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    Research progress in the role of M1/M2 polarization of macrophages in different liver diseases
    NIU Yuanyuan, WANG Longde, XU Wenjuan, LI Zhengju, ZHANG Ruiting, WU Yuqian
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (4): 509-517.   DOI: 10.3969/j.issn.1674-8115.2024.04.012
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    Macrophages have strong plasticity and heterogeneity, and can undergo functional transformation in response to different signal stimuli, such as classical activation of M1 type (M1 type polarization) and selective activation of M2 type (M2 type polarization). The pathways of macrophage M1/M2 polarization are quite extensive, involving nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway, interleukin-4 (IL-4)/signal transduction and activator of transcription 6 (STAT6) signaling pathway, Notch signaling pathway, Wnt/β-catenin signaling pathway, etc. At the same time, M1/M2 polarization of macrophages is also regulated by exosomes, metabolites, non-coding RNA, electrical stimulation, probiotics, etc., and its imbalance is closely related to the occurrence and development of different types of liver disease. In this paper, the mechanism of its polarization was reviewed, and it was found that M1 polarization of macrophages played a promoting role in the process of liver tissue injury, inflammation and fibrosis, while M2 polarization of macrophages played the opposite role. Among them, hepatocellular carcinoma, as the advanced stage of chronic liver disease, was characterized by increased M2 polarization and impaired M1 polarization of macrophages. Therefore, this paper pays attention to the role of M1/M2 polarization of macrophages in different types of liver diseases, in order to better establish the targeted therapy of macrophage subsets.

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    Research progress in ceruloplasmin regulation of lipid metabolism homeostasis
    JIANG Quanxin, CHEN Suzhen, LIU Junli
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 124-130.   DOI: 10.3969/j.issn.1674-8115.2024.01.014
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    Ceruloplasmin (Cp) is a crucial protein secreted by the liver and plays a vital role in regulating the distribution and transport of copper throughout the body, thereby maintaining copper homeostasis. Additionally, Cp functions as a significant enzyme known as ferroxidase, which is involved in iron metabolism within the body. Numerous studies have suggested a close relationship between Cp and metabolic disorders, such as diabetes and cardiovascular diseases. Recent research has also shed light on the involvement of Cp in the regulation of lipid metabolism. The various activities associated with lipid metabolism, including lipid synthesis, adipose hydrolysis, fatty acid oxidation, lipid transport, and absorption, collectively contribute to maintaining lipid homeostasis. Dysregulation of lipid metabolism can lead to metabolic disorders and cardiovascular complications. Cp regulates lipid metabolism through two main mechanisms. Firstly, Cp participates in the regulation of oxidative stress by modulating iron metabolism through its ferroxidase activity and involvement in redox reaction. Secondly, copper along with copper-dependent enzymes directly participates in the processes such as cholesterol metabolism, lipoprotein metabolism, and fatty acid synthesis. As a result, the role of Cp in maintaining the homeostasis of copper and iron allows it to regulate lipid metabolism by influencing copper or iron-dependent enzymes and related pathways. Although the correlation between Cp and lipid metabolism has been identified, an in-depth exploration of the precise mechanisms by which Cp governs lipid metabolism is warranted. This article provides an overview of the role of Cp in lipid metabolism and highlights the progress in related research, with the aim of providing new insights for the development and treatment of disorders related to lipid metabolism.

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    Review of the role of collagen in tumorigenesis and development
    TANG Lei, XU Yingchun, ZHANG Fengchun
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (12): 1577-1584.   DOI: 10.3969/j.issn.1674-8115.2023.12.014
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    Collagen is one of the most abundant proteins in the body and is the main component of the extracellular matrix. Collagen regulates cellular behavior, and its dysregulation can cause a variety of diseases, including cancer. Collagen in tumors is mainly produced by fibroblasts and plays an important role in cancer progression and metastasis. Collagen can act as a prognostic predictor for cancer patients and may be an effective target for the treatment and prevention of tumor progression and metastasis. Anti-tumor drugs targeting collagen and its receptors may be developed in the future. This review focuses on the newly discovered role of collagen in cancer in recent years, specifically the role of collagen in tumor cell dormancy and immune evasion, and the participation of collagen in tumor cell metabolism.

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    Research progress of m 6A methylation modification in regulating tumor immunity
    ZHOU Haixia, ZHANG Jing
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 137-144.   DOI: 10.3969/j.issn.1674-8115.2024.01.016
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    N6-methyladenosine (m6A) is the most prevalent modification that regulates gene expression in eukaryotes. It regulates splicing, degradation, stability, and translation of RNA. Numerous studies have demonstrated the close association between m6A methylation and tumor development, highlighting its crucial role in regulating tumor immune response. The m6A modification actively participates in governing immune cell differentiation and maturation as well as modulating anti-tumor immune responses. Within the tumor microenvironment, m6A modification can also impact the recruitment, activation, and polarization of immune cells, thereby either promoting or inhibiting tumor cell proliferation and metastasis. Consequently, it plays a pivotal role in reshaping the tumor immune microenvironment. In recent years, immunotherapy for tumors has been increasingly applied to clinical practice with notable success achieved through approaches such as immune checkpoint inhibitor therapy and adoptive cell immunotherapy. Targeting m6A modifications to interfere with the immune system, such as targeting dysregulated m6A regulators through small molecule inhibitors and inducing immune cell reprogramming, can improve anti-tumor immune response and strengthen immune cells′ ability to recognize and kill tumor cells. The m6A modification represents a novel avenue for potential clinical application within tumor immunotherapy. This review provides a comprehensive summary of the regulatory impact of m6A methylation modification on immune cells in the context of cancer, while also delving into novel targets for tumor immunotherapy.

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    Research progress in immune cells regulating drug resistance of tumor cells in tumor microenvironment
    ZHANG Yesheng, YANG Yijing, HUANG Yiwen, SHI Longyu, WANG Manyuan, CHEN Sisi
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (7): 830-838.   DOI: 10.3969/j.issn.1674-8115.2024.07.004
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    Tumor microenvironment (TME) is a complex cellular environment where tumor cells reside, along with various types of cells and extracellular components surrounding the tumor cells. Immune cells are key components of TME, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), lymphocytes, regulatory T cells (Tregs), natural killer cells (NK cells), dendritic cells (DCs), and many others. It is worth noting that drug resistance is currently a major factor limiting the efficacy of cancer treatment methods such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy, and a leading cause of treatment failure. Research has found that the development of drug resistance in tumor cells is the result of interactions between tumor cells and TME. Consequently, overcoming drug resistance in tumors caused by TME is considered a significant challenge in cancer treatment. In recent years, with in-depth research into immune cells within TME, significant progress has been made in understanding the specific mechanisms by which immune cells regulate drug resistance in tumor cells. Furthermore, therapeutic strategies that target these immune cells, signaling pathways, or cytokines have been shown to effectively combat tumor drug resistance and enhance the therapeutic outcomes of cancer treatment. This article reviews the research advancements regarding the roles of TAMs, MDSCs, Tregs, and NK cells in tumor drug resistance within TME and discusses the development of targeting strategies to overcome this resistance. Additionally, we explore the relationship of tumor-associated neutrophils (TANs) and B regulatory cells (Bregs) with tumor drug resistance. It is hoped that this review will offer insights and serve as reference for reducing tumor drug resistance and improving the efficacy of anti-tumor therapies.

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    Current status of development of Chinese versions of insomnia-related scales
    LUO Xin, YUAN Chengmei
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (11): 1436-1444.   DOI: 10.3969/j.issn.1674-8115.2023.11.012
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    Insomnia disorder is the most common sleep-wake disorder, and long-term insomnia has a serious negative impact on the physical and mental health of individuals. It is crucial for researchers and clinicians to select appropriate measurement tools as evaluative indicators for insomnia. There are some commonly used insomnia assessment scales in the world, including Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), etc. These scales are widely used to assess insomnia symptoms and sleep quality, providing researchers and clinicians with reliable quantitative tools. In addition to conventional insomnia assessment scales, some scales evaluate sleep cognition, sleep hygiene, and sleep conditions of different groups of people. Domestic scholars are actively developing sleep assessment tools suitable for the Chinese population, which also include sleep assessment for special groups. In addition, some sleep assessment with traditional Chinese medicine characteristics have also been developed to meet the needs of integrated traditional Chinese and Western medicine treatment. During the process of scale development, researchers should clarify the purpose of scale, select appropriate psychometric methods, and emphasize the reliability and validity of the scale. Furthermore, it is important to develop scales that can differentiate subtypes of insomnia and enhance the diversity of insomnia-related measures. This article summarizes the current situation of development of Chinese versions of insomnia-related scales, and provides evaluation and future prospects for existing scales.

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    Advances in stem cell therapy for sensory nerve injury
    CHEN Huidong, ZHANG Yunlong, ZHANG Zhijian, HUA Qingquan
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (11): 1450-1456.   DOI: 10.3969/j.issn.1674-8115.2023.11.014
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    Sensory nerves belong to the afferent nerve part of the peripheral nervous system. Their role is to accept the stimuli inside and outside the body and transmit them to the center nerve system to form sensations or reflexes. Sensory nerve damage can be caused by trauma, tumor invasion, surgical injury, etc. Sensory nerve injury may cause decline or loss of some sensory organs function in patients. Damage of important sensory nerves such as optic nerves and auditory nerves can bring profound troubles to patients' lives. So far, the main clinical method to repair sensory nerves is autologous nerve transplantation. However, its application is limited by various factors, and the recovery effect of nerve function is often limited. Stem cells have the potential of multi-directional differentiation, which can differentiate into Schwann cells, and then secrete neurotrophic factors to promote axonal growth and myelin regeneration. Schwann cells directionally proliferate and form Büngner zones which guide nerve regeneration. Stem cells can also differentiate into neurons and construct nerve defect repair materials, which is an ideal choice for nerve repair. At present, the tissue engineering technology based on stem cells, combined with several key biotechnology, such as the use of biopolymerized or artificial surface micro-patterning nerve conduit to bridge nerve defects, and the use of microspheres to achieve the controlled release of extracellular matrix proteins and neurotrophic factors, is being widely studied and has achieved certain research results. This article reviews the research progress of stem cells in the repair of several major sensory nerves, such as optic nerves, olfactory nerves, cochlear nerves and sensory nerve fibers of sciatic nerve, expecting to provide a new perspective for neural repair of stem cells, broaden the preclinical research in nerve repair, and provide reference for follow-up clinical application.

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    Study on intercellular communication and key genes of smooth muscle cells in human coronary atherosclerosis based on single cell sequencing technology
    SI Chunying, WANG Jianru, LI Xiaohui, WANG Yongxia, GUAN Huaimin
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 169-182.   DOI: 10.3969/j.issn.1674-8115.2024.02.003
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    Objective ·To use single-cell RNA sequencing (scRNA-Seq) technology to interpret the cellular communication landscape of coronary atherosclerosis (CA), and to explore the dominant cell subsets and their key genes. Methods ·The GSE131778 data set was downloaded and preprocessed, and quality controlling, dimension reduction clustering and annotation were carried out. Then cell communication analysis was conducted by using CellChat package to identify dominant cell subsets. The FindAllMarker function was used to screen differentially expressed genes (DEGs) between the dominant cell subpopulation and other cell subpopulations, and its protein-protein interaction (PPI) network was constructed. The DEGs ranked in the top five of the Degree algorithm were taken as key genes. Then, the key genes were matched and mined with the cell communication network analyzed by CellChat to obtain the ligand-receptor pairs (L-R) and the signal pathways mediated by the key genes, and the results were visualized. At the same time, the atherosclerosis mouse model was constructed and RT-PCR was used to detect the expression of key genes in carotid atherosclerosis lesions. Results ·A total of 11 cell subsets were identified in CA lesions, including smooth muscle cells, endothelial cells, macrophages, monocytes, etc. Cell communication results showed that CellChat detected 70 significant L-R and 26 related signal pathways in 11 cell subsets. Smooth muscle cell was the dominant cell subgroup with the most significant interaction frequency and intensity with other cell subgroups in the active state of communication. The results of DEGs screening showed that there were 206 DEGs between smooth muscle cell subsets and other cell subsets, among which ITGB2, PTPRC, CCL2, DCN and IGF1 were identified as key genes. The results of cell communication mediated by key genes showed that CCL2 and ACKR1 formed L-R and participated in the communication network between smooth muscle cells and endothelial cells through mediating CCL signaling pathway. ITGB2 formed receptor complexes with ITGAM and ITGAX respectively, and then formed L-R with C3 to mediate the complement signal pathway, participating in the communication network among smooth muscle cells, macrophages and monocytes. The validation results of hub genes in animal experiments were consistent with the results of bioinformatics analysis. Conclusion ·Smooth muscle cells are the dominant cells in the pathological process of CA, and have extensive communication networks with other cells. They can construct cellular communication networks with endothelial cells, macrophages and monocytes through CCL and complement signaling pathways mediated by CCL2-ACKR1, C3-(ITGAM+ITGB2) and C3-(ITGAX+ITGB2).

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    Causal relationship between atrial fibrillation and cognitive impairment: a Mendelian randomization study
    GAO Xiong, ZHANG Qiuxia, YANG Miaomiao, LUO Wei, WANG Yuegang, XIU Jiancheng
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (11): 1359-1365.   DOI: 10.3969/j.issn.1674-8115.2023.11.003
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    Objective ·To investigate the causal relationship between atrial fibrillation (AF) and cognitive impairment. Methods ·A two-sample Mendelian randomization (TSMR) analysis was used to assess the potential causality of AF on cognitive dysfunction. Single nucleotide polymorphisms (SNPs) strongly associated with AF were extracted as instrumental variables by using a dataset of a large-scale genome-wide association study (GWAS) on AF. The associations of SNPs with Alzheimer′s disease dementia, Parkinson′s disease dementia, vascular dementia, Lewy body dementia, frontotemporal dementia, undefined dementia, and overall cognitive function assessment were extracted separately from publicly available GWAS data on cognitive dysfunction. The inverse variance-weighted (IVW) method was used for the main analysis, and sensitivity analyses were conducted by using Cochran′s Q test, MR-Egger regression, and leave-one-out method. To verify the robustness of the results, replicate analyses and meta-analyses were performed by using different GWAS data. Results ·In the initial analysis, 101 SNPs were extracted as instrumental variables from a meta-analysis of a genome-wide association study involving up to 1 030 836 individuals. The IVW analysis showed no evidence for causal associations between AF and dementia [dementia (OR=1.032; 95%CI 0.973?1.094; P=0.290), Parkinson′s disease dementia (OR=1.004; 95%CI 0.780?1.291; P=0.977), vascular dementia (OR=1.123; 95%CI 0.969?1.301; P=0.125), or unspecified dementia (OR=1.013; 95%CI 0.910?1.129; P=0.807)]. In the replication analysis, 27 SNPs were extracted as instrumental variables from the FinnGen AF GWAS data, and the IVW analysis were consistent with the initial analysis [cognitive function (OR=0.999; 95%CI 0.982?1.016; P=0.874), Alzheimer′s disease dementia (OR=0.977; 95%CI 0.943?1.012; P=0.193), Lewy body dementia (OR=1.014; 95%CI 0.898?1.145; P=0.826), or frontotemporal dementia (OR=0.996; 95%CI 0.745?1.333; P=0.980)]. Both Mendelian randomization analyses and meta-analyses showed no evidence of an association between genetically predicted AF and different types of dementia or overall cognitive function assessment. MR-Egger regression suggested no horizontal pleiotropy and leave-one-out analysis showed stable results after individually removing each SNP. Conclusion ·No evidence of a causal relationship between AF and cognitive impairment was found. The associations observed in observational studies can be partially attributed to confounding factors such as shared biology or co-morbidities.

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    Comparative study on methods for colon polyp endoscopic image segmentation and classification based on deep learning
    CHEN Jian, WANG Zhenni, XIA Kaijian, WANG Ganhong, LIU Luojie, XU Xiaodan
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (6): 762-772.   DOI: 10.3969/j.issn.1674-8115.2024.06.012
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    Objective ·To compare the performance of various deep learning methods in the segmentation and classification of colorectal polyp endoscopic images, and identify the most effective approach. Methods ·Four colorectal polyp datasets were collected from three hospitals, encompassing 1 534 static images and 15 videos. All samples were pathologically validated and categorized into two types: serrated lesions and adenomatous polyps. Polygonal annotations were performed by using the LabelMe tool, and the annotated results were converted into integer mask formats. These data were utilized to train various architectures of deep neural networks, including convolutional neural network (CNN), Transformers, and their fusion, aiming to develop an effective semantic segmentation model. Multiple performance indicators for automatic diagnosis of colon polyps by different architecture models were compared, including mIoU, aAcc, mAcc, mDice, mFscore, mPrecision and mRecall. Results ·Four different architectures of semantic segmentation models were developed, including two deep CNN architectures (Fast-SCNN and DeepLabV3plus), one Transformer architecture (Segformer), and one hybrid architecture (KNet). In a comprehensive performance evaluation of 291 test images, KNet achieved the highest mIoU of 84.59%, significantly surpassing Fast-SCNN (75.32%), DeepLabV3plus (78.63%), and Segformer (80.17%). Across the categories of “background”, “serrated lesions” and “adenomatous polyps” , KNet's intersection over union (IoU) were 98.91%, 74.12%, and 80.73%, respectively, all exceeding other models. Additionally, KNet performed excellently in key performance metrics, with aAcc, mAcc, mDice, mFscore, and mRecall reaching 98.59%, 91.24%, 91.31%, 91.31%, and 91.24%, respectively, all superior to other models. Although its mPrecision of 91.46% was not the most outstanding, KNet's overall performance remained leading. In inference testing on 80 external test images, KNet maintained an mIoU of 81.53%, demonstrating strong generalization capabilities. Conclusion ·The semantic segmentation model of colorectal polyp endoscopic images constructed by deep neural network based on KNet hybrid architecture, exhibits superior predictive performance, demonstrating its potential as an efficient tool for detecting colorectal polyps.

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    Research progress of neuromodulation in the treatment of Parkinson 's disease
    HU Canfang, ZHONG Chuanyu, CAO Li
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 258-263.   DOI: 10.3969/j.issn.1674-8115.2024.02.012
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    Parkinson's disease (PD) is a common degenerative neurological disorder, characterized by static tremor, bradykinesia, myotonia and postural abnormalities. Dopaminergic drugs are the main drugs in the treatment of PD, but long-term use will lead to drug efficacy loss, and even cause some adverse reactions such as dyskinesia and "on-off" phenomenon. Neuromodulation is a kind of biomedical engineering technology that can stimulate or inhibit the activity of brain neurons and regulate the changes of neuroplasticity by means of electric energy, magnetic field, ultrasound and other methods, so as to achieve treatment and improvement of diseases. In the non-drug treatment of PD, neuromodulation, as a new therapeutic means, has shown good efficacy, and has the advantages of small adverse reactions and easy tolerance. Based on this, this article reviews the research progress of several common neuromodulation in PD, including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation and transcranial focused ultrasound.

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    Quantitative analysis of the developmental potential of cells and tissues based on evolutionary conservation of genes and regulatory regions
    WANG Zhiming, TONG Ran, YANG Chen, JIAO Huiyuan, WANG Yihao, LI Linying, WANG Yexin, ZHANG Feng, LI Lingjie
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (11): 1384-1395.   DOI: 10.3969/j.issn.1674-8115.2023.11.006
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    Objective ·To study the relationship between evolution and the developmental process from the perspective of DNA sequence conservation, and explore their inherent principles. Methods ·First, conservation rate (CR) was established by analyzing the conservation of amino acid sequences of coding genes in 100 species to quantify the evolutionary conservation of genes. The relationship between CR and developmental potential was verified by using the feature genes involved in embryonic stem cells pathways. Secondly, cell type-specific genes and their characteristics in conservation were studied by analyzing the RNA sequencing (RNA-seq) data of the three early germ layers (ectoderm, mesoderm and endoderm) and their corresponding mature organs (brain, heart, liver, etc). Then, chromatin immunoprecipitation sequencing (ChIP-seq) data of enhancer histone H3 acetylated at lysine 27 (H3K27ac) from early germ layers and mature organs were collected to search for enhancer sites and identify super enhancers in various cells and tissues by using the ROSE procedure. Functional enrichment and signaling pathway analysis of genes was used to examine the identity correlation between SEs-regulated genes and the corresponding cell characteristics, to clarify whether the SEs identified in this study were consistent with the characteristics reported in previous studies. Finally, PhastCons program was used to calculate the DNA conservation score (CS) of non-coding regulatory regions to study their relationship with developmental potential. Results ·In the coding region of DNA, CR was successfully established to quantify the conservation of genes. The gene expression data of early germ layers and mature organs showed that the genes with higher conservation rate were more relevant to the stemness and early developmental process, and the differences between the tissues from early and late development could be distinguished by using CR. In the non-coding regions of DNA, it was found that the conservation of regulatory regions was also correlated with development. The CS of the SE sequences in the early developmental germ layers was significantly higher than that of the SE sequences in the corresponding mature organs. However, cell-specific typical enhancers (TEs) did not show such a trend. Conclusion ·During the developmental process, CR of genes expressed in the coding region decreases, and CS of super-enhancer DNA in the non-coding region decreases.

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    Study on the relationship between comorbidities of chronic diseases, phase angle, and muscle mass decline related to sarcopenia in the elderly
    WANG Junlin, HAO Mingxiu, TANG Yinhan, WU Yunyun, JIN Yuhua, HU Yaomin
    Journal of Shanghai Jiao Tong University (Medical Science)   
    Online available: 06 February 2024

    An integrated prognostic model of nuclear-encoded mitochondrial gene signature and clinical information for hepatocellular carcinoma
    Aishanjiang Kedeerya, FU Yi, LAI Donglin, WU Hailong, GONG Wei
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 1-12.   DOI: 10.3969/j.issn.1674-8115.2024.01.001
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    Objective ·To establish a prognostic model for the overall survival (OS) of hepatocellular carcinoma (HCC) based on mitochondrial genes and clinical information. Methods ·The gene expression and the clinical data of 369 HCC patients and 50 controls with normal liver were downloaded from The Cancer Genome Atlas (TCGA) database. The nuclear-encoded mitochondrial genes (NEMGs) were obtained from the MitoCarta3.0 database. The "DESeq2" R package and univariate Cox analysis were used to select NEMGs [ubiquinol cytochrome C reductase hinge protein (UQCRH), ATP citrate lyase (ACLY), phosphoenolpyruvate carboxykinase 2 (PCK2), Bcl-2 homologous antagonist/killer1 (BAK1), Bcl-2-associated X protein (BAX) and Bcl-2/adenovirus E1B interacting protein 3-like (BNIP3L)] in HCC that were associated with OS of HCC and participated in dysregulation of oxidative phosphorylation, tricarboxylic acid cycle and cell apoptosis. Multivariate Cox analysis was applied to select independent risk factors for OS of HCC. A comprehensive prognostic model and a prognostic nomogram with 6-NEMG risk characteristics and TNM staging were established. By using the median of prognostic scores as a cut-off, HCC patients were classified into low-risk and high-risk group. Kaplan-Meier survival curve analysis was conducted and log-rank test was performed to evaluate the survival rates between the low-risk and high-risk group. The area under the curve (AUC) values of receiver operating characteristic (ROC) curve were calculated via using the "timeROC" package. The prognostic model for HCC was validated by using the GEO HCC cohort (GSE14520) for 1, 3 and 5 years. Finally, the relative expression level of 6-NEMG was validated in 34 clinical samples of HCC from Xinhua Hospital, Shanghai Jiao Tong University School of Medicine by using real-time quantitative polymerase chain reaction (qPCR) method. Results ·Compared to 6-NEMG risk signature only (AUCs for 1, 3 and 5 years were 0.77, 0.66 and 0.65, respectively) or TNM stage only (AUCs for 1, 3 and 5 years were 0.66, 0.67 and 0.63, respectively), ROC curve analysis showed that this integrated prognostic model displayed better predictive performance for 1-year (AUC, 0.78), 3-year (AUC, 0.73) and 5-year (AUC, 0.69) OS of HCC. The Kaplan-Meier survival curve analysis showed that the OS of HCC patients in the high-risk group was significantly worse than that in the low-risk group (P=0.001). In addition, predictive performance of the prognostic model (AUC for 1, 3 and 5 years is 0.67, 0.66 and 0.74, respectively) and prognostic differences between the high-risk and low-risk group (P=0.001) were further validated in GEO (GSE14520) external cohort, and these results were consistent with the TCGA data. In addition to BNIP3L, dysregulation of five other NEMGs in the clinical HCC cohort was validated. The correlation analysis in GSE14520 and HCC clinical cohort showed a positive correlation between prognosis score and the size and number of tumors. Conclusion ·A new prognostic model that combines 6-NEMG risk characteristics with TNM staging for predicting OS in HCC patients was constructed and validated. This model may help improve the prognosis prediction of HCC patients.

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    Exploration of the relationship between nicotinamide metabolism-related genes and osteoarthritis
    DENG Qingsong, ZHANG Changqing, TAO Shicong
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (2): 145-160.   DOI: 10.3969/j.issn.1674-8115.2024.02.001
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    Objective ·To explore the relationship between osteoarthritis and nicotinamide metabolism-related genes using bioinformatics analysis, and identify key genes with diagnostic value and therapeutic potential. Methods ·By using "Osteoarthritis" as a search term, GSE12021, GSE55235, and GSE55457 were obtained from the GEO database, with GSE55457 being used as the validation set. After removing batch effects from the GSE12021 and GSE55235 datasets, the standardized combined dataset was obtained and used as the training dataset. Differentially expressed genes (DEGs) were identified from the training dataset. All nicotinamide metabolism-related genes (NMRGs) were obtained from the GeneCards and MSigDB databases. The intersection of DEGs and NMRGs was taken to obtain nicotinamide metabolism-related differentially expressed genes (NMRDEGs). Gene set enrichment analysis (GSEA) was performed on the training dataset, while gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were performed on NMRDEGs. Key genes were selected by using least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM) analysis in NMRDEGs to build an osteoarthritis diagnosis model which was validated by using the GSE55457 dataset. Single sample gene set enrichment analysis (ssGSEA) was used to analyze the immune cell infiltration type. Interactions networks and drug molecule predictions were obtained for these key genes' mRNA with the DGIdb, ENCORI, and CHIPBase databases. siRNA was used to knock down the key genes in chondrocytes, and then real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of chondrogenesis-related genes. Results ·Seven NMRDEGs, including NAMPT, TIPARP, were discovered. GO and KEGG analysis enriched some signaling pathways, such as nuclear factor-κB signaling pathway and positive regulation of interleukin-1-mediated signaling pathway. GSEA enriched pathways such as Hif1 Tfpathway and syndecan 1 pathway. Key genes NPAS2, TIPARP, and NAMPT were identified through LASSO and SVM analysis, and used to construct an osteoarthritis diagnostic model. The validated results showed that the diagnostic model had high accuracy. Immune infiltration analysis results obtained by ssGSEA showed significant differences (all P<0.05) in 15 types of immune cells, including macrophages. Seven potential small molecules targeting key genes were identified, along with 19 miRNAs with the sum of upstream and downstream >10, 19 transcription factors with upstream and downstream >7, and 27 RNA binding proteins with clusterNum >19. The results of RT-qPCR showed that knocking down key genes reduced the expression of chondrogenesis-related genes. Conclusion ·Through bioinformatics analysis, key genes related to nicotinamide metabolism, NPAS2, TIPARP, and NAMPT, are discovered, and an osteoarthritis diagnostic model is constructed.

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    Progress in diagnosis and treatment of strabismus based on artificial intelligence technology
    GUO Yonglin, CHEN Moxin, LIU Zheyuan, LI Yifei, WANG Ziqi, SHU Qin, LI Lin
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (3): 393-398.   DOI: 10.3969/j.issn.1674-8115.2024.03.013
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    Strabismus, misalignment of the eyes arising from central nervous system dysregulation and extraocular muscles imbalance, commonly manifests in childhood, leading to amblyopia, binocular vision dysfunction, torticollis and other developmental and psychological disorders. This exerts a negative impact on individuals, families and society. Timely diagnosis and intervention are crucial to prevent permanent damage to vision and stereopsis. Presently, strabismus diagnosis is reliant on the ophthalmologists′ evaluations which results in a lack of efficiency and coverage. However, routine school screening proves inadequate in assessing strabismus degree with low accuracy. Therefore, how to improve the efficiency of strabismus screening is an issue of great importance. This paper delves into the present landscape of strabismus diagnosis and treatment, considering both local and global research advancements. It focuses on the evolution of artificial intelligence technology, illuminating the utilization of artificial intelligence models and algorithms in strabismus. By pinpointing and exploring their strengths and limitations, it offers valuable insights, paving the way for future investigations into artificial intelligence-assisted strabismus diagnosis and treatment.

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    Construction of an mRNA vaccine encoding hemagglutinin of influenza A H1N1 virus and investigation on booster immunization strategy
    SHEN Haiqian, YU Kangying, CHEN Yingying, JI Ping, WANG Ying
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (11): 1374-1383.   DOI: 10.3969/j.issn.1674-8115.2023.11.005
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    Objective ·To construct an mRNA vaccine encoding hemagglutinin (HA) of influenza A H1N1 virus, and explore the protective effects of different booster vaccination strategies. Methods ·Firefly luciferase (Fluc) was used as the reporter gene to construct Fluc mRNA vaccine enveloped in lipid nanoparticles (LNP). The in vivo expression of Fluc mRNA-LNP after intramuscular injection was determined by live imaging assay in mice. Furthermore, M15-HA mRNA-LNP derived from H1N1 subtype (A/Michigan/45/2015) was constructed. Mice were immunized with 20, 10, 5, or 1 μg doses of M15-HA mRNA-LNP twice (with an interval of 3 weeks) through intramuscular injection. Serum antibody titers were measured by enzyme-linked immunosorbent assay (ELISA) at 2 weeks and 4 weeks after the second immunization, and functional antibody levels were detected by hemagglutination inhibition test. The third booster vaccination was performed 40 d after the second immunization in 1 μg dose group with 1 μg M15-HA mRNA-LNP or 10 μg HA subunit vaccine. The levels of specific antibody and functional antibody were detected by ELISA and hemagglutination inhibition test, respectively 2 weeks and 4 weeks later. Results ·Live imaging assay showed that luciferase activity could be detected in mice 1 d after injection of Fluc mRNA-LNP. At 2 weeks and 4 weeks after the second immunization of M15-HA mRNA-LNP, HA-specific antibodies were significantly higher than those before the immunization in all vaccination groups at different doses (P=0.000). The hemagglutination inhibition test showed that the levels of functional antibodies in the 20 μg dose and 10 μg dose groups were significantly higher than those in the PBS control group (P<0.05). After 1 μg dose group mice were immunized with HA protein or M15-HA mRNA-LNP, higher levels of HA-specific antibody and functional antibody were induced and maintained for a long time. There was no significant difference between the two different booster immunization strategies. Conclusion ·M15-HA mRNA-LNP vaccine is constructed with immunogenicity and antibody neutralization activity. Low-dose mRNA priming vaccination followed by both homologous mRNA vaccine and heterologous protein subunit vaccine booster vaccination can induce stronger immune recall responses.

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    Fabrication of self-healing injectable hyaluronic acid hydrogel for promoting angiogenesis
    YANG Shu, CUI Wenguo, WEI Jie, CAI Zhengwei
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (12): 1480-1492.   DOI: 10.3969/j.issn.1674-8115.2023.12.003
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    Objective ·To construct a self-healing injectable hyaluronic acid (HA)-based hydrogel (HAPD-Cu) and investigate the effects of different copper ions on the properties of the hydrogel and its vasogenic efficacy to evaluate its feasibility for clinical wound healing. Methods ·Bisphosphonated hyaluronic acid (HAPD) was prepared via a blue-light mediated thiol-ene click reaction between thiolated hyaluronic acid (HASH) and acrylated bisphosphonate (Ac-PD) in the presence of photoinitiator 2959. Then, HAPD was further interacted with Cu2+ through metal coordination to prepare HAPD-Cu hydrogels with different Cu2+ concentrations, i.e. HAPD-Cu1, HAPD-Cu2, HAPD-Cu3 and HAPD-Cu4. The molecular structures of HASH, Ac-PD, HAPD and HAPD-Cu were verified with 1HNMR and FTIR. Microscopic morphology of HAPD-Cu was observed under SEM. The shear-thinning and self-healing properties of HAPD-Cu were verified by rheometer. The Cu2+ release from HAPD-Cu was determined with ICP. Live-dead staining and CCK-8 assay were applied to evaluate the biocompatibility of HAPD-Cu. The in vitro vasculogenic activity of HAPD-Cu was determined by a tubule-forming assay with human umbilical vein vascular endothelial cells and the in vivo vasculogenic activity of HAPD-Cu was assessed by CD31 tissue staining. A rat wound defect model was established in vitro to evaluate its actual repair effect. Results ·The preparation of the materials was demonstrated through chemical qualitative and quantitative analytical means. In vitro studies showed that all HAPD-Cu with a loose porous internal structure exhibited outstanding self-healing, injectability and degradability, with a one-week degradation cycle and abrupt release behavior, which can meet the needs of wound healing cycle. All HAPD-Cu showed good biocompatibility except HAPD-Cu4, due to its high Cu2+ concentrations. Moreover, its angiogenic effect in vitro or in vivo was enhanced with increasing Cu2+ concentrations within the permissible Cu2+ concentration range. In vitro wound model experiments also showed that the HAPD-Cu hydrogel significantly promoted wound healing compared with the control group. Conclusion ·HAPD-Cu hydrogel constructed via the metal coordination shows excellent shape plasticity, allowing the filling of defective sites in a minimally invasive form, and the release of Cu2+ greatly facilitates the establishment of early vascular networks, with giant potential for use in the repair of clinically irregular wounds.

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    Advances in drug therapy of diabetic retinopathy
    CHEN Minghao, LIU Peiyu, WANG Xuan, WU Yixiang, JIANG Yujin, ZHANG Chaoyang, ZHANG Jingfa
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (7): 822-829.   DOI: 10.3969/j.issn.1674-8115.2024.07.003
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    Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and has become one of the leading causes of blindness and visual impairment in diabetes patients. The pathogenesis of DR is multifaceted, involving inflammation, oxidative stress, neurovascular abnormalities, and other factors that present potential targets for disease management interventions. Currently, anti-vascular endothelial growth factor (VEGF) drugs serve as the primary treatment for advanced stages of DR when irreversible neurovascular damage and visual impairment have occurred. Additionally, some patients show poor or no response to anti-VEGF treatment. There is a lack of early intervention options for the initial phases of the disease. Therefore, there is an urgent need to develop novel local or systemic therapies based on the underlying mechanisms of DR to enable early prevention and treatment with the aim of preserving patients′ vision. Medications targeting various pathways including anti-inflammatory agents (corticosteroids and nonsteroidal anti-inflammatory drugs), neurotrophic and neuroprotective drugs, drugs modulating biochemical pathways, antioxidant phytochemicals, and gene therapy can complement each other in terms of therapeutic effects to benefit a larger number of individuals affected by DR. This article reviews previous research reports on the pathogenesis, drug treatment methods, and potential therapeutic targets associated with DR in order to provide guidance for clinical practice.

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    Clinicopathologic characteristics, gene mutation profile and prognostic analysis of thyroid diffuse large B-cell lymphoma
    DU Zhishan, WANG Yue, SHI Ziyang, SHI Qing, YI Hongmei, DONG Lei, WANG Li, CHENG Shu, XU Pengpeng, ZHAO Weili
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (1): 64-71.   DOI: 10.3969/j.issn.1674-8115.2024.01.007
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    Objective ·To analyze the clinicopathologic characteristics, gene mutation profile, and prognostic factors of thyroid diffuse large B-cell lymphoma (DLBCL). Methods ·From November 2003 to December 2021, a total of 66 patients with thyroid DLBCL [23 cases (34.8%) with primary thyroid DLBCL, and 43 cases (65.2%) with secondary thyroid DLBCL] admitted to Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data, survival and prognostic factors. Gene mutation profiles were evaluated by targeted sequencing (55 lymphoma-related genes) in 40 patients. Results ·Compared to primary thyroid DLBCL, secondary thyroid DLBCL had advanced ratio of Ann Arbor stage Ⅲ?Ⅳ (P=0.000), elevated serum lactate dehydrogenase (LDH) (P=0.043), number of affected extranodal involvement ≥2 (P=0.000), non-germinal center B cell (non-GCB) (P=0.030), BCL-2/MYC double expression (DE) (P=0.026), and international prognostic index (IPI) 3?5 -scores (P=0.000). The proportion of patients who underwent thyroid surgery (P=0.012) was lower than that of patients with primary thyroid DLBCL. The complete remission (CR) rate in primary thyroid DLBCL patients was higher than that in secondary thyroid DLBCL patients (P=0.039). Fifty-five patients (83%) received rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-based first-line regimen. The estimated 5-year progression free survival (PFS) rate of primary thyroid DLBCL patients was 95.0%, higher than the 49.7% of the secondary patients (P=0.010). Univariate analysis showed that Ann Arbor Ⅲ?Ⅳ (HR=4.411, 95%CI 1.373?14.170), elevated LDH (HR=5.500, 95%CI 1.519?19.911), non-GCB (HR=5.291, 95%CI 1.667?16.788), and DE (HR=6.178, 95%CI 1.813?21.058) were adverse prognostic factors of PFS in patients with thyroid DLBCL. Ann Arbor Ⅲ?Ⅳ (HR=7.088, 95%CI 0.827?60.717), elevated LDH (HR=6.982, 95%CI 0.809?60.266), and DE (HR=18.079, 95%CI 1.837?177.923) were adverse prognostic factors of overall survival (OS). Multivariate analysis showed that Ann Arbor Ⅲ?Ⅳ (HR=4.693, 95%CI 1.218?18.081) and elevated LDH (HR=5.058, 95%CI 1.166?21.941) were independent adverse prognostic factors of PFS in patients with thyroid DLBCL. Targeted sequencing data showed mutation frequency >20% in TET2 (n=14, 35%), KMT2D (n=13, 32%), TP53 (n=11, 28%), GNA13 (n=10, 25%), KMT2C (n=9, 22%), and TP53 were adverse prognostic factors of PFS in patients with thyroid DLBCL (P=0.000). Conclusion ·Patients with primary thyroid DLBCL have better PFS and OS than those with secondary thyroid DLBCL. Ann Arbor Ⅲ?Ⅳ, elevated LDH, non-GCB, and DE (MYC and BCL2) are adverse prognostic factors in thyroid DLBCL. TET2,KMT2D, TP53, GNA13, and KMT2C are commonly highly mutated genes in thyroid DLBCL, and the prognosis of patients with TP53 mutations is poor.

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