.33 ± 6.51 days for previous relapses. The attack frequency before and after vaccination was 3.56 ± 2.07 and 9.11 ± 7.34 times per year (P = 0.044). Higher daily doses of corticosteroids, IOP-lowering drugs and ganciclovir were needed to maintain stable course, though the difference did not reach statistical significance.DiscussionMore frequent relapses and harder control of IOP were found in PSS relapse following COVID-19 vaccination. Ophthalmologists need to be aware of the group vulnerability and take precautions, though the pathogenesis is still under investigation.

Abstract Background Positive fluid overload (FO) may cause adverse effect. This study retrospectively analyzed the relationship between early FO and in-hospital mortality in children with mechanical ventilation (MV) in pediatric intensive care unit (PICU). Methods This study retrospectively enrolled 309 children (ages 28 days to 16 years) receiving invasive MV admitted to the PICU of Xinhua Hospital from March 2014 to March 2019. Children receiving MV for less than 48 h were excluded. The FO in the first 3 days of MV was considered to the early FO. Patients were divided into groups according to early FO and survival to evaluate the associations of early FO, percentage FO(%FO) > 10%, and %FO > 20% with in-hospital mortality. Results A total of 309 patients were included. The mean early FO was 8.83 ± 8.81%, and the mortality in hospital was 26.2% (81/309). There were no significant differences in mortality among different FO groups (P = 0.053) or in early FO between survivors and non-survivors (P = 0.992). Regression analysis demonstrated that use of more vasoactive drugs, the presence of multiple organ dysfunction syndrome, longer duration of MV, and a non-operative reason for PICU admission were related to increased mortality (P 10% were not associated with in-hospital mortality (β = 0.030, P = 0.090, 95% CI = 0.995–1.067; β = 0.479, P = 0.153, 95% CI = 0.837–3.117), %FO > 20% was positively correlated with mortality (β = 1.057, OR = 2.878, P = 0.029, 95% CI = 1.116–7.418). Conclusions The correlation between early FO and mortality was affected by interventions and the severity of the disease, but %FO > 20% was an independent risk factor for in-hospital mortality in critically ill MV-treated children.

Injury to the adult mammalian central nervous system induces compensatory plasticity of spared axons—referred to as collateral axon sprouting—that can facilitate neural recovery. The contribution of reactive astrocytes to axon sprouting remains elusive. Here, we sought to investigate the role of axon degeneration-reactive astrocytes in the regulation of collateral axon sprouting that occurs in the mouse spinal cord after unilateral photothrombotic stroke of the primary motor cortex. We identified astrocytic leucine zipper-bearing kinase (LZK) as a positive regulator of astrocyte reactivity to corticospinal axon degeneration. Remarkably, genetic stimulation of astrocyte reactivity, via LZK overexpression in adult astrocytes, enhanced corticospinal axon sprouting. LZK promoted the production of astrocyte-derived ciliary neurotrophic factor (CNTF) that likely enhanced axon growth in mice with astrocytic LZK overexpression after injury. Our finding that LZK-dependent stimulation of astrocyte reactivity promotes corticospinal axon sprouting highlights the potential of engineering astrocytes to support injury-induced axon plasticity for neural repair.

Sepsis most often involves the kidney and is one of the most common causes of acute kidney injury. The prevalence of septic acute kidney injury has increased significantly in recent years. The gut microbiota plays an important role in sepsis. It interacts with the kidney in a complex and multifactorial process, which is not fully understood. Sepsis may lead to gut microbiota alteration, orchestrate gut mucosal injury, and cause gut barrier failure, which further alters the host immunological and metabolic homeostasis. The pattern of gut microbiota alteration also varies with sepsis progression. Changes in intestinal microecology have double-edged effects on renal function, which also affects intestinal homeostasis. This review aimed to clarify the interaction between gut microbiota and renal function during the onset and progression of sepsis. The mechanism of gut–kidney crosstalk may provide potential insights for the development of novel therapeutic strategies for sepsis.

BackgroundTo observe and compare the efficacy of 2% ganciclovir eye drops in the treatment of Posner-Schlossman Syndrome relapses with/without cytomegalovirus intraocular reactivation.MethodsA prospective cohort study enrolling 101 patients diagnosed unilateral Posner-Schlossman Syndrome in Eye & ENT hospital, Fudan University, Shanghai, China. Thorough ophthalmic examinations were given. Aqueous humor sample was collected from the attacked eye of each patient and all pathogen immunoglobulins tests were performed. All patients were treated with appropriate corticosteroids and intraocular pressure-lowering drugs. 2% ganciclovir eye drops were given to patients whose cytomegalovirus antibody aqueous humor/serum correction ratio >0. Patients were followed up for 2 months. Ocular manifestations and cumulative drug dose were recorded.ResultsA cytomegalovirus ratio >0.40 was considered cytomegalovirus reactivation. The reactivation group (N = 46) had significantly higher percent of iris depigmentation (78.26%, P < 0.05) and endothelial cell loss rate (19.46%, P < 0.001) than the latent group (N = 55, 58.18% and 10.86%, respectively). The cumulative treatment time and 2% ganciclovir doses were 6.50 ± 4.67 weeks and 181.70 ± 130.95 drops for the reactivation group; 5.95 ± 4.11 weeks and 161.89 ± 110.66 drops for the latent group (P > 0.05). The median cumulative 2% ganciclovir estimated for inflammation control were 252.00 ± 50.71 and 224.00 ± 32.45 drops for the reactivation and latent group. The residual rate of uncontrolled cases was 0.19 ± 0.15 and 0.00, respectively (P < 0.05).ConclusionsA treatment course of 8–9 weeks' 2% ganciclovir is recommended to relapses both with and without cytomegalovirus intraocular reactivation. Preventive ganciclovir application may benefit patients with historical cytomegalovirus infections.Clinical Trial Registrationwww.chictr.org.cn, identifier: ChiCTR1900022340, Date: 2019/04/06.

PurposeTo evaluate peripapillary vascular reactivity in primary open-angle glaucoma (POAG) with and without high myopia (HM) by using optical coherence tomography angiography (OCTA).MethodsThis prospective study enrolled 48 eyes with POAG, including 16 and 32 eyes with and without HM, respectively. The retinal peripapillary vessel density (VD) was repeatedly assessed using OCTA at baseline and after a hyperoxia test (breathing 80% oxygen). The VD changes between different oxygenation conditions were calculated to reflect the vasoreactivity. Linear regression was performed to determine the relationship between myopia and retinal vascular reactivity in patients with POAG. Systemic hemodynamic characteristics were also evaluated under both conditions.ResultsThe VD was significantly reduced after hyperoxia in the whole image (baseline and hyperoxia: 41.4 ± 4.5 and 38.8 ± 4.4, respectively, P < 0.001) and in the peripapillary regions (44.3 ± 5.7 and 41.1 ± 5.4, respectively, P < 0.001) in POAG eyes without HM. However, in eyes with HM, the whole-image VD in hyperoxia was not significantly different from the baseline (baseline and hyperoxia: 40.5 ± 6.2 and 40.2 ± 6.2, respectively, P = 0.481). The VD changes in eyes with HM were significantly smaller than those in eyes without HM in both the whole image (0.3 ± 1.8 and 2.6 ± 2.0, respectively, P < 0.001) and peripapillary regions (1.1 ± 2.0 and 3.2 ± 2.3, respectively, P = 0.003). Linear regression results showed a significant correlation between retinal vascular reactivity and spherical equivalent (SE) (β = 0.28, P < 0.001, R2 = 0.31) and axial length (AL) (β = −0.72, P < 0.001, R2 = 0.33).ConclusionRetinal vasoreactivity of peripapillary capillaries in POAG eyes with HM was significantly impaired in comparison with that in POAG eyes without HM. A lower peripapillary vascular response was significantly associated with worse SE and elongated AL.

Introduction. To compare accelerated and standard corneal collagen cross-linking (CXL) treatments in experimental Aspergillus keratitis models. Methods. Twenty-six New Zealand rabbits were divided into two groups: a 1% voriconazole combined with standard CXL group, and a 1% voriconazole combined with accelerated CXL group. The ulcer area, corneal opacity, and corneal neovascularization score were measured via slit-lamp imaging, and the corneal and corneal epithelial thickness and ulcer depth were measured via anterior segment optical coherence tomography (AS-OCT). The duration of the hyphae was observed via in vivo confocal microscopy (IVCM), and the cornea was taken for pathological examination after modeling and at the end of the study to determine the hyphae and corneal repair. The observation times were as follows: at successful modeling (day 0) and at 1, 4, 7, 14, 21, and 28 days after the intervention. Results. The area and depth of the ulcer decreased in both groups after CXL (all P

Abstract Background Wolfram Syndrome (WFS) is a rare autosomal recessive neurodegenerative disease which has a wide spectrum of manifestations including diabetes insipidus, diabetes mellitus, optic atrophy and deafness. WFS1 and CISD2 are two main causing genes of WFS. The aim of this study was to illustrate the ophthalmologic manifestations and determine the genotype of Chinese WFS patients. Results Completed ophthalmic examinations and family investigations were performed on 4 clinically diagnosed WFS patients from 4 unrelated families. Genetic testing was done by the next generation sequencing of candidate genes. One patient carried a homozygous mutation (c.272_273del) in CISD2, two patients carried compound heterozygous mutations (c.1618 T > G + c.2020G > A and c.1048 T > A + c.2020G > A) in WFS1, and one patient carried a heterozygous mutation (c.937C > T) in WFS1. Three of them were novel mutations. Conclusions Our study indicated WFS in Chinese is a neurodegenerative disease with both wide spectrum of clinical features and genetic heterogeneity. We found three novel mutations in WFS patients, and to our best knowledge, this is the first report of Chinese WFS patient with mutation in CISD2.

Purpose: To investigate the changes in the retinal vessels (RVs) in different sectors in patients with primary open-angle glaucoma (POAG), and their possible correlations with retinal nerve fiber layer thickness (RNFLT) and visual-field defects in the temporal parapapillary region.Methods: The RV diameters, RNFLTs, and visual-field parameters were measured. The temporal parapapillary region was divided into the temporal (T, 315°-45°), temporal superior (TS, 45°-90°), and temporal inferior sectors (TI, 270°-315°). The changes in the RV diameters in each sector were determined, and their relationships with RNFLT, the mean deviation (MD), and visual field sensitivity (VFS) were examined.Results: Fifty POAG patients (50 eyes) and 50 healthy subjects (50 eyes) were included. Compared with the healthy subjects, the POAG group had a significantly smaller accumulated parapapillary RV diameter (P < 0.001), which was positively correlated with the MD and RNFLT. When the different temporal sectors were examined, the accumulated RV diameters were significantly smaller in the POAG group than in the healthy controls in the TI and T sectors, but not in the TS sector. The accumulated diameters in the TI and T sectors were correlated with the corresponding RNFLTs (all P < 0.05), but only the accumulated diameter in the TI sector was correlated with the VFS.Conclusions: In POAG, the changes in the RVs differed between different temporal sectors, with the most prominent changes occurring in the TI and T sectors.

BackgroundHypoxia contributes to a cascade of inflammatory response mechanisms in kidneys that result in the development of renal interstitial fibrosis and subsequent chronic renal failure. Nonetheless, the kidney possesses a self-protection mechanism under a certain degree of hypoxia and this mechanism its adaptation to hypoxia. As the hypoxia-inducible factor (HIF)–vascular endothelial growth factor (VEGF) axis is a key pathway for neovascularization, the activation of this axis is a target for renal hypoxia therapies.MethodsSprague–Dawley rats were exposed to normobaric hypoxia and subdivided into three groups, namely group A (21% O2), group B (10% O2), and group C (7% O2). Renal tissue samples were processed and analyzed to determine pathological morphological changes, the expression of HIF, VEGF, inflammation factor and vascular density.ResultsWe found that as the duration of hypoxia increased, destructive changes in the kidney tissues became more severe in group C (7% O2). In contrast, the increased duration of hypoxia did not exacerbate kidney damage in group B (10% O2). As the hypoxia was prolonged and the degree of hypoxia increased, the expression of HIF-1α increased gradually. As hypoxia time increased, the expression of VEGF increased gradually, but VEGF expression in group B (10% O2) was the highest. Group C (7% O2) had higher levels of IL-6, IL-10, and TNF-alpha. Additionally, the highest vascular density was observed in group B.ConclusionThese findings suggest that activating the HIF–VEGF signaling pathway to regulate angiogenesis after infliction of hypoxic kidney injury may provide clues for the development of novel CKD treatments.

Glaucoma is the second leading cause of blindness globally characterized by progressive loss of retinal ganglion cells (RGCs) and irreversible visual deficiency. As the most common type of glaucoma, primary open angle glaucoma (POAG) is currently an unmet medical need with limited therapy by lowering intraocular pressure (IOP). However, some patients continue to progress even though their IOP are controlled. Although early diagnosis and prompt treatment are crucial in preventing irreversible visual impairment, there are currently no biomarkers for screening POAG. Metabolomics has the advantages of illustrating the final downstream products of the genome and establishing the closest link to the phenotype. So far, there is no study investigating the metabolomic profiles in both aqueous humor and plasma of POAG patients. Therefore, to explore diagnostic biomarkers, unveil underlying pathophysiology and potential therapeutic strategies, a widely targeted metabolomic approach was applied using ultrahigh-resolution mass spectrometry with C18 liquid chromatography to characterize the metabolomic profiles in both aqueous humor and plasma of 28 POAG patients and 25 controls in our study. Partial least squares-discriminant analysis (PLS-DA) was performed to determine differentially expressed metabolites (DEMs) between POAG and age-matched controls. The area under the receiver operating characteristic curve (AUC) was calculated to assess the prediction accuracy of the DEMs. The correlation of DEMs with the clinical parameters was determined by Pearson correlation, and the metabolic pathways were analyzed using MetaboAnalyst 4.0. PLS-DA significantly separated POAG from controls with 22 DEMs in the aqueous humor and 11 DEMs in the plasma. Additionally, univariate ROC analysis and correlation analysis with clinical parameters revealed cyclic AMP (AUC = 0.87), 2-methylbenzoic acid (AUC = 0.75), 3′-sialyllactose (AUC = 0.73) in the aqueous humor and N-lac-phe (AUC = 0.76) in the plasma as potential biomarkers for POAG. Moreover, the metabolic profiles pointed towards the alteration in the purine metabolism pathway. In conclusion, the study identified potential and novel biomarkers for POAG by crosslinking the metabolomic profiles in aqueous humor and plasma and correlating with the clinical parameters. These findings have important clinical implications given that no biomarkers are currently available for glaucoma in the clinic, and the study provided new insights in exploring diagnostic biomarkers and potential therapeutic strategies of POAG by targeting metabolic pathways.

Purpose. To analyze how keratic precipitate (KP) morphology changes during Posner–Schlossman syndrome (PSS) prognosis and raise medication suggestions on 2% ganciclovir eye drops. Materials and Methods. Clinical retrospective cohort study in the Eye & ENT Hospital of Fudan University, Shanghai, China. The attacked eyes of 98 eligible subjects diagnosed unilateral PSS were enrolled between 2016 and 2019. All patients were treated with intraocular pressure-lowering drugs and anti-inflammatory steroids. 2% ganciclovir eye drops were given to cytomegalovirus (CMV) immunoglobulin G (IgG) correction ratio positive patients. Frequent follow-ups and examinations were performed. KP morphology was focused and categorized into coin-shaped, mutton-fat, and pigmented. Medical histories were noted. Multidimensional analysis was given. Results. Totally 47 patients in 98 achieved all-KP disappearance. Mean treatment time was (5.13 ± 3.66) weeks. Total KP disappearance was negatively correlated with mutton-fat and pigmented KPs at the first visit (P=0.020, P=0.007) and treatment time was also longer (P=0.018, P=0.014). Mean cumulative steroids dosage for 47 subjects was (159.66 ± 161.84) drops. CMV IgG correction ratio positive patients had smaller corneal endothelial cell density (P

Background: The mortality prediction scores were widely used in pediatric intensive care units. However, their performances were unclear in Chinese patients and there were also no reports based on large sample sizes in China. This study aims to evaluate the performances of three existing severity assessment scores in predicting PICU mortality and to identify important determinants.Methods: This prospective observational cohort study was carried out in eight multidisciplinary, tertiary-care PICUs of teaching hospitals in China. All eligible patients admitted to the PICUs between Aug 1, 2016, and Jul 31, 2017, were consecutively enrolled, among whom 3,957 were included for analysis. We calculated PCIS, PRISM IV, and PELOD-2 scores based on patient data collected in the first 24 h after PICU admission. The in-hospital mortality was defined as all-cause death within 3 months after admission. The discrimination of mortality was assessed using the area under the receiver-operating characteristics curve (AUC) and calibrated using the Hosmer–Lemeshow goodness-of-fit test.Results: A total of 4,770 eligible patients were recruited (median age 18.2 months, overall mortality rate 4.7%, median length of PICU stay 6 days), and 3,957 participants were included in the analysis. The AUC (95% confidence intervals, CI) were 0.74 (0.71–0.78), 0.76 (0.73–0.80), and 0.80 (0.77–0.83) for PCIS, PRISM IV, and PELOD-2, respectively. The Hosmer–Lemeshow test gave a chi-square of 3.16 for PCIS, 2.16 for PRISM IV and 4.81 for PELOD-2 (p ≥ 0.19). Cox regression identified five predictors from the items of scores better associated with higher death risk, with a C-index of 0.83 (95%CI 0.79–0.86), including higher platelet (HR = 1.85, 95% CI 1.59–2.16), invasive ventilation (HR = 1.40, 1.26–1.55), pupillary light reflex (HR = 1.31, 95% CI 1.22–1.42) scores, lower pH (HR 0.89, 0.84–0.94), and extreme PaO2 (HR 2.60, 95% CI 1.61–4.19 for the 1st quantile vs. 4th quantile) scores.Conclusions: Performances of the three scores in predicting PICU mortality are comparable, and five predictors were identified with better prediction to PICU mortality in Chinese patients.

Summary: Reactive astrocytes influence post-injury recovery, repair, and pathogenesis of the mammalian CNS. Much of the regulation of astrocyte reactivity, however, remains to be understood. Using genetic loss and gain-of-function analyses in vivo, we show that the conserved MAP3K13 (also known as leucine zipper-bearing kinase [LZK]) promotes astrocyte reactivity and glial scar formation after CNS injury. Inducible LZK gene deletion in astrocytes of adult mice reduced astrogliosis and impaired glial scar formation, resulting in increased lesion size after spinal cord injury. Conversely, LZK overexpression in astrocytes enhanced astrogliosis and reduced lesion size. Remarkably, in the absence of injury, LZK overexpression alone induced widespread astrogliosis in the CNS and upregulated astrogliosis activators pSTAT3 and SOX9. The identification of LZK as a critical cell-intrinsic regulator of astrocyte reactivity expands our understanding of the multicellular response to CNS injury and disease, with broad translational implications for neural repair. : Reactive astrocytes are recognized increasingly for their role in CNS injury and disease. Chen et al. find that leucine zipper-bearing kinase (LZK) is a positive regulator of astrocyte reactivity that controls glial scar formation after spinal cord injury. These findings have broad implications for understanding injury responses and promoting neural repair. Keywords: CNS injury, spinal cord injury, astrogliosis, glial scar, astroglial reactivity, reactive astrocytes, LZK, MAP3K, SOX9, STAT3

The Posner–Schlossman syndrome (PSS) is a disease with clinically recurrent unilateral anterior uveitis with markedly elevated intraocular pressure (IOP) and subsequent progression to optic neuropathy. Retrospective studies have reported increased annual incidence of PSS, especially in China. While currently, the clinical management of PSS is still challenging. Metabolomics is considered to be a sensitive approach for the development of novel targeted therapeutics because of its direct elucidation of pathophysiological mechanisms. Therefore, we adopted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) technology-based non-targeted metabolomics approach to measure comprehensive metabolic profiles of aqueous humor (AH) samples obtained from patients with PSS, with an aim to demonstrate the underlying pathophysiology, identify potential biomarkers specific to PSS, and develop effective treatment strategies. A comparative analysis was used to indicate the distinct metabolites of PSS. Pathway analysis was conducted using MetaboAnalyst 4.0 to explore the metabolic reprogramming pathways involved in PSS. Logistic regression and receiver-operating characteristic (ROC) analyses were employed to evaluate the diagnostic capability of selected metabolites. Comparative analysis revealed a clear separation between PSS and control groups. Fourteen novel differentiating metabolites from AH samples obtained from patients with PSS were highlighted. Pathway analysis identified 11 carbohydrate, amino acid metabolism and energy metabolism pathways as the major disturbed pathways associated with PSS. The abnormal lysine degradation metabolism, valine–leucine–isoleucine biosynthesis, and citrate circle were considered to weigh the most in the development of PSS. The ROC analysis implied that the combination of glycine and homogentisic acid could serve as potential biomarkers for the discrimination of control and PSS groups. In conclusion, these results revealed for the first time the identity of important metabolites and pathways contributing to the development/progression of PSS, enabled the better understanding of the mechanism of PSS, and might lead to the development of metabolic biomarkers and novel therapeutic strategies to restrict the development/progression of PSS.

Whole-brain volumetric microscopy techniques such as serial two-photon tomography (STPT) can provide detailed information on the roles of neuroinflammation and neuroplasticity throughout the whole brain post-stroke. STPT automatically generates high-resolution images of coronal sections of the entire mouse brain that can be readily visualized in three dimensions. We developed a pipeline for whole brain image analysis that includes supervised machine learning (pixel-wise random forest models via the “ilastik” software package) followed by registration to a standardized 3-D atlas of the adult mouse brain (Common Coordinate Framework v3.0; Allen Institute for Brain Science). These procedures allow the detection of cellular fluorescent signals throughout the brain in an unbiased manner. To illustrate our imaging techniques and automated image quantification, we examined long-term post-stroke motor circuit connectivity in mice that received a motor cortex photothrombotic stroke. Two weeks post-stroke, mice received intramuscular injections of pseudorabies virus (PRV-152), a trans-synaptic retrograde herpes virus driving expression of green fluorescent protein (GFP), into the affected contralesional forelimb to label neurons in descending tracts to the forelimb musculature. Mice were sacrificed 3 weeks post-stroke. We also quantified sub-acute neuroinflammation in the post-stroke brain in a separate cohort of mice following a 60 min transient middle cerebral artery occlusion (tMCAo). Naive e450+-labeled splenic CD8+ cytotoxic T cells were intravenously injected at 7, 24, 48, and 72 h post-tMCAo. Mice were sacrificed 4 days after stroke. Detailed quantification of post-stroke neural connectivity and neuroinflammation indicates a role for remote brain regions in stroke pathology and recovery. The workflow described herein, incorporating STPT and automated quantification of fluorescently labeled features of interest, provides a framework by which one can objectively evaluate labeled neuronal or lymphocyte populations in healthy and injured brains. The results provide region-specific quantification of neural connectivity and neuroinflammation, which could be a critical tool for investigating mechanisms of not only stroke recovery, but also a wide variety of brain injuries or diseases.

To compare various biometric parameters between fellow eyes of acute primary angle closure (glaucoma) [APAC(G)] and fellow eyes of chronic primary angle closure (glaucoma) [CPAC(G)].Ultrasound biomicroscopy examinations were performed on 47 patients with unilateral APAC(G) and 41 patients with asymmetric CPAC(G) before laser peripheral iridotomy and pilocarpine treatment. Anterior chamber depth and width (ACD and ACW), lens vault (LV), iris curvature (IC), iris root distance (IRD), trabecular-ciliary process distance (TCPD), iris-ciliary process distance (ICPD), trabecular-ciliary angle (TCA), and other biometric parameters were compared between fellow eyes of APAC(G) and fellow eyes of CAPC(G).Compared with fellow eyes of CPAC(G), fellow eyes of APAC(G) had smaller ACD (P < 0.001), ACW (P = 0.007), TCPD (P = 0.016), ICPD (P = 0.008), and TCA (P = 0.006), as well as larger LV (P = 0.002), IC (P = 0.012), and IRD (P = 0.003). On multivariate logistic regression analyses, a 0.1 mm decrease in ACD (odds ratio [OR]: 0.705, 95%CI: 0.564-0.880, P = 0.002), ICPD (OR: 0.557, 95%CI: 0.335-0.925, P = 0.024), and a 0.1 mm increase in IRD (OR: 2.707, 95%CI: 1.025-7.149, P = 0.045), was significantly associated with occurrence of acute angle closures.Fellow eyes of APAC(G) had smaller anterior segment dimensions, higher LV, more posterior iris insertion, greater IC, and more anteriorly rotated ciliary body compared with fellow eyes of CPAC(G). ACD, ICPD, and IRD were the three most important parameters that distinguish eyes predisposed to APAC(G) or CPAC(G).

Objective. To evaluate and compare the clinical effects of Ahmed glaucoma valves (AGVs) and EX-PRESS implants on glaucoma secondary to silicone oil (SO) emulsification. Methods. A retrospective case-series study was designed. A total of 23 eyes with late intraocular pressure (IOP) elevation secondary to SO emulsification were included in the study. Antiglaucoma surgery with implantation of AGVs or EX-PRESS devices was performed. Pre- and postoperative ocular parameters were recorded at each visit during a 1-year follow-up period. The rates of complete success (IOP

The impairment of retinal vascular autoregulation can be an early manifestation of many systemic and ocular diseases. Therefore, quantifying retinal vascular autoregulation in a non-invasive manner is very important. This study evaluated the effects of a Valsalva maneuver (VM)-induced blood pressure increases on retinal vascular autoregulation. Parafoveal and peripapillary retinal vessel density were measured with optical coherence tomography angiography before (baseline) and 5 s after each subject completed a VM (Phase IV [VM-IV]). Hemodynamic parameters and intraocular pressure (IOP) were examined. Blood pressure (systolic, diastolic, and mean arterial) and ocular perfusion pressure significantly increased during VM-IV, but IOP and heart rate (HR) did not change. The VM-induced blood pressure overshoot significantly decreased parafoveal (8.43%) and peripapillary (1.57%) perfused retinal vessel density (both P < 0.001). The response in the parafoveal region was greater than that in the peripapillary region (P < 0.001), and was age-dependent (r = 0.201, P < 0.05). Foveal avascular zone area detectable with OCTA significantly increased from baseline by 6.63% during VM-IV (P < 0.05). Autoregulatory responses to a VM did not show gender-related differences in either retinal region. The autoregulation of retinal vessels may vary in different regions of the fundus. Optical coherence tomography angiography could be a useful method for evaluating the autoregulation of the retinal vascular system.

To evaluate the peripapillary and perifoveal retinal perfusions of young healthy eyes with a tessellated fundus using optical coherence tomography (OCT) angiography.Thirty-five Chinese subjects with a tessellated fundus and 35 subjects without a tessellated fundus from a population-based cross-sectional study in Shanghai were included. All participants underwent OCT angiography. The flow index and vessel density were examined in the peripapillary and perifoveal retinal areas, and their relationships with other ocular parameters were analyzed.In the peripapillary area, the eyes with a tessellated fundus had a lower retinal nerve fiber layer (RNFL) flow index (0.055 ± 0.009 vs. 0.061 ± 0.007, P = 0.006), RNFL vessel density (61.8 ± 7.3 vs. 65.9 ± 5.2, P = 0.010), retinal flow index (0.086 ± 0.010 vs. 0.092 ± 0.008, P = 0.012), and retinal vessel density (83.7 ± 5.0 vs. 86.4 ± 3.7, P = 0.018) than the control eyes, and the difference remained significant even after adjustments were made for gender and RNFL thickness. No difference was found in the perifoveal area. Multivariable linear regression analysis showed that the retinal flow index and vessel density in the peripapillary area were significantly correlated with the tessellated fundus diagnosis (flow index: β = -0.006, P = 0.005; vessel density: β = -2.597, P = 0.006), gender (flow index: β = 0.005, P = 0.019; vessel density: β = 3.129, P = 0.002) and RNFL thickness (flow index: β = 0.000, P = 0.002; vessel density: β = 0.190, P = 0.002). The RNFL flow index and vessel density were significantly associated with the tessellated fundus diagnosis (flow index: β = -0.005, P = 0.005; vessel density: β = -3.572, P = 0.008) and the thickness of RNFL (flow index: β = 0.001, P < 0.001; vessel density: β = 0.421, P < 0.001).Eyes with tessellated fundus with a relative decreased peripapillary retinal perfusion compared with eyes without a tessellated fundus were observed. The findings whether indicate causality that the reduction in the peripapillary perfusion and the peripapillary atrophy in myopia, need further study.

Purpose. The study was aimed at comparing the long-term effects of different antiglaucoma eye drops on conjunctival structures using laser scanning confocal microscopy. Methods. Eighty patients diagnosed with primary open-angle glaucoma and twenty healthy volunteers were included in this study. The participants were divided into 5 groups according to the different medications. The lachrymal film break-up time, Schirmer’s I test, and Ocular Surface Disease Index Questionnaire were performed in all subjects. The confocal microscopy was used to observe the basal epithelial cell density (ECD), goblet cell density (GCD), dendritic cell density (DCD), and subepithelial collagen fiber diameter (SFD). Results. Statistically significant differences were found among the control group and the antiglaucoma therapy groups in the values of three clinical data (P

Previously, we found that the incidence of kidney injury in patients with chronic hypoxia was related to the partial pressure of arterial oxygen. However, at oxygen concentrations that contribute to kidney injury, the changes in the relationship between microRNAs (miRNAs) and the hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) axis and the key miRNAs involved in this process have not been elucidated. Therefore, we elucidated the relationship between VEGF and kidney injury at different oxygen concentrations and the mechanisms mediated by miRNAs. Sprague-Dawley rats were exposed to normobaric hypoxia and categorized into six groups based on the concentration of the oxygen inhaled and injection of the angiogenesis inhibitor bevacizumab, a humanized anti-VEGF monoclonal antibody. Renal tissue samples were processed to determine pathological and morphological changes and HIF-1α, VEGF, and miRNA expression. We performed a clustering analysis of highrisk pathways and key hub genes. The results were validated using two Gene Expression Omnibus datasets (GSE94717 and GSE30718). As inhaled oxygen concentration decreased, destructive changes in the kidney tissues became more severe. Although the kidney possesses a self-protective mechanism under an intermediate degree of hypoxia (10% O2), bevacizumab injections disrupted this mechanism, and VEGF expression was associated with the ability of the kidney to repair itself. rno-miR-124-3p was identified as a crucial miRNA; a key gene target, Mapk14, was identified during this process. VEGF plays an important role in kidney protection from injury under different hypoxia levels. Specific miRNAs and their target genes may serve as biomarkers that provide new insights into kidney injury treatment. NEW & NOTEWORTHY Renal tolerance to hypoxic environments is limited, and the degree of hypoxia does not show a linear relationship with angiogenesis. VEGF plays an important role in the kidney's self-protective mechanism under different levels of hypoxia. miR-124-3p may be particularly important in kidney repair, and it may modulate VEGF expression through the miR-124-3p/Mapk14 signaling pathway. These microRNAs may serve as biomarkers that provide new insights into kidney injury treatment. [ABSTRACT FROM AUTHOR]