1.Identification of shared key genes and pathways in osteoarthritis and sarcopenia patients based on bioinformatics analysis.
Yuyan SUN ; Ziyu LUO ; Huixian LING ; Sha WU ; Hongwei SHEN ; Yuanyuan FU ; Thainamanh NGO ; Wen WANG ; Ying KONG
Journal of Central South University(Medical Sciences) 2025;50(3):430-446
OBJECTIVES:
Osteoarthritis (OA) and sarcopenia are significant health concerns in the elderly, substantially impacting their daily activities and quality of life. However, the relationship between them remains poorly understood. This study aims to uncover common biomarkers and pathways associated with both OA and sarcopenia.
METHODS:
Gene expression profiles related to OA and sarcopenia were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between disease and control groups were identified using R software. Common DEGs were extracted via Venn diagram analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify biological processes and pathways associated with shared DEGs. Protein-protein interaction (PPI) networks were constructed, and candidate hub genes were ranked using the maximal clique centrality (MCC) algorithm. Further validation of hub gene expression was performed using 2 independent datasets. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of key genes for OA and sarcopenia. Mouse models of OA and sarcopenia were established. Hematoxylin-eosin and Safranin O/Fast Green staining were used to validate the OA model. The sarcopenia model was validated via rotarod testing and quadriceps muscle mass measurement. Real-time reverse transcription PCR (real-time RT-PCR) was employed to assess the mRNA expression levels of candidate key genes in both models. Gene set enrichment analysis (GSEA) was conducted to identify pathways associated with the selected shared key genes in both diseases.
RESULTS:
A total of 89 common DEGs were identified in the gene expression profiles of OA and sarcopenia, including 76 upregulated and 13 downregulated genes. These 89 DEGs were significantly enriched in protein digestion and absorption, the PI3K-Akt signaling pathway, and extracellular matrix-receptor interaction. PPI network analysis and MCC algorithm analysis of the 89 common DEGs identified the top 17 candidate hub genes. Based on the differential expression analysis of these 17 candidate hub genes in the validation datasets, AEBP1 and COL8A2 were ultimately selected as the common key genes for both diseases, both of which showed a significant upregulation trend in the disease groups (all P<0.05). The value of area under the curve (AUC) for AEBP1 and COL8A2 in the OA and sarcopenia datasets were all greater than 0.7, indicating that both genes have potential value in predicting OA and sarcopenia. Real-time RT-PCR results showed that the mRNA expression levels of AEBP1 and COL8A2 were significantly upregulated in the disease groups (all P<0.05), consistent with the results observed in the bioinformatics analysis. GSEA revealed that AEBP1 and COL8A2 were closely related to extracellular matrix-receptor interaction, ribosome, and oxidative phosphorylation in OA and sarcopenia.
CONCLUSIONS
AEBP1 and COL8A2 have the potential to serve as common biomarkers for OA and sarcopenia. The extracellular matrix-receptor interaction pathway may represent a potential target for the prevention and treatment of both OA and sarcopenia.
Sarcopenia/genetics*
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Osteoarthritis/genetics*
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Computational Biology/methods*
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Humans
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Protein Interaction Maps/genetics*
;
Animals
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Mice
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Gene Expression Profiling
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Gene Ontology
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Transcriptome
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Male
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Signal Transduction/genetics*
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Gene Regulatory Networks
2.Mechanism by which mechanical stimulation regulates chondrocyte apoptosis and matrix metabolism via primary cilia to delay osteoarthritis progression.
Huixian LING ; Sha WU ; Ziyu LUO ; Yuyan SUN ; Hongwei SHEN ; Haiqi ZHOU ; Yuanyuan FU ; Wen WANG ; Thai Namanh NGO ; Ying KONG
Journal of Central South University(Medical Sciences) 2025;50(5):864-875
OBJECTIVES:
Osteoarthritis (OA) is one of the most common chronic degenerative diseases, with chondrocyte apoptosis and extracellular matrix (ECM) degradation as the major pathological changes. The mechanical stimulation can attenuate chondrocyte apoptosis and promote ECM synthesis, but the underlying molecular mechanisms remain unclear. This study aims to investigate the role of primary cilia (PC) in mediating the effects of mechanical stimulation on OA progression.
METHODS:
In vivo, conditional knockout mice lacking intraflagellar transport 88 (IFT88flox/flox IFT88 knockout; i.e., primary cilia-deficient mice) were generated, with wild-type mice as controls. OA models were established via anterior cruciate ligament transection combined with destabilization of the medial meniscus, followed by treadmill exercise intervention. OA progression was evaluated by hematoxylin-eosin staining, safranin O-fast green staining, and immunohistochemistry; apoptosis was assessed by TUNEL staining; and limb function by rotarod testing. In vitro, primary articular chondrocytes were isolated from mice and transfected with lentiviral vectors to suppress IFT88 expression, thereby constructing a primary cilia-deficient cell model. Interleukin-1β (IL-1β) was used to induce an inflammatory environment, while cyclic tensile strain (CTS) was applied via a cell stretcher to mimic mechanical loading on chondrocytes. Immunofluorescence and Western blotting were used to detect the protein expression levels of type II collagen α1 chain (COL2A1), primary cilia, IFT88, and caspase-12; reverse transcription polymerase chain reaction was performed to assess COL2A1 mRNA levels; and flow cytometry was used to evaluate apoptosis.
RESULTS:
In vivo, treadmill exercise significantly reduced Osteoarthritis Research Society International (OARSI) scores and apoptotic cell rates, and improved balance ability in wild-type OA mice, whereas IFT88-deficient OA mice showed no significant improvement. In vitro, CTS inhibited IL-1β-induced ECM degradation and apoptosis in primary chondrocytes; however, this protective effect was abolished in cells with suppressed primary cilia expression.
CONCLUSIONS
Mechanical stimulation delays OA progression by mediating signal transduction through primary cilia, thereby inhibiting cartilage degeneration and chondrocyte apoptosis.
Animals
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Chondrocytes/cytology*
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Apoptosis/physiology*
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Mice
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Cilia/metabolism*
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Osteoarthritis/pathology*
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Extracellular Matrix/metabolism*
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Mice, Knockout
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Disease Progression
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Interleukin-1beta
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Male
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Cells, Cultured
3.Erratum: Author correction to "SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade" Acta Pharm Sin B 9 (2019) 304-315.
Mingxia ZHAO ; Wenjie GUO ; Yuanyuan WU ; Chenxi YANG ; Liang ZHONG ; Guoliang DENG ; Yuyu ZHU ; Wen LIU ; Yanhong GU ; Yin LU ; Lingdong KONG ; Xiangbao MENG ; Qiang XU ; Yang SUN
Acta Pharmaceutica Sinica B 2025;15(5):2810-2812
[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].
4.Impacts of radiotherapy on anti-tumor immunity: a comprehensive review from the fundamental to the clinical
Yingmei WEN ; Jinxiong XIA ; Yuanyuan WANG ; Yi YAO
Journal of International Oncology 2025;52(4):231-236
Radiotherapy is a crucial component of the treatment of tumors. In addition to directly causing DNA damage in tumor cells and inducing cell apoptosis, radiotherapy is also involved in the regulation of systemic immune status. Increasing evidence indicates that radiotherapy can remodel the tumor immune microenvironment (TIME) and reverse the immunosuppressive state, thereby enhancing anti-tumor effects and demonstrating stronger immune responses and therapeutic benefits when combined with immune checkpoint inhibitors. Taking lung cancer as an example to explore the impacts and potential mechanisms of radiotherapy on the TIME and anti-tumor immunity, which can provide a scientific basis for optimizing the treatment strategies of lung cancer.
5.Effect of fisetin against venous thrombosis in rats and its mechanism
Lihui LONG ; Shuang WEI ; Qing LIU ; Yang YAO ; Juanni DONG ; Yuanyuan CHANG ; Enhui WEN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(3):383-387
Objective To analyze the effect of fisetin against venous thrombosis in rats.Methods Seventy SD rats were randomly divided into the following groups:sham-operation group,model group,fisetin 45 mg/kg,15 mg/kg,5 mg/kg groups,and aspirin group(47 mg/kg).The corresponding medication was administered by gavage once a day consecutively(the sham-operation group and the model group were given 0.5%carboxymethyl cellulose sodium solution with 10 mL/kg,respectively)for 7 consecutive days.One hour after the last administration,the rats were anesthetized,the lower part of the intersection of inferior vena cava and left renal vein was ligated with silk thread(no ligation in the sham-operation group),and the abdominal wall was sutured.Two hours later,the abdominal cavity was reopened,the other venous branches 1.5 cm away from the ligation site were closed with the artery clamp,and blood was collected from the abdominal aorta.The anticoagulant ratio of 3.8%sodium citrate∶whole blood was 1∶9.The venous thrombus 1 cm down from the ligation point of the intersection of inferior vena cava and left renal vein was cut and the thrombus was separated.The residual blood was dried with filter paper,weighed and recorded.Plasma was taken after anticoagulant blood centrifugation.The levels of plasma antithrombin-Ⅲ(AT-Ⅲ),protease C(PC),plasminogen(PLG),and plasminogen activator inhibitor(PAI-1)were detected by ELISA kits.Results Compared with the model group,the weight of thrombus in fisetin 45 mg/kg group and aspirin 47 mg/kg group decreased(P<0.01).The content of AT-Ⅲ in three fisetin groups increased(all P<0.05).The content of PC in fisetin 45 mg/kg increased(P<0.05).The content of PLG and PAI-1 in fisetin 45 mg/kg group decreased(both P<0.05).Conclusion Fisetin has the effect against venous thrombosis in vivo,and the effect is related to the upregulation of AT-Ⅲ and PC and the downregulation of PLG and PAI-1.
6.Association between congenital hypothyroidism and in-hospital adverse outcomes in very low birth weight infants
Sha ZHU ; Jing XU ; Ranran SHI ; Xiaokang WANG ; Maomao SUN ; Shina LI ; Lingling GAO ; Yuanyuan LI ; Huimin WEN ; Changliang ZHAO ; Shuai LI ; Juan JI ; Cuihong YANG ; Yonghui YU
Chinese Journal of Pediatrics 2024;62(1):29-35
Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.
7.Effects of broken window effect and narrative nursing intervention on adolescent non-suicidal self-injury
ZHANG Yuanyuan ; WANG Wen ; TANG Xinlong ; JIANG Aiguo
Journal of Preventive Medicine 2024;36(7):553-557
Objective:
To evaluate the intervention effectiveness of broken window effect combined with narrative nursing on non-suicidal self-injury (NSSI) in adolescents, so as to provide the basis for NSSI prevention in adolescents.
Methods:
Totally 134 adolescents with NSSI admitted to Mental Health Center of the Affiliated Hospital of Anhui West Health Vocational College from January 2022 to December 2023 were enrolled and randomly assigned into the control and treatment group. All were given narrative nursing and routine care, and the adolescents in the treatment group were given additional intervention based on broken window effect. The effects were evaluated using Self-Rating Depression Scale (SDS), Hamilton Depression Scale (HAMD), Self-Rating Idea of Suicide Scale (SIOSS), Ottawa Self-injury Inventory-Functions (OSI-F) and Nursing Satisfaction Scale, and the two groups were compared before and after intervention.
Results:
The treatment and control groups comprised 67 cases each, had a median age of 14.12 (interquartile range, 2.01) years and 14.10 (interquartile range, 1.52) years, included 71.64% and 68.66% girls, and 79.10% and 74.63% junior high school students, respectively. There were no statistically significant differences between the treatment and control groups in terms of gender, age or educational level (all P>0.05). The results of analysis of variance for repeated measures showed that there were interactions between time and group for SDS, HAMD and SIOSS scores (all P<0.05), and the decrease in scores before and after intervention was greater in the treatment group than in the control group. After intervention, the SDS, HAMD, SIOSS score and incidence of suicidal behaviors in the treatment group were all lower than the control group [SDS: (32.54±1.27) vs. (44.25±2.23); HAMD: (10.54±1.83) vs. (18.73±1.89); SIOSS: (10.37±2.20) vs. (15.76±1.62); incidence of suicidal behavior: 14.93% vs. 32.84%; all P<0.05]. The nursing satisfaction rate was significantly higher in the treatment group than in the control group (98.51% vs. 88.06%, P<0.05).
Conclusion
The broken window effect combined with narrative nursing would improve the depressive symptoms in adolescents with NSSI, and reduce the suicidal ideation and self injury.
8.Effect and its mechanism of esketamine on anxiety and depression in mice
Jingwen Zhou ; Yuanhai Li ; Gaolin Qiu ; Wen Cai ; Yuanyuan Zhao ; Xiaoqiong Xia
Acta Universitatis Medicinalis Anhui 2024;59(1):106-110
Objective :
To explore the effect of esketamine on anxiety-depressive-like behavior in mice and its rela- tionship with inflammation.
Methods :
SPF grade healthy adult male C57BL/6J mice,weighing 20 -24 g,were used in the exprement.The random number table method was used to divide into 5 groups (n = 8) : control group ( Con group) ,esketamine group (ESK group) ,model group ( LPS group) ,model + esketamine prevention group (LPS + ESK1 group) and model + esketamine treatment group ( LPS + ESK2 group) .An inflammation-induced anxiety-depression model was prepared by intraperitoneal injection of LPS 0. 83 mg / kg.The ESK group was injec- ted with esketamine 10 mg / kg ; LPS group was injected with LPS 0. 83 mg / kg ; LPS + ESK1 group was injected with LPS 0. 83 mg / kg before 24 hours intraperitoneal injection of esketamine 10 mg / kg ; and the LPS + ESK2 group was injected with LPS 0. 83 mg / kg and 30 minutes later with esketamine 10 mg / kg.24 h after intraperitoneal injec- tion of LPS,the anxiety-depression-like behaviors of mice were measured using behavioral experiments.At the end of behavioral experiments,the spleen was taken immediately ; hippocampal tissues were taken and enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of interleukin-1 β (IL-1 β) ,tumor necrosis factor al- pha (TNF-α) and interleukin 6 (IL-6) and neuronal pathological changes in hippocampal tissues were observed by HE staining.
Results :
Compared with the Con group,mice in the LPS group showed increased anxiety and depres- sion-like behavior (P<0. 05) ,increased spleen weight / body weight (P <0. 05 ) ,increased hippocampal tissue concentrations of IL-1 β , TNF-α and IL-6 (P<0. 05) ,and increased neuronal degeneration necrosis,there was no statistically significant difference in these indicators in the ESK group compared with the Con group.Compared with the LPS group,mice in the LPS + ESK1 and LPS + ESK2 groups showed reduced anxiety-depression-like behavior (P<0. 05) ,decreased splenic weight / body weight (P <0. 05) ,hippocampal tissue IL-1 β , TNF-α , IL- 6 con- centrations were reduced (P<0. 05) ,and neuronal degeneration necrosis was reduced.Compared with the LPS + ESK1 group,the LPS + ESK2 group showed an increase in the distance travelled in the central area of the open field experiment and the distance into the open arm of the elevated cross maze experiment (P<0. 05) ,a decrease in IL-6 and TNF-α concentrations (P<0. 05) ,and a reduction in the degree of neuronal damage.
Conclusion
Esketamine ameliorates LPS-induced anxiety-depression-like behavior and neuronal damage in mice by a mechanism that may be related to reduced inflammation.
9.Application progress of predictive models in the prevention and control of myopia in children and adolescents
Zihang XU ; Yuanyuan HU ; Ying WEN ; Hongsheng BI
International Eye Science 2024;24(5):727-730
In medical research,predictive models have been widely used to predict disease progression and identify high-risk populations in advance, especially in the prevention and diagnosis of chronic diseases. In ophthalmology, the predictive and diagnostic models for fundus diseases such as age-related macular degeneration and diabetic retinopathy have demonstrated expert-level accuracy. However, the application of predictive models is still in the exploratory stage as for myopia prevention and control. The establishment of a predictive model is helpful to identify the high-risk myopic children in advance, so that preventive measures such as adequate outdoor activities and reducing near work can be taken in time, which is of great significance to prevent or slow down the occurrence and development of myopia. Because the mechanism of myopia has not been fully elucidated, there are still challenges and limitations in the selection of application objects, predictors and predictive outcomes. This paper reviews the research progress of different types of myopia predictive models in order to provide reference for further development and improvement.
10.Application of TPS combined with microlecture teaching model in nursing teaching of general surgery
Yuanyuan LI ; Ping SUN ; Fen WANG ; Yi YANG ; Xue SONG ; Wen SUN
Chinese Journal of Medical Education Research 2024;23(5):692-697
Objective:To study the effects of applying the think-pair-share (TPS) method combined with the microlecture teaching model in nursing teaching of general surgery.Methods:We assigned 48 nursing students interning in the department of general surgery of The First Affiliated Hospital of Air Force Medical University from August 2020 to August 2021 into control group to receive traditional teaching and 48 nursing students who interned from September 2021 to August 2022 into observation group to receive TPS+microlecture teaching. The two groups were compared in terms of test results, critical thinking abilities, post competencies, and satisfaction with teaching. SPSS 22.0 was used to perform the t test and chi-square test. Results:The observation group showed a significantly higher theoretical score [(93.21±4.34) vs. (88.65±3.69)], a significantly higher basic nursing skills score [(94.21±3.85) vs. (89.45±5.47)], and a significantly higher specialized skills score [(90.76±4.59) vs. (88.96±3.63)] than the control group ( P<0.05). The total score of the critical thinking ability scale and the scores of individual dimensions were significantly increased after training for both groups, and all the scores were significantly higher in the observation group than in the control group ( P<0.05). Both groups had significant improvements in the total and individual scores of post competencies after training, and the observation group had significantly higher scores than the control group ( P<0.05). Compared with the control group, the observation group had significantly higher proportions of students feeling satisfied with teaching, in terms of all evaluation items and also overall ( P<0.05). Conclusions:Applying the TPS+microlecture teaching model in general surgery nursing teaching can help nursing students improve theoretical and practical levels, critical thinking abilities, and post competencies, also with a high level of satisfaction with teaching.


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