1.The Role of NEAT1 in Bone and Cartilage Metabolism and Bone Diseases
Rui-Ming WEN ; Rui-Qi HUANG ; Yi-Xing CHANG ; Ke XU ; Xue-Jie YI
Progress in Biochemistry and Biophysics 2025;52(4):930-945
In the process of maintaining the steady state of bone tissue, the transcription network and signal pathway of the body play a vital role. These complex regulatory mechanisms need precise coordination to ensure the balance between bone formation and bone absorption. Once this balance is broken, it may lead to pathological changes of bone and cartilage, and then lead to various bone diseases. Therefore, it is of great significance to understand these regulatory mechanisms for the prevention and treatment of bone diseases. In recent years, with the deepening of research, more and more lncRNA has been found to be closely related to bone health. Among them, nuclear paraspeckle assembly transcript 1 (NEAT1), as an extremely abundant RNA molecule in mammalian nuclei, has attracted extensive attention. NEAT1 is mainly transcribed from a specific site in human chromosome 11 by RNA polymerase II (RNaseP), which can form two different subtypes NEAT1_1 and NEAT1_2. These two subtypes are different in intracellular distribution and function, but they participate in many biological processes together. Studies have shown that NEAT1 plays a specific role in the process of cell growth and stress response. For example, it can regulate the development of osteoblasts (OB), osteoclasts (OC) and chondrocytes by balancing the differentiation of bone marrow mesenchymal stem cells (BMSCs), thus maintaining the steady state of bone metabolism. This discovery reveals the important role of NEAT1 in bone development and remodeling. In addition, NEAT1 is closely related to a variety of bone diseases. In patients with bone diseases such as osteoporosis (OP), osteoarthritis (OA) and osteosarcoma (OS), the expression level of NEAT1 is different. These differential expressions may be closely related to the pathogenesis and progression of bone diseases. By regulating the level of NEAT1, it can affect a variety of signal transduction pathways, and then affect the development of bone diseases. For example, some studies show that by regulating the expression level of NEAT1, the activity of osteoclasts can be inhibited, and the proliferation and differentiation of osteoblasts can be promoted, thus improving the symptoms of osteoporosis. It is worth noting that NEAT1 can also be used as a key sensor for the prevention and treatment of bone diseases. When exercising or receiving some natural products, the expression level of NEAT1 will change, thus reflecting the response of bones to external stimuli. This feature makes NEAT1 an important target for studying the prevention and treatment strategies of bone diseases. However, although the role of NEAT1 in bone biology and bone diseases has been initially recognized, its specific mechanism and regulatory relationship are still controversial. For example, the expression level, mode of action and interaction with other molecules of NEAT1 in different bone diseases still need further in-depth study. This paper reviews the role of NEAT1 in maintaining bone and cartilage metabolism, and discusses its expression and function in various bone diseases. By combing the existing research results and controversial points, this paper aims to provide new perspectives and ideas for the prevention and treatment of bone diseases, and provide useful reference and enlightenment for future research.
2.In situ Analytical Techniques for Membrane Protein Interactions
Zi-Yuan KANG ; Tong YU ; Chao LI ; Xue-Hua ZHANG ; Jun-Hui GUO ; Qi-Chang LI ; Jing-Xing GUO ; Hao XIE
Progress in Biochemistry and Biophysics 2025;52(5):1206-1218
Membrane proteins are integral components of cellular membranes, accounting for approximately 30% of the mammalian proteome and serving as targets for 60% of FDA-approved drugs. They are critical to both physiological functions and disease mechanisms. Their functional protein-protein interactions form the basis for many physiological processes, such as signal transduction, material transport, and cell communication. Membrane protein interactions are characterized by membrane environment dependence, spatial asymmetry, weak interaction strength, high dynamics, and a variety of interaction sites. Therefore, in situ analysis is essential for revealing the structural basis and kinetics of these proteins. This paper introduces currently available in situ analytical techniques for studying membrane protein interactions and evaluates the characteristics of each. These techniques are divided into two categories: label-based techniques (e.g., co-immunoprecipitation, proximity ligation assay, bimolecular fluorescence complementation, resonance energy transfer, and proximity labeling) and label-free techniques (e.g., cryo-electron tomography, in situ cross-linking mass spectrometry, Raman spectroscopy, electron paramagnetic resonance, nuclear magnetic resonance, and structure prediction tools). Each technique is critically assessed in terms of its historical development, strengths, and limitations. Based on the authors’ relevant research, the paper further discusses the key issues and trends in the application of these techniques, providing valuable references for the field of membrane protein research. Label-based techniques rely on molecular tags or antibodies to detect proximity or interactions, offering high specificity and adaptability for dynamic studies. For instance, proximity ligation assay combines the specificity of antibodies with the sensitivity of PCR amplification, while proximity labeling enables spatial mapping of interactomes. Conversely, label-free techniques, such as cryo-electron tomography, provide near-native structural insights, and Raman spectroscopy directly probes molecular interactions without perturbing the membrane environment. Despite advancements, these methods face several universal challenges: (1) indirect detection, relying on proximity or tagged proxies rather than direct interaction measurement; (2) limited capacity for continuous dynamic monitoring in live cells; and (3) potential artificial influences introduced by labeling or sample preparation, which may alter native conformations. Emerging trends emphasize the multimodal integration of complementary techniques to overcome individual limitations. For example, combining in situ cross-linking mass spectrometry with proximity labeling enhances both spatial resolution and interaction coverage, enabling high-throughput subcellular interactome mapping. Similarly, coupling fluorescence resonance energy transfer with nuclear magnetic resonance and artificial intelligence (AI) simulations integrates dynamic structural data, atomic-level details, and predictive modeling for holistic insights. Advances in AI, exemplified by AlphaFold’s ability to predict interaction interfaces, further augment experimental data, accelerating structure-function analyses. Future developments in cryo-electron microscopy, super-resolution imaging, and machine learning are poised to refine spatiotemporal resolution and scalability. In conclusion, in situ analysis of membrane protein interactions remains indispensable for deciphering their roles in health and disease. While current technologies have significantly advanced our understanding, persistent gaps highlight the need for innovative, integrative approaches. By synergizing experimental and computational tools, researchers can achieve multiscale, real-time, and perturbation-free analyses, ultimately unraveling the dynamic complexity of membrane protein networks and driving therapeutic discovery.
3. Lycium barbarian seed oil activates Nrf2/ARE pathway to reduce oxidative damage in testis of subacute aging rats
Rui-Ying TIAN ; Wen-Xin MA ; Zi-Yu LIU ; Hui-Ming MA ; Sha-Sha XING ; Na HU ; Chang LIU ; Biao MA ; Jia-Yang LI ; Hu-Jun LIU ; Chang-Cai BAI ; Dong-Mei CHEN
Chinese Pharmacological Bulletin 2024;40(3):490-498
Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.
4.Meta-analysis of Distribution Frequency of Traditional Chinese Medicine Syndrome in Primary Osteoporosis
Hailong WU ; Tianying CHANG ; Yan LU ; Zongjian LUO ; Xiangyang LENG ; Xing LIAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):111-117
ObjectiveTo systematically evaluate the distribution of traditional Chinese medicine(TCM) syndromes of primary osteoporosis(POP) in China by using evidence-based medicine methods, and to understand the distribution law of the syndromes. MethodChina National Knowledge Infrastructure(CNKI), VIP Chinese Science and Technology Journal Database(VIP), WanFang Data Knowledge Service Platform(WanFang) and China Biology Medicine(CBM) were searched to obtain representative literature, and each database was searched from the 1994 World Health Organization defined diagnostic criteria for osteoporosis until May 1, 2023. Two researchers independently screened literature according to the criteria, extracted data, and cross-checked them. Meta analysis was conducted using R4.1.3, and subgroup analysis was performed. ResultA total of 56 Chinese papers were included, involving 14 415 patients. After standardized classification of syndromes, 11 articles were excluded, and Meta analysis results of the ultimately included 45 Chinese articles showed that the distribution frequencies of liver-kidney Yin deficiency syndrome, spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome in 12 723 patients were 27%[95% confidence interval(CI) 0.24-0.31], 32%(95% CI 0.29-0.36), 36%(95% CI 0.30-0.42). Subgroup analysis showed that there was a statistically significant difference in the distribution of the three TCM syndromes in the north and south(P<0.05). In addition, the incidence of TCM syndrome fractures in different types of POP was 15%(95% CI 0.09-0.24) for liver-kidney Yin deficiency syndrome, 20%(95% CI 0.12-0.30) for spleen-kidney Yang deficiency syndrome, and 31%(95% CI 0.25-0.39) for kidney deficiency and blood stasis syndrome. ConclusionThe distribution of syndromes in POP patients is mainly kidney deficiency, accompanied by liver and spleen dysfunction. Liver-kidney Yin deficiency syndrome, spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome are all the main syndromes of POP and osteoporotic fractures, and kidney deficiency and blood stasis syndrome is most closely related to the development of osteoporotic fractures. The reference standards for syndrome determination among the included studies are inconsistent, and in the future, it is necessary to focus on their determination standards to obtain consensus research results, at the same time, conduct large-scale syndrome research to obtain representative research results, providing a basis for clinical practice and research.
5.Analysis of the predictive value of the protein level of oncogenes C-myc,N-ras,PLK 1,and FGF2 in the serum of hepatitis B-related liver cancer patients on the prognosis after TACE
Yang ZHOU ; Xing YIN ; Min FU ; Huan CHANG ; Yanli XING ; Yixing LI ; Xianzhe YIN
International Journal of Laboratory Medicine 2024;45(3):347-352,357
Objective To investigate the predictive value of serum oncogene[proliferation-related gene(C-myc),transformation gene(N-ras),silk/threonine kinase 1(PLK1),fibroblast growth factor 2(FGF2)]protein levels in patients with hepatitis B associated hepatocellular carcinoma(HCC)after hepatic arterial chemoem-bolization(TACE).Methods A total of 127 patients with hepatitis B-associated hepatocellular carcinoma ad-mitted to a hospital from July 2016 to January 2021 were selected and divided into death group and survival group according to the follow-up results.The serum oncogene C-myc,N-ras,PLK1 and FGF2 protein levels were determined by double-antibody sandwich enzyme-linked immunosorbent assay.Univariate and multivari-ate Cox analysis were used to analyze the risk factors of serum oncogene C-myc,N-ras,PLK1 and FGF2 pro-tein levels in patients with hepatitis B-associated hepatocellular carcinoma after TACE.The receiver operating characteristic curve was used to evaluate the prognostic value of the serum oncogene C-myc,N-ras,PLK1 and FGF2 protein levels,and the patients were divided into high expression group and low expression group ac-cording to the corresponding cutoff value.Kaplan-Meier survival curve was used to evaluate the prognosis of different serum oncogene C-myc,N-ras,PLK1 and FGF2 protein level.Results Multivariate Cox regression a-nalysis indicated that TNM stage Ⅲ to Ⅳ(HR=2.998,95%CI:1.239-7.257),portal vein metastasis(HR=3.737,95%CI:1.941-7.193),abdominal metastasis(HR=3.482,95%CI:1.709-7.097),Child-Pugh grade B(HR=2.587,95%CI:1.045-6.406),high serum oncogene C-myc protein level(HR=1.224,95%CI:1.090-1.374),high serum oncogene N-ras protein level(HR=1.218,95%CI:1.097-1.353),high serum oncogene PLK1 protein level(HR=1.237,95%CI:1.110-1.379)and high serum oncogene FGF2 protein level(HR=1.141,95%CI:1.060-1.228)were independent risk factors for the prognosis of hepatitis B-asso-ciated hepatocellular carcinoma patients after TACE(all P<0.05).The overall survival rate of low expression group of serum oncogene C-myc,N-ras,PLK1,FGF2 protein level was significantly higher than that of high expression group of serum oncogene C-myc,N-ras,PLK1,FGF2 protein level,the difference was statistically significant(all P<0.001).Conclusion Serum oncogene C-myc,N-ras,PLK1,FGF2 protein levels have predic-tive value for the prognosis of patients with HBV-related liver cancer after TACE.
6.Biological scaffold materials and printing technology for repairing bone defects
Xiangyu KONG ; Xing WANG ; Zhiwei PEI ; Jiale CHANG ; Siqin LI ; Ting HAO ; Wanxiong HE ; Baoxin ZHANG ; Yanfei JIA
Chinese Journal of Tissue Engineering Research 2024;28(3):479-485
BACKGROUND:In recent years,with the development of biological scaffold materials and bioprinting technology,tissue-engineered bone has become a research hotspot in bone defect repair. OBJECTIVE:To summarize the current treatment methods for bone defects,summarize the biomaterials and bioprinting technology for preparing tissue-engineered bone scaffolds,and explore the application of biomaterials and printing technology in tissue engineering and the current challenges. METHODS:Search terms were"bone defect,tissue engineering,biomaterials,3D printing technology,4D printing technology,bioprinting,biological scaffold,bone repair"in Chinese and English.Relevant documents published from January 1,2009 to December 1,2022 were retrieved on CNKI,PubMed and Web of Science databases.After being screened by the first author,high-quality references were added.A total of 93 articles were included for review. RESULTS AND CONCLUSION:The main treatment methods for bone defects include bone transplantation,membrane-guided regeneration,gene therapy,bone tissue engineering,etc.The best treatment method is still uncertain.Bone tissue engineering technology is a new technology for the treatment of bone defects.It has become the focus of current research by constructing three-dimensional structures that can promote the proliferation and differentiation of osteoblasts and enhance the ability of bone formation.Biological scaffold materials are diverse,with their characteristics,advantages and disadvantages.A single biological material cannot meet the demand for tissue-engineered bone for the scaffold.Usually,multiple materials are combined to complement each other,which is to meet the demand for mechanical properties while taking into account the biological properties of the scaffold.Bioprinting technology can adjust the pore of the scaffold,build a complex spatial structure,and is more conducive to cell adhesion,proliferation and differentiation.The emerging 4D printing technology introduces"time"as the fourth dimension to make the prepared scaffold dynamic.With the synchronous development of smart materials,4D printing technology provides the possibility of efficient repair of bone defects in the future.
7.Mechanism of negative pressure wound therapy in the auxiliary treatment of bone and soft tissue infection
Hao XING ; Qingfeng MENG ; Zhengqi CHANG
Chinese Journal of Tissue Engineering Research 2024;28(4):621-626
BACKGROUND:As the population ages at an accelerated rate in China,the incidence of bone and soft tissue infections is likewise on the rise.Bone and soft tissue infections can involve all bone and surrounding soft tissues,including the periosteum,cortex,cancellous bone and bone marrow.Examples of such infections include diabetes foot,osteomyelitis,surgical incision infection,and infection around joint prostheses.Owing to the intricate pathogenesis and challenging treatment,it has become increasingly noteworthy in clinical settings.Negative pressure wound therapy is a modern wound treatment which has been gaining popularity,especially in the area of bone and soft tissue infection. OBJECTIVE:To analyze the global research progress in the utilization of negative pressure wound therapy for treating bone and soft tissue infection in recent years. METHODS:Relevant articles in Chinese and English published in PubMed,Web of Science,and CNKI from 1990 to 2022 were retrieved.Search terms were"negative pressure wound therapy,vacuum assisted closure,negative pressure,osteomyelitis,bone infection"in English and Chinese,separately.A total of 711 articles were initially retrieved,out of which 65 articles were included for further review. RESULTS AND CONCLUSION:Negative pressure wound therapy,as an auxiliary approach to treating wounds,has a range of positive effects such as stabilizing wounds,diminishing edema,decreasing bacterial load,encouraging granulation tissue and angiogenesis,enhancing tissue perfusion,modulating peripheral nerves,modulating biological immunity and promoting the growth and differentiation of osteoblasts.This is a more effective method for managing complex wounds,such as bone and soft tissue infections,than traditional dressings with one-dimensional benefits.Numerous studies,both basic and clinical,have demonstrated the safety and efficacy of negative pressure wound therapy in the auxiliary treatment of bone and soft tissue infections.
8.Application value of radiomics model based on multiparametric MRI glioma peritumoral region in glioma prognosis evaluation
Qiuyang Hou ; Chengkun Ye ; Chang Liu ; Jianghao Xing ; Yaqiong Ge ; Jiangdian Song ; Kexue Deng
Acta Universitatis Medicinalis Anhui 2024;59(1):154-161
Objective :
To evaluate the prognostic value of a radiomics model based on the peritumoral region of gli- oma.
Methods :
138 patients with glioma were retrospectively analyzed ,medical imaging interaction toolkit ( MITK) software was used to obtain the magnetic resonance imaging (MRI) images of peritumoral area 5 mm,10 mm and 20 mm from the tumor edge and extract texture features.The texture features were screened the radiomics model was established and the radiomic score was calculated.A clinical prediction model and a combined predic- tion model along with Rad-score and clinical risk factors were established.The combined prediction model was dis- played as a nomogram,and the predictive performance of the model for survival in glioma patients was evaluated.
Results :
In the validation set,the C-index value of the radiomics model based on the peritumoral region 10 mm a- way from the tumor edge based on T2 weighted image (T2WI) images was 0. 663 (95% CI = 0. 72-0. 78) ,resul- ting in the best prediction performance.On the training set and validation set,the C-index of the nomogram was 0. 770 and 0. 730,respectively,indicating that the prediction performance of nomogram was better than those of the radiomics model and clinical prediction model.The model had the highest prediction effect on the 3-year survival rate of glioma patients (training set area under curve (AUC) = 0. 93,95% CI = 0. 83 - 0. 98 ; validation set AUC = 0. 88,95% CI = 0. 76 -0. 99) .The calibration curve showed that the joint prediction nomogram in both the training set and the validation set had good performance.
Conclusion
The combined prediction model based on the preoperative T2WI images in the peritumoral region 10 mm from the tumor edge and the clinicopathological risk factors can accurately predict the prognosis of glioma,providing the best effect of prediction on the 3-year survival rate of glioma.
9.Efficacy and safety of nicorandil and ticagrelor de-escalation after percutaneous coronary intervention for elderly patients with acute coronary syndrome
Xiang SHAO ; Ning BIAN ; Hong-Yan WANG ; Hai-Tao TIAN ; Can HUA ; Chao-Lian WU ; Bei-Xing ZHU ; Rui CHEN ; Jun-Xia LI ; Tian-Chang LI ; Lu MA
Medical Journal of Chinese People's Liberation Army 2024;49(1):75-81
Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.
10.Application of"rotation-correction loop technique"in the retrieval of complex inferior vena cava filters
Jie HU ; Maolin QIAO ; Qinqin TIAN ; Heng WANG ; Sheng YAN ; Wenbo ZHAO ; Yongbin SHI ; Peilu SHI ; Miao XING ; Haifeng LI ; Haijiang JIN ; Ping WANG ; Wenkai CHANG ; Yuwen WANG ; Honglin DONG
Journal of Interventional Radiology 2024;33(3):289-294
Objective To discuss the application of the"rotating guidewire and correcting the filter recovery hook direction technique"("rotation-correction loop technique"for short),a technique invented by the authors in clinical practice,in the retrieval of complex inferior vena cava filter(IVCF),and to discuss its technical skills and advantages.Methods The clinical data of 417 patients carrying an IVCF,who were admitted to the Department of Vascular Surgery of Second Hospital of Shanxi Medical University of China to retrieve IVCF between January 2022 and December 2022,were retrospectively analyzed.Taking the time spent on the retrieval of IVCF and the intraoperative radiation dose as the evaluation indicators,the advantages and disadvantages of the standard filter retrieval technique,the"rotation-correction loop technique"and the other loop-assisted techniques were compared.Results Both the intraoperative radiation dose and the time spent on the retrieval of IVCF using"rotation-correction loop technique"were remarkably lower than those of other loop-assisted techniques(P<0.000 1).Conclusion For the retrieval of complex IVCF,especially for the IVCF which is heavily tilted and/or its recovered hook is attached to the vascular wall,the use of"rotation-correction loop technique"can shorten the time spent on the the retrieval of IVCF and reduce the intraoperative radiation dose.This technique carries high safety and practicability,the device is simple and it can be manipulated by single physician,which is conducive to clinical application and promotion.(J Intervent Radiol,2024,33:289-294)


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