BACKGROUND: Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported. METHODS: The expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), microRNA-142-3p (miR-142-3p), and high mobility group box 1 (HMGB1) and the levels of ER stress, pyroptosis, and metabolic markers in normal and OA chondrocytes were investigated by western blotting, quantitative polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone (FAM-YVAD-FMK)/Hoechst 33342/propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and cell viability assessments. The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. The mechanistic contribution of EZH2, miR-142-3p, and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically, histologically, and immunohistochemically in surgically induced OA rats. RESULTS: Increased EZH2 and HMGB1, decreased miR-142-3p, enhanced ER stress, and activated pyroptosis in chondrocytes were associated with OA occurrence and progression. EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes. EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation, and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3'-UTR of the HMGB1 gene. Moreover, ER stress mediated the effects of EZH2, miR-142-3p, and HMGB1 on chondrocyte pyroptosis. In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2, miR-142-3p, and HMGB1 and their effects on chondrocyte ER stress and pyroptosis. CONCLUSIONS A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA, contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.
Enhancer of Zeste Homolog 2 Protein/genetics* ; Osteoarthritis, Knee/pathology* ; Chondrocytes/metabolism* ; Pyroptosis/physiology* ; HMGB1 Protein/genetics* ; MicroRNAs/metabolism* ; Endoplasmic Reticulum Stress/genetics* ; Humans ; Animals ; Rats ; Male ; Rats, Sprague-Dawley ; Middle Aged

Adaptive optics(AO)is a technology designed to enhance the performance of optical systems through real-time measurement and correction of optical aberrations. With continuous advancements in refractive surgery techniques and rising patient expectations for surgical outcomes, the precise implementation of personalized refractive corrections has become a critical focus. The integration of AO technology into refractive surgery provides novel technical support. Specifically, the adaptive optics vision simulator(VAO)facilitates accurate preoperative objective and subjective refraction by dynamically measuring and correcting ocular wavefront aberrations, thereby improving refractive efficiency. Additionally, it enables effective prediction of postoperative aberrations for personalized procedures, assists clinicians in making data-driven preoperative decisions, facilitates comparative analysis of different surgical techniques, and allows intuitive evaluation of postoperative visual quality. This review comprehensively examines the advances in VAO applications for refractive surgery and analyzes both its clinical advantages and technical limitations.

With the accelerating process of population aging, binocular vision disorders have become increasingly prevalent, posing new challenges for both social aging strategies and ophthalmic clinical practice. Non-strabismic binocular vision anomalies(NSBVAs)are notably prevalent among elderly populations; however, current research predominantly focuses on the abnormality rates derived from individual binocular vision clinical tests, while data on the actual prevalence based on comprehensive diagnostic criteria remain limited. This review synthesizes existing scientific literature to provide a concise yet comprehensive overview of the prevalence, risk factors, and clinical diagnostic methods of NSBVAs in pre-presbyopic and presbyopic populations, with an in-depth examination of age-related changes in binocular vision function among older adults. By integrating and comparing analyses of the correlations between age and various binocular vision parameters, this review aims to enhance understanding of age-related binocular vision dysfunction and establish a theoretical foundation for developing targeted diagnostic and therapeutic approaches. Ultimately, these insights could contribute to improved visual performance and life satisfaction in elderly individuals.

Objective : To investigate the effectiveness of an extraoral guide plate system targeting the superior and inferior heads of the lateral pterygoid muscle in improving the accuracy of injection therapy for anterior disc displacement (ADD) of the temporomandibular joint (TMJ) with lateral pterygoid myalgia, and to provide a reference for precise clinical treatment. Methods: With approval from the institutional medical ethics committee and informed consent from patients, spiral CT scans were performed on seven patients with ADD accompanied or not accompanied by lateral pterygoid myalgia to acquire craniofacial data. Mimics 21.0 software was used to reconstruct three-dimensional craniofacial structures, identify attachment points of the superior and inferior heads of the lateral pterygoid muscle, and design dual injection paths along with a retention system. Personalized templates were fabricated using digital light procession-based 3D printing. Under the guide plate, a single targeted injection of 20 U of botulinum toxin type A (BTX-A) was administered into both the superior and/or inferior heads of the lateral pterygoid muscle. Immediate postoperative CT scans were conducted to compare actual needle placement with preoperative plans. Pain was assessed using the visual analogue scale (VAS) at 3 days and 1, 2, and 4 weeks postoperatively. Joint clicking was recorded at 2 and 4 weeks, and complications were monitored throughout the duration of the study. Results : A total of 15 sites in 7 patients were injected into the upper / lower head of the lateral pterygoid muscle under the guidance of the guide plate. Under the guide plate, all of the injections achieved an angular deviation within 2.5° (superior head: 2.49° ± 0.17°, inferior head: 2.31° ± 0.16°) and a needle tip positional deviation within 2 mm [superior head: (1.96 ± 0.25) mm, inferior head: (1.65 ± 0.21) mm]. The significant pain improvement rate (defined as ≥3-point reduction in VAS score) increased from 60% (9/15) at day 3 to 85% (13/15) at 2 weeks post-operation, stabilizing at 86.7% (13/15) at 4 weeks post-operation. Joint clicking improvement rates reached 72% (11/15) at 2 weeks post-operation and 75% (11/15) at 4 weeks post-operation. Regarding safety, only one case of injection site swelling and one case of transient paresthesia were observed; both resolved spontaneously within a short period of time. No neurovascular injury events occurred. Conclusion CT-guided guide plate achieves precise targeting design to minimize injection errors in the lateral pterygoid muscle. This technology is effective and safe, and it can provide an anatomically specific and operationally versatile targeted therapy for temporomandibular disorders.

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Objective To investigate the effects of varying durations of overwork on cardiomyocyte pyroptosis in mice.Methods A total of 24 SPF KM mice were randomly divided into four groups(n=6)using a random number table:control group,2-week overwork(W2)group,4-week overwork(W4)group,and 6-week overwork(W6)group.Mice in control group were normally raised,while those in W2,W4,and W6 groups were forced to stand in water for 8 h and then restrained for 3 h daily for 2,4,6 weeks,respectively.The general condition and weekly weight changes of the mice were observed.After modeling,blood samples were collected,and hearts were excised.Myocardial histopathological changes were assessed using hematoxylin and eosin(HE)staining.The localization of gasdermin D(GSDMD)protein in myocardial tissue was detected through immunohistochemical staining,and the expression levels of pyroptosis-related proteins[NOD-like protein receptor 3(NLRP3),Caspase-1,GSDMD]in myocardial tissue were analyzed using Western blotting.The contents of interleukin-1β(IL-1β)and interleukin-18(IL-18)in serum and myocardial tissues were measured using ELISA.Results(1)The weight of control group mice increased steadily within 2 weeks.In W2 group,there was no significant weight change within 2 weeks,while in W4 and W6 groups,the body weights were higher than their initial values from the 2nd to 6th week.Compared with control group,the body weights of W2,W4,and W6 groups were lower than those of control group in the 1st and 2nd week,with statistically significant differences(P<0.05).The activity levels of the mice in W2,W4,and W6 groups initially increased and then decreased,with their fur becoming dull and falling out,and their mental state deteriorating.(2)In control group,cardiomyocytes were neatly arranged,and the nuclear morphology was normal.Compared with control group,in W2 group,cardiomyocyte arrangement was less regular,and capillary congestion was increased.In W4 group,the vascular congestion in the myocardium was significantly increased,the interstitial tissue was hyperplastic,and vacuolization appeared around the nuclei.In W6 group,the myocardial interstitium was loose,fat infiltration was increased,vacuolization around the nuclei was increased,and myocardial fibers were swollen,and the arrangement was disordered.(3)GSDMD was mainly located in the cytoplasm of cardiomyocytes.Compared with control group,the expression levels of NLRP3,Caspase-1,and GSDMD proteins in W2,W4,and W6 groups were significantly increased,and the expression levels were in the order of W6 group>W4 group>W2 group,with significant differences(P<0.05).(4)Compared to control group,the levels of IL-1β in serum and myocardial tissues of W2,W4,and W6 groups were significantly increased.In serum,the level of IL-1β in W6 group was higher than those in W2 and W4 groups,and in myocardial tissue,the levels in W4 and W6 groups were higher than those in the W2 group,with significant differences(P<0.05).There were no significant differences in IL-1β levels in serum among W2 and W4 groups,nor were there significant differences in myocardial tissue between W4 and W6 groups(P>0.05).Compared with control group,the levels of IL-18 in serum and myocardial tissue of W4 and W6 groups were significantly increased(P<0.05).In serum,the levels of IL-18 in W4 and W6 groups were higher than that in W2 group,and in myocardial tissue,the level in W6 group was higher than those in W2 and W4 groups,with the differences being statistically significant(P<0.05).Conclusions Overwork can cause structural damage to mouse myocardial tissue,increase the expression of pyroptosis proteins NLRP3,Caspase-1,GSDMD,and aggravate myocardial inflammatory responses in overworked mice.Cardiomyocyte pyroptosis may be one of the factors contributing to sudden cardiac death induced by overwork.

Objective To investigate gender differences and age-related changes in body composition(BC)among Miao adults in Rongshui,Guangxi Province,and to provide the basis for assessing nutritional status and health.Methods With informed consent,630 Miao adults(218 males,412 females)were randomly selected for this study.Body composition was assessed using bioelectrical impedance analysis(BIA).Results Weight,fat-free mass,muscle mass,trunk muscle mass,limb muscle mass,waist-to-hip ratio(WHR),body water,presumtion of bone mass and protein were significantly higher in males than in females.And the fat mass,trunk fat mass,limb fat mass,visceral fat content,subcutaneous fat content and percentage of body fat were significantly higher in females than in males.According to the evaluation of body mass index(BMI)and WHR,the proportion of overweight and obesity of Miao adults was higher than the average level of Miao residents,and their obesity was characterized by central obesity.With age,weight,fat mass,muscle mass,fat-free mass,limb muscle mass,limb fat mass,subcutaneous fat content,percentage of body fat,body water,presumtion of bone mass,and protein of Rongshui Miao adults showed a gradual decreasing trend,while visceral fat content and WHR increased progressively.BMI in male Miao adults,along with BMI,fat mass,trunk fat mass,subcutaneous fat content,percentage of body fat,and body water in female Miao adults,showed a trend of increasing followed by decreasing,peaking at the age of 40-49 years.Conclusion The body composition of Miao adults in Rongshui,Guangxi,exhibits significant gender differences and age-related variation change patterns,which may increase the risk of sarcopenia and metabolic diseases with aging.

AIM: To assess the repeatability and agreement of higher-order aberration obtained by adaptive optics visual simulator(VAO)compared with OPD-Scan Ⅲ.METHODS: A cross-sectional study was conducted from August to September 2023, including a total of 204 patients(204 eyes)with myopia whose right eyes were measured. The examinations were performed by the same skilled examiner using both devices separately. The VAO device was used to measure higher order aberrations of orders 3 to 6 at a pupil diameter of 4.5 mm, while both the VAO and OPD-Scan Ⅲ devices were utilized to measure total higher-order aberration(tHOA), spherical aberration(SA), coma aberration(Coma), and trefoil aberration(Trefoil)of the entire eye at pupil diameters ranging from 3 to 6 mm. Furthermore, the repeatability of whole eye aberration measurements obtained with the VAO device was evaluated and the agreement of the two devices was assessed.RESULTS: The whole-eye higher-order aberrations measured by VAO demonstrated excellent repeatability(0.767≤ICC≤0.941, Sw<0.01 μm, TRT<0.1 μm). There was no statistically significant difference in Coma measured by VAO or OPD-Scan Ⅲ for pupil diameters ranging from 4 to 6 mm(P>0.05), while a statistically significant difference was observed in whole-eye tHOA of other pupil diameters(all P<0.05). The agreement of aberration measurements for each order between VAO and OPD-Scan Ⅲ for 3 mm pupil diameters, SA at 4 and 5 mm pupil diameter and Coma at 4 mm pupil diameter showed a 95% limit of agreement(LoA)<0.1, indicating good agreement; however, poor agreement was found for the remaining aberration measurements at different pupil diameters, with a 95%LoA>0.1, and there were significant differences in higher-order aberrations measured by two devices under a pupil diameter of 3 mm(r=0.218-0.317, P<0.01), 4 mm(r=0.406-0.672, P<0.01), 5 mm(r=0.538-0.839, P<0.01 and r=0.030-0.109, P>0.01)and 6 mm(r=0.369-0.766, P<0.01).CONCLUSION: The VAO demonstrates favorable repeatability when assessing whole-eye higher order aberration under pupil diameters of 3-6 mm. However, there is inadequate agreement and interchangeability in whole-eye higher order aberration at 3-6 mm pupil diameter between VAO and OPD-Scan Ⅲ for clinical purposes.

Abstract: Integrated stress response is an adaptive response produced by eukaryotic cells after intracellular and extracellular stimulation. The activation of integrated stress response inhibits the translation of most proteins, yet it can promote the translation of certain proteins to cope with complex cellular microenvironment changes. A large number of studies have found that in a variety of nervous system diseases, the integrated stress response can be activated by stress signals of disease-related cells and participates in the occurrence and progression of diseases through processes such as learning and memory consolidation, myelin regeneration and synaptic plasticity. This article summarizes the role, mechanism and possible drug targets of integrated stress response in central nervous system diseases and discusses the potential of pharmacological methods to regulate integrated stress response in the treatment of central nervous system diseases, in order to provide reference for pathological research on and drug development for central nervous system diseases.

Objective:To evaluate the optical performance of two aspheric intraocular lenses (IOL) AcrySof IQ SN60WF and Proming A1-UV with identical negative spherical aberration values, using the optical bench OptiSpheric IOL R&D through an in vitro study. Methods:The optical performance of + 20.0 D blue-light filtering SN60WF and monofocal high-order aspheric non blue-light filtering A1-UV IOL was evaluated through cornea models with the spherical aberration of 0 μm (ISO-1) and + 0.28 μm (ISO-2) under apertures of 3.0 mm and 4.5 mm via the optical bench OptiSpheric IOL R&D.The modulation transfer function (MTF) and USAF 1951 resolution test chart were employed to measure the IOL with centering, decentration of 0.3, 0.5, 0.7, 0.9 and 1.1 mm, as well as tilt of 3°, 5°, 7°, 9° and 11°.The spectral transmittance of IOL was measured with the UV-3300 UV-VIS spectrophotometer.Results:Compared with the A1-UV IOL, the spectral transmittance of SN60WF for blue light with wavelengths of 400-500 nm was significantly reduced, which effectively reduced the passage of blue light.At an aperture of 3.0 mm, the MTF values at 100 lp/mm spatial frequency for the centered SN60WF and A1-UV were 0.576 and 0.598 under ISO-1 corneal measurement conditions, 0.564 and 0.563 under ISO-2 conditions.At an aperture of 4.5 mm, the MTF values were 0.238 and 0.404 under ISO-1 corneal measurement conditions, and 0.438 and 0.339 under ISO-2 conditions.The MTF values of A1-UV and SN60WF at 3.0 mm aperture and 100 lp/mm spatial frequency under ISO-1 corneal measurement conditions were larger than those under ISO-2 corneal measurement conditions.Under ISO-1 corneal measurement conditions with a 3.0 mm aperture, A1-UV had a better optical quality compared to SN60WF, whereas under ISO-2 corneal measurement conditions, the optical quality of both IOLs was similar.Under the 3.0 mm aperture, the MTF values of SN60WF and A1-UV at a decentration of 0.3 mm and 100 lp/mm spatial frequency were 0.414 and 0.571 under ISO-1 corneal measurement conditions, 0.438 and 0.512 under ISO-2 corneal measurement conditions, respectively.The MTF values of SN60WF and A1-UV at a tilt of 3° were 0.522 and 0.597 under ISO-1 corneal measurement conditions, and 0.532 and 0.531 under ISO-2 corneal measurement conditions.The MTF values and USAF resolution test chart of A1-UV had no significant change between the two corneal measurement conditions.When subjected to equal degrees of decentration or tilting, except for the ISO-1 corneal measurement conditions at a 4.5 mm aperture, the MTF values of A1-UV showed a gradual decline across various spatial frequencies compared to SN60WF.With the increase in aperture size, the impact of IOL decentration or tilting on MTF values and USAF 1951 resolution test chart became more notable for A1-UV relative to SN60WF.Conclusions:The SN60WF IOL effectively filters blue light within the wavelength range of 400-500 nm.However, when both IOL experience decentration greater than 0.3 mm or tilting beyond 3°, the optical quality of the IOL will decline.A1-UV has a distinct advantage over SN60WF in terms of resistance to both decentration and tilting-induced optical performance degradation in vitro.