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*
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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*
;
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
;
Cells, Cultured
3.Association of intestinal microecology with the development and progression of autoimmune hepatitis
Yuyan XIA ; Qiongrong ZENG ; Fujian LI ; Fengyan LI ; Qi LI ; Lixia TANG ; Guo ZHANG
Journal of Clinical Hepatology 2024;40(2):374-379
Autoimmune hepatitis (AIH) is an autoimmune disease characterized by chronic liver inflammation, with a gradually increasing incidence rate, and its social and medical burdens cannot be neglected. Intestinal microecology is becoming a research hotspot in the field of autoimmune disease. In recent years, it has been believed that changes in intestinal microecology can cause changes in autoimmune state, microbial metabolites, and intestinal barrier, which is one of the driving factors for the onset of AIH. Early diagnosis and correct treatment can help to improve the prognosis of AIH patients. This article introduces the characteristics of gut microbiota in AIH patients, elaborates on the impact of intestinal microflora imbalance on the pathogenesis of AIH, and briefly describes related treatment regimens from the perspective of intestinal microecology, so as to comprehensively understand and explain the role of intestinal microecology in AIH and the impact of intestinal microecology balance on the pathogenesis, diagnosis, and treatment of AIH.
4.Research progress on applications and mechanisms of osteogenesis effect of magnetic fields in oral field
CHEN Jinquan ; LIU Yuyan ; WANG Guoqing ; SUN Xiumei
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(4):302-309
Magnetic fields are safe and used in noninvasive physical therapies. Numerous studies have confirmed that magnetic fields have good osteogenic effects and certain value for clinical application in accelerating orthodontic tooth movement, promoting bone-implant integration, promoting fracture healing and improving the effects of distraction osteogenesis. Magnetic fields are expected to become applied as effective auxiliary methods for treating oral diseases. To support the clinical application of magnetic fields, this article reviews the applications of magnetic fields in the oral cavity, the biological effects on bone cells and the molecular mechanisms through which magnetic fields regulate bone metabolism. The biological effects of magnetic fields on bone cells include promoting osteogenesis by osteoblasts and mesenchymal stem cells and inhibiting bone resorption by osteoclasts. At the molecular level, bone cells sense and respond to magnetic stimulation, and through various mechanisms, such as displacement currents, Lorentz forces, and free radical pair effects, stimuli are transformed into biologically recognizable electrical signals that activate complex downstream signaling pathways, such as the P2 purinergic receptor signaling pathway, adenosine receptor signaling pathway, transforming growth factor-β receptor signaling pathway, mammalian target of rapamycin (mTOR) pathway, and Notch pathway. In addition, magnetic parameters, which are the factors affecting the osteogenic effects of magnetic fields, are discussed. However, the mechanisms of the osteogenic effects of magnetic fields are unclear, and further studies of these mechanisms could provide effective strategies for bone regeneration and periodontal tissue regeneration. In addition, considering the target of magnetic field therapies, combination with other drugs could lead to new strategies for the treatment of oral diseases.
5.Discussion of factors influencing preclinical studies based on fecal bacteria transplantation in mice
Shiqi SUN ; Lu LIU ; Shuangyuan HU ; Yuyan WANG ; Mingsheng SUN ; Ling ZHAO
Acta Laboratorium Animalis Scientia Sinica 2024;32(1):100-117
Fecal microbiota transplantation(FMT)is a therapeutic approach that targets intestinal microorganisms by transplanting fecal microorganisms from healthy individuals into the gastrointestinal tract of diseased individuals,thus restoring the recipient's disordered gastrointestinal microbiota by restructuring the intestinal flora.However,the mechanism of action and adverse effects of FMT in different diseases have not yet been clarified,thus limiting its wide clinical application.Its use still relies on in-depth preclinical studies;however,highly inconsistent or incomplete experimental details provided in current reports,coupled with a lack of authoritative standards and recommendations,seriously affect the interpretation of the study findings and replication of the experimental procedures,as well as hindering the clinical translation of the result.We therefore review and discuss the key steps of recipient selection and graft sample collection,storage,graft material preparation,and grafting route,with the aim of improving the utilization of experimental animals,consumables,and labor,and providing method ological recommendations and references to achieve replicability and standardization of preclinical FMT studies.
6.The Influence of In Vitro Diagnostic Technology on Health and Its Application in Economic Evaluation
Hui SUN ; Haiyin WANG ; Haode WANG ; Yuyan FU ; Chunlin JIN ; Yingyao CHEN
Chinese Health Economics 2024;43(1):17-20
In vitro diagnostic technology is an important aid for disease prevention,treatment,and prognostic monitoring.The de-velopment of its new technologies,methods and products is of great significance for improving medical quality and protecting public health.On the basis of exploring the mechanism of health impact of in vitro diagnostic technology,it takes dry chemical method and wet chemical method as an example,and compares the economy of the two diagnostic technologies for hyperkalemia diagnosis from the perspective of health system,with a view to draw references for the practical application and evaluation of new in vitro diagnostic techniques,methods and products in the future.
7.Application of a modified U-shaped forearm flap for the repair of small and medium-sized defects in the oral and maxillary areas
Libo SUN ; Yun HE ; Yuyan LAN ; Xiaoqiang SUN ; Chunfeng ZHANG ; Changmi WANG ; Yunhong LIANG
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(7):517-522
Objective To evaluate the applicability of a modified U-shaped forearm flap for the repair of small-and medium-sized defects in the oral and maxillary areas to provide a reference for clinicians.Methods This study was re-viewed and approved by the Ethics Committee,and informed consent was obtained from the patients.Ten patients with small-and medium-sized defects in the oral and maxillary areas underwent surgical repair using modified U-shaped fore-arm flaps.There were 8 males and 2 females aged 43-72 years.The donor site was apposed primarily after harvesting the modified U-shaped forearm skin flap.The flaps ranged from 6 cm × 4 cm to 8 cm × 5 cm in size.Six months after the operation,hand movements(finger extension,fist clenching,wrist rotation upward and wrist rotation downward),the forearm donor site,hand sensations and the satisfaction score for the postoperative quality of the scar at the donor site were evaluated(0 to 10;0:very unattractive,10:very satisfactory).Results A total of 10 patients with modified U-shaped forearm flaps survived.One patient developed venous crisis 24 hours after surgery and survived after surgical ex-ploration.Delayed healing occurred at the donor site of the forearm in 1 patient,and the wounds at the donor site of the forearm in the other patients all healed in the first stage.One patient presented with dysesthesia in the hand 2 weeks af-ter surgery and recovered within 3 months.Six months after surgery,all patients had no limited hand movement and no paresthesia at the forearm donor site or hand.The patients were basically satisfied with the appearance of the donor site,and the average satisfaction score of the subjective questionnaire was 8.4 points.Conclusion Modified U-shaped fore-arm flaps can directly close forearm donor site wounds,which avoids surgical trauma to the secondary donor site and sig-nificantly reduces related complications.Modified U-shaped forearm flaps provide an alternative to conventional forearm flaps for the repair of small-and medium-sized defects in the oral and maxillary areas.
8.Development status among infants at ages of 0 to 36 months in Xiaoshan District
LI Qing ; ZHONG Bihua ; SUN Jiarui ; DAI Fengpo ; DING Yina ; MIAO Xiangqing ; FU Yaxian ; TU Yuyan ; TAN Wenjuan ; YU Yinfei
Journal of Preventive Medicine 2024;36(3):255-259
Objective:
To learn the status and influencing factors of development among infants at ages of 0 to 36 months in Xiaoshan District, Hangzhou City, so as to provide the reference for promoting healthy development of infants.
Methods:
Infants at ages of 0-36 months who underwent physical examination in Child Health Clinic of Xiaoshan District Community Health Service Center were selected in 2022. General data of infants and their mothers were collected through questionnaires, and the development status of infants was screened by Age and Stages Questionnaire (third edition). Factors affecting the development status were identified using a multivariable logistic regression model.
Results:
A total of 2 519 infants were investigated, including 1 339 males (53.16%) and 1 180 females (46.84%). There were 608 infants with abnormal development of at least one functional area of communication (CM), gross motor (GM), fine motor (FM), problems solving (CG) and personal-social (PS). The abnormal rate was 24.14%, and the abnormal rates of the above functional areas were 9.77%, 6.59%, 7.98%, 6.39% and 9.33%, respectively. Multivariable logistic regression analysis showed that gender (male, OR=1.563, 95%CI: 1.191-2.052), mother's childbearing age (≥35 years, OR=1.411, 95%CI: 1.001-1.988), mother's educational level (lower than junior college, OR=1.460, 95%CI: 1.116-1.912) were factors affecting abnormal development of CM; preterm birth (OR=2.323, 95%CI: 1.315-4.103) was factors affecting abnormal development of GM; gender (male, OR=1.654, 95%CI: 1.225-2.232) was factors affecting abnormal development of FM; gender (male, OR=1.511, 95%CI: 1.086-2.102) and mode of delivery (cesarean section, OR=1.460, 95%CI: 1.060-2.010) were factors affecting abnormal development of CG; gender (male, OR=1.340, 95%CI: 1.019-1.763) and birth weight (low birth weight, OR=1.985, 95%CI: 1.149-3.432) were factors affecting abnormal development of PS.
Conclusions
The rate of abnormal development among infants at ages of 0 to 36 months in Xiaoshan District is 24.14%. Gender, preterm birth, mode of delivery, birth weight, mother's childbearing age and mother's educational level could affect the development status of infants.
9.Application of NNN-linked early care intervention in children with autism spectrum disorders
Caixiao SHI ; Yuyan SUN ; Qianqian QI ; Minghui SHI ; Mengyao LI ; Linqi ZHANG
Chinese Journal of Modern Nursing 2024;30(34):4739-4744
Objective:To explore the application effect of early nursing intervention based on NNN-link in social disorders of children with autism spectrum disorders (ASD) .Methods:A total of 126 hospitalized children with ASD in the Rehabilitation Center of Henan Children's Hospital from January to May 2023 were selected as research subjects by convenience sampling. They were randomly divided into an intervention group ( n=63) and a control group ( n=63) using a random number table. The control group received routine care, while the intervention group received early nursing intervention based on NNN-link in addition to routine care. The Social Disorder-related Nursing Diagnosis Outcome Scales and the Childhood Autism Rating Scale (CARS) scores were compared between the two groups before and after intervention. Results:After the early nursing intervention, the scores for family atmosphere, participation in leisure activities, participation in play, social skills, and social participation were higher in the intervention group compared to the control group, the differences were statistically significant ( P<0.05). The CARS scores of the intervention group were also lower than those of the control group, the differences were statistically significant ( P<0.05) . Conclusions:Early nursing intervention based on NNN-link can effectively improve the social disorder conditions of children with ASD, reduce their autism symptoms, and promote recovery.
10.Diagnostic efficacy of alpha-fetoprotein and alpha-fetoprotein L3% in hepatitis B virus-related early-stage hepatocellular carcinoma
Yuyan TANG ; Shibin XIE ; Jianyun ZHU
Journal of Clinical Hepatology 2023;39(11):2607-2613
ObjectiveTo investigate the diagnostic efficacy and optimal cut-off values of alpha-fetoprotein (AFP) and alpha-fetoprotein variant L3 (AFP-L3) in hepatitis B virus (HBV)-related early-stage hepatocellular carcinoma (HCC). MethodsA total of 1 080 patients with HBV-related HCC (HBV-HCC) who were diagnosed for the first time and not yet treated in The Third Affiliated Hospital of Sun Yat-Sen University from January 2019 to July 2022 were enrolled as HCC group in the study, among whom there were 620 patients with CNLC Ⅰa-Ⅱa HCC, and in addition, 346 patients with HBV-related chronic hepatitis B (CHB group) and 293 patients with HBV-related liver cirrhosis (LC group) were enrolled as controls. The diagnostic efficacy of AFP and AFP-L3% in screening for HBV-related early-stage HCC was analyzed, including sensitivity, specificity, and the area under the ROC curve (AUC). The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups; the Kruskal-Wallis H test was used for comparison between multiple groups, and the Bonferroni method was used for further comparison between two groups. ResultsThe HCC group had significantly higher levels of AFP and AFP-L3% than the CHB group and the LC group (H=542.479 and 418.974, both P<0.001). In early-stage HCC, AFP and AFP-L3% had an optimal cut-off value of 8.7 ng/mL and 5%, respectively, and AFP alone had the largest AUC of 0.816, with a sensitivity of 66.9% and a specificity of 85.1%. There was no significant difference in AUC between AFP-L3%+AFP and AFP alone (Z=0.609, P=0.543), but both AFP-L3%+AFP and AFP alone had a significantly larger AUC than AFP-L3% alone (AFP vs AFP-L3%: Z=8.173, P<0.001; AFP+AFP-L3% vs AFP-L3%: Z=8.802, P<0.001). ConclusionAFP has a good value and is superior to AFP-L3% in the diagnosis of HBV-related early-stage HCC, and the screening cut-off value of AFP should be lowered in order to improve the detection rate of early-stage HCC.


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