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

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.

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.

OBJECTIVE To investigate the effect of pharyngeal cavity and genoglossus muscle exercises in patients with mild obstructive sleep apnea syndrome(OSAHS)left over after palatopharyngoplasty with diastolic cardiac dysfunction.METHODS A total of 75 patients with mild OSAHS left after palatopharyngoplasty with diastolic cardiac dysfunction from January 2021 to August 2023 were selected for retrospective study.Among them,37 patients underwent pharyngeal cavity and mentoglossum muscle exercise(observation group),while 38 patients did not(control group).Using postoperative data as baseline value.mean blood oxygen saturation(MSpO2),lowest oxygen saturation(LSpO2),sleep efficiency,apnea index(AI),sleep latency,apnea hypopnea index(AHI),hypopnea index(HI),microarousal index(MAI),rapid eye movement latency,arterial blood pressure of carbon dioxide(PaCO2),pH,arterial partial oxygen pressure(PaO2),left ventricular end-systolic diameter(LVDs),blood lactic acid,left ventricular ejection fraction(LVEF),Tei index,left ventricular end-diastolic diameter(LVDd),daytime Epworth sleepiness scale(ESS)score,Pittsburgh sleep quality index(PSQI)score and incidence of adverse cardiovascular events(MACE)were compared at baseline and 3 months later.RESULTS After 3 months,AHI,HI and AI in observation group were lower than those in control group,and MSpO2 and LSpO2 were higher than those in control group(P<0.05);Sleep efficiency of observation group was higher than control group,daytime ESS score,PSQI score and MAI were lower than control group(P<0.05).There were no significant differences in PaCO2,LVDd,PaO2,blood lactic acid,sleep latency,pH,LVEF,rapid eye movement latency,LVDd,Tei index between the observation group and the control group(P>0.05).The incidence of MACE in the observation group was 5.41%(2/37),compared with 13.16%(5/38)in the control group,there was no significant difference(P>0.05).CONCLUSION In patients with mild OSAHS left after palatopharyngoplasty with diastolic cardiac dysfunction,the exercise of pharyngeal cavity and genoglossus can improve hypopnea,alleviate clinical symptoms and improve sleep quality,but it has limited effect on the improvement of cardiac function.

To investigate the epidemiology of avian infectious bronchitis virus(IBV)and study the pathogenicity of IBV isolate,we isolated the IBV field strain from a clinical sample of chickens sus-pected to be infected with infectious bronchitis virus(IBV)from Hefei,Anhui Province,named HF210416.Sequencing analysis of the S1 gene showed that HF210416 belonged to the GI-22 geno-type,which was significantly differed from that of the reference GI-22-type strains,with homology ranging only from 84.5％to 87.8％.Recombinant analysis showed that HF210416 was a recombi-nant strain,with YX10(GI-19)as the major parent and YN(GI-19)as the minor parent.2-day-old SPF chicks infected with the HF210416 isolate showed clinical symptoms such as breathing with difficulty,depression and excreting watery droppings;the infected chicks had a rapid onset of dis-ease,with mortality occurring on the second day of inoculation,and mortality persisted until the fifth day,with 33.33％(5/15)mortality rate.The infected chicks recovered the 14th day after inoculation.RT-PCR detection of pharyngeal-anal swabs showed that the virus shedding by infected chicks could be continuously detected within 14 days of the test period;Enlarged and pale kidney as well as urate deposition in the kidney were observed in infected dead and undead chicks;and the HE staining of histopathological slices showed that the cilia of trachea were removed.Immunohis-tochemistry showed that obvious viral signals were observed in the trachea,lungs,and kidneys.The viral load of various tissues was detected by RT-qPCR and it showed that HF210416 had the high-est replication efficiency in kidney tissues,then in cecum tonsils and trachea.The results of serum neutralization test showed that HF210416 had a better neutralization effect on GI-22 homologous strains,but poorer neutralization effect on other genotypes strains,suggesting that HF210416 is not suitable for vaccine candidate.In conclusion,the GI-22 isolate HF210416 is highly pathogenic and nephrotropic to chicks,and its genomic genetic characteristics and immunogenicity are differ-ent from those of other strains.This study enriches the resources of IBV strains and provides refer-ence data for understanding of the prevalence and pathogenicity of GI-22 genotypes in China.

Objective:To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with CEBPA-bZIP mutation. Methods:Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with CEBPA-bZIP mutation. The nomogram model for leukemia-free survival (LFS) rate was generated by combining genetic abnormalities and clinical data. Risk stratification was conducted based on prognostic variables and the effect of risk-adjusted consolidation therapy was investigated by Kaplan-Meier method. Results:Four variables were finally included in our nomogram model after multivariate Cox analysis,and an equation for risk score calculation was obtained,risk score=1.3002×white blood cell (WBC) (≥18.77×109/L)+1.4065×CSF3R mutation positive+2.6489×KMT2A mutation positive+1.0128×DNA methylation-related genes mutation positive. According to the nomogram model,patients were further divided into low-risk group (score=0,n=46) and high-risk group (score>0,n=95). Prognostic analysis showed that the 5-year LFS rate,5-year overall survival (OS) rate,and 5-year cumulative incidence of relapse (CIR) of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the high-risk group were 93.5％,97.1％,and 3.5％,while those in patients who received maintenance chemotherapy were 32.9％,70.5％,and 63.4％,respectively. The differences were statistically significant (all P<0.05). Allo-HSCT could significantly improve the prognosis of patients in high-risk group. However,no corresponding benefit was observed in the low-risk group. Conclusion:Adult CN-AML with CEBPA-bZIP mutation has a complex co-mutation pattern. The nomogram model based on mutations of CFS3R,KMT2A and DNA methylation-related genes together with WBC count can further divide this subset of patients into a relatively low-risk group and a relatively high-risk group. For individuals in the high-risk group,allo-HSCT is proposed as post-remission therapy. The above data will benefit the prognosis estimation and treatment decision for adult CN-AML with CEBPA-bZIP mutation.