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    28 September 2024, Volume 44 Issue 9 Previous Issue    Next Issue

    Basic research
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    Basic research
    Application of fluoroscopic stereophotogrammetric analysis in the detection of aseptic loosening of prostheses
    YANG Han, LEI Hao, XU Bide, WU Hao, MA Xunjun, HUANG Yanbo, MAO Yuanqing, ZHANG Jingwei, WANG Jinwu
    2024, 44 (9):  1061-1068. 
    doi: 10.3969/j.issn.1674-8115.2024.09.001

    Abstract ( 128 )   HTML ( 22 )   PDF (4126KB) ( 56 )  

    Objective ·To verify the accuracy and clinical feasibility of fluoroscopic stereophotogrammetric analysis (FSA) technology based on two dimension (2D)-three dimension (3D) registration for early migration detection of aseptic loosening of joint prostheses. Methods ·2D-3D registration algorithms centering on the light source and projected object respectively in FSA technology were verified under various working conditions through image synthesis experiments, and the feasibility of clinical application was verified through real model experiments. The image synthesis experiment established a perspective projection environment with the same parameters as the real environment in a virtual environment, the 2D perspective images of the 3D model (bone or prosthesis) during the six degrees of freedom transformation were recorded, and the six degrees of freedom transformation of the 3D model was restored by using different 2D-3D registration algorithms. The error of each registration algorithm was calculated. For real model validation, the migration between bone and prosthesis after joint replacement surgery was simulated with a high precision bone prosthesis migration simulator. The 3D model of the bone or prosthesis was reconstructed by using computed tomograph (CT) images and optical scanning, and the 2D perspective images before and after prosthesis migration were captured by using a fluoroscopy device. The migration of the prosthesis was restored by using FSA technology based on 2D-3D registration, and the error of FSA technology was calculated. Results ·The accuracy of the 2D-3D registration algorithm centering on the light source was higher than that of the algorithm centering on the projected object under different working conditions. When the initial registration conditions were favorable, the algorithm centering on the light source reduced the rotation error compared to the algorithm centering on the projected object, with a statistical difference (P=0.021), and the displacement error decreases, with a significant statistical difference (P=0.000). Moreover, algorithms centering on the light sources required lower similarity and fewer registration times to meet clinical application requirements. Conclusion ·The accuracy of FSA technology based on 2D-3D registration in early migration detection of artificial joint prostheses meets clinical application requirements. This technology can warn of late aseptic loosening of prostheses by detecting early migration of prostheses after joint replacement surgery, and is expected to be applied to clinical practice through further research.

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    CTCF regulates lipid metabolism and gene expression in mouse AML12 liver cell line
    CHEN Huaihuang, ZUO Wu, BIAN Qian
    2024, 44 (9):  1069-1082. 
    doi: 10.3969/j.issn.1674-8115.2024.09.002

    Abstract ( 151 )   HTML ( 24 )   PDF (4515KB) ( 136 )  

    Objective ·To clarify the regulatory role of CCCTC-binding factor (CTCF) in lipid metabolism in liver cells, and explore the mechanisms by which CTCF regulates liver cell gene expression. Methods ·Immortalized AML12 liver cell line was used as a model to investigate the functions of CTCF in liver cells. To stably knock down Ctcf, DNA sequences stably expressing Ctcf shRNA were integrated into AML12 cells through lentivirus. The knockdown efficiency of Ctcf was verified by RT-qPCR and Western blotting. The effects of Ctcf knockdown on cell growth and cell cycle were assessed by performing CCK-8 assay and propidium iodide (PI) staining. Intracellular lipids, labeled with Oil Red O staining, were analyzed and quantified to detect the effect of CTCF on lipid metabolism and lipid droplet accumulation in AML12 cells. Changes in CTCF genome distribution after Ctcf knockdown were analyzed using the Cleavage Under Targets and Tagmentation (CUT&Tag) method. Transcriptome changes in AML12 cells after Ctcf knockdown were quantified by RNA sequencing (RNA-seq). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and gene set enrichment analysis (GSEA) were employed to evaluate the functions of differentially expressed genes. The correlation between gene expression changes and CTCF binding changes was further assessed by performing statistical analyses. Results ·The result of RT-qPCR showed that Ctcf is downregulated 63.4% in mRNA level and 57.7% in protein level (both P<0.05). Assay of the growth curve and cycle phase confirmed that cell proliferation was inhibited in the G1/G0 phase after Ctcf knockdown. After Ctcf knockdown, AML12 cells exhibited spontaneous accumulation of intracellular lipids, indicating dysregulation of lipid metabolism (P<0.05). Genome-wide CTCF binding analysis revealed significant changes, with most differential CTCF peaks showing decreased binding, although a subset of regions exhibited increased CTCF binding. Transcriptome analyses revealed that knocking down Ctcf resulted in significant expression changes in 1 344 genes. These differentially expressed genes were enriched in lipid metabolism pathways. Further analysis showed that genes associated with regions of increased CTCF binding were enriched in pathways related to lipid transport and localization, whereas genes associated with regions of decreased CTCF binding were mainly enriched in processes such as DNA damage repair, apoptosis, and cell cycle regulation. However, the binding changes of CTCF in the genome were not sufficient to lead to the expression changes of their neighboring genes. Conclusion ·CTCF affects the metabolic function of liver cells by regulating the expression of lipid metabolism-related genes. However, the binding changes of CTCF in the genome lack significant correlation with the expression of their neighboring genes, suggesting that CTCF mainly influences liver gene expression through long-distance regulation, possibly by modulating higher-order chromatin structure and enhancer-promoter interactions.

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    Dual-directional effect of all-trans retinoic acid on osteogenic differentiation of jaw bone marrow mesenchymal stem cells in vitro
    LIU Yuanqi, SUN Siyuan, DAI Qinggang, JIANG Lingyong, SHEN Guofang
    2024, 44 (9):  1083-1093. 
    doi: 10.3969/j.issn.1674-8115.2024.09.003

    Abstract ( 136 )   HTML ( 9 )   PDF (4266KB) ( 50 )  

    Objective ·To explore the effect of all-trans retinoic acid (ATRA) of different concentrations on osteogenic differentiation of jaw bone mesenchymal stem cells (jBMSCs) in rats. Methods ·jBMSCs from 4-week-old Sprague-Dawley (SD) rats were isolated and cultured with whole bone marrow adherence method. The surface antigens were identified by using flow cytometry. Alkaline phosphatase (ALP) staining/alizarin red staining, oil red O staining and alcian blue staining were used to prove the multilineage differentiation potential of jBMSCs after osteogenic, adipogenic and chondrogenic induction respectively. jBMSCs were induced in osteogenic medium with ATRA of concentration of 0.01, 0.1, 1, 5, 10, 20 μmol/L in vitro, and dimethyl sulfoxide (DMSO) was used as control group. Cell viability of jBMSCs in different groups were determined by CCK8. ALP staining and alizarin red staining were used to investigate the osteogenic ability of jBMSCs in each group and screened the concentrations for subsequent experiments. Quantitative real-time polymerase chain reaction (qPCR) and immunofluorescence staining were used to analyze the expressions of osteogenesis-related genes and proteins in jBMSCs of different concentrations. Results ·The flow cytometry analysis showed that more than 98% of P1 jBMSCs were positive for CD29+CD90+CD31-CD45-, which was congruent with the characteristics of bone mesenchymal stem cells. The results of ALP staining/alizarin red staining, oil red O staining and alcian blue staining indicated that the P1 jBMSCs had the multilineage differentiation potential of osteogenesis, adipogenesis and chondrogenesis. The results of ALP staining/alizarin red staining showed that the osteogenic activity and mineralization ability of jBMSCs in 0.01, 0.1 and 1 μmol/L ATRA groups were increased compared with those in the control group, while the osteogenic activity and mineralization ability were decreased when the concentration of ATRA increased, especially higher than 5 μmol/L (all P<0.05). qPCR analysis showed that the mRNA expression levels of osteogenesis-related genes such as Alp, bone sialoprotein (Bsp), collagen type Ⅰ α1 (Col1a1) and osteocalcin (Ocn) were higher in the 0.1 and 1 μmol/L ATRA groups compared to the control group. However, further increasing the concentration of ATRA led to a decrease in gene expression levels, and when the concentration exceeded 5 μmol/L, it began to be lower than the control group level (all P<0.05). The immunofluorescence staining showed that the expression of osteogenic related proteins SP7, ALP and OCN in the 0.1 and 1 μmol/L ATRA groups were increased compared to the control group, while further increasing the concentration of ATRA led to a decrease in protein expression. When the concentration was higher than 5 μmol/L, it began to be lower than the control group level (all P<0.05). Conclusion ·Lower concentrations (0.1, 1 μmol/L) of ATRA can promote the osteogenic differentiation of rat jBMSCs, and the promoting effect reaches its peak at 0.1 μmol/L, while the effect can be weakened by further increasing the concentration. Higher concentrations (5, 10, 20 μmol/L) of ATRA could inhibit the osteogenic differentiation of rat jBMSCs, showing an inhibitory effect. In this study, the dual-directional effect of retinoic acid on osteogenic differentiation of jBMSCs was demonstrated in vitro, and 0.1 μmol/L ATRA was identified as the optimal concentration for osteogenic differentiation of jBMSCs in rats, which provided a reference basis for the development of in vivo studies and clinical application of ATRA.

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    Analysis of hair follicle microbiota in non-lesional areas of patients with moderate-to-severe acne vulgaris: a single-center cross-sectional study
    LIANG Mengchen, LI Jiaqi, WU Xinyi, MO Xiaohui, JU Qiang
    2024, 44 (9):  1094-1103. 
    doi: 10.3969/j.issn.1674-8115.2024.09.004

    Abstract ( 104 )   HTML ( 4 )   PDF (4774KB) ( 75 )  

    Objective ·To study the differences in the structure and load of hair follicle microbiota in non-lesional areas among patients with moderate-to-severe acne vulgaris and healthy individuals, and to explore the relationship between microorganisms and the severity of acne vulgaris. Method ·A cross-sectional study was used. Patients with moderate or severe acne vulgaris (referred to as acne) and healthy volunteers who visited the Department of Dermatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, from August 2022 to August 2023. 16S rRNA high-throughput sequencing and quantitative real-time polymerase chain reaction (qPCR) were performed on the follicular contents from the non-lesional areas of the faces of patients with moderate or severe acne and healthy volunteers to analyze the diversity, species composition, and microbial load differences in hair follicle bacteria in patients with different severity of acne. Results ·Ten patients with moderate acne, eleven patients with severe acne, and eleven healthy volunteers were included. There were no statistically differences in general data such as age and gender ratio among the three groups. Bacterial α-diversity was significantly lower in both the moderate and severe acne groups compared to the healthy group (P=0.020, P=0.013). The principal coordinates analysis (PCoA) plot showed that the sample distribution of the healthy group was relatively concentrated, with small differences within the group, and the distribution of samples in the moderate and severe acne groups exhibited a certain trend but was relatively scattered, with differences between the groups. There were differences in the trend distribution of the three sample groups, and there were differences in the microbial community structure between the groups. The results of similarity analysis showed significant differences in β-diversity and low similarity in species composition between the healthy and moderate acne groups (P=0.027) and between the healthy and severe acne groups (P=0.017), and high species similarity between the moderate acne and severe acne groups (P=0.160). The dominant bacterial groups at the phylum level were Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes. At the genus level, the dominant bacteria in the healthy group were Propionibacterium and unclassified Actinomycetales, and the dominant bacteria in both acne groups were Staphylococcus and Propionibacterium. Compared to the healthy group, the relative abundance of Staphylococcus species in the hair follicles in non-lesional areas of the moderate and severe acne groups was significantly increased (P=0.010, P=0.019). Compared with the healthy control group, the hair follicle microbiota load in non-lesional areas of both the moderate and severe acne groups was significantly increased (both P=0.001). Compared with the moderate acne group, the bacterial load in the hair follicle samples of the severe acne group was significantly increased (P=0.017). Conclusion ·The microbial community structure of hair follicles in non-lesional areas of patients with moderate or severe acne is different from that of healthy individuals, and the microbial diversity in the acne group is significantly reduced. The relative abundance of Staphylococcus species in the hair follicles in non-lesional areas of the moderate or severe acne groups is significantly increased compared to the healthy group. As the severity of acne increases, the bacterial load in hair follicles in non-lesional areas significantly increases. This research suggests that the occurrence and severity of acne may be related to the community structure and load of hair follicle microbiota.

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    A dormant cancer mouse model established by combining preimmune strategy with mVenus-p27K - system
    MUTAILIFU Musitaba, WANG Junjie, QIAN Yunzhen, CHEN Suyuan, SHAO Da, ZHANG Zhigang, LI Dongxue
    2024, 44 (9):  1104-1114. 
    doi: 10.3969/j.issn.1674-8115.2024.09.005

    Abstract ( 134 )   HTML ( 5 )   PDF (4613KB) ( 87 )  

    Objective ·To establish a mouse model with dormant cancer and no obvious metastasis by combining the preimmune strategy with the mVenus-p27K cell G0 phase indicator system, the DTR-HSV/TK suicide gene system, and the Luc2-tdTomato tracer system. Methods ·The KPC1199 mouse pancreatic cancer cell line was transfected with the mVenus-p27K cell G0 phase indicator system, the DTR-HSV/TK suicide gene system, and the Luc2-tdTomato tracer system to construct a stable expression cell line, KPC1199-PDL. After being cultured in the serum-free condition, KPC1199-PDL cells were sorted into mVenus (+) cells and mVenus (-) cells by flow cytometry, and the expression of G0 phase-related genes was verified by real-time fluorescence quantitative PCR (qPCR). Sensitivity of KPC1199-PDL cells to diphtheria toxin (DTX) and ganciclovir (GCV) was evaluated by CCK-8 assay. A transsplenic portal vein-hepatic metastasis model was constructed in wild-type C57BL/6 mice to validate the function of KPC1199-PDL cells in vivo by immunofluorescence technology. The KPC1199-PDL cells were injected subcutaneously into C57BL/6 mice, followed by in situ injection of DTX and GCV to ablate subcutaneous tumors 5 d later, to obtain preimmunized mice. The transsplenic portal vein-hepatic metastasis models were constructed in these mice. Bioluminescence imaging was used to evaluate subcutaneous tumor ablation and hepatic metastasis in the mice, and immunofluorescence assay was used to detect the distribution and dormant state of tumor cells in the livers of preimmunize mice. Results ·The three tool systems were stably expressed in KPC1199-PDL cells, and their proliferative ability was not affected. In the serum starving condition, some KPC1199-PDL cells expressed the mVenus protein, indicating entry into the G0 phase; the mVenus (+) cells sorted out by flow cytometry exhibited significantly higher expression of G0 phase-related genes (all P<0.05) and significantly lower expression of the proliferation-related gene compared with mVenus (-) cells (P<0.05). The CCK-8 assay demonstrated high sensitivity of KPC1199-PDL cells to DTX and GCV. In vivo experiments confirmed that KPC1199-PDL cells could be effectively traced through tdTomato protein expression, and could indicate entry into the G0 phase through mVenus protein expression. Following subcutaneous tumor implantation and drug ablation, preimmunized mice were successfully obtained. In the subsequent transsplenic portal vein-hepatic metastasis model, no metastatic signals were observed in the liver by bioluminescence imaging, but single or small clusters of G0 phase tumor cells expressing both mVenus and tdTomato, not expressing the proliferation marker Ki67, were detected in liver tissue sections by immunofluorescence analysis. Conclusions ·A recognizable and traceable dormant cancer model is constructed with the combination of the preimmune mouse model of pancreatic cancer, the mVeneus-p27K indicator system, the DTR-HSV/TK suicide gene system, and the Luc2-tdTomato tracer system.

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    Effects of sevoflurane exposure on proliferation and differentiation of primary oligodendrocytes
    SHI Lingling, CHENG Yanyong, ZHANG Lei
    2024, 44 (9):  1115-1123. 
    doi: 10.3969/j.issn.1674-8115.2024.09.006

    Abstract ( 95 )   HTML ( 7 )   PDF (2880KB) ( 59 )  

    Objective ·To investigate the effects of multiple sevoflurane exposures on the proliferation and differentiation of primary oligodendrocytes. Methods ·Oligodendrocyte precursor cells (OPCs) were extracted from the cortex of rats on the day of birth and cultured in vitro. The cells were divided into control and sevoflurane groups. To simulate the clinical situation of sevoflurane exposure, cells in the sevoflurane group were exposed to 3% sevoflurane for 3 consecutive days, 2 h for each time. After the OPCs were differentiated and matured, immunofluorescence staining and Western blotting were used to detect the expression of myelin basic protein (MBP) and the myelin-associated glycoprotein (MAG). Cell proliferation assays (BrdU and Ki67) and a cell viability assay (CCK8) were used to detect the effects of sevoflurane on the proliferation ability of OPCs and the survival rate of oligodendrocytes. Western blotting was used to detect the protein content of caspase-3. Lentiviral transfection technology was used to overexpress YTH N6-methyladenosine RNA binding protein F1 (YTHDF1) in OPCs, and then CCK8 was used to detect cell proliferation and survival. Results ·Immunofluorescence results showed that multiple sevoflurane exposures led to a decrease in the number of primary oligodendrocytes expressing mature myelin surface markers (MBP, MAG); Western blotting results showed that these exposures led to upregulation of caspase-3 expression in primary OPCs; CCK8 results showed that the survival rate of primary OPCs decreased with the increase in the number of sevoflurane treatments; however, BrdU and Ki67 staining results showed that the proliferation ability of primary OPCs was enhanced after sevoflurane exposure. In addition, overexpression of YTHDF1 could partially improve the decreased survival rate of primary OPCs caused by multiple sevoflurane exposures (all P<0.05). Conclusion ·Multiple sevoflurane exposures impair the myelinating ability and survival rate of primary oligodendrocytes, manifested by apoptosis of some primary OPCs. In contrast, sevoflurane exposure compensatorily increases the proliferation ability of surviving primary OPCs.

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    Study on the effect and mechanism of sorting nexin 1 on inhibiting the proliferation and migration of colorectal cancer cells
    QIAN Liheng, WEN Kailing, LIAO Yingna, LI Shuxin, NIE Huizhen
    2024, 44 (9):  1124-1135. 
    doi: 10.3969/j.issn.1674-8115.2024.09.007

    Abstract ( 95 )   HTML ( 8 )   PDF (7099KB) ( 78 )  

    Objective ·To explore the expression of sorting nexin 1 (SNX1) in colorectal cancer (CRC) and its impact on the proliferation and migration of CRC cells. Methods ·Transcriptomic data and clinical pathological information of CRC were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases for enrichment analysis with Gene Set Enrichment Analysis (GSEA) software. The expression of SNX1 in CRC tissues and cells was detected by quantitative real-time polymerase chain reaction (qPCR), Western blotting, and immunohistochemistry staining (IHC). Small interfering RNA (siRNA) was used to knock down the expression of SNX1 to observe its effect on tumor cell proliferation and migration. Correlation analysis was conducted to explore the potential molecular mechanisms underlying SNX1-mediated CRC cell migration, and mRNA level validation was performed in SNX1 knockdown cell lines. Results ·Analysis of CRC patients data in TCGA and tissue microarrays revealed that SNX1 expression was downregulated in CRC tissues and correlated with tumor diameter and distant metastasis. Knockdown of SNX1 enhanced tumor cell proliferation and migration. The expression of SNX1 was negatively correlated with metastasis associated in colon cancer 1 (MACC1), mesenchymal to epithelial transition factor (MET), and Notch; knockdown of SNX1 led to upregulation of these genes. Silencing SNX1 resulted in the downregulation of the epithelial marker cadherin 1 (CDH1) and the upregulation of vimentin (VIM) and Snail family transcriptional repressor 1 (SNAI1). Conclusion ·SNX1 expression was significantly downregulated in CRC tissues and correlated with patient prognosis. Low expression of SNX1 enhanced the proliferation and migration of CRC cells and was associated with the MACC1-MET pathway and EMT. SNX1 may serve as a potential biomarker for poor prognosis and a novel therapeutic target in CRC.

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    Electron microscopic study of the non-canonical polycomb repressive complex 1.6
    CAI Dan, HUANG Jing
    2024, 44 (9):  1136-1145. 
    doi: 10.3969/j.issn.1674-8115.2024.09.008

    Abstract ( 81 )   HTML ( 8 )   PDF (4966KB) ( 40 )  

    Objective ·To analyse the structure of non-canonical polycomb repressive complex 1.6 (PRC1.6) by negative staining and transmission electron microscopy (TEM), and obtain the three-dimensional (3D) profile information of human PRC1.6 heptameric complex. Methods ·Seven PRC1.6 components, RNF2, PCGF6, RYBP, L3MBTL2, CBX3, E2F6, and TFDP1, were cloned into the pMLink vector with a 6×His-3×Flag tag at the N-terminus, respectively. The proteins were expressed in Expi293F cells grown in suspension cultures by using transfection with polyethylenimine. The tagged proteins were isolated via affinity purification with anti-DYKDDDDK G1 affinity resin, followed by gel filtration chromatography with Superdex 200 Increase 10/300 GL and glycerol density gradient centrifugation. The components of the PRC1.6 heptameric complex were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The in vitro ubiquitination activity and nucleosome-binding affinity of the purified heptameric complex were verified by the ubiquitination activity assay and the electrophoretic mobility shift assay (EMSA). The protein samples were stained by uranyl acetate and observed by TEM. The 3D information of the PRC1.6 complex was studied by single particle analysis. To predict the localization of the seven components within the structure model of PRC1.6 complex, the structure models of proteins in Protein Data Bank (PDB) were docked into the electron density map of PRC1.6 complex by using UCSF Chimera software. Results ·The PRC1.6 complex with high purity and good homogeneity was obtained by eukaryotic expression, affinity purification, gel filtration chromatography and glycerol density gradient centrifugation, and confirmed as the heptameric complex by LC-MS/MS. The purified proteins showed ubiquitination activity and nucleosome-binding affinity in vitro. The 3D structure of the PRC1.6 heptameric complex with a resolution of 15.2 ? (1 ?=10-10 m) was preliminarily resolved by negative staining, TEM, and single particle analysis. The available structure models of RNF2, PCGF6, RYBP, L3MBTL2, CBX3, and DP1 proteins, as well as the predicted E2F6 structure by AlphaFold2, were docked into the reconstructed density map of PRC1.6 complex. The position of each component in the complex was preliminarily confirmed. Conclusion ·The 3D structural model of the human PRC1.6 heptameric complex is obtained by negative staining, TEM, and single particle analysis.

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    Clinical research
    Correlation between computer-assisted quantitative autofluorescence imaging results and the pathological grading of oral epithelial dysplasia in oral leukoplakia
    LI Chenxi, WANG Zirui, JIN Tianhao, ZHOU Zengtong, TANG Guoyao, SHI Linjun
    2024, 44 (9):  1146-1154. 
    doi: 10.3969/j.issn.1674-8115.2024.09.009

    Abstract ( 85 )   HTML ( 3 )   PDF (4529KB) ( 59 )  

    Objective ·To explore the correlation between the quantitative results of autofluorescence imaging under computer assistance and the grade of epithelial dysplasia in oral leukoplakia. Methods ·From April 2016 to January 2024, 357 patients with oral leukoplakia who visited the Department of Oral Mucosal Diseases at Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, were included. Autofluorescence images of the lesions were obtained using a handheld autofluorescence device. These images were converted to grayscale images to obtain quantitative metrics. An ordered multinomial Logistic regression model was fitted in Python, and cumulative probability plots were generated. The dataset was divided into training and testing sets, and a decision tree was generated. Different hyperparameters were adjusted to achieve optimal model performance. Accuracy, precision, and F1 scores were calculated. The model performance was visualized using a confusion matrix. Results ·As the degree of epithelial dysplasia increased, the relative mean color level showed a declining trend. In the binary classification of epithelial dysplasia, there was no overlap between the cumulative probability curves of different categories. In the four-category classification, only severe epithelial dysplasia overlapped with other category curves, indicating good discriminative ability of the model. In binary pathological grading, when the training and testing set ratio was 4∶1 and the maximum depth was 2, the accuracy, precision, and F1 scores were 0.792, 0.801, and 0.795, respectively. In the four-category pathological grading, when the training and testing set ratio was 9∶1 and the maximum depth was 4, the accuracy, precision, and F1 scores were 0.611, 0.537, and 0.569, respectively. Conclusion ·Computer-assisted quantitative analysis of autofluorescence images can be used by oral mucosal specialists as a reference to predict the degree of epithelial dysplasia in patients with oral leukoplakia and to monitor their risk of cancer.

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    Clinical and imaging analyses of primary mediastinal yolk sac tumor
    MA Meili, TENG Jiajun, GAO Zhiqiang, SHI Chunlei, ZHONG Hua, HAN Baohui
    2024, 44 (9):  1155-1161. 
    doi: 10.3969/j.issn.1674-8115.2024.09.010

    Abstract ( 97 )   HTML ( 8 )   PDF (2269KB) ( 56 )  

    Objective ·To summarize the clinical features, imaging features, and diagnosis and treatment experience of primary mediastinal yolk sac tumor (YST). Methods ·Data of 29 patients with primary mediastinal YST, who attended Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine from September 2016 to May 2023, were collected and comprehensively analyzed, including imaging examination results, serum indicators, pathology reports and treatment methods. Results ·There were 22 cases of pure YST and 7 cases of mixed YST comprising 28 males and 1 female. The mean age of onset was (24.5±5.9) years. The initial symptoms were chest tightness (34.5%), chest pain (27.8%), cough (34.5%), expectoration (34.5%) and no specific symptoms (24.1%). Chest computerized tomography (CT) enhancement showed that all the 29 lesions were located in the anterior mediastinum. The maximum diameter of the lesions ranged from 5.6 cm to 18.2 cm. The lesions were irregular in shape, uneven in density, partially cystic and solid in density. The enhancement scan showed the solid part was slightly and moderately enhanced, and the low-density area was not enhanced. Tumor boundary was not clear because tumors often compressed and invaded surrounding tissues. Among the 29 newly diagnosed patients, serum alpha-fetoprotein (AFP) was significantly increased in 28 cases (1 case was not tested). Patients received multidisciplinary comprehensive treatment, including chemotherapy (25/29), surgery (26/29), and radiotherapy (8/29). Seven patients directly received surgery after diagnosis. Nineteen patients received chemotherapy first and then surgery; 16 (84.2%) cases were evaluated as lesion shrinkage after chemotherapy. After surgery, 73.1% (19/26) patients had a significant decrease in serum AFP. After chemotherapy, 56.0% (14/25) patients had decreased serum AFP. Conclusion ·Primary mediastinal YST usually occurs in middle-aged and young men, with certain clinical and radiographic features and elevated serum AFP, which requires multidisciplinary comprehensive treatment.

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    Clinicopathologic characteristics of patients with kidney-involved diffuse large B-cell lymphoma
    WANG Boen, CHEN Siyuan, SHI Qing, ZHANG Muchen, YI Hongmei, DONG Lei, WANG Li, CHENG Shu, XU Pengpeng, ZHAO Weili
    2024, 44 (9):  1162-1168. 
    doi: 10.3969/j.issn.1674-8115.2024.09.011

    Abstract ( 78 )   HTML ( 4 )   PDF (2421KB) ( 37 )  

    Objective ·To analyze the clinicopathologic characteristics of patients with kidney-involved diffuse large B-cell lymphoma (DLBCL), including clinical characteristics, pathological characteristics, gene mutation profiles, and prognostic factors. Methods ·One hundred and forty-nine patients with kidney-involved DLBCL, admitted to Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from July 2005 to November 2021, were retrospectively analyzed for their clinicopathological data, survival and prognostic factors, which included therapeutic methods, clinical outcomes, staging, etc. Gene mutation profiles were evaluated by targeted sequencing of 54 lymphoma-related genes. Prognostic factors were also analyzed based on the information mentioned above. Results ·A total of 149 kidney-involved DLBCL cases were included, of which 89 patients (58.4%) were aged over sixty, 121 patients (81.2%) were staged Ann Arbor Ⅲ?Ⅳ, 27 patients (18.1%) had an Eastern Cooperative Oncology Group (ECOG) performance status of two or more, 121 patients (81.2%) had elevated serum lactate dehydrogenase (LDH) level, 111 patients (74.5%) had extranodal invasion in at least two organs and 131 patients (87.9%) scored over 2 points on the international prognosis index (IPI). The estimated 5-year overall survival (OS) rate and progression-free survival (PFS) rate of kidney-involved DLBCL patients were 52.2% and 50.4% respectively. Univariate analysis revealed that elevated serum LDH levels were an adverse prognostic factor for both OS (P=0.048) and PFS (P=0.033). In pathological characteristics, 145 patients (97.3%) belonged to DLBCL, not otherwise specified (NOS) and 39 patients (26.3%) belonged to germinal center B-cell (GCB) according to Hans classification. Among 144 patients who could be evaluated for clinical outcomes, 87 patients (60.4%) got complete response (CR). Targeted sequencing data from 75 kidney-involved DLBCL patients showed high mutation frequency in PIM1 (n=23, 31%), MYD88 (n=22, 29%), CD79B (n=21, 28%) and KMT2D (n=18, 24%), with CD79B mutation indentified as an adverse prognostic factor for OS in patients with kidney-involved DLBCL (P=0.034). Conclusion ·Elevated serum LDH level is an adverse prognostic factor in patients with kidney-involved DLBCL. The prognosis of patients with CD79B mutations is poor.

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    Evaluation of machine learning prediction of altered inflammatory metabolic state after neoadjuvant therapy for breast cancer
    WU Qizhen, LIU Qiming, CHAI Yezi, TAO Zhengyu, WANG Yinan, GUO Xinning, JIANG Meng, PU Jun
    2024, 44 (9):  1169-1181. 
    doi: 10.3969/j.issn.1674-8115.2024.09.012

    Abstract ( 99 )   HTML ( 5 )   PDF (4625KB) ( 62 )  

    Objective ·To develop a machine learning approach for early identification of metabolic syndromes associated with inflammatory metabolic state changes in breast cancer patients after neoadjuvant therapy, using common laboratory and transthoracic echocardiography indices. Methods ·Female patients with primary invasive breast cancer diagnosed at the Department of Breast Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, between September 2020 and September 2022, were included. General patient information, laboratory test results, and transthoracic echocardiography data were collected. After feature extraction, five machine learning algorithms, including random forest (RF), gradient boosting (GB), support vector machine (SVM), K-nearest neighbor (KNN), and decision tree (DT), were applied to construct a prediction model for the changes of the patients′ metabolic state after neoadjuvant therapy, and the prediction performances of the five models were compared. Results ·A total of 232 cases with valid clinical data were included, comprising 135 cases before neoadjuvant therapy and 97 cases after completing 4 cycles of neoadjuvant therapy. Feature extraction identified five key features: white blood cell count, hemoglobin, high-density lipoprotein (HDL), interleukin-2 receptor, and interleukin-8. In the multi-feature analysis, the area under the receiver operating characferistic curve (AUC) was higher in the combination of white blood cell count, hemoglobin and HDL compared to the combination of interleukin-2 receptor and interleukin-8 (RF: 0.928 vs 0.772, GB: 0.900 vs 0.792, SVM: 0.941 vs 0.764, KNN: 0.907 vs 0.762, DT: 0.799 vs 0.714). The RF, SVM, and GB models showed higher AUC (0.928, 0.941, 0.900) and accuracy (0.914, 0.897, 0.776). The SVM model exhibited superior accuracy in the training data compared to the RF and GB models (P=0.394, 0.122 and 0.097, respectively). Conclusion ·The SVM model can be used to establish a prediction model for identifying breast cancer patients at high risk of developing inflammatory metabolic state-related metabolic syndrome after neoadjuvant therapy by incorporating five common clinical indicators, namely, white blood cell count, hemoglobin, high-density lipoprotein, interleukin-2 receptor, and interleukin-8. SVM modeling may be useful for clinicians to establish individualized screening protocols based on a patient′s inflammatory metabolic state.

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    Study of imaging characteristics of Kimura disease in the head and neck
    LUO Rui, YANG Gongxin, SHI Huimin, HAN Yongshun, HE Yining, TIAN Zhen, WU Yingwei
    2024, 44 (9):  1182-1189. 
    doi: 10.3969/j.issn.1674-8115.2024.09.013

    Abstract ( 96 )   HTML ( 6 )   PDF (2769KB) ( 46 )  

    Objective ·To investigate the imaging features of computed tomography (CT) and magnetic resonance imaging (MRI) in the patients with Kimura disease (KD) in the head and neck. Methods ·Sixty-four cases of KD in the head and neck comfirmed by histopathology were retrospectively collected from 2009 to 2023 in Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine. All patients completed CT and/or MRI enhancement imaging before surgery. Clinical and imaging characteristics were collected, recorded and analyzed, including age, gender, peripheral blood eosinophilic ratio, serum IgE level, the lesion location, shape, size, CT density and degree of enhancement, MRI signal intensity and degree of enhancement, apparent diffusion coefficient (ADC), time-signal intensity curve (TIC) patterns, wash-in rate, and time to peak (TTP). Results ·The average age of the 64 KD patients was (40±19) years, and 92.2% were males. A total of 73.5% of the patients showed an elevated ratio of peripheral blood eosinophil, and all 10 tested patients exhibited increased serum IgE levels. There were 82 extranodal (subcutaneous and glandular) lesions and 144 lymph node lesions detected by CT and MRI. Among the extranodal lesions, 80.5% were subcutaneous or glandular patchy lesions with unclear boundaries, and the rest were nodular lesions with clear boundaries. All lesions exhibited isodensity on CT scans and showed isointensity on T1-weighted imaging (T1WI) and hyperintensity on T2-weighted imaging (T2WI) in MRI. Most extranodal lesions tended to show heterogeneous enhancement, while most lymph node lesions showed homogeneous enhancement. The median ADCs of the extranodal lesions and the lymph node lesions were 1.04×10 -3 mm 2/s and 0.67×10 -3 mm 2/s, respectively, which were significantly different ( P=0.000). The dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) results showed that the TIC patterns of extranodal lesions were predominantly type Ⅰ and Ⅱ, accounting for 57.5% and 42.5%, respectively; while the TIC patterns of lymph node lesions were predominantly type Ⅱ (96.6%). The difference in the TTP and the wash-in rate between the extranodal lesions and the lymph node lesions were both statistically significant ( P=0.000). Conclusion ·Extranodal lesions and lymph node lesions of KD both show isodensity on CT, and isointensity on T1WI and hyperintensity on T2WI in MRI. Extranodal lesions often show high ADC, TIC type Ⅰ or Ⅱ, and mostly heterogeneous enhancement; lymph node lesions often show low ADC, TIC type Ⅱ, and mostly homogenous enhancement.

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    Review
    Research progress in food preferences mechanisms and their impact on obesity
    KANG Piao, ZHANG Ying, LI Huating
    2024, 44 (9):  1190-1196. 
    doi: 10.3969/j.issn.1674-8115.2024.09.014

    Abstract ( 131 )   HTML ( 15 )   PDF (2104KB) ( 136 )  

    In recent years, the global prevalence of obesity has continued to rise, with a preference for high-sugar and high-fat foods being one of the primary contributors to this condition. Food preference refers to the degree of individual liking for specific foods, and its formation is closely related to the physiological effects such as satiety, satisfaction and reward that occur after food digestion in the gastrointestinal tract. With the continuous advancement of technologies such as neuroimaging and chemogenetics, the underlying neural and physiological mechanisms of food preference behavior are gradually being elucidated. Studies have shown that the digestion and absorption of food in the gastrointestinal tract can release chemical or electrical signals, which are transmitted to the central nervous system via neural pathways, humoral pathways and the gut-brain axis mediated by gut microbiota. Subsequently, these signals regulate feeding behavior by activating or inhibiting neurons in the nucleus of the solitary tract, the dopaminergic reward pathways and relevant neural circuits in the hypothalamus. Based on this, the article introduces the definition, evaluation methods and mechanisms of food preference, and reviews the pathways of food information transmission within the gut-brain axis, the reward circuits that modulate food preference and the application of food preference behavior to the treatment of obesity, in order to provide reference for research in the field of food preference and obesity treatment.

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    Forum
    Exploration of strategies for improving clinical research level in medical universities
    KANG Li, WANG Wei, FENG Tienan, CUI Tingting, WANG Suping
    2024, 44 (9):  1197-1204. 
    doi: 10.3969/j.issn.1674-8115.2024.09.015

    Abstract ( 77 )   HTML ( 6 )   PDF (4486KB) ( 43 )  

    Objective ·To analyze the development trend and current situation of high-level clinical research at Shanghai Jiao Tong University School of Medicine (SJTUSM) from 2015 to 2023, and to summarize the strategies for improving clinical research capability of SJTUSM, aiming to provide reference and inspiration for medical universities to promote high-level clinical research. Methods ·Papers published by first authors from SJTUSM or its affiliated hospitals during this period were retrieved in the Web of Science core collection database. General descriptive methods were used to quantify the number of clinical research papers, registered clinical trials, clinical research talent teams, and the current status of clinical research cooperation. Bibliometric methods were used to visualize the international collaboration and topic distribution of retrieved clinical research papers. The differences in the number of clinical research publications, Q1 publications, publications in top clinical medical journals, and full-time researchers between the periods of 2015?2018 and 2019?2023 were compared and analyzed. Results ·From 2015 to 2023, a total of 9 468 clinical research papers were published by SJTUSM or its affiliated hospitals as the first author′s institution, showing an increasing trend year by year. During this period, the number of Q1 publications of SJTUSM′s clinical research, publications in top clinical medical journals, clinical studies registered on the United States Clinical Trial Registry website, clinical studies registered on the Chinese Clinical Trial Registry website, clinical guidelines and expert consensus publications, full-time research team members, and newly added national-level talents all showed an overall upward trend. Tumors, cardiovascular and cerebrovascular diseases, major chronic diseases, and mental illnesses were the main research hotspots. A total of 1 308 papers (13.82%) were international collaborative papers. Developed countries/regions such as the United States (733 papers), Australia (137 papers), and the United Kingdom (99 papers) were closely cooperating with SJTUSM. From 2019 to 2023, there was a significant increase in the number of clinical research papers, Q1 publications, publications in top clinical medical journals, and newly added full-time research team members in affiliated hospitals compared to the period from 2015 to 2018 (all P<0.05). Conclusion ·SJTUSM has strengthened top-level design, conducted in-depth major diseases, and constructed a systematic, integrated and closed-loop model for enhancing clinical research level along the “platform-talent-methodology” pathway, resulting in a number of high-quality clinical research outcomes.

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    Influencing factors of the approval of the Young Scientists Fund of National Natural Science Foundation of China: a case study of Shanghai Jiao Tong University School of Medicine
    CHEN Lihong, WANG Yan, ZHOU Xiangtian, ZHENG Junke, YAN Xiaoxiang
    2024, 44 (9):  1205-1212. 
    doi: 10.3969/j.issn.1674-8115.2024.09.016

    Abstract ( 113 )   HTML ( 10 )   PDF (1866KB) ( 74 )  

    Objective ·In view of the low funding rate of the Young Scientists Fund of National Natural Science Foundation of China in the medical field, this research conducted an in-depth investigation of the applicants in a medical school and quantitatively analyzed the influencing factors of project establishment, so as to provide reference for further improving the quality of project application and strengthening the training of young medical talents. Methods ·A cross-sectional survey was used to select applicants from secondary schools of Shanghai Jiao Tong University School of Medicine and its 13 affiliated hospitals who had experience in applying for the fund from 2020 to 2022. Logistic stepwise regression model was applied to modeling and analysis by using the project application result as the dependent variable and the applicants' basic information and application status as independent variables. Results ·The analysis results of 921 applicants showed that educational background (OR=1.86, 95%CI 1.14?3.04), graduate university (OR=2.45, 95%CI 1.47?4.08), sufficient preliminary work foundation (OR=4.22, 95%CI 2.44?7.29), average impact factor of representative works (OR=1.10, 95%CI 1.04?1.17), and total self-evaluation score of application documents (OR=1.06, 95%CI 1.04?1.08) were the main influencing factors for project approval. The average impact factor and the highest impact factor of the approved representative works showed an increasing trend year by year. In addition, the influencing factors for the approval of young doctors and full-time researchers were different. The longer the graduation time of young doctors, the lower the approval rate. Conclusion ·The funding rate of Young Scientists Fund is low, and the requirements for scientific research achievements are increasing year by year. Attention should be paid to early accumulation and improving the quality of application writing. Further measures should be taken to strengthen the early training of young medical talents, improve cultivation measures and consolidate research foundations.

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