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Abstract Background Diabetic retinopathy (DR) is the foremost cause of vision loss among the global working-age population, and statins are among the most frequently prescribed drugs for lipid management in patients with DR. The exact relationship between statins and DR has not been determined. This study sought to validate the causal association between statins usage and diabetic retinopathy. Methods The summary-data-based Mendelian randomization (SMR) method and inverse-variance-weighted Mendelian randomization (IVW-MR) were used to identify the causal relationship between statins and DR via the use of expression quantitative trait loci (eQTL) data for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (31,684 blood samples), low density lipoprotein cholesterol-related GWAS data (sample size: 440,546), and DR-related GWAS data (14,584 cases and 176,010 controls). Additionally, a cross-sectional observational study based on the data from the National Health and Nutrition Examination Survey (NHANES) was conducted to supplement the association between DR and statins (sample size: 106,911). The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) was employed to evaluate the results. Results Based on the results of the MR analysis, HMGCR inhibitors were causally connected with a noticeably greater incidence of DR (IVW: OR = 0.54, 95% CI [0.42, 0.69], p = 0.000002; SMR: OR = 0.66, 95% CI [0.52, 0.84], p = 0.00073). Subgroup analysis revealed that the results were not affected by the severity of DR. The sensitivity analysis revealed the stability and reliability of the MR analysis results. The results from the cross-sectional study based on NHANES also support the association between not taking statins and a decreased risk of DR (OR = 0.54, 95% CI [0.37, 0.79], p = 0.001). Conclusions This study revealed that a significant increase in DR risk was causally related to statins use, providing novel insights into the role of statins in DR. However, further investigations are needed to verify these findings.

Abstract Background Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease and rapidly escalating epidemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pathogenesis of COVID-19 remains to be elucidated. We aimed to clarify correlation of systemic inflammation with disease severity and outcomes in COVID-19 patients. Methods In this retrospective study, baseline characteristics, laboratory findings, and treatments were compared among 317 laboratory-confirmed COVID-19 patients with moderate, severe, or critically ill form of the disease. Moreover, the longitudinal changes of serum cytokines, lactate dehydrogenase (LDH), high-sensitivity C-reactive protein (hsCRP), and hsCRP to lymphocyte count ratio (hsCRP/L) as well as their associations with disease severity and outcomes were investigated in 68 COVID-19 patients. Results Within 24 h of admission, the critically ill patients showed higher concentrations of inflammatory markers including serum soluble interleukin (IL)-2 receptor, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), ferritin, procalcitonin, LDH, hsCRP, and hsCRP/L than patients with severe or moderate disease. The severe cases displayed the similar response patterns when compared with moderate cases. The longitudinal assays showed the levels of pro-inflammatory cytokines, LDH, hsCRP, and hsCRP/L gradually declined within 10 days post admission in moderate, severe cases or those who survived. However, there was no significant reduction in cytokines, LDH, hsCRP, and hsCRP/L levels in critically ill or deceased patients throughout the course of illness. Compared with female patients, male cases showed higher serum concentrations of soluble IL-2R, IL-6, ferritin, procalcitonin, LDH, and hsCRP. Multivariate logistic regression analysis revealed that IL-6 > 50 pg/mL and LDH > 400 U/L on admission were independently associated with disease severity in patients with COVID-19. Conclusion Exuberant inflammatory responses within 24 h of admission in patients with COVID-19 may correlate with disease severity. SARS-CoV-2 infection appears to elicit a sex-based differential immune response. IL-6 and LDH were independent predictive parameters for assessing the severity of COVID-19. An early decline of these inflammation markers may be associated with better outcomes.

Abstract Background Retinitis pigmentosa (RP) is a kind of inherited retinal degenerative diseases characterized by the progressive loss of photoreceptors. RP has been a conundrum without satisfactory countermeasures in clinic until now. Acetaldehyde dehydrogenase 2 (ALDH2), a major enzyme involved in aldehyde detoxification, has been demonstrated to be beneficial for a growing number of human diseases, such as cardiovascular dysfunction, diabetes mellitus and neurodegeneration. However, its protective effect against RP remains unknown. Our study explored the impact of ALDH2 on retinal function and structure in N-methyl-N-nitrosourea (MNU)-induced RP rats. Methods Rats were gavaged with 5 mg/kg Alda-1, an ALDH2 agonist, 5 days before and 3 days after MNU administration. Assessments of retinal function and morphology as well as measurement of specific proteins expression level were conducted. Results Electroretinogram recordings showed that Alda-1 administration alleviated the decrease in amplitude caused by MNU, rendering protection of retinal function. Mitigation of photoreceptor degeneration in MNU-treated retinas was observed by optical coherence tomography and retinal histological examination. In addition, Western blotting results revealed that ALDH2 protein expression level was upregulatedwith increased expression of SIRT1 protein after the Alda-1 intervention. Besides, endoplasmic reticulum stress (ERS) was reduced according to the significant downregulation of GRP78 protein, while apoptosis was ameliorated as shown by the decreased expression of PARP1 protein. Conclusions Together, our data demonstrated that ALDH2 could provide preservation of retinal function and morphology against MNU-induced RP, with the underlying mechanism at least partly related to the modulation of SIRT1, ERS and apoptosis.

Abstract Background Oxidative stress (OS) is an essential factor in the pathogenesis of branch retinal vein occlusion (BRVO). Studies have demonstrated the role of hydrogen gas in the regulation of OS. This study was designed to evaluate the efficacy of hydrogen gas on the BRVO rat model. Methods Twenty-four BRVO rats were randomly divided into two groups: the hydrogen gas (H) group (42% H2, 21% O2, 37% N2) and the model (M) group (21% O2, 79% N2). Rats in the H group inhaled hydrogen gas for 8 h every day up to 30 d post-occlusion. Twelve age-matched healthy rats served as the control (C) group. Retinal function and morphology were detected at 1, 7, 14 and 30 d post-occlusion. Furthermore, the expression of vascular endothelial growth factor (VEGF-α) was detected by immunofluorescent staining. Results Full-field electroretinography (ffERG) revealed that the amplitude of the b-wave (dark-adaptation 3.0 response), the amplitude of the OPs2 wave and the light-adapted flicker response in the H group were all higher than those in the M group at 7 d post-occlusion (all p 0.05). Conclusions Our findings demonstrate that inhalation of hydrogen gas could alleviate retinal oedema, shorten reopen time and improve retinal function, and the potential mechanism might be related to a decrease in VEGF-α expression.

Abstract Aims To investigate the fundus characteristics and macular optical coherence tomography angiography (OCTA) metrics in patients with myelinated retinal nerve fibers (MRNF) and to identify the associations among myopic parameters, fundus metrics, and OCTA metrics. Methods The single-center case-control study included 15 patients with monocular MRNF and 15 patients without MRNF, matched for age, affected eyes’ spherical equivalent error (SER), and axial length (AL) between May 2021 and December 2021. Fundus features, including the entire MRNF area (Area1), the denser MRNF area (Area2), and the shortest distance from the fovea to the MRNF border (Df−m), along with ocular parameters, including SER, AL, best corrected visual acuity (BCVA), and OCTA metrics at the fovea, including choroidal (ChT) and retinal (ReT) thicknesses at the fovea, the foveal avascular zone area (FAZ), foveal avascular zone perimeter (FAZP), FAZ-circularity index (FAZ-CI), and foveal vessel density in a 300-µm wide region (FD-300), were assessed. Results The SER, AL, and BCVA were significantly different, and the ChT was thinner in the affected eyes than in the contralateral eyes. Compared with matched eyes, affected eyes had reduced BCVA and thinner ReT. In the affected eyes, both Area1 and Area2 were negatively correlated with SER (r 1 = -0.84, r 2 = -0.65), △SER (r 1 = -0.86, r 2 = -0.61), ReT at the vertical superior 3 mm (VS) (r 1 = -0.78, r 2 = -0.67), and ChT_VS (r 1 = -0.64, r 2 = -0.62), and positively correlated with AL (r 1 = 0.82, r 2 = 0.52) and BCVA (r 1 = 0.54, r 2 = 0.59). Df−m was negatively correlated with BCVA (r = -0.57). Conclusion The presence of MRNF affects BCVA and ReT at the fovea. The area of the MRNF, as well as the distance from the MRNF to the fovea, are closely associated with the affected eyes’ BCVA, SER, AL, and the degree of anisometropia.

Abstract Background Over the years, with the improvement of diagnostic and therapeutic capabilities for hip joint diseases and the advancements in surgical technology, hip arthroscopy has been extensively used. At present, there is ongoing controversy among scholars about whether it is necessary to close the joint capsule after hip arthroscopy. In addition, the clinical effect of repairing the hip joint capsule after hip arthroscopy remains uncertain. Purpose To evaluate the effect of our modified shoelace suture technique on postoperative hip function and to investigate whether complete closure of the hip capsule is reliable and safe. Study Design Retrospective study; Levels of evidence: III. Methods A retrospective review was conducted on patients undergoing hip arthroscopy by a solitary high-volume hip arthroscopic surgeon. The patients were categorized into two groups. The first group consisted of patients who underwent the modified shoelace continuous capsular closure technique. The other group consisted of those who did not receive capsular closure after hip arthroscopy. Patient-reported outcomes including modified Harris Hip Score (mHHS), Hip Outcome Score of Activities of Daily Living (HOS-ADL), Hip Outcome Score Sport-Specific Subscale (HOS-SSS), and visual analogue scale (VAS) were obtained at a minimum of 12 months. Any complications during follow-up were identified and recorded. Results A total of 100 patients were followed up for 12–15 months, with an average of (12.3 ± 5.3) months in the study. There were 50 patients in the shoelace capsular closure group (CC group) and 50 patients in the non-capsular closure group (NC group). The surgical time in the suture group was significantly longer than that in the non-suture group. However, there was no statistically significant disparity in the length of hospital stay between the two groups. The mHHS, HOS-SSS, HOS-ADL, and VAS of the CC and NC group were significantly improved compared to preoperative scores at 6 and 12 postoperative months (P

Abstract Background Myopia is one of the most common eye diseases causing visual impairment and blindness, and the high prevalence in adolescents remains a major public health concern. Based on clinical studies using optical defocus to regulate ocular growth and refractive changes through visual feedback, we hypothesize that early wearing of peripheral myopic defocusing spectacles in children with high risk of myopia may slow the process of emmetropization and even prevent the onset of myopia by inducing more peripheral myopic defocus. The aim of this study is to investigate whether the wearing of peripheral focus-out glasses can be effective in delaying emmetropization in non-myopic children aged 6–8 years. Methods The study is a 2-year randomized controlled trial. A total of 160 subjects will be randomized into the experimental group or the control group. The experimental group will be fitted with direct emmetropia with focus-out glasses (DEFOG) to guide the emmetropization process. The control group will not receive any treatment and will serve as a blank control group. The primary aim is to determine whether non-myopic children wearing DEFOG lenses are superior to those who do not receive any intervention on the progression of cycloplegic objective refraction over 2 years. Discussion This is the first randomized controlled trial aiming at myopic prevention by non-invasive intervention in non-myopic children. This study aims to initially investigate whether wearing peripheral focus-out glasses can effectively delay the process of emmetropization in children aged 6–8 years with high risk of myopia, which might give potential clues for further exploration on early prevention of myopia. Trial registration ClinicalTrials.gov NCT05689567. Registered on 10 January 2023.

Abstract Aims The purpose of this study is to elucidate the correlation between thyroid hormone, glycosylated hemoglobin (HbA1c), vitamin D and type 2 diabetes mellitus (T2DM) with Hashimoto’s thyroiditis (HT), and to seek the independent predictors affecting disease development. Methods The study included 44 T2DM with HT, 94 T2DM, and 112 healthy subjects. We investigated some laboratory factors like thyroid hormone and compared the levels. Independent predictors determination by logistic univariate regression analysis were analyzed. The diagnostic value of thyroid-stimulating hormone (TSH) and threshold concentration were determined by ROC curve. Results In T2DM with HT group, levels of PTH, HbA1c were lower and levels of TSH were significantly higher, when compared with T2DM group. But there was no significant difference in vitamin D between these two groups. In both logistic univariate regression analysis and multiple logistic regression analysis, TSH, HbA1c were independent predictors for T2DM with HT. Based on the ROC curve, the best cut-off value of the TSH was 4 mIU/L (sensitivity 72.7%, specificity 94.6%, AUC = 0.832) for predicting T2DM with HT in T2DM patients. Conclusions TSH has increased risk for T2DM evolving into T2DM complicated with HT, so it is important to monitor the concentrations of TSH in patients with T2DM. Although vitamin D was not the independent predictor in T2DM with HT development, effect of vitamin D deficiency on the progress of diabetes and its complications should be taken into consideration.

Abstract Purpose To determine the pattern of axial variation in subjects with initial shortened axial length during the entire period of orthokeratology and to discuss the possibility of shortened AL after one month of orthokeratology becoming a predictor of myopia control. Method This study retrospectively included 106 children with myopia aged 8 to 14 wearing OK lenses. Fifty-four eyes with shortened axial length (AL) at the first-month visit were enrolled in the axial length shortening (ALS) group, and fifty-two eyes without shortened AL were enrolled in the no axial length shortening (NALS) group. Axial length and refractive error at baseline and within the entire period of orthokeratology (20 months), including fitting, washout period and re-wear, were measured. Eighty-five children who started wearing single vision spectacle were also included as a control group. Results In the ALS group, AL became longer after shortening and slowly exceeded baseline; afterward, AL experienced a rebound during the washout period and shortened again if OK lenses were re-worn. After washout period, significant difference in AL (ALS:0.28 ± 0.19 mm, NALS: 0.52 ± 0.17 mm) and spherical equivalent (ALS:-0.43 ± 0.44D, NALS:-0.91 ± 0.40D) between the two groups were found(P

Abstract Background To investigate the impact of the ablation ratio on 5-year postoperative posterior corneal stability in myopic eyes after small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) surgery. Methods A prospective, nonrandomized, cohort study: 80 eyes of 43 patients underwent SMILE surgery and 63 eyes of 32 patients underwent FS-LASIK surgery at the EYE & ENT Hospital, Fudan University. Ablation ratio was defined as lenticule thickness (SMILE cases) or ablation depth (FS-LASIK cases) divided by central corneal thickness (CCT). Posterior corneal elevation changes were recorded as posterior central elevation (PCE), posterior corneal surface at thinnest point (PTE) and posterior corneal mean elevation (PME). Patients were followed up at 6-month and 5-year interval to investigate the impact of the ablation ratio on posterior corneal elevation after SMILE and FS-LASIK surgery. Results PCE dropped at the 6-month follow-up for both SMILE (decreased by −1.11 ± 2.93 μm, P 0.05) and PTE (elevation change: SMILE −0.08 ± 4.28 μm; FS-LASIK 1.42 ± 3.85 μm, P > 0.05) for both groups were recorded at the 5-year follow-up compared to the 6-month visit. Ablation ratio was strongly correlated with 5-year postoperative PCE (β = 2.68 ± 1.05, P

Abstract Background Hydrocephalus is a common and major complication that affects outcome after intraventricular hemorrhage (IVH). While aging impacts the occurrence of hydrocephalus in patients with IVH this and the underlying mechanisms have received little attention. The present investigation, therefore, studied the impact of aging on hydrocephalus after IVH in a rat model. Methods Young and aged (3 and 18 months old, respectively) male Fischer 344 rats had an intraventricular injection of 200 μl autologous blood or saline. Ventricular volume was estimated using magnetic resonance imaging (MRI), while ventricular wall damage, heme oxygenase-1 (HO-1) and epiplexus cell activation were quantified by histological staining and Western blot. Additionally, the impact of intraventricular iron injection was examined in young and aged rats. Results Intraventricular injection of autologous blood induced hydrocephalus in both young and aged rats but ventricular volumes were larger in aged rats compared to young rats from day 3 to day 14 followed IVH. In addition, ventricular wall damage and periventricular HO-1 upregulation were greater in aged versus young rats on day 1 after IVH. Aged rats also had more choroid plexus epiplexus cells on day 14 after IVH. Additionally, organized hematomas were observed in 23% (3/13) of aged rats but not in young rats after IVH. Organized hematomas in aged rats showed larger T2* lesions on MRI compared to rats with non-organized hematomas. Similar to the effects of IVH, intraventricular injection of iron resulted in more epiplexus cells activation and more severe hydrocephalus in aged compared to young rats. Conclusions IVH causes more severe hydrocephalus in aged compared to young rats. Enhanced ventricular wall damage, epiplexus cell activation and iron overload may contribute to this aggravated hydrocephalus development in aged animals.

Abstract Background According to recent studies, the phospholipase A2 receptor 1 (PLA2R1) may be used as a biomarker to diagnose idiopathic membranous nephropathy (iMN). Moreover, the immune-dominant regions of PLA2R1 have been identified. The aim of the present study was to construct a diagnostic antigen based on the immune-dominant region of PLA2R1 and develop a specific serological detection method for PLA2R1 antibodies. Results The tandem multi-epitope diagnostic antigen (designated ‘R101’), which includes aa 39–130 (CysR), aa 238–356 (CTLD1), and aa 1136–1234 (CTLD7) of PLA2R1; thioredoxin at the N-terminus; and a His tag at the C-terminus, was prepared at a concentration of 2.36 mg/mL and purity of 97.32% using Escherichia coli expression and affinity and anion exchange chromatography purification. The integrity and antigenicity of the R101 protein was demonstrated by western blot analysis using anti-Trx, anti-His, and anti-PLA2R1 monoclonal antibodies as the primary antibodies. By analysing 120 positive serum samples identified by biopsy-proven iMN (gold standard) and 240 negative samples identified by an established ELISA based on R101 protein, we concluded that the cut-off value, kappa value, sensitivity, specificity, and agreement rate were 0.305, 0.881, 91.67, 96.25, and 94.72% respectively. The receiver operating characteristic (ROC) curve illustrated that the diagnostic accuracy and practicability of the ELISA was excellent. The area under the curve was 0.986. Conclusions Using prokaryotic expression and chromatography purification, immune-dominant regions of PLA2R1 with excellent antigenicity can be prepared and applied to serological detection of PLA2R1 antibodies.