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*
;
Osteoarthritis/genetics*
;
Computational Biology/methods*
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Humans
;
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.Effect of the different doses of remifentanil combined with dexmedetomide on the reduction in clam-ping reduction of cricoarytenoid joint dislocation
Lixiang YU ; Zhenkun YU ; Chuanzong YANG ; Yuanyuan LU ; Mengzhen ZHOU ; Chenhui JIANG ; Wen KONG ; Guangkui LU ; Li LU
The Journal of Clinical Anesthesiology 2024;40(10):1034-1038
Objective To compare the analgesic effect and the effect on the success rate of reduc-tion of three doses of remifentanil combined with dexmedetomidine in the clamping reduction of cricoarytenoid joint dislocation.Methods Fifty-one patients with cricoarytenoid joint dislocation,30 males and 21 females,aged 18-80 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅰ-Ⅲ,were selected from April 2021 to December 2022 in the department of otolaryngology,head and neck surgery.The patients were randomly divided into three groups according to remifentanil dose:remifentanil 0.5 μg·kg-1·min-1 group(group A,n=17),remifentanil 1.0 μg·kg-1·min-1 group(group B,n=18),and remifentanil 1.5 μg·kg-1·min-1 group(group C,n=16).After admission,dexmedetomidine 0.6 μg·kg 1·h-1 was injected intravenously,and an ear,nose and throat anesthetic spray(2%lidocaine 2 ml)was used to administer surface anesthesia to the base of the tongue.A second surface anesthesia was administered to the throat at 5 minutes,and dexmedetomidine was stopped at 10 minutes.The supraglottic and periarticular cri-coarytenoid joints were subjected to superficial anesthesia for a third time under visual laryngoscope,and then remifentanil at corresponding doses was injected intravenously in three groups for 5 minutes,and the reduction operation began after the pumping was stopped.The success of the first reduction,the anesthesia quality satisfaction score of the surgeon and the recovery of remifentanil during the operation were recorded.VAS pain scores were recorded at the time of entry,3 minutes,30 minutes,and 6 hours after operation.The adverse reactions during operation and recovery were recorded.Results Compared with group B,the success rate of first reduction and the score of anesthesia quality satisfaction were significantly decreased in groups A and C(P<0.05).Compared with group A,the ratio of additional remifentanil supplementation in groups B and C was significantly reduced,and the VAS pain score 3 minutes after surgery was significant-ly decreased(P<0.05).Compared with group C,the proportion of mandibular manipulation ventilation in groups A and B was significantly reduced(P<0.05).There was no significant difference in the incidence of bradyheart rate,nausea and vomiting,agitation,delirium and laryngeal spasm between the three groups.Conclusion Compared with remifentanil 0.5 and 1.5 μg·kg-1·min-1,remifentanil 1.0 μg·kg-1·min-1 combined with dexmedetomide sequential pumping provided good analgesic effect for the clamping reduction of cricoarytenoid joint dislocation,improved the success rate of the first reduction,more stable respiratory circulation and fewer perioperative adverse reactions.
5.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.
6.The role of NLRP3 signaling pathway in allergic rhinoconjunctivitis
Yubo GONG ; Xiaohua GUO ; Wen-Jun LU ; Yuanchao LI ; Changyu QIU ; Yuanyuan SHI ; Liping XIA ; Lin SHI ; Wei WU ; Ling LUO
The Journal of Practical Medicine 2024;40(14):1922-1927
Objective The objective of this study was to establish a mouse model of allergic rhinoconjunctivitis and investigate the role of the NLRP3 signaling pathway in allergic rhinoconjunctivitis.Methods Thirty-three female C57 mice(SPF)were randomLy divided into 3 groups:the control group,the experimental group,and the NLRP3-/-group.On days 0,4,7,14,and 21,the experimental group and NLRP3-/-group received a 0.2 mL intraperitoneal injection of medicine containing OVA(100 μg)and adjuvant Al(OH)3(4 mg),respectively.After an interval of 3 days,each eye and nose were dosed with 10 μL of 5%OVA for five consecutive days a week to induce allergic symptoms.During sensitization and excitation stages,the control group was replaced with an equiva-lent amount of PBS.Ocular and nasal symptoms were observed and scored.The levels of OVA-specific IgE,IL-4,IL-17,and IL-18 in serum were measured using ELISA,while changes in palpebral conjunctiva and nasal mucosa were assessed by hematoxylin-eosin staining.The expression of NLRP3 mRNA in conjunctival tissue and nasal mucosa was determined using real-time PCR analysis.Statistical analysis was performed using SPSS17.0 software with P<0.05 considered as statistically significant difference.Results The experimental group and NLRP3-/-group exhibited induced nasal and ocular allergic symptoms.In the experimental group,the duration of nasal allergy symptoms was(10.500±1.080)days,while the duration of eye allergy symptoms was(20.300±2.058)days.In the NLRP3-/-group,the duration of nasal allergy symptoms was(13.400±1.955)days,and for eye allergy symp-toms it was(20.900±2.132)days.The duration of nasal allergies in the NLRP3-/-group significantly exceeded that in the experimental group(P<0.05),whereas there were no significant differences observed in eye allergy durations between these two groups(P>0.05).Levels of OVA-specific IgE,IL-4,and IL-17 were significantly higher in both the experimental and NLRP3-/-groups compared to those in the control group(P<0.05).Additionally,serum IL-18 content increased significantly in the experimental group when compared with both control and NLRP3-/-groups(P<0.05).Conjunctival tissue lesions as well as nasal mucosa damage were evident in both experimental and NLRP3-/-groups.mRNA expression levels of NLRP3 within conjunctival tissue and nasal mucosa from the experimental group showed a significant increase when compared to those from both control and NLRP3-/-groups(P<0.05).Conclusion Allergic rhinoconjunctivitis pathogenesis is influenced by various factors;however,the involvement of NLPR3 signaling pathway promotes its development.
7.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.
8.Expression and clinical significance of KIFC1 in endometrioid carcinoma
Tao DENG ; Yuanyuan WEN ; Hui HE ; Liyong QIAN
Chinese Journal of Clinical and Experimental Pathology 2024;40(3):298-302
Purpose The aim of this study is to investigate the relationship between the expression of kinesin family member C1(KIFC1)in endometrioid carcinoma and clinicopathological features and prognosis of endometrioid carcinoma patients.Methods The expression of KIFC1 in 30 cases of paracancer-ous endometrium and 95 cases of endometrioid carcinoma was detected by immunohistochemical SP method.qRT-PCR and Western blot were used to detect the expression level of mRNA and protein of KIFC1 in 30 pairs of fresh cancer tissues and ad-jacent non-cancer tissues.Furthermore,the relationship between KIFC1 protein expression and survival time was analyzed by TC-GA database,and their clinicopathologic features were analyzed.Results The immunohistochemistry results showed the positive rate of KIFC1 in endometrioid carcinoma(61.05%)was signifi-cantly higher than that in the neighboring noncancerous tissue(13.33%),and the difference was statistically significant(P<0.05).The expression of KIFC1 was correlated with myometrial invasion,FIGO stage and lymphatic metastasis(all P<0.05).The relative expression of KIFC1 mRNA in endometrioid carci-noma(2.99±0.59)was significantly higher than that in the neighboring noncancerous tissue(1.00±0.29),and there was significant difference(P<0.05).The relative expression of KIFC1 protein in endometrioid carcinoma(1.70±0.36)was significantly higher than that in the neighboring noncancerous tissue(0.72±0.17),and there was significant difference(P<0.05).Furthermore,elevated KIFC1 expression was positive-ly correlated with a poorer prognosis.Conclusion KIFC1 is upregulated in endometrioid carcinoma and associated with poor prognosis of patients,KIFC1 was expected to be a potential ther-apeutic target and prognostic indicator for endometrioid carcino-ma.
9.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.
10.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.


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