1.Identification and drug sensitivity analysis of key molecular markers in mesenchymal cell-derived osteosarcoma
Haojun ZHANG ; Hongyi LI ; Hui ZHANG ; Haoran CHEN ; Lizhong ZHANG ; Jie GENG ; Chuandong HOU ; Qi YU ; Peifeng HE ; Jinpeng JIA ; Xuechun LU
Chinese Journal of Tissue Engineering Research 2025;29(7):1448-1456
BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.
2.Immunoregulatory mechanisms in the aging microenvironment: Targeting the senescence-associated secretory phenotype for cancer immunotherapy.
Haojun WANG ; Yang YU ; Runze LI ; Huiru ZHANG ; Zhe-Sheng CHEN ; Changgang SUN ; Jing ZHUANG
Acta Pharmaceutica Sinica B 2025;15(9):4476-4496
The aging microenvironment, as a key driver of tumorigenesis and progression, plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype (SASP). SASP consists of a variety of interleukins, chemokines, proteases, and growth factors. It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms, thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment. Furthermore, these secreted factors activate key signaling pathways such as NF-κB, cGAS-STING, and mTOR, which regulate the expression of immune-related molecules (such as PD-L1) and promote the recruitment of immunosuppressive cells, including regulatory T cells and myeloid-derived suppressor cells. This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment. Furthermore, the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms, including approaches to inhibit SASP secretion or eliminate senescent cells. Although these strategies have shown promise in certain tumor models, the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies. This highlights the need for further research into adaptive stratification and personalized treatment approaches. Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.
3.Predictive value and efficacy evaluation of plasma miR-132,miR-134 combined with miR-124 in patients with depression
Wenpeng DENG ; Haojun XIONG ; Guangtao HU ; Wenjing YU ; Junjie FAN ; Yupeng LONG
International Journal of Laboratory Medicine 2024;45(16):1962-1965,1972
Objective To explore the predictive value and efficacy evaluation of plasma microRNA(miR)-132,miR-134 combined with miR-124 in patients with depression.Methods A total of 75 patients diagnosed with depression in the psychiatric department of the hospital from June 2021 to July 2023 were selected as the study group,and 75 healthy subjects who underwent physical examination in the hospital during the same pe-riod were selected as the control group.The relative expression levels of miR-132,miR-134 and miR-124 in plasma of the two groups were detected.The levels of miR-132,miR-124,miR-134,brain-derived neurotrophic factor(BDNF).inflammatory factors[interleukin(IL)-6,IL-18,tumor necrosis factor-a(TNF-a)]were com-pared between the two groups before and after 8 weeks of treatment.Multiple linear regression analysis was used to construct a joint prediction model.The application value of plasma miR-132,miR-134,miR-124 and combined prediction in the diagnosis of depression was evaluated by receiver operating characteristic(ROC)curve.Results The relative expression levels of miR-132 and miR-124 in plasma of the study group were sig-nificantly higher than those of the control group,with statistical significance(P<0.05).The relative expres-sion level of miR-134 in the study group was significantly lower than that in the control group,and the differ-ence was statistically significant(P<0.05).ROC curve analysis showed that the area under the curve of plas-ma miR-132,miR-134,miR-124 and combined prediction of depression were 0.858 8,0.851 9,0.763 1 and 0.971 4,respectively.Compared with 8 weeks before treatment,plasma miR-132,miR-124,IL-6,IL-18 and TNF-a levels were significantly down-regulated,while plasma miR-134 and BDNF levels were significantly up-regulated after 8 weeks of treatment.Conclusion miR-132,miR-134 and miR-124 are closely related to the oc-currence of depression,and the combination of the three can be used to predict and early diagnose depression patients and evaluate the drug efficacy of depression patients.
4.Comparison of the image quality between total-body PET/CT with 1 min acquisition and conventional PET/CT: a self-control study
Runjun YANG ; Xueqi CHEN ; Haojun YU ; Pengcheng HU ; Hongcheng SHI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(1):12-15
Objective:To investigate whether the image quality of total-body PET/CT (TB PET/CT) with 1 min acquisition can meet the clinical diagnostic requirements.Methods:From May 2019 to September 2021, a total of 90 malignant tumor patients (60 males, 30 females, age 31-86 years) with primary lesions confirmed by pathological diagnosis in Zhongshan Hospital, Fudan University were respectively analyzed. All patients underwent conventional PET/CT (C PET/CT) scan with conventional clinical acquisition and TB PET/CT scan with 1 min acquisition after injecting 18F-FDG in random order. Paired t test or Wilcoxon signed rank test was used to analyze the image quality of these two scans. Results:SUV max of primary lesions in TB PET/CT group was significantly higher than that in C PET/CT group (15.9(7.9, 24.6) vs 12.5(5.8, 16.6); z=8.14, P<0.001), so were signal-to-noise ratio (SNR) of the blood pool, liver, muscles (9.3±3.0, 11.4(9.5, 14.2), 8.3(7.3, 10.1) vs 6.2±1.7, 9.4(7.7, 11.8), 6.0(4.9, 7.1)), tumor-to-blood pool ratio (TBR) (9.3(4.3, 14.8) vs 8.5(4.3, 11.1)), tumor-to-liver ratio (TLR) (6.7(3.0, 10.4) vs 6.1(2.9, 7.7)), tumor-to-muscle ratio (TMR) (23.2(11.5, 38.0) vs 18.3(9.6, 26.6); t=9.36, z values: 4.44-7.40, all P<0.001). Conclusion:The image quality of TB PET/CT scan with 1 min acquisition can meet the diagnostic requirements, and is better than the C PET/CT image quality with conventional clinical acquisition.
5.Expert consensus on operational guideline for 68Ga-DOTATATE/18F-FDG two-day total-body PET/CT imaging of neuroendocrine neoplasms
Haojun YU ; Yushen GU ; Zhi YANG ; Ruimin WANG ; Hubing WU ; Xinming ZHAO ; Xiaohua ZHU ; Zhaoping CHENG ; Wei FAN ; Zhifang WU ; Sijin LI ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2024;31(4):687-690,封3
68Ga-DOTATATE/18F-FDG two-day low-dose total-body PET/CT imaging is increasingly employed to facilitate the diagnosis,prognosis,and heterogeneity assessment of neuroendocrine neoplasms.We present a consensus on operational guideline for a two-day combined imaging from experts in low-dose/ultra-low-dose total-body PET/CT from several domestic medical institutions.
6.Glia Connect Inflammation and Neurodegeneration in Multiple Sclerosis.
Ye SUN ; Haojun YU ; Yangtai GUAN
Neuroscience Bulletin 2023;39(3):466-478
Multiple sclerosis (MS) is regarded as a chronic inflammatory disease that leads to demyelination and eventually to neurodegeneration. Activation of innate immune cells and other inflammatory cells in the brain and spinal cord of people with MS has been well described. However, with the innovation of technology in glial cell research, we have a deep understanding of the mechanisms of glial cells connecting inflammation and neurodegeneration in MS. In this review, we focus on the role of glial cells, including microglia, astrocytes, and oligodendrocytes, in the pathogenesis of MS. We mainly focus on the connection between glial cells and immune cells in the process of axonal damage and demyelinating neuron loss.
Humans
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Multiple Sclerosis
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Neuroglia
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Inflammation/pathology*
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Brain/pathology*
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Spinal Cord/pathology*
7.Advances in disease-modifying therapy of neuromyelitis optica spectrum disorders
Hongyan LI ; Kan WANG ; Haojun YU ; Rui RUI ; Xiaoying YAO ; Yangtai GUAN
Chinese Journal of Neurology 2023;56(12):1435-1446
Neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune-mediated inflammatory demyelinating diseases of the central nervous system, characterized by optic nerve and spinal cord lesions, with high chance of recurrence and disability. Disease-modifying therapy, including immunosuppressants, monoclonal antibodies, stem cell transplantation etc., is the key to prevent recurrence. This article made a systematic review about the sequential treatment or prognosis of NMOSD by searching for the related articles published on PubMed from 2017 to 2022 to provide recommendations and references for disease-modifying therapy of NMOSD.
8.Clinical guideline on first aid for blast injury of the chest (2022 edition)
Zhiming SONG ; Jianming CHEN ; Jing ZHONG ; Yunfeng YI ; Lianyang ZHANG ; Jianxin JIANG ; Mao ZHANG ; Yang LI ; Guodong LIU ; Dingyuan DU ; Jiaxin MIN ; Xu WU ; Shuogui XU ; Anqiang ZHANG ; Yaoli WANG ; Hao TANG ; Qingshan GUO ; Yigang YU ; Xiangjun BAI ; Gang HUANG ; Zhiguang YANG ; Yunping ZHAO ; Sheng LIU ; Lijie TAN ; Lei TONG ; Xiaoli YUAN ; Yanmei ZHAO ; Haojun FAN
Chinese Journal of Trauma 2022;38(1):11-22
Blast injury of the chest injury is the most common wound in modern war trauma and terrorist attacks, and is also the most fatal type of whole body explosion injury. Most patients with severe blast injury of the chest die in the early stage before hospitalization or during transportation, so first aid is critically important. At present, there exist widespread problems such as non-standard treatment and large difference in curative effect, while there lacks clinical treatment standards for blast injury of the chest. According to the principles of scientificity, practicality and advancement, the Trauma Society of Chinese Medical Association has formulated the guidance of classification, pre-hospital first aid, in-hospital treatment and major injury management strategies for blast injury of the chest, aiming to provide reference for clinical diagnosis and treatment.
9.Myelin-oligodendrocyte glycoprotein antibody-associated disease
Chinese Journal of Neurology 2022;55(6):643-649
Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently-established autoimmune central nervous system demyelinating disease, characterized by the detection of serum anti-myelin-oligodendrocyte glycoprotein antibody of IgG1 type. Sharing similar clinical manifestations with multiple sclerosis and aquaporin-4 antibody positive neuromyelitis optica spectrum disorder, it has yet demonstrated a unique disease course, pathological and radiological features. Therefore, MOGAD should be regarded as a disease entity to carry out further investigation. This review intends to summarize its pathogenesis, diagnosis and treatment progresses, so as to provide guidance for clinical practice.
10.Clinical application of 18F-FDG PET/CT imaging in diagnosis of focal organizing pneumonia
Jun ZHOU ; Wujian MAO ; Yushen GU ; Haojun YU ; Shuguang CHEN ; Hongcheng SHI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2020;40(8):464-469
Objective:To explore the imaging features of 18F-fluorodeoxyglucose (FDG) PET/CT (high-resolution CT, HRCT) imaging in focal organizing pneumonia (FOP). Methods:Patients with solid nodular FOP ( n=45; 33 males, 12 females, age (58±9) years) and early peripheral non-mucinous solid lung adenocarcinoma ( n=47; 21 males, 26 females, age (63±10) years) confirmed by postsurgical pathology between May 2012 and December 2018 in Zhongshan Hospital, Fudan University were retrospectively analyzed. All patients underwent 18F-FDG PET/CT (HRCT) imaging followed by surgery within 3 weeks. The imaging findings and characteristics of the lesions were recorded. Differences of the maximum standardized uptake value (SUV max) and maximum diameter between FOP and adenocarcinoma were analyzed by Mann-Whitney U test or t′ test. Spearman correlation or Pearson correlation analysis was performed to analyze the relation between SUV max and maximum diameter. Binary logistic regression analysis was performed to identify the predictive factors for FOP. Finally, the receiver operating characteristic (ROC) curve analysis was used for evaluation of diagnostic efficiency. Results:The SUV max of FOP was lower than that of lung adenocarcinoma (3.1(1.7, 4.9) vs 6.5(3.8, 9.3); z=-4.598, P<0.01), and the maximum diameter of FOP was smaller than that of lung adenocarcinoma ((18.0±6.3) mm vs (21.8±4.3) mm; t′=-3.424, P<0.01). The SUV max was positively correlated with the maximum diameter in FOP group ( r s=0.509, P<0.01), while the SUV max of lung adenocarcinoma was not correlated with the lesion size ( r=0.076, P>0.05). HRCT of the PET/CT system showed the fusiform shape were more common in FOP ( χ2=9.549, P<0.05). Multivariate regression analysis identified that SUV max≤7.1, diameter≤18.3 mm, and fusiform shape were independent factors to predict FOP, with odds ratio ( OR) of 10.585, 4.674, 9.073, respectively (all P<0.05). ROC curve analysis showed that the area under the curve (AUC) of SUV max≤7.1 combined with diameter≤18.3 mm and fusiform nodule was 0.860, and the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 97.8%(44/45), 70.2%(33/47), 75.9%(44/58), 97.1%(33/34), and 83.7%(77/92), respectively. Conclusion:SUV max≤ 7.1 combined with maximum diameter≤ 18.3 mm and fusiform shape may predict solid nodular FOP.

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