Objective: To investigate the associations between 24 hour activity and the quality of life (QoL) in children with autism spectrum disorder (ASD), and to explore their isotemporal substitution effects, providing a reference for developing intervention strategies of their QoL. Methods: From March to June 2025, 288 children with ASD from 7 special education schools in Jinan were selected by using a cluster random sampling method. The 24 hour activity was measured by using ActiGraph wGT3X-BT triaxial accelerometers, and their QoL was assessed by applying a parent proxy Pediatric Quality of Life Inventory. Multiple linear regression was employed to analyze the associations between 24 hour activity and QoL in children with ASD. Isotemporal substitution analysis was applied to analyze the dose response relationship of 24 hour activity time and the QoL scores in children with ASD. Results: Within the 24 hour activities of children with ASD, the daily time spent in sleep, sedentary behavior (SB), light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were 610.49，605.80，195.49，28.22 minutes, respectively. Multiple linear regression analysis showed that, after controlling for confounding factors such as gender, age, and parental education level, the proportion of time spent in MVPA was positively associated with QoL scores ( β =1.75) in children with ASD, whereas the proportion of time spent in SB was negatively associated with QoL scores ( β =-1.00)(both P <0.01). In the dose response relationship, reallocating time from sleep, SB, and LPA to MVPA was associated with an improvement in QoL in children with ASD, with increased scores of 1.38, 1.55, 1.47, respectively; conversely, the reverse substitution was associated with a decline in QoL, and the scores decreased by 2.31, 2.99 and 2.68, respectively, with the latter demonstrating a more pronounced effect(all P <0.05). Conclusions Enhancing the QoL for children with ASD should be grounded in the overall balance of 24 hour activity. Time reallocation strategies should be implemented with an emphasis on relatively increasing MVPA and reducing SB.

Objective To compare the efficacy and safety of transurethral blue laser vaporization of the prostate, transurethral resection of the prostate (TURP) or plasmakinetic resection of the prostate in the treatment of benign prostatic hyperplasia (BPH). Methods The domestic and foreign clinical studies on transurethral blue laser vaporization of the prostate (observation group), TURP or plasmakinetic resection of the prostate (control group) in the treatment of BPH during Jan. 2015 and Mar. 2025 were retrieved. The data were extracted with Cochrane systematic review method. The operation time, decrease in hemoglobin, bladder irrigation time, catheter indwelling time, total complication rate, retrograde ejaculation rate and urinary incontinence rate of the two groups were compared with RevMan 5.3.0 statistical software. Results A total of 5 Chinese studies involving 491 patients (248 in the observation group and 243 in the control group) were included in the Meta-analysis. Compared with the control group, the observation group had shorter operation time [MD=-20.80, 95%CI:-26.88—-14.72, P＜0.00001], less decrease in hemoglobin [MD=-10.61, 95%CI: -20.21—-1.01, P=0.03], shorter bladder irrigation time [MD=-17.85, 95%CI: -32.62—-3.09, P=0.002], shorter catheter indwelling time [MD=-1.71, 95%CI: -2.81—- 0.62, P=0.002], lower total complication rate [OR=0.11, 95%CI: 0.06—0.21, P＜0.00001], lower retrograde ejaculation rate [OR=0.05, 95%CI: 0.02—0.16, P＜0.00001] and lower urinary incontinence rate [OR=0.24, 95%CI: 0.07—0.79, P=0.02]. There were no significant differences in other complications between the two groups (P＞0.05). The international erectile function score (IIEF-5) of the observation group was significantly higher than that of the control group [MD=1.87, 95%CI:1.16—2.57, P＜0.00001]. There were no significant differences in international prostate symptom score (IPSS), maximum urinary flow rate (Qmax) and post-voiding residual (PVR) between the two groups (P＞0.05). Conclusion All three surgical procedures can effectively improve the lower urinary tract symptoms of BPH patients. Compared with TURP or plasmakinetic resection of the prostate, transurethral blue laser vaporization of the prostate has obvious advantages in terms of perioperative recovery, reduction of total complications, urinary incontinence and retrograde ejaculation rates, and preservation of sexual function.

ObjectiveTo address the shortage of high-caliber multidisciplinary professionals in China's rehabilitation engineering field and the prominent issue of "separation between medicine and engineering" in existing curricula, this study introduces the World Health Organization rehabilitation competency framework (RCF) to construct a systematic curriculum system for rehabilitation engineering. MethodsGuided by the four core competency domains of RCF (practice, professionalism, learning and development, management and leadership) and their associated supporting knowledge, the rehabilitation engineering curriculum was restructured into a modular framework, piloted and validated within the Biomedical Engineering (Intelligent Robotics) program at University of Health and Rehabilitation Sciences. ResultsA four-tiered curriculum system comprising General Education-Disciplinary Platform-Professional Core-Diverse Electives with a total of 160 credits was established, achieving precise mapping between competency objectives and course content. The students in the pilot cohort demonstrated outstanding academic performance (50% ranked in the top ten of their major), they also gained a deeper understanding and mastery of interdisciplinary knowledge integrating medicine and engineering. ConclusionThe RCF-based curriculum system effectively promotes the organic integration of medical and engineering knowledge, providing an internationally aligned competency-oriented paradigm for rehabilitation engineering talent cultivation, which holds significant value for broader application.

ObjectiveThis study aimed to investigate the anti-Mycoplasma pneumoniae (MP) activity of luteolin and elucidate its underlying mechanisms. MethodsLuteolin was identified as the primary active compound from the polyphenol extract ofF. diotrys using network pharmacology. Its efficacy was evaluated against two MP strains: the standard strain M129 and the multidrug-resistant strain M19. A modified culture medium with visual characteristics was employed to determine the minimum inhibitory concentration (MIC) of luteolin. The expression of key proteins involved in MP growth and pathogenicity was assessed by qRT-PCR following luteolin treatment. Additionally, the viability of A549 cells infected with MP was compared between luteolin-treated and untreated groups. In vivo anti-MP activity was evaluated using a mouse model, and the expression of inflammatory cytokines in lung tissues was analyzed. ResultsLuteolin effectively inhibited both MP strains, with MIC₉₀ values of 100 mg/L for M19 and M129. Treatment with luteolin significantly downregulated the expression of adhesion proteins P1 and P30 in both strains. However, the expression of P65, HMW3, TrmB, and CARDS TX was reduced only in the M19 strain following luteolin intervention. Luteolin also enhanced the growth and viability of A549 cells infected with MP. In the mouse model, luteolin treatment resulted in steady weight gain and was well tolerated. The bacteriostatic rate of luteolin in lung tissues was 50.7%, significantly higher than the 25.2% observed in the roxithromycin group. Furthermore, luteolin reduced the expression of inflammatory factors, including IL-6, TNF-α, and HMGB1, in MP-infected mice. ConclusionLuteolin effectively and safely inhibits the proliferation and pathogenicity of MP, particularly the drug-resistant M19 strain, by downregulating the expression of toxicity-associated proteins (P1, P30, P65, HMW3, TrmB, CARDS TX) and modulating host inflammatory responses. These findings suggest that luteolin may offer a novel therapeutic strategy for treating MP infections, especially those caused by drug-resistant strains.

ObjectiveThis paper aims to investigate the mechanism by which Erchentang improves body weight in obese mice by regulating the AMP‑activated protein kinase （AMPK）/peroxisome proliferator‑activated receptor γ coactivator‑1α （PGC‑1α） signaling pathway and inducing browning of inguinal white adipose tissue （iWAT）. MethodsObese mouse models were established by feeding a high‑fat diet. After successful modeling， mice were randomly divided into a model group and low‑， medium‑， and high‑dose Erchentang groups （7.5， 15， 30 g·kg^-1）， with six mice in each group. Another six normal mice were set as the normal group. Mice in the treatment groups were administered with corresponding doses of the drug by gavage， while those in the normal and model groups were administered with an equal volume of pure water by gavage for four consecutive weeks. Obesity was evaluated by body weight and Lee's index. The levels of low‑density lipoprotein cholesterol （LDL‑C） and high‑density lipoprotein cholesterol （HDL‑C） in serum were detected by biochemical assays. The leptin content in serum was measured by enzyme‑linked immunosorbent assay （ELISA）. Hematoxylin and eosin （HE） staining was used to observe the pathological morphology of the liver and iWAT. Immunofluorescence staining was applied to detect the protein expression levels of glucose transporter 4 （GLUT4） in the liver and iWAT. Molecular docking was performed to simulate the binding affinity between the key components of Erchentang （nobiletin， diosmetin， naringenin） and the key pathway proteins AMPK and PGC‑1α. Western blot was used to detect the protein expression levels of uncoupling protein‑1 （UCP‑1）， AMPK， phosphorylated AMP-activated protein kinase （p‑AMPK）， and PGC‑1α in iWAT. ResultsCompared with those in the normal group， the mice in the model group showed significantly increased body weight and Lee's index， elevated levels of HDL‑C， LDL‑C， and leptin in serum， enlarged adipocytes in iWAT， down‑regulated protein expression levels of GLUT4 in iWAT and liver， and decreased protein expression levels of UCP‑1 and PGC‑1α in iWAT（P<0.05， P<0.01）， the expression level of p-AMPK / AMPK protein was up-regulated， but the difference was not statistically significant. Compared with those in the model group， the mice in the Erchentang groups with different doses exhibited significantly reduced body weight and Lee's index， decreased levels of HDL‑C， LDL‑C， and leptin in serum， smaller adipocytes in iWAT， up‑regulated GLUT4 protein expression levels in iWAT and liver， and increased protein expression levels of UCP‑1， p‑AMPK/AMPK， and PGC‑1α in iWAT （P<0.05， P<0.01）. Molecular docking results show that nobiletin， diosmetin， and naringenin have strong binding energies with both AMPK and PGC‑1α. ConclusionErchentang may improve body weight in obese mice by regulating the AMPK/PGC‑1α signaling pathway and inducing iWAT browning.

BACKGROUND:Myocardial hypertrophy often leads to severe cardiovascular diseases and is difficult to diagnose due to its early stages being hard to detect.Circulating inflammatory proteins have been found to be significantly associated with cardiovascular diseases,yet the specific mechanisms linking them to myocardial hypertrophy remain unclear.OBJECTIVE:To investigate the relationship between circulating proteins and myocardial hypertrophy using multiple Mendelian randomization approaches.METHODS:Utilizing data from 91 circulating inflammatory proteins in the GWAS Catalog database and the latest myocardial hypertrophy data from the R11 FinnGen database,we employed bidirectional two-sample Mendelian randomization,multivariate Mendelian randomization,and Genome-Wide Association Studies co-localization to investigate the causal relationship between circulating inflammatory proteins and myocardial hypertrophy.The accuracy of the results was verified through sensitivity tests including MR-PRESSO,Cochran's Q test,MR-Egger intercept assessment,leave-one-out analysis,and funnel plot analysis.RESULTS AND CONCLUSION:In the results of two-sample Mendelian randomization,the primary method used for evaluation was the Inverse Variance Weighting(IVW)approach.It was found that the level of T-cell surface glycoprotein CD6 isoform(IVW:P=0.046,OR=0.74,95％Cl:0.66-1.00),level of slit chemokine(IVW:P=2.1×10-2,OR=0.74,95％CI:0.556-0.95),level of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-4,OR=0.66,95％CI:0.49-0.87),level of interleukin-2(IVW:P=3.8×103,OR=0.667,95％CI:0.50-0.88),and sulfotransferase 1A1(IVW:P=1.42×102,OR=0.80,95％CI:0.67-0.96)had a unidirectional causal effect on cardiac hypertrophy.(2)Among the findings in multivariate Mendelian randomization,the levels of the CD6 isoform of T-cell surface glycoprotein(IVW:P=1.39×102,OR=0.81,95％CI:0.69-0.96)and the levels of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-2,OR=0.73,95％CI:0.55-0.98)were positive,indicating that the results remained significant after excluding the effects of other circulating inflammatory proteins that had an impact on myocardial hypertrophy.(3)In colocalization,T-cell surface glycoprotein CD6 isoform levels had H3+H4=0.96,with the most significant single nucleotide polymorphism being rs59570070,suggesting an intrinsic link between T-cell surface glycoprotein CD6 isoform levels and myocardial hypertrophy.(4)Sensitivity results showed no abnormalities,indicating no heterogeneity or pleiotropic effects influencing the results.(5)These results verified that T cell surface glycoprotein CD6 isoforms,Slit chemokine,Delta and Notch-like epidermal growth factor-related receptors,interleukin-2,and sulfotransferase 1A1 had a unidirectional causal effect on myocardial hypertrophy.T cell surface glycoprotein CD6 isoforms and Delta and Notch-like epidermal growth factor-related receptors had the deepest impact,suggesting that there may be related pathways between T cell surface glycoprotein CD6 isoforms and myocardial hypertrophy.Mendelian randomization studies require large amounts of clinical data and therefore often use European samples from international databases for analysis.Since this analytical method has significant advantages in causal inference,precision medicine,and cross-population validation,its research results still hold great significance for the medical development in China.As Mendelian randomization research deepens,it also promotes the collection and analysis of clinical data in China to some extent.In the future,we can further analyze key protein mechanisms,combine multiomics and clinical validation,develop an inflammatory marker monitoring system and novel anti-inflammatory therapies,thereby promoting the prevention and control of cardiovascular diseases and the development of personalized medicine.

BACKGROUND:Upper lumbar spinal stenosis is a multifactorial degenerative disorder of the spine.For narrowing of the spinal canal in the upper lumbar region(L1-L4),surgical decision-making is particularly complex.Existing minimally invasive surgeries each have their own advantages and limitations.Currently,there are few reports on biomechanical comparison and finite element analysis of different surgical methods for the treatment of high lumbar spinal stenosis.OBJECTIVE:To analyze the biomechanical impact of endoscopic unilateral laminotomy for bilateral decompression,transforaminal endoscopic lumbar decompression,and cross-overtop decompression in the treatment of upper lumbar spinal stenosis using endoscopy,and to verify the reliability and effectiveness of these three surgical techniques in treating upper lumbar spinal stenosis,providing a biomechanical basis for clinical decision-making.METHODS:The CT images of the lumbar spine of a healthy volunteer were selected,and the finite element model M0 of the normal lumbar L1-L5 segments was established using Mimics,Geomagic,Solid works,and Ansys software.The L2-L3 segment,representing upper lumbar characteristics,was chosen.Based on this model,the surgical models for endoscopic unilateral laminotomy for bilateral decompression(M1),transforaminal endoscopic lumbar decompression(M2),and cross-overtop decompression(M3)were established.Using software,the changes in the range of motion of the entire lumbar segment and the maximum Von Mises stress of the intervertebral discs were simulated and evaluated for each group of models under six loading conditions:flexion,extension,left lateral bending,right lateral bending,left rotation,and right rotation.RESULTS AND CONCLUSION:(1)Compared with model MO,the range of motion in M1,M2,and M3 increased under all six conditions,with M1 showing a greater increase.(2)M1 and M2 demonstrated significant increases in range of motion under forward bending,extension,and right rotation,while the increase under other conditions remained below 7％.(3)Compared with model M3,model M1 exhibited slightly increased overall joint range of motion during extension and left bending,while no significant changes were observed in other aspects,and the L1-L5 lumbar segments did not reach an unstable state.(4)In model M1,the maximum Von Mises stress of the intervertebral discs increased most significantly under flexion and extension loading conditions.However,under left lateral bending,right lateral bending,left rotation,and right rotation loading conditions,the increase did not exceed 5％.(5)These findings suggest that due to the sagittal anatomical characteristics of the facet joints,the unilateral laminotomy for bilateral decompression technique,while decompressing,involves resection of more facet joints,which impacts overall segmental stability.The transforaminal endoscopic lumbar decompression technique is suitable for patients with foraminal stenosis but cannot achieve complete decompression for those with severe ventral central stenosis.The Cross-Overtop technique effectively enlarges the volume of the central canal and lateral recess,optimizing decompression,and shows unique advantages in treating upper lumbar spinal stenosis.

BACKGROUND:Studies have shown that disorders of mineral metabolism may be responsible for premature aging and that the kl/FGF23 axis plays an important role in mineral metabolism.OBJECTIVE:To explore the effect of long-term endurance exercise on the kl/FGF23 axis in naturally aging mice,and to observe the impact of long-term endurance exercise on calcium and phosphorus metabolism,so as to provide a reference for the influence of long-term endurance exercise on natural aging.METHODS:Twenty-two 5-week-old SPF male balb/c mice were randomly divided into three groups:young and quiet control group,natural aging quiet group and natural aging exercise group.Mice in the young and quiet control group were then killed immediately.Mice in the natural aging quiet group were raised normally until 60 weeks of age.Mice in the natural aging exercise group were subjected to adaptive exercise for 1 week,followed by the maximum running speed test.The official exercise speed was set at 70％of the maximum running speed,and exercise was performed on Mondays,Wednesdays,and Fridays for 50 minutes each.Maximum running speed was retested at 8-week intervals to adjust the official exercise speed until the age of 60 weeks.(3)Enzyme-linked immunoassay was used to measure the levels of femoral fibroblast growth factor 23,renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2D3.RESULTS AND CONCLUSION:(1)Compared with the young and quiet control group,serum calcium and phosphorus levels in natural aging quiet group had no significant changes(P＞0.05),but bone calcium and phosphorus levels were significantly reduced(P＜0.01).Compared with the natural aging quiet group,the serum phosphorus level was significantly reduced(P＜0.05),the serum calcium level did not change(P＞0.05),and bone calcium and phosphorus levels were significantly increased in the natural aging exercise group(P＜0.05).(2)Compared with the young and quiet control group,the level of fibroblast growth factor 23 in the femur of the natural aging quiet group was significantly increased(P＜0.05).Compared with the natural aging quiet group,the level of fibroblast growth factor 23 in the femur of the natural aging exercise group was reduced,but it was not statistically significant(P＞0.05).(3)Compared with the young and quiet control group,the renal Klotho protein expression,the renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2 D3 levels in the natural aging quiet group were significantly decreased(P＜0.05,P＜0.01).Compared with the natural aging quiet group,the levels of the above-mentioned indicators were significantly increased in the natural aging exercise group(P＜0.05,P＜0.01).To conclude,long-term endurance exercise can regulate Klotho protein and fibroblast growth factor 23 through the kl/FGF23 axis,thereby affecting the expression of 1α-hydroxylase and the level of 1,25(OH)2D3,and further regulating the body's calcium and phosphorus metabolism,especially phosphate metabolism.This indicates that long-term endurance exercise can delay the natural aging of the body through the kl/FGF23 axis.

ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.