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

Objective To use a physics-informed neural network(PINN)-based model to predict hemodynamics in intracranial aneurysms and address the problems of long simulation time and high computational cost in traditional computational fluid dynamics(CFD)simulations.Methods The PINN model was trained using only the computational domain coordinates and sparse velocity measurement points from CFD data of clinical patients.The predicted blood flow velocity,pressure,and wall shear stress(WSS)from the PINN model were compared with CFD simulation results.Results The proposed method was used to test and validate data from four different patients.For velocity prediction,the average mean absolute error(MAE),average mean relative error(MRE),average mean squared error(MSE)was 4.60％,6.61％,and 0.229％,respectively.For WSS prediction,the average MAE,MRE and MSE was 5.54％,8.58％,and 0.510％,respectively.The PINN model demonstrated a good generalization capability across different aneurysm models and could reduce the computation time of hemodynamics from several hours to just a few seconds.Conclusions The PINN model can effectively compensate for incomplete measurement data through physical constraints,even when boundary conditions are unknown and measurement data are sparse.It can rapidly and accurately simulate the hemodynamics of intracranial aneurysms.This method has the potential to provide effective support for clinical risk prediction in intracranial aneurysms.

Adhering to the guidance of party building is an essential requirement for comprehensively promoting the high-quality development of public hospitals.How to solve the problem of"two skins"of party building and business,further promote the deep integration of the party and business has become an important topic for the party building of public hospitals in the new era.Taking Jieyang People's Hospital as an example,this paper introduces the innovation and exploration experience on the par-ty building work round in the hospital,the working mechanism of which is"1+5+5+4"of"Party building leading,five re-sponsibility coordination,five-step linkage and four-type integration".This approach effectively promotes the deep integration and promotion of the party and business,which further lead the high-quality development of various work in the hospital.It can pro-vide reference for exploring and improving the system and mechanism of the integration of party and business,and further promote party leadership in promoting high-quality development in public hospitals.

Objective:To evaluate the effectiveness of the Total Nutritional Therapy (TNT) course initiated by the Chinese Society for Parenteral and Enteral Nutrition (CSPEN) over the 20 years since its implementation in China.Methods:Participants who attended the CSPEN-organized TNT course between 2005 and 2024 were randomly selected as survey subjects. A four-level questionnaire (reaction, learning, behavior, and results) was developed via expert consensus, based on the Kirkpatrick model. An electronic link to the survey, created via Wenjuanxing, was distributed to invite participants to complete the questionnaire.Results:A total of 1,548 healthcare professionals from various specialties who had received TNT course participated in the online survey. Over 93% of participants reported improvements in theoretical knowledge and 94% in enhanced clinical diagnosis and treatment capabilities. Additionally, 65.4% of participants reported a "significant" or "noticeable" increase in the frequency of nutritional screening and assessments, with the frequency of nutritional support therapy utilization increased by 91.2%. Furthermore, 52.6% of respondents perceived a "significant" or "noticeable" career advancement, particularly in professional title promotion and international academic exchanges. The TNT course also positively impacted discipline development and management: 63.6% of the trainees' hospitals established clinical nutrition departments, 58.98% opened nutrition outpatient clinics, and 56.9% formed nutrition support teams. The adoption rate of standardized procedures, such as nutritional screening, exceeded 92.5% in relevant departments.Conclusions:Over the past 20 years, the CSPEN-led TNT course has successfully established a virtuous cycle of "knowledge dissemination–practice transformation–system innovation" in China. It has played a positive role in enhancing the professional competencies of healthcare workers and promoting the development of clinical nutrition as a discipline.

Objective:To investigate the relationship between dynamic alterations in serum albumin (ALB) concentrations and clinical outcomes in hospitalized surgical patients, thus providing a basis for optimizing clinical management strategies.Methods:This study utilized data from a prospective observational cohort study on nutritional status among 7 122 elderly hospitalized patients across 34 tertiary hospitals in 18 Chinese cities. A total of 1 714 surgical patients hospitalized for 7-30 days with complete data were included. Standardized protocols were used to collect demographic data, clinical outcomes, and a range of laboratory results, including nutritional and hematological parameters. Heterogeneous effects of ALB on clinical outcomes were explored. Receiver operating characteristic (ROC) curves were used to determine cutoff values for infection-related complications. Correlation analyses and multiple linear regression models were used to identify independent predictors of the absolute change in ALB (?ALB).Results:Among the surgical patients, 69.7% (1 195/1 714) experienced a decline in ALB levels during their hospital stay, which was significantly associated with the occurrence of both infection- and non-infection-related complications. Simultaneously, a marked decrease in ALB was also significantly correlated with changes in nutritional and inflammatory status during hospitalization, worsening of gastrointestinal symptoms at discharge, and functional activity abnormalities (all P<0.05). ?ALB exhibited a close association with outcome variables such as infection-related complications. Based on the incidence of infection-related complications, a cutoff value for ALB was calculated, dividing patients into a high-risk group ( n=179) and a low-risk group ( n=1 535), and a statistically significant difference in the incidence of infection-related complications was found between these two groups ( P<0.05). Correlation analysis and multiple linear regression modeling revealed that female gender, a higher baseline ALB level, a poorer baseline inflammatory status, an exacerbation of inflammatory status, larger alterations in platelet-to-lymphocyte ratio, and the presence of infection-related complications were predictive factors for a decline in ALB levels among surgical patients during their hospital stay. Conclusions:?ALB serves as a critical indicator of the inflammatory-nutritional interplay, with its magnitude of decline effectively predicting clinical outcomes and nutritional status changes and guiding multidisciplinary interventions in surgical patients.

The high prevalence of frailty in older adults and its close link to adverse outcomes make it a critical public health challenge in the aging global population. Frailty, characterized by multisystem functional decline, significantly increases the risk of falls, disability, and even death, yet its underlying mechanisms remain poorly understood. While the role of gut microbiota as the "second genome" in disease regulation has been widely recognized, its specific mechanisms in the development of frailty syndrome remain to be systematically investigated. This review synthesizes findings from the last decade of international literature to analyze the mechanisms by which gut microbiota dysbiosis contributes to frailty syndrome. We focus on pathways including metabolic disorders, chronic inflammation, oxidative stress, and the oral-gut microbiota axis, aiming to provide insights for clinical diagnosis and treatment.

Metabolic and bariatric surgery (MBS) is an effective treatment for obesity as it can dramatically reduce body weight and improve obesity-related comorbidities. However, postoperative changes from MBS can impair gastrointestinal structure and function, leading to micronutrient (MN) deficiencies and potentially severe organ dysfunction. MNs, including vitamins and trace elements, are crucial for human metabolism and can influence disease progression and outcomes. By reviewing the domestic and international literature in the past 5 years, we summarized and analyzed MN changles and nutritional management after various MBS procedures, aiming to further inform clinical practice.

Gut microorganisms are central to the intestinal microecosystem, regulating digestive functions and related to immune regulation, metabolic disorders, and nervous system development. Recent studies reveal the multifaceted interactions between micronutrients (MNs) and gut microbiota, where MNs provide essential nutrients to the intestinal flora and influence the production and absorption of various MNs through direct or indirect pathways. This article reviews the recent advances in the effects of water-soluble vitamins, fat-soluble vitamins, and micronutrients on the intestinal microecology, aiming to provide new ideas for future research.

Objective To find the molecular mechanism underlying the effect of congenital cataract related 129th single-site mutation G129C on the thermal stability of human γC crystallin(HγC)protein structure.Methods HγC-WT and HγC-G129C were expressed and purified in vitro.The changes of intrinsic fluorescence intensity and static light scattering intensity of proteins with temperature were measured,and the temperature dependence of the folding and aggregation structures of HγC-WT and HγC-G129C was compared.Results When temperature was be-low 65 ℃,the barycentric mean of the intrinsic fluorescence of HγC-WT and HγC-G129C shifted towards a longer wavelength and the fluorescence intensity decreased with the increasing temperature,which was believed to be the evidence of unfolded protein conformation.When the temperature was higher than 65 ℃,the static light scattering intensity increased significantly with the temperature,indicating the protein aggregation upon heating.The wild-type HγC-G129C showed a stronger aggregation potency.During the thermal de-naturation process of HγC-WT and HγC-G 129C,the crossing-point temperatures were 74.5 ℃ and 55.5 ℃,respectively.HγC-WT showed higher thermal stability.Conclusions The congenital cataract-associated G129C mutation significantly weakens conforma-tional stability of γC-crystallin.

Objective:To examine the prevalence of malnutrition and evaluate the impact of nutritional support on clinical outcomes in elderly patients diagnosed with gastric and colorectal cancer.Methods:A retrospective cohort study was conducted, analyzing elderly patients with gastrointestinal tumors who underwent surgical treatment in the general surgery department from January 2019 to June 2020.The Global Leadership Initiative on Malnutrition(GLIM)criteria were utilized to diagnose malnutrition, and the effects of malnutrition and nutritional support on clinical prognosis were investigated.Results:A total of 426 elderly hospitalized patients with gastric and colorectal tumors who underwent surgical treatment were included in this study.This cohort comprised 199 cases of gastric cancer and 227 cases of colorectal cancer, with ages ranging from 65 to 91 years(mean age: 72.05±5.99).According to the GLIM criteria, 43.7%(186/426)of the patients were diagnosed with malnutrition, of which 25.6%(109/426)were moderately malnourished and 18.1%(77/426)were severely malnourished.Among the gastric cancer patients, 73.4%(146/199)were identified as having nutritional risk, with 48.7%(97/199)being malnourished and 22.6%(45/199)experiencing severe malnutrition.In the colorectal cancer group, 63.9%(145/227)were at nutritional risk, 39.2%(89/227)were malnourished, and 14.1%(32/227)had severe malnutrition.Additionally, 60.3%(257/426)of the patients received nutritional support therapy: 25.4%(108/426)received parenteral nutrition(PN), 11.3%(48/426)received enteral nutrition(EN), 23.7%(101/426)received a combination of EN and PN, while 39.7%(169/426)did not receive any nutritional support.Regardless of the presence or degree of malnutrition, patients who received nutritional support had significantly shorter total hospital stays compared to those who did not receive nutritional support, and this difference was statistically significant( t=5.58, 3.69, 2.21, 3.03, all P<0.05). Conclusions:Providing nutritional support to malnourished patients can reduce the length of hospital stay and improve clinical outcomes.