Top Read Articles

    Published in last 1 year |  In last 2 years |  In last 3 years |  All
    Please wait a minute...
    For Selected: Toggle Thumbnails
    Construction and characterization of mice with conditional knockout of Stat3 gene in microglia
    ZHU Xiaochen, XIE Xinyi, ZHAO Xuri, XU Lina, HE Zhiyan, ZHOU Wei
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (6): 689-698.   DOI: 10.3969/j.issn.1674-8115.2023.06.005
    Abstract496)   HTML36)    PDF(pc) (6326KB)(255)       Save

    Objective ·To construct mice with conditional knockout of Stat3 gene in microglia based on the Cre-Loxp system and validate their knockout efficiency. Methods ·Cx3cr1creERT2 and Stat3fl/fl genotypic mice were bred for conditional knockout mice (CKO) and Wild Type mice (WT). The mouse genotypes were determined by extracting DNA from mouse tissues through Polymerase Chain Reaction (PCR) combined with the amplification results of cre and flox primers. Stat3 knockdown was induced by intraperitoneal injection of tamoxifen in the CKO and WT mice at 6 weeks of age. The CKO mice (n=4) and WT mice (n=4) were randomly selected for the detection. After two weeks of observation, microglia cells were sorted out by Magnetic Activated Cell Sorting (MACS). Real-time PCR (RT-PCR) was used to detect gene knockout efficiency at the gene level. The expression of STAT3 in microglia was observed by brain immunofluorescence staining. The expression rate of STAT3 in microglia was detected by flow cytometry. The expression rate of STAT3 in macrophages of the spleen was detected by flow cytometry. The condition of neuronal cells was examined by Nissl staining. The condition of the microglia in the cortex and hippocampus was observed by brain immunofluorescence staining. The phenotype of the microglia was detected by flow cytometry. Results ·The CKO mice and WT mice were successfully bred. MACS boosted the proportion of microglia in brain cells from 10% to 85%. RT-PCR results showed that mRNA levels of Stat3 were down-regulated in microglia of CKO mice, compared with the WT mice (P=0.001). The relative mRNA expression of Stat3 in microglia of the CKO mice was 0.331 7±0.041 4. Immunofluorescence staining of brain tissues showed that the fluorescence intensity of STAT3 in microglia of the CKO mice was weaker than that of the WT mice. Flow cytometry of brain tissues showed that the STAT3-positive cells in microglia of the WT mice was (85.30±5.69)% and the CKO mice was (39.70±3.88)%. STAT3 expression was decreased in microglia of the CKO mice (P=0.001). Flow cytometry of spleen tissues showed that there was no statistical difference in the percentage of STAT3-positive cells in splenic macrophages between the CKO and WT mice (P>0.05). Nissl staining showed that there were no significant differences between the neuronal cells of the CKO mice and WT mice. Immunofluorescencestaining of brain tissues showed that there was no significant difference in the shape of microglia between the CKO mice and WT mice. Flow cytometry showed that the phenotype of microglia in the CKO mice was not remarkably different from that of the WT mice. Conclusion ·We successfully construct the STAT3 gene conditional knockout mice from microglia, which provides the foundation for subsequent related studies.

    Table and Figures | Reference | Related Articles | Metrics
    Research progress in the pathogenesis and prognosis of ZNF384 fusion subtype acute leukemia
    LI Ying, TAN Yangxia, YIN Hongxin, JIANG Yanling, CHEN Li, MENG Guoyu
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (5): 631-640.   DOI: 10.3969/j.issn.1674-8115.2023.05.015
    Abstract331)   HTML13)    PDF(pc) (2268KB)(173)       Save

    Gene fusions caused by chromosomal translocations have become the main pathogenic factors that initiate leukemogenesis. Zinc finger protein 384 (ZNF384) fusion, as an atypical fusion gene in acute leukemia (AL), has widely been identified in different age groups. ZNF384 rearranged 18 genes, with E1A binding protein p300 (EP300), transcription factor 3, (TCF3), and TATA-box binding protein-associated factor 15 (TAF15) being the most common fusion partners. These fusion proteins maintain the complete structure of ZNF384, but the fusion partners are missing in varying degrees, indicating that the mechanisms behind different subtypes of carcinogenesis have similarities. The mechanism of ZNF384-rearranged AL is also being actively investigated. It is mainly believed that the fusion protein regulates the transcription and expression of downstream proteins through chromatin remodeling, and plays a potential role in the differentiation of hematopoietic stem cells, the proliferation and apoptosis of cancer cells and genome repair. Patients with ZNF384 fusions express both lymphoid and myeloid-specific antigens, which have lineage-transforming properties during disease progression. The diversity of immunophenotypes leads to ambiguity in treatment options and diverse outcomes in prognosis studies, and affects the clinical outcome of patients together with fusion subtype and age of onset. Through the statistical analysis of published cases and large-scale cohort studies in the past 10 years, the incidence of ZNF384 fusion in AL and the frequency of each fusion subtype in the context of existing research were further confirmed. The impact of different treatment methods on the prognosis of patients was analyzed, and the identified mechanisms were summarized in order to provide reference for subsequent diagnosis, treatment and research of this unique AL subtype.

    Table and Figures | Reference | Related Articles | Metrics
    SIRT2 regulates macrophage chemotaxis by de-modifying histone H4K8 lactylation
    SONG Wenting, TAO Yue, PAN Yi, MO Xi, CAO Qing
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (8): 1008-1016.   DOI: 10.3969/j.issn.1674-8115.2023.08.008
    Abstract319)   HTML35)    PDF(pc) (4083KB)(199)       Save

    Objective ·To explore the regulatory role of silent information regulator 2 (SIRT2) in modulating the immune phenotype of macrophages after infection by removing the lactylation at H4K8 site of histone and the corresponding mechanism. Methods ·Human THP-1 leukemia cells were induced by phorbol 12-myristate 13-acetate (PMA) and stimulated by lipopolysaccharide (LPS) to establish a macrophage infection model. Macrophages without LPS treatment (pTHP-1) were set as the control (CTRL) group, and macrophages with LPS treatment were set as the infected (LPS) group. Western blotting was used to detect the level of histone modification and SIRT2 protein in macrophages. RT-qPCR was used to detect the expression level of glycolytic key enzymes [phosphofructokinase liver type (PFKL), lactate dehydrogenase A (LDHA)] and modulators genes hypoxia inducible factor 1α (HIF-1α), and the expression level of Sirtuin genes and HDAC genes between the two groups. Transwell was used to detect the ability of macrophage chemotaxis. Lentivirus packaging and cell infection were used to construct SIRT2 overexpression cell line. The interaction analysis method of RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) was used to analyze the difference and pathway enrichment of the genes specifically bound to H4K8 lactylation (H4K8la). Results ·Compared to the CTRL group, macrophage glycolysis was upregulated and the level of H4K8la was significantly increased in the LPS group (P<0.05), while the level of lactylation in other sites remained unchanged. Among all known enzymes with deacetylation modification function, only SIRT2 showed a significant decrease after LPS treatment (P<0.05), and overexpression of SIRT2 could significantly inhibit the level of H4K8la modification, while the level of H4K8ac remained unchanged (P>0.05). The interactive analysis of ChIP-seq and RNA-seq revealed that chemotaxis-related genes were regulated by H4K8la, and macrophage chemotaxis ability significantly decreased after the overexpression of SIRT2 and downregulation of H4K8la (P<0.05). Conclusion ·SIRT2 can change the expression of target genes related to chemotaxis by removing H4K8la modification, thereby reducing the chemotaxis ability of macrophages. Targeting SIRT2 and H4K8la modification may help control inflammation mediated by macrophages.

    Table and Figures | Reference | Related Articles | Metrics
    Ameliorative effects on osteoporosis of small extracellular vesicles derived from bone marrow mesenchymal stem cells
    LI Xuran, TAO Shicong, GUO Shangchun
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (4): 406-416.   DOI: 10.3969/j.issn.1674-8115.2023.04.002
    Abstract288)   HTML390)    PDF(pc) (7654KB)(268)       Save

    Objective ·To investigate the effects of small extracellular vesicles (sEVs) derived from human bone marrow mesenchymal stem cells (BMSCs) on the regulation of osteoclast differentiation and macrophage polarization in mice, and mouse model of osteoporosis. Methods ·BMSCs were cultured and sEVs were isolated through differential centrifugation. The isolated sEVs were identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). RAW264.7 cells were cultured and stimulated with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) to differentiate the cells into osteoclasts. Tartrate-resistant acid phosphatase (TRAP) staining and phalloidin staining were performed to assess the effect of sEVs on osteoclast formation. The expression levels of osteoclast marker genes, i.e., cAMP-response element binding protein (CREB), cathepsin K (CTSK), and Jun proto-oncogene (c-Jun) were examined by real-time quantitative PCR. To polarize RAW264.7 cells to M1 phenotype, they were cultured with lipopolysaccharides; to polarize them to M2 phenotype, they were cultured with interleukin-4 (IL-4) and IL-13. Flow cytometry was performed to detect the effect of sEVs on macrophage polarization. Micro-computed tomography (micro-CT) and TRAP staining were performed to investigate the effect of sEVs on the bone tissues of lumbar vertebrae in osteoporosis mouse models. Results ·TEM and NTA demonstrated that the isolated sEVs had a typical globular structure with a diameter ranging from 30?150 nm. TRAP staining and phalloidin staining showed that BMSC-derived sEVs inhibited the fusion of RAW264.7 cells to form osteoblasts. PCR revealed that sEVs could decrease the expression of CREB, CTSK, and c-Jun (all P<0.05). Flow cytometry analysis indicated that BMSC-derived sEVs inhibited RAW264.7 macrophages polarization to M1 phenotype and induced RAW264.7 macrophages polarization to M2 phenotype. Micro-CT indicated that the number of trabeculae and the bone volume fraction of lumbar vertebrae were significantly higher in the sEV-intervened group than those in the control group (both P<0.05). TRAP staining revealed a reduction of osteoclast number in the lumbar vertebrae after intervention with sEVs. Conclusion ·The sEVs from human BMSCs can delay bone loss in osteoporosis mice, which may be related to its effects of inhibiting osteoclast differentiation and promoting the polarization of M2 type macrophages.

    Table and Figures | Reference | Related Articles | Metrics
    Research progress in biological activities and mechanisms of theabrownin
    WANG Jieyi, ZHENG Dan, ZHENG Xiaojiao, JIA Wei, ZHAO Aihua
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (6): 768-774.   DOI: 10.3969/j.issn.1674-8115.2023.06.014
    Abstract287)   HTML31)    PDF(pc) (1358KB)(268)       Save

    Tea is beneficial to human health, which is rich in tea pigments with important biological activities. Theabrownin, derived from theaflavins and thearubigins by oxidative polymerization, mainly distributes in semi-fermented oolong tea, and completely fermented black tea and dark tea. As a kind of macromolecular substance, theabrownin cannot be directly absorbed by the gut, but it can directly interact with intestinal microbiota to regulate and maintain the homeostasis of intestinal flora. Theabrownin has multiple physiological roles via modulating the gut microbiota, including inhibiting hepatic cholesterol production, promoting the catabolism of cholesterol and triglyceride, and promoting energy metabolism in adipose tissues, thereby improving lipid metabolism. Theabrownin can also directly influence the gut absorption of glucose to improve carbohydrate metabolism and maintain blood glucose homeostasis. Theabrownin plays an anti-tumor role by inducing apoptosis and regulating gene expression in tumor cells. Theabrownin also plays an anti-inflammatory role via participating in the regulation of the immune cell differentiation and the levels of inflammatory factors. This review summarizes the formation process, the extraction procedures, and the chemical structure of theabrownin, and reviews the effects and mechanisms of theabrownin on intestinal microbiota, lipid metabolism, blood glucose homeostasis, cancer and inflammation.

    Table and Figures | Reference | Related Articles | Metrics
    Effect of maternal high-fat diet on placental phenotype in mice
    XU Yidan, ZHANG Qianren, LU Xingyu, DONG Yan
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (4): 397-405.   DOI: 10.3969/j.issn.1674-8115.2023.04.001
    Abstract276)   HTML384)    PDF(pc) (4365KB)(329)       Save

    Objective ·To analyze the effects of maternal high-fat diet on placental phenotype, and investigate the role of placental microenvironment in the intergenerational transmission. Methods ·The 3-week-old C57BL/6J female mice were fed with either the high-fat diet (HFD group) or the control diet (CD group) for 5 weeks before mating and throughout gestation. Placentas and fetal liver tissues were collected from maternal mice after 20 d of gestation. The effects of maternal HFD on the placental inflammation and placental structure were investigated by hematoxylin-eosin staining (H-E staining), immunohistochemistry, Western blotting and RT-PCR. The lipid deposition levels in fetal livers were also detected. Body weight changes, fasting blood glucose and glucose tolerance levels of the 3-week-old weaned mice were also detected. Results ·The body weight of female mice in the HFD group increased significantly, and the liver triacylglycerol (TAG) and total cholesterol (TC) levels were higher than those in the CD group (all P<0.05). Compared to the CD group, the liver cells of fetus in the HFD group showed steatosis, lipid vacuoles of different sizes, and the content of TAG in the fetal livers in the HFD group increased, but the difference was not statistically significant (P>0.05). Compared to the CD group, the body weight, fasting blood glucose level and the area under the glucose tolerance curve of the 3-week-old weaned mice of the HFD group were increased significantly (all P<0.05). The immunohistochemical results showed that the levels of interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the placenta in the HFD group were significantly increased (both P<0.05), and the level of IL-1β did not change significantly. In addition, H-E staining of placentas showed that the area proportion of the labyrinth zone (the maternal-fetal exchange area) in the HFD group decreased significantly, which was statistically significant by ImageJ software (P<0.05). The intervascular membrane thickened, and the maternal blood sinuses were narrow. RT-PCR results showed the expressions of placental tight-junction-related protein Zo-1 (zonula occludens 1) and claudin were increased (both P<0.05). Conclusion ·Maternal high-fat diet may result in placental inflammation and abnormal structure, which may be related to glucose and lipid metabolism disorder in offspring.

    Table and Figures | Reference | Related Articles | Metrics
    CXCL9 expression in breast cancer and its correlation with the characteristics of tumor immunoinfiltration
    DU Shaoqian, TAO Mengyu, CAO Yuan, WANG Hongxia, HU Xiaoqu, FAN Guangjian, ZANG Lijuan
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (7): 860-872.   DOI: 10.3969/j.issn.1674-8115.2023.07.008
    Abstract256)   HTML30)    PDF(pc) (7698KB)(125)       Save

    Objective ·To explore the effect of C-X-C motif chemokine ligand 9 (CXCL9) expression on the prognosis of breast cancer patients and its correlation with tumor-infiltrating immune cells (TIICs). Methods ·Transcriptome data of 1 100 breast tumor tissues and 112 adjacent tissues were obtained from The Cancer Genome Atlas (TCGA) database. CIBERSORT deconvolution algorithm was used to analyze the proportion of TIIC subgroups in breast cancer immune microenvironment and its effect on the prognosis of patients. Differentially expressed genes, immune-related genes and breast cancer prognostic-related genes were downloaded from TCGA database, ImmPort database and GEPIA2 data platform, respectively. The intersection relationships of the three gene sets were analyzed by using R language, and the target genes were screened. Based on the downloaded transcriptome data, CXCL9 positive-related genes, the difference of CXCL9 mRNA expression in breast cancer tissues and adjacent tissues and its effect on the prognosis of patients were analyzed. STRING data platform was used to analyze the protein-protein interaction (PPI) network of CXCL9. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis were performed on CXCL9 positive correlation genes and the genes corresponding to the interacting proteins obtained from the PPI network by using R language. Spearman correlation coefficient was used to analyze the correlation between CXCL9 mRNA expression and TIIC subgroups and immune checkpoint-related genes. Paraffin tissue samples of 60 clinical breast cancer patients were collected and made into tissue chips. The correlation between CXCL9 expression and CD8+ T cells infiltration in the tissue chips was detected by immunohistochemical staining (IHC). The types of CXCL9+ cells in breast cancer interstitium were analyzed by multiplex immunohistochemistry staining (mIHC). Kaplan-Meier (KM) survival curve was used to analyze the effect of CXCL9 mRNA expression and CD8+ T cell infiltration on the prognosis of breast cancer patients. Results ·CIBERSORT algorithm analysis showed that the distribution proportion of TIIC subgroups in breast cancer immune microenvironment varied greatly, and their effect on patients′ prognosis was also different. The Venn diagram of three types of gene sets was drawn, and CXCL9 was screened out. The top 150 positive correlation genes with CXCL9 were obtained. CXCL9 mRNA expression levels in four molecular types of breast cancer were higher than those in adjacent tissues (all P=0.000), and their high expressions were significantly associated with good prognosis of patients (P=0.013). A total of 41 interacting proteins were obtained through PPI network analysis. GO and KEGG analysis showed that CXCL9 and its related genes were mainly enriched in biological functions and pathways related to immune regulation. Spearman correlation coefficient analysis showed that the expression level of CXCL9 mRNA was positively correlated with CD8+ T cells infiltration ratio, negatively correlated with M2-type macrophages infiltration ratio, and positively correlated with most immune checkpoint genes expression (all P<0.05). IHC experiments showed that CXCL9 was highly expressed in breast cancer tissues compared with adjacent tissues, accompanied by an increased percentage of CD8+ T cells infiltration (P=0.000). mIHC results showed that CXCL9 was expressed in some CD68+ tumor-associated macrophages (TAMs) and CD11c+ dendritic cells (DCs) in the stroma of breast cancer. KM survival curve showed that when CXCL9 was highly expressed, CD8+ T cells high infiltration could prolong the survival of breast cancer patients. Conclusion ·CXCL9 can be used as a biomarker for good prognosis of breast cancer patients. The high expression of CXCL9 in the microenvironment of breast cancer is positively correlated with the infiltration ratio of CD8+ T cells and may activate its anti-tumor effect. The expression of CXCL9 may be closely related to the recruitment of lymphocytes into the tumor microenvironment for anti-tumor immune response.

    Table and Figures | Reference | Related Articles | Metrics
    Progress in relationship between chronotype and technology addiction and its mechanism
    WU Yujing, GUO Qian, LIU Xiaohua, LI Guanjun
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (4): 487-494.   DOI: 10.3969/j.issn.1674-8115.2023.04.012
    Abstract252)   HTML44)    PDF(pc) (1361KB)(257)       Save

    In the era of digitalization, the Internet has changed people's lifestyle and circadian rhythm, and has also brought the global problem of technology addiction. Many studies have shown that chronotype is significantly related to specific technology addiction (such as Internet, smartphones, video games and social media), which makes chronotype become a new perspective to explore the occurrence, development and maintenance of technology addiction. Individuals can be classified into three chronotypes: morning type (M-type), neither type (N-type) and evening type (E-type). Most studies showed that E-type was the risk factor in the onset and maintenance of problematic technology use. At present, most of the prior research focused on the relationship between chronotype and technology addiction, and there were few studies on the mechanism. Based on this situation, this paper discusses physiological factors (such as reward system), psychological factors (such as depression), individual factors (such as gender, age, personality traits and sleep patterns) and environmental factors (such as parental style), analyzes the relationship with Interaction of Person-Affect-Cognition-Execution (I-PACE) model and life history theory from the perspectives of etiology and evolution, and reviews the relationship between chronotype and technology addiction and its mechanism.

    Table and Figures | Reference | Related Articles | Metrics
    Epidemiological characteristics and risk factors of severe asthma in children: a single-center prospective cohort study
    WANG Yingwen, LI Xiaoling, DAI Jiajia, LIU Fang, HUANG Jianfeng, WANG Libo, ZHANG Xiaobo, FENG Rui
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (6): 665-672.   DOI: 10.3969/j.issn.1674-8115.2023.06.002
    Abstract247)   HTML27)    PDF(pc) (1773KB)(146)       Save

    Objective ·To explore the epidemiological characteristics of severe asthma in children and analyze the risk factors. Methods ·A single-center prospective cohort study was conducted. Six hundred and seventy four children with difficult-to-treat asthma who visited the Children′s Hospital of Fudan University from January 1 to December 31, 2021 were included to establish a dynamic cohort. Basic information (including gender, age, gestational age at birth, birth weight, etc.) and comorbidity of the cohort members were collected. The asthma control status, drug inhalation technique level, medication compliance, pulmonary function parameters [forced expiratory volume in one second (FEV1) as a percent-age of the predicted value (FEV1%pred), FEV1/ forced vital capacity (FVC), and the rate of estimated values of forced expiratory flow at 50% of FVC exhaled (FEF50), FEF75, and FEF25-75 in percent-predicted value, respectively], airway inflammation index [fraction exhaled nitric oxide (FeNO)], and allergy status parameters [eosinophil (EOS) and immunoglobulin E (IgE)] of all cohort members were evaluated. All cohort members underwent re-evaluation respectively at the specialist asthma clinic of the hospital at 3, 6, 9, and 12 months. Results ·At the endpoint of the cohort, 52 children were diagnosed with severe asthma, accounting for 7.7%. A high proportion of severe asthma was found in children who were exposed to secondhand smoke, used air conditioning at home all year round, or had coexisting rhinitis/nasosinusitis, FEV1%pred<80%, FEV1/FVC<80%, small airway dysfunction, EOS>300/μL, IgE>200 IU/L, or FeNO>20/25 ppb [FeNO>20 ppb (≤12 years old) or >25 ppb (>12 years old), 1 ppb=1×10-9 mol/L]. A high proportion of non-severe asthma was found in children who were breastfed for 6 months or longer, or had good medication compliance. The differences were statistically significant (all P<0.05). There were more males in children with severe asthma aged 6?11 years, and more females in children with severe asthma aged 12?17 years, with statistical significance (both P<0.05). Multiple-factor Logistic regression analysis showed that only small airway dysfunction was an independent risk factor for severe asthma [OR=5.158 (95%CI 2.516?10.572)]. Conclusion ·The proportion of children with severe asthma has a significantly decrease after one year of standardized management in children with difficult-to-treat asthma. Small airway dysfunction is an independent risk factor for the progression to severe asthma.

    Table and Figures | Reference | Related Articles | Metrics
    Research progress in the roles of airway epithelial cells in the pathogenesis of asthma
    XU Yinglian, TIAN Jing, ZHANG Xiang, ZHAO Shunying
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (5): 619-623.   DOI: 10.3969/j.issn.1674-8115.2023.05.013
    Abstract225)   HTML13)    PDF(pc) (1246KB)(187)       Save

    Asthma is a common chronic respiratory disease, and as a heterogeneous disease, it is driven by a combination of immune, genetic, and environmental factors and involves multiple cells. In recent years, there has been increasing evidence that airway epithelial cells play a core role in the pathogenesis of asthma. As the first line of defense of the respiratory system against the external environment, airway epithelial cells mainly prevent harmful stimuli from entering through various intercellular connections and remove harmful foreign factors such as allergens and viruses through the mucus and cilia system and the antimicrobial peptides. The airway epithelial barrier can be disrupted when the airway mucosa is exposed to foreign harmful stimuli, and epithelial cells can release various epithelial-derived cytokines that effectively activate dendritic cells and type Ⅱ innate lymphoid cells, thereby triggering a subsequent helper T cell 2 immune cascade response that leads to the development of asthma. In view of these roles of airway epithelial cells in asthma, targeted therapeutic agents targeting the cytokines from airway epithelial cells such as thymic stromal lymphopoietin, are gradually coming into clinical use. This article reviews the role of airway epithelial cells in the pathogenesis of asthma and the future clinical applications of therapies targeting airway epithelial cells as potential targets.

    Reference | Related Articles | Metrics
    Development and application of Chinese customized total temporomandibular joint prosthesis
    CHEN Xuzhuo, MAO Yi, YUAN Dan, ZHANG Shanyong, YANG Chi
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (5): 524-531.   DOI: 10.3969/j.issn.1674-8115.2023.05.002
    Abstract220)   HTML11)    PDF(pc) (2636KB)(155)       Save

    Alloplastic total joint replacement is one of the effective methods for temporomandibular joint (TMJ) reconstruction. As the first choice for TMJ reconstruction, alloplastic total joint replacement has the advantages of no need to open up a second operative area, short operation duration and immediate functional restoration, compared with autogenous bone graft. The customized prosthesis has the edge over the stock prosthesis due to its excellent suitability and less intraoperative bone trimming. However, there are no commercialized counterparts in China yet. Hence, it is urgent to develop a Chinese customized total TMJ prosthesis for Chinese patients. Since 2009, the authors′ team has begun to develop the customized total TMJ prostheses suitable for Chinese anatomical features independently. Through three generations of products, the team gradually realized the stable connection of porous titanium alloys and ultra-high molecular weight polyethylene (UHMWPE), and finally achieved a key technological breakthrough in 2017. The third generation of customized total TMJ prosthesis was successfully developed by friction stir welding technology. The mechanical properties of Chinese customized prostheses have prevailed over its international counterparts, with satisfactory short-term follow-up results based on its preliminary clinical application. Furthermore, in order to ensure high efficiency and accuracy of the procedures from design and manufacture to clinical application, the authors′ team has developed a relatively mature standardized process, and improved the surgical procedures. This review systematically summarizes the research and development of Chinese customized total TMJ prosthesis system in the past decade, and looks forward to the future development of Chinese customized prosthesis system.

    Table and Figures | Reference | Related Articles | Metrics
    Research progress in the relationship between mitochondrial dysfunction and osteoporosis
    JIN Fangquan, FAN Chenghu, TANG Xiaodong, CHEN Yantong, QI Bingxian
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (6): 761-767.   DOI: 10.3969/j.issn.1674-8115.2023.06.013
    Abstract220)   HTML32)    PDF(pc) (1922KB)(201)       Save

    Osteoporosis (OP) is a chronic senile bone disease characterized by decreased bone mass and increased bone fragility. There are many inducing factors and the pathogenesis is complex. To explore the mechanism of OP and improve clinical efficacy has always been a hot topic in life science. In recent years, it has been found that mitochondria play an important role in the pathogenesis of OP. Functional abnormalities such as mitochondrial energy metabolism, mitochondrial oxidative stress, mitochondrial autophagy, mitochondrial-mediated apoptosis and mitochondrial dynamics can interfere with the differentiation of bone marrow mesenchymal stem cells through different signal pathways, cytokines and protein expression to regulate osteoblast activity, proliferation and differentiation, and start the process of osteoclast apoptosis. Therefore, taking mitochondria as the target, regulating the functions of mitochondrial energy metabolism, oxidative stress, autophagy and kinetics, inducing osteogenic differentiation of bone marrow mesenchymal stem cells, promoting osteoblast differentiation and mineralization, and inducing osteoclast apoptosis are potential strategies for the prevention and treatment of OP. In this article, the mechanism of mitochondrial dysfunction in OP was reviewed by referring to relevant literature at home and abroad, in order to lay a foundation for further research.

    Table and Figures | Reference | Related Articles | Metrics
    Exploratory analysis of gut microbiota differences in childhood asthma with different severity
    WEN Yajin, HE Wen, HAN Xiao, ZHANG Xiaobo
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (6): 655-664.   DOI: 10.3969/j.issn.1674-8115.2023.06.001
    Abstract217)   HTML30)    PDF(pc) (3425KB)(194)       Save

    Objective ·To explore the characteristics and differences of gut microbiota in children with different severity of bronchial asthma, and build a prediction model of gut microbiota in severe asthma. Methods ·In this study, children aged 5 to 14 diagnosed with asthma in the Department of Respiratory Medicine of Children's Hospital of Fudan University from Sep 1, 2020 to Aug 31, 2022 were selected, and children with severe asthma (SA) according to the Recommendations for Standardized Diagnosis and Managementof Bronchial AsthmainChildren (2020) were included. Children with mild to moderate asthma (MMA) and healthy children in the same period were matched according to age and gender. Stool samples collected from the three groups were subjected to 16S rRNA gene sequencing and the gut microbiota diversity, structure, and composition were assessed. The area under the receiver operating characteristic (ROC) curve (AUC) was applied to compare the predictive efficacy for SA. Results ·Fifty children were enrolled in the SA group, 54 children matched by gender and age were in the MMA group and 39 healthy children were in the healthy control group. The α diversity of gut microbiota significantly decreased in the asthma children (P<0.05), compared with that in the healthy control group. The relative abundance of Treponema was the highest in the SA group, followed by the MMA group and healthy control group (P<0.001). The relative abundance of Lactobacillus in the MMA group and SA group was higher than that in the healthy control group (both P<0.05). The SA group had a higher relative abundance of Prevotella, Lactobacillus, Eubacterium_eligens_group, Treponema, and Fusicatenibacter. The MMA group had a higher relative abundance of Barnesiella, Holdemanella, Romboutsia and Turicibacter. The healthy control group had a higher relative abundance of the uncultured and Muribaculaceae. Among them, the relative abundance of Barnesiella decreased in the SA group, and it was found to have the highest sensitivity and specificity in predicting SA (AUC 0.713, 95%CI 0.604?0.815). Conclusion ·The diversity of gut microbiota in asthma children is lower than that in healthy children, and the composition of gut microbiota differs among childhood asthma with different severity. The abundance of Barnesiella decreases in the SA group significantly, suggesting that analysis of gut microbiota may help in the assessment of childhood asthma with different severity.

    Table and Figures | Reference | Related Articles | Metrics
    Research progress in the role of gut microbiota in the pathogenesis and treatment of IgA nephropathy
    LI Junru, OUYANG Yan, XIE Jingyuan
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (8): 1044-1048.   DOI: 10.3969/j.issn.1674-8115.2023.08.013
    Abstract217)   HTML34)    PDF(pc) (1212KB)(117)       Save

    As the most common form of glomerulonephritis worldwide, IgA nephropathy (IgAN) is characterized by the diffuse deposition of immune complexes formed by glycosylation-deficient IgA1 (Gd-IgA1) and its specific antibodies (Gd-IgA1-IgG) in the glomerular mesangium. Although the mechanisms of Gd-IgA1 production are still unknown, there is accumulating evidence that Gd-IgA1-producing plasma cells are primarily derived from gut-associated lymphoid tissue, giving rise to the "gut-kidney axis" theory. Further research has discovered that gut microbiota may be involved in IgAN development and progression, and that several interventions to regulate gut microbiota, such as probiotics, fecal microbiota transplantation, and intestinal immunity modulation, may be used in the treatment of IgAN. In patients with IgAN, targeted-release formulation-budesonide has been shown to reduce urinary protein levels and delay kidney progression. Gut microbiota has promising potential as a preventive, diagnostic and therapeutic target for IgAN, and further research is needed.

    Reference | Related Articles | Metrics
    Effects of Escherichia coli outer membrane vesicles on proliferation of breast cancer cells and tumor growth of tumor-bearing mice
    WANG Lanxi, MA Guanrong, JIANG Yongzhu, CHANG Xiulin, FANG Liaoqiong, BAI Jin
    Journal of Shanghai Jiao Tong University (Medical Science)   
    Online available: 31 August 2023

    RBX1 regulates uveal melanoma immune-related genes via STAT1
    ZHOU Xiaowen, LI Qian, ZHANG Zhe, SHEN Jianfeng, FAN Xianqun
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (6): 709-717.   DOI: 10.3969/j.issn.1674-8115.2023.06.007
    Abstract206)   HTML31)    PDF(pc) (3226KB)(133)       Save

    Objective ·To investigate the role of RBX1 (ring-box protein 1) in the regulation of immune-related genes in uveal melanoma (UVM) tumor cells. Methods ·The Cancer Genome Atlas (TCGA) was searched to analyze the expression levels of RBX1 in tumors and the correlation with clinical stages and survival prognosis. RBX1 was transiently knocked down in the UVM cell lines, i.e., 92.1, OMM2.3 and MEL290 by using small interfering RNAs (siRNAs) targeting RBX1. RNA sequencing was performed on the 92.1 cells with transient knockdown of RBX1, and the differentially expressed genes between the siRBX1-transfected cells and control cells were analyzed by gene set enrichment analysis (GSEA) to investigate the relationship between RBX1 and tumor immune-related genes. Based on the results of the analysis, signal transducer and activator of transcription 1 (STAT1) and its downstream CXC chemokine ligand 9 (CXCL9) and CXCL10 mRNA expression levels were detected by real-time fluorescence quantitative PCR (qPCR) in 92.1, OMM2.3 and MEL290 cells with transient knockdown of RBX1, respectively. The protein expression levels of STAT1 and p-STAT1 in 92.1 cells were detected by Western blotting. The cell lines OMM2.3 and MEL290, in which RBX1 was transiently knocked down, were treated with 5 nmol/L or 10 nmol/L STAT1 inhibitor fludarabine for 48 h, and the mRNA expression levels of CXCL9 and CXCL10 were detected by qPCR. Results ·TCGA database analysis showed that RBX1 was highly expressed in a variety of tumors compared to the normal tissues, particularly in adrenocortical carcinoma and UVM. In addition, the patients with late stage of these two kinds of tumors had higher expression level of RBX1, and the patients with higher expression level of RBX1 had shorter overall survival time (P<0.05). RNA sequencing of 92.1 cells with transiently knocked down RBX1 and control cells revealed differential genes, and GSEA showed that RBX1 was involved in the regulation of tumor immune-related pathways. Heat map analysis showed an increase in STAT1 expression after RBX1 knockdown. In the 92.1, OMM2.3 and MEL290 cell lines, qPCR showed increases in STAT1, CXCL9 and CXCL10 mRNA expression after transient knockdown of RBX1, and Western blotting showed that STAT1 and p-STAT1 expression increased after knockdown of RBX1 in 92.1 cell lines. The increases of CXCL9 and CXCL10 mRNA in OMM2.3 and MEL290 cell lines were suppressed by STAT1 inhibitors. Conclusion ·RBX1 may regulate CXCL9 and CXCL10 expression via STAT1 in UVM cells and is involved in tumor immune regulation.

    Table and Figures | Reference | Related Articles | Metrics
    Analysis of m 6A methylation expression profiles in liver tissue of high -fat diet -induced mouse models of NAFLD
    LIU Junjun, LU Sumei, ZHANG Bingyang, LI Yongqing, MA Wanshan
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (10): 1227-1235.   DOI: 10.3969/j.issn.1674-8115.2023.10.002
    Abstract206)   HTML22)    PDF(pc) (3120KB)(96)       Save

    Objective ·To detect the differences in m6A methylation modification and gene expression of liver tissue mRNA in high-fat diet-induced mouse models of non-alcoholic fatty liver disease (NAFLD) using microarray technology. Methods ·The NAFLD models were established in 6-8 weeks old male C57BL/6J mice fed with high-fat chow for 16 weeks (high-fat group, n=10). The basal group (n=10) was given 10% fat diet. Hematoxylin-eosin (H-E) staining was used to assess the histopathological changes in liver tissue and to determine the success of the NAFLD models. The changes of mRNA m6A methylation and expression levels in the liver tissues of the two groups were detected by using methylated RNA immunoprecipitation (MeRIP) and microarray expression profiling. Results ·The livers of the mice in the basal group were bright red with few fat deposits, while the livers of the mice in the high-fat group were yellowish with diffuse infiltration and fusion of lipid droplets in the hepatocytes by H-E staining, suggesting that the high-fat diet-induced NAFLD models were successfully constructed. The results of the MeRIP-microarray showed that the m6A methylation levels of 320 genes in the livers of mice in the high-fat group were significantly altered compared with those in the basal group (P<0.05 and fold change>1.5), of which 108 genes were up-regulated and 212 genes were down-regulated. Genes with significant differences in m6A methylation levels between the two groups were intersected with those with differentially expressed mRNAs, and 163 genes were found to have significant differences in both m6A methylation level and mRNA expression level. Conclusion ·The change in m6A modification of liver tissue mRNA in the high-fat diet-induced mouse models of NAFLD is significant and the change is associated with the gene expression of mRNA.

    Table and Figures | Reference | Related Articles | Metrics
    Advances in fluorescence imaging of malignant tumors
    WANG Wenbo, ZHANG Fangrong, SHI Tingwang, CHEN Yunfeng
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (4): 474-479.   DOI: 10.3969/j.issn.1674-8115.2023.04.010
    Abstract204)   HTML46)    PDF(pc) (1491KB)(172)       Save

    Malignant tumors are common diseases that threaten human health. Early diagnosis and complete resection can significantly improve the prognosis of patients with malignant tumors. At present, the imaging techniques used clinically for malignant tumor detection have problems such as poor sensitivity and temporal-spatial resolution, long scanning time, etc., which cannot achieve early diagnosis and meet the requirements of surgical navigation. As a new imaging technology with excellent imaging characteristics, fluorescence imaging can perform real-time imaging of the structure and function of biological tissues and organs. It can realize the accurate detection of malignant tumors by designing fluorescent probes with high sensitivity, high selectivity and specificity. The sensitivity of fluorescence imaging mainly depends on the fluorophore of the probe, and the selectivity and specificity mainly depend on whether the probe adopts an effective targeting strategy. Studies have shown that near infrared fluorophores with emission wavelengths in the near infrared window, especially those in the near infrared Ⅱ window, have excellent optical properties, which can effectively improve the sensitivity of fluorescence imaging of malignant tumors; at the same time, based on the unique structure and metabolic features of malignant tumors, various targeting strategies have been developed to design "always-on" fluorescent probes and "turn-on" fluorescent probes, which significantly improved the selectivity and specificity of fluorescent imaging of malignant tumors. In this paper, the newly developed near infrared fluorophores and the strategies of fluorescent probes targeting malignant tumors are reviewed.

    Table and Figures | Reference | Related Articles | Metrics
    Effect of hydrogel stiffness on nucleus pulposus cell phenotypes in vitro and its repairment of intervertebral disc in vivo
    CHEN Zehao, LÜ Zhendong, ZHANG Zhen, CUI Wenguo, ZHANG Yuhui
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (7): 804-813.   DOI: 10.3969/j.issn.1674-8115.2023.07.002
    Abstract201)   HTML29)    PDF(pc) (4157KB)(168)       Save

    Objective ·To investigate the effect of hydrogel stiffness on nucleus pulposus cell phenotype and its function in repairing intervertebral disc degeneration in rats. Methods ·Methacrylate gelatin (GelMA) hydrogels with different concentrations were constructed. The stiffness of the hydrogels was investigated by using rheological analysis and uniaxial compression test. The microstructure and morphology of the hydrogels were observed by scanning electron microscopy (SEM). Nucleus pulposus cells with normal phenotype were inoculated on the surface of GelMA hydrogels. The biocompatibility of the hydrogel was evaluated by live-dead cell staining and the growth pattern of nucleus pulposus cells on hydrogels with different stiffness was observed with phalloidin staining under microscope. Immunofluorescence staining was performed to examine the nuclear localization of Yes-associated protein (YAP) and real-time quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression levels of nucleus pulposus cell-associated genes [neural cell adhesion molecule 1 (Ncam-1), aggrecan (Acan), sex-determing region of Y chromosome (SRY)-box transcription factor 9 (Sox9)]. A rat caudal acupuncture intervertebral disc degeneration model was established. Nucleus pulposus cells cultured on different hydrogels were harvested and injected into the degenerated discs separately. Four weeks after surgery, magnetic resonance imaging (MRI) was performed to analyze the water content of the intervertebral discs in each group. Histological tests were performed to examine the disc structure and proteoglycan levels. Results ·The elastic modulus of the hydrogels was 1 kPa and 200 kPa when the concentration of GelMA prepolymerisation solution was at 4% and 15% respectively. SEM observation revealed that the hydrogels showed a loose and porous microstructure, and the porosity of hydrogels decreased significantly with the decrease of their stiffness. In vitro experiments demonstrated that both GelMA hydrogel mediums showed good biocompatibility and the ability to support cell proliferation. Nucleus pulposus cells cultured on the soft matrix (4%GelMA) had a lower elongation and spreading area than those cultured on the stiff matrix (15%GelMA), showing a tendency of YAP concentration in the cytoplasm. The gene expression of nucleus pulposus cells was examined and the levels of Sox9, Acan and Ncam-1 in the soft matrix hydrogel group were 23.7, 6.6 and 12.7 times of those in the control group respectively. In vivo experiments on rat disc degeneration showed that the soft hydrogel matrix group had higher disc water content and structural integrity than the stiff hydrogel matrix group. Conclusion ·Compared to stiff GelMA hydrogels, hydrogels with low stiffness better maintain the growth phenotypes in the nucleus pulposus cells and have better therapeutic effect on disc degeneration in vivo.

    Table and Figures | Reference | Related Articles | Metrics
    Research progress on the neural circuit of pain emotion mediated by amygdala
    MA CUI, YE Yujuan, YAN Xingke
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (10): 1304-1310.   DOI: 10.3969/j.issn.1674-8115.2023.10.012
    Abstract198)   HTML19)    PDF(pc) (1243KB)(87)       Save

    The occurrence of pain emotion is closely related to the functional and structural changes of specific central nervous circuit. When pain is accompanied by depression, anxiety, pain aversion memory and other emotional states, it activates or inhibits different neural circuits. The amygdala (AMY) of the limbic system participates in the regulation of pain, anxiety, depression, aversive memory and other emotions, and has extensive connections with brain nuclei related to pain and emotion, jointly regulating pain, anxiety, depression, aversive memory and other responses. This article summarizes the main circuits related to pain emotions mediated by AMY. It is concluded that the neural circuits related to depression include central amygdala → parafascicular nucleus of thalamus (CeA GABA → PF Glu), dorsal raphe nucleus → central amygdala (DRN 5-HT → CeA SOM), central amygdala → ventrolateral periaqueductal gray (CeA GABA → vlPAG GABA). Nerve circuits related to anxiety include ventral tegmental area → central amygdala (VTA→CeADA), locus coeruleus → basolateral amygdala (LCNE→BLA). The neural circuit related to pain aversion memory is lateral parabrachial nucleus → central amygdala (lPBN CGRP→CeA CGRP). Among them, activating the CeA GABA→PF Glu circuit can lead to depression accompanied by pain, activating the CeA GABA→vlPAG GABA circuit can alleviate pain sensitivity caused by depression, and activating the DRN 5-HT→CeA SOM circuit can alleviate pain perception and depressive emotions; activating the VTA→CeA DA loop can alleviate pain sensitivity and anxiety like behavior, inhibiting LC NE→BLA loop can alleviate anxiety caused by pain; activating the lPBN CGRP→CeA CGRP loop can generate pain aversion memory.

    Reference | Related Articles | Metrics