1.EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis by regulating endoplasmic reticulum stress in knee osteoarthritis.
Yang CHEN ; Shanshan DONG ; Xin ZENG ; Qing XU ; Mingwei LIANG ; Guangneng LIAO ; Lan LI ; Bin SHEN ; Yanrong LU ; Haibo SI
Chinese Medical Journal 2025;138(1):79-92
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*
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Osteoarthritis, Knee/pathology*
;
Chondrocytes/metabolism*
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Pyroptosis/physiology*
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HMGB1 Protein/genetics*
;
MicroRNAs/metabolism*
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Endoplasmic Reticulum Stress/genetics*
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Humans
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Animals
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Rats
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Male
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Rats, Sprague-Dawley
;
Middle Aged
3.How Fear Memory is Updated: From Reconsolidation to Extinction?
Jiahui CHEN ; Zhuowen FANG ; Xiaolan ZHANG ; Yanrong ZHENG ; Zhong CHEN
Neuroscience Bulletin 2025;41(6):1054-1084
Post-traumatic stress disorder (PTSD) is a psychiatric disorder caused by traumatic past experiences, rooted in the neurocircuits of fear memory formation. Memory processes include encoding, storing, and recalling to forgetting, suggesting the potential to erase fear memories through timely interventions. Conventional strategies such as medications or electroconvulsive therapy often fail to provide permanent relief and come with significant side-effects. This review explores how fear memory may be erased, particularly focusing on the mnemonic phases of reconsolidation and extinction. Reconsolidation strengthens memory, while extinction weakens it. Interfering with memory reconsolidation could diminish the fear response. Alternatively, the extinction of acquired memory could reduce the fear memory response. This review summarizes experimental animal models of PTSD, examines the nature and epidemiology of reconsolidation to extinction, and discusses current behavioral therapy aimed at transforming fear memories to treat PTSD. In sum, understanding how fear memory updates holds significant promise for PTSD treatment.
Fear/psychology*
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Extinction, Psychological/physiology*
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Animals
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Stress Disorders, Post-Traumatic/psychology*
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Humans
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Memory Consolidation/physiology*
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Memory/physiology*
4.Evaluation and management of nutritional consequences in patients with alcoholic cirrhosis
Lijie WANG ; Yanrong YANG ; Yu CHEN ; Jinling DONG
Journal of Clinical Hepatology 2025;41(4):761-767
Patients with alcoholic cirrhosis often experience varying degrees of malnutrition, and the patients with malnutrition are more susceptible to complications such as infections and ascites, which may lead to a poor prognosis. Therefore, it is particularly important to conduct nutritional risk screening for patients in clinical practice, and appropriate nutritional assessment tools should be used to evaluate the nutritional status of patients and develop individualized nutritional supplementation regimens, thereby promoting disease recovery and improving prognosis and quality of life. This article elaborates on the specific methods for nutritional screening, assessment, and management in patients with alcoholic cirrhosis and points out that systematic nutritional screening and assessment can help to identify the patients with malnutrition in the early stage and provide timely intervention. Individualized nutritional supplementation regimens should be adjusted based on the conditions of patients, so as to meet their nutritional needs, promote the recovery of liver function, improve overall health status, and enhance long-term quality of life.
5.Analysis on current situation of drug use in Chinese aeromedical rescue
Aobo LI ; Wei WANG ; Yanrong ZHU ; Chunyan XIN ; Chen LI ; Xu GE
China Pharmacy 2025;36(9):1035-1039
OBJECTIVE To analyze the current situation of drug use in domestic aeromedical rescue, and provide references for the development of aeromedical rescue services and the rational use of drugs on board. METHODS All literature on aeromedical rescue in China were retrieved from the databases of SinoMed, CNKI, VIP, and Wanfang data up to September 1st, 2024. Extracting descriptive analysis were conducted on the literature screened by the inclusion and exclusion criteria. RESULTS A total of 36 literature were included. Aeromedical rescue cases had been reported in China since 1985, with a cumulative total of 5 370 cases reported. Prehospital rescue performed 861 cases, with 96.40% of them involving the use of at least 9 categories, totaling at least 10 different drugs, primarily emergency drugs. Interhospital rescue performed 4 509 cases, and 85.23% of them used over 48 kinds of drugs across 19 categories, mainly emergency drugs supplemented by specialty drugs. From the view of transportation, 5 166 air transfers were made by helicopters, of which 88.00% involved the use of drugs, and 204 cases by fixed-wing aircraft, of which 91.18% involved the use of drugs. CONCLUSIONS Drugs are frequently used in aeromedical rescue involving a wide variety of types in China. It is imperative to strengthen the focus on the equipment and rational use of drugs in aeromedical rescue, thereby facilitating the establishment of a standardized theoretical framework.
6.Value of evaluation model for dimension of safe management in standardized management for medical equipment in department of orthopedics
Yanrong LIU ; Meng WANG ; Yingdong LI ; Xiaowei CHEN
China Medical Equipment 2025;22(7):151-156
Objective:To analyze the application value of evaluation model for dimension of safe management in standardized management for medical equipment in department of orthopedics.Methods:The management objectives were refined from the aspects of management objects,goal refinement,problem analysis,index screening,and evaluation feedback in the safe management for medical equipment in department of orthopedics,and an evaluation model for dimension of safe management was constructed to conduct whole-process management for medical equipment in department of orthopedics.A total of 73 clinically medical equipment that were used in department of orthopedics of Beijing Chao-yang Hospital,Capital Medical University from January 2022 to December 2023 were selected.In them,36 equipment during January to December 2022 were managed by adopting conventional management model,and 37 equipment during January to December 2023 were managed by adopting the evaluation model for dimension of safe management(model management mode).The clinical service quality,incidence of risk,and scores of quality management capability for equipment between the two management modes were compared.Results:The mean values of consistency rate of the requirement for average configuration,compliance rate of performance parameter,stability rate of quality detection,and qualification rate of cleaning and disinfection of the equipment of adopting the model management mode were respectively(91.69±4.36)%,(92.36±3.54)%,(91.80±3.54)%and(92.36±4.20)%,all of which were higher than those of adopting the conventional management mode,with statistically significant differences(t=15.003,14.545,11.529,11.921,P<0.05).The failure rate,defect rate of components,unqualified rate of cleaning and disinfection,and improper rate of managing equipment of the 37 equipment of adopting the model management mode were respectively 5.41%,5.41%,2.70%and 8.11%,all of which were lower than those of adopting the conventional management model,with statistically significant differences(x2=9.182,10.538,11.696,9.667,P<0.05).The scores of resource allocation,technical support,and information foundation for equipment of adopting the model management mode were all higher than those of adopting the conventional management mode,with statistically significant differences(t=11.494,10.089,13.831,P<0.05).Conclusion:The application of evaluation model for dimension of safe management for medical equipment in department of orthopedics can improve the operational quality of equipment,and reduce safety hazards and failure rates of equipment,and enhance use efficiency of equipment.
7.Correlations of chest CT quantitative parameters and readmission within one year in patients with acute exacerbation of chronic obstructive pulmonary disease
Guoqing SUN ; Lu YANG ; Liyu HE ; Min TIAN ; Bingjie ZHU ; Bahadori PARDIS ; Yanrong CHEN ; Chenwang JIN
Chinese Journal of Medical Imaging Technology 2025;41(7):1097-1102
Objective To observe the correlations of chest CT quantitative parameters and one-year readmission in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods Totally 225 AECOPD patients were included and divided into the readmission group(group A,n=61)and non-readmission group(group B,n=164)according to whether readmitted due to acute exacerbation within one year or not.Quantitative CT parameters,including the percentage of low attenuation area volume to total lung volume(LAA%)and intrapulmonary vascular volume(IPVV)of the whole lung,left/right lung and each lobe,as well as the bronchial lumen area(LA)and percentage of bronchial wall area(WA%)of grades 3-8 were compared between groups.Spearman correlations were used to analyze the correlations between quantitative CT parameters and one-year readmission.Results LAA%of the whole lung,right lung,upper lobe of both lungs,middle lobe of the right lung,and lower lobe of the right lung in group A were higher than that in group B(all P<0.05),which were weakly positively correlated with readmissions within one year(r=0.142-0.187,all P<0.05).Significant differences of the upper lobe of right lung LAgrade 6,lower lobe of left lung LAgrade 6,lower lobe of left lung LAgrade 8,upper lobe of right lung WA%grade 5,upper lobe of right lung WA%grade 8 and lower lobe of left lung WA%grade 8 were found between groups,which were all correlated with readmissions within one year except for the lower lobe of the left lung LAgrade 6(all P<0.05).Conclusion One-year readmission in AECOPD patients might be associated with severe airway remodeling and emphysema.
8.Effect of ciprofol on intraoperative hypotension in patients undergoing bronchoscopy procedures
Xiaoyun CHEN ; Wei DU ; Yanrong LI ; Dongliang MU ; Ting DING
Chinese Journal of Anesthesiology 2025;45(4):415-418
Objective:To evaluate the effect of ciprofol on intraoperative hypotension in patients undergoing bronchoscopy procedures.Methods:In this randomized controlled study, 112 adult patients of either sex, aged 18-64 yr, with a body mass index of 19.8-28.3 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with estimated operation time of ≥1 h, undergoing elective bronchoscopy procedures, were assigned to one of two groups ( n=56 each) using a random number table method: ciprofol group (C group) and propofol group (P group). All the patients received total intravenous anesthesia. The induction dose of ciprofol was 0.1-0.3 mg/kg, and the maintenance dose was 0.4-1.2 mg·kg -1·h -1 in group C. The induction dose of propofol was 1-3 mg/kg, and the maintenance dose was 4-12 mg·kg -1·h -1 in group P. The primary outcome was the incidence of intraoperative hypotension, and the secondary outcomes were the time of emergence from anesthesia, sleep quality, patients′ and surgeons′ satisfaction with anesthesia, and the incidence of complications within 30 days after surgery. Results:Compared with group P, the incidence of intraoperative hypotension was significantly decreased, and the time of emergence from anesthesia was shortened in group C ( P<0.05). There was no statistically significant difference in secondary outcomes between the two groups ( P>0.05). Conclusions:Ciprofol is superior to propofol in reducing the risk of intraoperative hypotension and facilitates a more rapid emergence from anesthesia in patients undergoing bronchoscopy procedures.
9.Relationship between social support and family resilience of primary caregivers of first-stroke patients:a chain mediation model
Dandan CHEN ; Yi ZHA ; Qin WANG ; Sai SHA ; Yanrong LUO ; Yu ZHANG ; Yuying CHEN ; Sailu MAO ; Longjuan YU
Academic Journal of Naval Medical University 2025;46(4):451-457
Objective To explore the relationships between social support,positive coping,caregiver burden and family resilience of primary caregivers of first-stroke patients.Methods A questionnaire survey was conducted among 307 primary caregivers of first-stroke patients in 2 tertiary hospitals in Shanghai by convenience sampling method.Social support rating scale,simplified coping style questionnaire,Zarit caregiver burden interview,and family resilience assessment scale were used for questionnaire survey.Pearson correlation analysis and structural equation models were used for data analysis.Results A total of 288 valid questionnaires were collected,and the effective recovery rate was 93.81%.Pearson correlation analysis showed that there was a positive correlation between family resilience and social support,family resilience and positive coping,and social support and positive coping(r=0.375,0.627,and 0.277;all P<0.01),while caregiver burden and social support,caregiver burden and positive coping,and family resilience and caregiver burden were all negatively correlated(r=-0.203,-0.343,and-0.444;all P<0.01).The mediating effect model was constructed with positive coping and caregiver burden as mediating variables,social support as independent variables,and family resilience as dependent variables.The results showed that social support could mediate family resilience through positive coping,with a mediating effect of 0.164,accounting for 26.1%of the total effect;social support could also affect the family resilience of the primary caregivers of first-stroke patients through the partial chain mediating effect of positive coping and caregiver burden,with a mediating effect value of 0.032,accounting for 5.1%of the total effect.Conclusion Social support can predict family resilience among primary caregivers of first-stroke patients,and positive coping and caregiver burden play chain mediating roles in the impact of social support on family resilience.
10.Interpretation of Chinese expert consensus on flow cytometric detection of hematological malignant cells in tissue samples
Liangmei LI ; Shuang CHEN ; Lian LI ; Zailin YANG ; Xia MAO ; Mingxia ZHU ; Hongmei JING ; Min XIAO ; Yao LIU ; Yanrong LIU
International Journal of Laboratory Medicine 2025;46(11):1281-1289
Hematologic malignancies,such as lymphoma,myeloma,and myeloid neoplasms,can occur in extramedullary tissues.Traditional histopathological morphology and immunohistochemical staining have lim-itations,including time-consuming specimen processing,prolonged reporting cycles,and relatively low sensi-tivity in cases of limited cell numbers.Flow cytometry offers significant advantages in detecting tissue sam-ples,such as rapid processing,shorter reporting cycles,and high accuracy and sensitivity,making it an effective complement to histopathological and immunohistochemical methods.However,the application of flow cytome-try in tissue sample detection currently lacks standardized protocols for sample collection and preservation,single-cell suspension preparation,antibody panel design for limited samples,data analysis,and result repor-ting.To promote the standardized application of flow cytometry in detecting hematologic tumor cells in tissue samples,the Cell Analysis Professional Committee of the Chinese Society of Biotechnology organized experts to develop the Chinese Expert Consensus on Flow Cytometry for Detecting Hematologic Tumor Cells in Tis-sue Samples(hereinafter referred to as the Consensus).This Consensus elaborates on the technical aspects of flow cytometry for tissue sample detection,covering sample processing,antibody panel design,data analysis,reporting content,and quality management.It particularly emphasizes recommended antibody panels and data analysis methods for flow cytometry when tissue sample cell counts are low.This article aims to interpret the key points of the Consensus to facilitate its better application in clinical practice.

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