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    Research progress in the role and mechanism of lactylation in diseases
    GE Lingling, HUANG Hongjun, LUO Yan
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (3): 374-379.   DOI: 10.3969/j.issn.1674-8115.2023.03.014
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    Lactic acid is a product of cell respiration. After entering into cells, glucose is metabolized to pyruvate by glycolysis. When the oxygen supply is sufficient, pyruvate is converted to acetyl coenzyme A through pyruvate dehydrogenase in the mitochondrial matrix to participate in the tricarboxylic acid cycle and provide necessary energy for cells. Pyruvate is catalysed by lactate dehydrogenase in the cytoplasm to produce lactate while cells are grown under hypoxic conditions. Lactate not only provides energy for mitochondrial respiration, but also plays important roles in inflammatory responser, wound repair, memory formation and neuroprotection as well as tumor growth and metastasis and other pathophysiological processes through autocrine, paracrine, and endocrine forms, which affects the development and prognosis of diseases. Epigenetic modification regulates gene replication, transcription and translation by covalently adding or hydrolyzing functional groups on histones and DNA through related enzymes and affects the biological effects of cells. Histones are the major structural proteins of eukaryotic chromosomes. Their post-translational modifications, such as methylation and acetylation, affect their affinity with DNA, change chromatin structures, and are widely involved in regulation of gene expression. Recent studies have found that histones can undergo lactylation, which is a new epigenetic modification by adding lactate to lysine residues on histones. As the research deepens, numerous evidences reveal that lactylation also occurs on non-histone proteins. The discovery of lactylation has expanded our understanding of lactate functions in the pathogenesis of diseases. In this review, we summarize the roles and mechanisms of lactylation in tumor, inflammatory and neural system diseases, in order to provide new ideas for the research, diagnosis and treatment of these diseases.

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    New progress and prospects of blood glucose monitoring technology
    JIA Weiping
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1171-1175.   DOI: 10.3969/j.issn.1674-8115.2022.09.002
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    Glucose monitoring is an important part of diabetes management. For over a century, diabetes monitoring technology has developed from the initial urine glucose test, to the later blood glucose test, and finally to the current continuous glucose monitoring (CGM), which is evolving in a more convenient, accurate, minimally invasive, and even non-invasive direction. CGM refers to the technology that continuously measures glucose concentrations in the subcutaneous interstitial fluid by glucose sensors. It can detect hyperglycemia and hypoglycemia that are not easily recognized by traditional monitoring methods. Using the huge amounts of glucose data generated by CGM technology, diabetes management is expected to be more targeted, with glucose control more accurate. In this context, novel measure of glucose control represented by time in range (TIR) has been popularized, which can provide comprehensive information including hyperglycemia, hypoglycemia, and glucose fluctuation. Hence, the modern approach to glucose control should focus not only on glycosylated hemoglobin, but also pay attention to new metrics such as TIR. In the future, more mature, minimally invasive and even non-invasive glucose monitoring technologies that are comfortable, stable and highly accurate should be further developed to greatly improve the experience and enthusiasm of the patients in blood glucose monitoring. Meanwhile, closed-loop insulin infusion system should be further developed, to truly realize individualized and automated glucose control, as well as further improvement of glucose control in the patients with diabetes.

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    Progress in metabolism of the immune cells in tumor microenvironment
    LIN Jiayu, QIN Jiejie, JIANG Lingxi
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (8): 1122-1130.   DOI: 10.3969/j.issn.1674-8115.2022.08.018
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    Metabolic reprogramming refers to cells' mechanism to change their metabolic patterns in order to meet the increased energy demand caused by growth and proliferation. By way of metabolic reprogramming such as the Warburg effect, tumor cells gain rich energy to support their own survival, growth, and metastasis. The tumor microenvironment (TME) is the internal environment in which tumor cells survive, containing not only tumor cells, but also stromal cells, immune cells, and other components that are closely related to tumor cells. Meanwhile, tumor cells regulate intercellular function and signaling via secreting cytokines, metabolites, and other molecules and shape a commonly hypoxic, acidic, and nutrient-deprived TME which contributes the most to immune resistance. However, rapidly proliferating tumor cells compete for relatively scarce nutrients with immune cells, consequently, producing an immunosuppressive metabolism microenvironment. Under the influence of immunosuppressive TME, immune cells generate tolerance phenotype-related metabolic adaptations through metabolic reprogramming to satisfy their own needs and further perform anti-tumor or immunosuppressive roles. The response of immune cells to tumor cells mainly depends on respective unique metabolic pathways, which are related to the type and function of immune cells. Moreover, the functional properties of immune cells are directly associated with the immunotherapy effects. Regulating metabolic pathways of immune cells provides a great direction for cancer therapy. In this paper, the main metabolic pathways of immune cells in TME is described, the relationship between their metabolic characteristics and immune functions is summarized, and the mechanism of metabolic pathways underlying the functions of immune cells is further discussed, providing new insights for unveiling tumor immunosuppressive microenvironment and improving the efficacy of tumor immunotherapy.

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    Research progress of cytokines in treatment of osteoarthritis
    DONG Yushan, ZHANG Wenjie
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (11): 1627-1632.   DOI: 10.3969/j.issn.1674-8115.2022.11.016
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    Osteoarthritis (OA) is a common joint disease in clinic. OA mostly involves the load-bearing joints of the lower limbs, which is easy to cause joint deformity and affect the quality of life after the disease. At present, early treatment of OA focuses on symptomatic treatment and slowing down the wear of articular cartilage. Various cytokines play an important role in the development of OA. Among the interleukin (IL) family, IL-1β/6/8 are associated with the occurrence and progression of OA and are major inflammatory factors. IL-4/10 play a protective role in the joints as an anti-inflammatory component. Tumor necrosis factor-α is also a major component that promotes joint inflammation. In vitro and in vivo studies show that transforming growth factor-β,insulin-like growth factor, and fibroblast growth factor (FGF) can delay the progression of OA. By investigating the roles of the relevant cytokines, we can not only gain insight into the pathogenesis of OA, but also provide new ideas for the treatment of OA. Cytokines are expected to solve the dilemma of suboptimal efficacy of current traditional treatments for OA. At present, many beneficial research results are achieved in the field of cytokine application to the prevention and treatment of OA, and a part of them begins to enter clinical trials and applications. This review summarizes the research progress and partial mechanisms of several classes of cytokines with potential effects on OA.

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    Summary of clinical research of Pediococcus pentosaceus in treatment of infantile colic
    WU Shiyin, CAI Meiqin
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (11): 1633-1637.   DOI: 10.3969/j.issn.1674-8115.2022.11.017
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    Infantile colic is a common disease. Its etiology is not clear, which may be related to the imbalance of intestinal flora. Pediococcus pentosaceus is a probiotic of Pediococcus of Lactobacillaceae. It can enhance host immunity and improve the diversity of intestinal flora. This paper will introduce the characteristics of probiotics such as antibacterial capability, intestinal colonization ability and antibiotic sensitivity of Pediococcus pentosaceus, and the probiotic functions such as antioxidant, antiviral and immune regulation, and elaborate on the possible pathogenesis of infantile colic, the efficacy and potential mechanism of Pediococcus pentosaceus in the treatment of infantile colic, and the current situation of clinical research at home and abroad, in order to provide a scientific basis for Pediococcus pentosaceus in the treatment of infantile colic.

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    Construction and characterization of mice with conditional knockout of Stat3 gene in microglia
    ZHU Xiaochen, XIE Xinyi, ZHAO Xuri, XU Lina, HE Zhiyan, ZHOU Wei
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (6): 689-698.   DOI: 10.3969/j.issn.1674-8115.2023.06.005
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    Objective ·To construct mice with conditional knockout of Stat3 gene in microglia based on the Cre-Loxp system and validate their knockout efficiency. Methods ·Cx3cr1creERT2 and Stat3fl/fl genotypic mice were bred for conditional knockout mice (CKO) and Wild Type mice (WT). The mouse genotypes were determined by extracting DNA from mouse tissues through Polymerase Chain Reaction (PCR) combined with the amplification results of cre and flox primers. Stat3 knockdown was induced by intraperitoneal injection of tamoxifen in the CKO and WT mice at 6 weeks of age. The CKO mice (n=4) and WT mice (n=4) were randomly selected for the detection. After two weeks of observation, microglia cells were sorted out by Magnetic Activated Cell Sorting (MACS). Real-time PCR (RT-PCR) was used to detect gene knockout efficiency at the gene level. The expression of STAT3 in microglia was observed by brain immunofluorescence staining. The expression rate of STAT3 in microglia was detected by flow cytometry. The expression rate of STAT3 in macrophages of the spleen was detected by flow cytometry. The condition of neuronal cells was examined by Nissl staining. The condition of the microglia in the cortex and hippocampus was observed by brain immunofluorescence staining. The phenotype of the microglia was detected by flow cytometry. Results ·The CKO mice and WT mice were successfully bred. MACS boosted the proportion of microglia in brain cells from 10% to 85%. RT-PCR results showed that mRNA levels of Stat3 were down-regulated in microglia of CKO mice, compared with the WT mice (P=0.001). The relative mRNA expression of Stat3 in microglia of the CKO mice was 0.331 7±0.041 4. Immunofluorescence staining of brain tissues showed that the fluorescence intensity of STAT3 in microglia of the CKO mice was weaker than that of the WT mice. Flow cytometry of brain tissues showed that the STAT3-positive cells in microglia of the WT mice was (85.30±5.69)% and the CKO mice was (39.70±3.88)%. STAT3 expression was decreased in microglia of the CKO mice (P=0.001). Flow cytometry of spleen tissues showed that there was no statistical difference in the percentage of STAT3-positive cells in splenic macrophages between the CKO and WT mice (P>0.05). Nissl staining showed that there were no significant differences between the neuronal cells of the CKO mice and WT mice. Immunofluorescencestaining of brain tissues showed that there was no significant difference in the shape of microglia between the CKO mice and WT mice. Flow cytometry showed that the phenotype of microglia in the CKO mice was not remarkably different from that of the WT mice. Conclusion ·We successfully construct the STAT3 gene conditional knockout mice from microglia, which provides the foundation for subsequent related studies.

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    Aptamer-drug conjugates (ApDCs): new trend for cancer precision therapy
    HAN Yongqi, HAN Da, XIA Qian, JI Dingkun, TAN Weihong
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1176-1181.   DOI: 10.3969/j.issn.1674-8115.2022.09.003
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    Cancer is a worldwide medical issue that seriously threatens human health. Precision molecular medicine provides a new strategy for cancer theranostics. As excellent targeting recognition molecules and drug delivery platforms, aptamers and aptamer drug-conjugates (ApDCs) have provided a series of useful molecular tools for cancer precision therapy. In this paper, the properties and the selection techniques of aptamers, the construction of ApDCs and their applications to clinical tumor-targeting therapy are reviewed. Additionally, the challenges and perspective of ApDCs in precision molecular medicine for cancers are presented. This review may provide new horizons for molecular-targeted anti-tumor drugs in the therapy of clinical malignant tumors.

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    Research progress of clinical application of ASPECT score in acute ischemic stroke
    WEI Xuemin, GAO Chengjin
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (7): 919-924.   DOI: 10.3969/j.issn.1674-8115.2022.07.011
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    Acute ischemic stroke (AIS) is characterized by a high rate of disability and mortality, and rapid and accurate diagnosis and appropriate treatment are the keys. The severity of AIS patients depends on the location of early ischemic changes (EIC) in the brain tissue and the size of the lesion, so it is necessary to evaluate the patients' conditions by combining with imaging. The Alberta stroke program early CT score (ASPECT score) is a 10-point imaging score system that evaluates the EIC in the middle cerebral artery supplying region of the stroke patients in an accurate and simple way by quantifying the severity in terms of the imaging to help clinicians make medical decisions. ASPECT score is not only widely used to predict the prognosis of stroke patients, but also to identify the population benefiting from the endovascular therapy and evaluate the risk of endovascular therapy for patients. ASPECT score combined with multimodal imaging has also been used to predict ischemic core volumes and the prognosis. In recent years, with the development of artificial intelligence, automatic ASPECT scoring methods based on machine learning have emerged. This paper reviews ASPECT scoring methods, its value in the treatment and the assessment of prognosis in AIS, multimodal ASPECT scoring, and the application of automated ASPECT scoring combined with artificial intelligence.

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    Anatomical structure of laminar specific subtypes of medial prefrontal cortex-basolateral amygdala projection neurons
    HE Luyao, HUANG Dongping, SHAO Mengmeng, ZHANG Kai, REN Baihui, KONG Qingdan, XU Tianle, LÜ Jiangteng
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1216-1224.   DOI: 10.3969/j.issn.1674-8115.2022.09.008
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    Objective ·To dissect the fine anatomical structure of medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) projection neurons based on regional and laminar specificity in the cortex in mice. Methods ·The retrograde tracer of adeno-associated viral (AAV) vectors were injected into BLA of C57BL/6 mice. Twenty-one days after the injection, the mice were sacrificed and the brains were harvested. The coronal sections containing mPFC were prepared by using a cryostat microtome. The images were taken by fluorescence microscopy. Then the representative brain slices containing mPFC were selected and the distribution of virus-labeled cell bodies in different subregions of mPFC was analyzed. By using transgenic mouse lines (Tbr2-CreER::LSL-Flp mice and Rbp4-Cre mice) with Flp- or Cre-dependent AAV, layer 2 (L2) and layer 5 (L5) projection neurons in mPFC and their axons in BLA were marked, respectively. Twenty-eight days after the injection, the mice were sacrificed and the brains were also harvested. Coronal sections of the BLA were collected. The brain slices were imaged by fluorescence microscopy after immunofluorescence staining. By measuring the fluorescence intensity of projecting axons in different regions within BLA, the spatial distributions of the axons in BLA of mPFC L2 and L5 projection neurons were compared. Results ·Through fluorescence microscopy and quantitative analysis, it was found that the cell bodies of BLA projection neurons were mainly located at L2 and L5 in the dorsal mPFC (dmPFC) which contains anterior cingulate cortex and prelimbic cortex. However, the distribution of BLA projection neurons in the ventral mPFC (vmPFC) including medial orbital cortex and infralimbic cortex did not exhibit the similar distribution. When studying the axonal distribution of dmPFC projection neurons in two layers, it was found that the axons of L2 projection neurons dispersed in the BLA, while the axons of L5 projection neurons were mainly located in the dorsal region of BLA. Conclusion ·The cell body distribution of mPFC-BLA projection neurons shows regional specificity and laminar specificity. The axon projections initiated from different layers of dmPFC also exhibit regional specificity in BLA.

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    Progress in mechanism of transcranial direct current stimulation
    WANG Yang, CHENG Jiayue, WANG Zhen
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (7): 952-957.   DOI: 10.3969/j.issn.1674-8115.2022.07.016
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    Transcranial direct current stimulation (tDCS), as a non-invasive brain stimulation technique,is widely used in improving brain function and behavior. Growing evidence shows its broad therapeutic promise in neuropsychiatric disorders. However, there is a lot of uncertainty about how this approach works. This review focuses on the current research on the mechanism of tDCS. The immediate effect of tDCS is mainly reflected in the change of membrane potential of neurons, while the aftereffect of tDCS can cause dynamic changes in Ca2+ concentration, regulate the release and distribution of various neurotransmitters, directly or indirectly alter synaptic plasticity, and play an important role in the regulation of synaptic metaplasticity. In addition to regional effects, tDCS results in widespread network-level changes across the brain. This review probes into the predicament of current research and puts forward some unsolved problems.

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    Transcriptomic analysis of metabolic characteristics of the immune cells in systemic lupus erythematosus patients
    HAN Xiaxia, JIANG Yang, GU Shuangshuang, DAI Dai, SHEN Nan
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1197-1207.   DOI: 10.3969/j.issn.1674-8115.2022.09.006
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    Objective ·To study the metabolic pathway activity level of the immune cell subsets in the patients with systemic lupus erythematosus (SLE) by bioinformatics analysis. Methods ·The matrix expression data of PBMCs collected from SLE patients and healthy controls were downloaded from Gene Expression Omnibus (GEO) Datasets, as well as the transcriptome data of T cell and B cell subsets from SLE patients and healthy controls. The differentially-expressed genes (DEGs) were identified in the standardized sequence data. Pathway enrichment analysis of DEGs was performed by online Enrichr tools, and the common up-regulated pathways were determined by comparative analysis. Gene set enrichment analysis (GSEA) was used to identify pathways that were enriched in the experiment processed with the whole gene expression matrix. RNA-seq data from PBMCs samples of SLE patients and healthy controls were used to characterize the immune cell composition. The targeted pathway was annotated with gene expression. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) technique was performed to detect the chromatin accessibility of glycolysis-related genes in SLE patients and healthy controls. Results ·① Venn diagram depicted 139 common upregulated pathways in GSE169080, GSE144390 and GSE139350 data sets, and GSEA results showed that multiple classical metabolic pathways, including glycolysis, oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO), were up-regulated in SLE patients. ② Immune cell composition analysis of PBMCs showed that the proportions of T cells, B cells and NK cells were higher in SLE patients, and the expression of genes encoding multiple enzymes of metabolic pathway in T cells and B cells were higher than those in healthy controls. ③ Compared to healthy controls, the intensity of ATAC-seq signal was significantly enhanced at transcriptional regulatory sites of SLC2A3, PKM and LDHA in peripheral B cells from SLE patients. ④ GSEA results and visualization analysis of metabolic pathways of SLE B cell subsets showed that the memory B cells and plasmablasts displayed a higher metabolic state than na?ve B cells. Conclusion ·Multiple metabolic pathways are altered in SLE patients and the metabolic level of effector B cells is higher than na?ve B cells in SLE patients.

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    Adaptation and adaptability investigation of Improving Parents as Communication Teachers (ImPACT) program for autism spectrum disorder
    WU Danping, REN Fang, SHEN Lixiao, XUE Minbo, WANG Junli, LI Fei, XU Mingyu
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1239-1246.   DOI: 10.3969/j.issn.1674-8115.2022.09.010
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    Objective ·To adapt and investigate the adaptability of the parent-mediated intervention program “Improving Parents as Communication Teachers (ImPACT)” for autism spectrum disorder (ASD) under the background of Chinese culture. Methods ·There were 4 procedures of adaptation: information gathering, preliminary adaptation design, preliminary adaptation test, and adaptation refinement. In the information collection part, 8 experts (6 pediatrics and 2 psychotherapists) were invited to have 6 focus group discussions, and preliminary adaptation was made in the aspects of language, intervention form, program structure, cultural customs, etc., according to expert suggestions. Then 16 ASD parents were recruited to participate in the ImPACT program after the preliminary adaptation. Adaptative investigation of ImPACT was carried out simultaneously in the preliminary adaptation test stage. Results ·The adaptability investigation results of preliminary adaptation program showed that all parents believed that “the pace of the program was well controlled, and they could follow the rhythm of the therapist to complete the learning of skills”. Among these parents, 66.67% believed that “the course was fully prepared, the explanation was clear, and the goal was clear”, and 33.34% believed that “rich examples were provided to help understand intervention skills” in the learning process. As for the feedback of skill practice homework after each session, 83.33% of parents believed that “homework could be easily completed, and help them better learn intervention skills”, and all parents believed that “comments were timely, and the content of comments could help them answer questions and solve doubts”. The difficulties in mastering, i.e., the 7th session (shaping the interaction), the 6th session (teaching new imitation and play skills), and the 5th session (teaching new communication skills) were further adjusted after discussion with the expert group to make the final plan more convenient for parents to master. Conclusion ·After adaptation and adaptability investigation, a parent-mediated intervention program ImPACT which is more suitable for the families of ASD children in China has been formed.

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    Research progress in the role of Akkermansia muciniphila in gut-related diseases
    JIANG Yi, JIANG Ping, ZHANG Mingming, FANG Jingyuan
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1490-1497.   DOI: 10.3969/j.issn.1674-8115.2022.10.016
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    Akkermansia muciniphila (A. muciniphila) is one of the normal gut symbionts using mucin as the sole source of carbon and nitrogen elements to maintain colonization and growth. Intestinal homeostasis is crucial for maintaining physiological functions. Intestinal dysfunction is closely related to the occurrence and development of metabolic diseases, immune diseases, infectious diseases and tumors. Gut microbiota is a key factor that influences the intestinal health. As a member of the gut microbes, A. muciniphila plays a convincing role in intestinal inflammation, intestinal tumor and other intestinal disorders involving diseases such as liver diseases and metabolic diseases. The mechanism is under exploration and revealed gradually. Hence, A. muciniphila is considered to be a promising candidate of probiotics. The characteristics of A. muciniphila, its distribution in the gut, its relationship with gut-related diseases and the mechanism are reviewed.

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    Advances in postoperative adjuvant targeted therapy for patients with stage ⅠB-ⅢA non-small cell lung cancer
    LI Ruonan, CHEN Xiaoke, XU Yuanyuan, TAN Qiang
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (11): 1612-1619.   DOI: 10.3969/j.issn.1674-8115.2022.11.014
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    As the cancer with the highest mortality rate in the world, the treatment of lung cancer has always been a difficult problem for a wide range of patients and physicians alike. Based on the degree of differentiation, morphological features and biological characteristics, lung cancer can be divided into small cell lung cancer and non-small cell lung cancer (NSCLC). The incidence of NSCLC accounts for 80%?85%. Clinically, the treatment options of NSCLC include surgery, chemotherapy, radiotherapy, targeted drug therapy, immunotherapy, etc. For the patients with stage ⅠB?ⅢA NSCLC, in addition to the first choice of surgical treatment, postoperative adjuvant therapy is applied to reduce tumor recurrence and metastasis. Studies have shown that targeted drugs are efficient and safe in the adjuvant therapy for NSCLC patients, and the most attention has been given to agents that target mutations in the epidermal growth factor receptor (EGFR) gene, such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). At present, three generations of EGFR TKIs have been approved for clinical use. Among them, the first generation EGFR-TKIs are dominant in the research and application of adjuvant therapy. For example, erlotinib and gefitinib can prolong the disease-free survival (DFS) and overall survival (OS) of patients after surgery, and icotinib has been approved for postoperative adjuvant therapy in China because of its obvious improvement of patients' DFS. Compared with the placebo, the third generation EGFR-TKIs drug osimertinib demonstrated a more significant DFS advantage in the ADAURA trial, decreased tumor recurrence in central nervous system and brought greater benefits in DFS to patients previously treated with standard chemotherapy regime. Osimertinib or chemotherapy combined with osimertinib has therefore become the standard of care for the patients with postoperative adjuvant therapy of stage ⅠB?ⅢA NSCLC. As the third generation EGFR-TKIs new drugs, the clinical trials of almonertinib and furmonertinib for postoperative adjuvant therapy are also underway. This article systematically summarizes the structure of EGFR, the types and detection methods of EGFR gene mutations, introduces the treatment strategies of clinical use of EGFR-TKIs, and discusses the problems that may be encountered in the clinical use of EGFR-TKIs.

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    Renewal of esophageal and gastric macrophages by circulating monocytes
    ZHU Yiwen, YU Qing, WU Xinrui, LU Jie, CHEN Zihao, GINHOUX Florent, SU Bing, LIU Zhaoyuan
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1208-1215.   DOI: 10.3969/j.issn.1674-8115.2022.09.007
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    Objective ·To reveal the renewal kinetics of esophageal and gastric macrophages by circulating monocytes. Methods ·The monocytes of the Ms4a3Cre -RosaTdT fate mapping model mice carry an irreversible tdTomato red fluorescent marker. The macrophages derived from these monocytes will also carry red fluorescence, distinguishing them from the embryonic-derived macrophages. The contribution of monocytes to esophageal and gastric macrophages was determined by detecting the number and the proportion of red fluorescence labeling in the ionized calcium-binding adapter molecule 1 (IBA1) positive macrophages in the esophagus and stomach from Ms4a3Cre -RosaTdT mice of different ages (2 weeks, 8 weeks and 15 months of age) by immunofluorescence imaging. Results ·In the esophagus and stomach of 2-week-old Ms4a3Cre -RosaTdT mice, most macrophages were tdTomato negative, indicating that the esophageal macrophages and gastric macrophages of young mice were mainly embryonic derived. In 8-week-old adult mice, many tdTomato positive monocyte-derived macrophages could be detected in the stomach. In 15-month-old mice, most of the esophageal and gastric macrophages were tdTomato positive, indicating that the esophagus and stomach macrophages of the old mice were mainly produced by monocytes. Conclusion ·In juvenile mice, esophageal and gastric macrophages are mainly embryonic-derived macrophages, while with age, monocyte-derived macrophages gradually replace tissue-resident macrophages in the esophagus and stomach. Esophageal and gastric macrophages in aged mice are mainly derived from circulating monocytes. Thus, the macrophage pool in the esophagus and stomach of mice consists of embryonic- and mononuclear-derived cells with their proportions changing with age.

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    Immune inhibitory receptor LILRB2 enhances SARS-CoV-2 spike protein-mediated immune inflammation
    YANG Wenqian, CHEN Chiqi, ZHAO Lu, CAO Liyuan, XIA Yiqiu, LU Zhigang, ZHENG Junke
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1188-1196.   DOI: 10.3969/j.issn.1674-8115.2022.09.005
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    Objective ·To explore the possible roles of immune inhibitory receptor leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) in the immune inflammation after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and provide a potential therapeutic way for the coronavirus disease 2019 (COVID-19). Methods ·The supernatants containing the extracellular domain of spike protein (S-ECD) were collected, and the detection of the protein expression and activity in the conditional medium by Western blotting and flow cytometric analysis was followed by. The binding of S-ECD with LILRB2 was measured by co-immunoprecipitation and flow cytometric analysis. The mRNA expression levels of several inflammation genes in a human mononuclear cell line (THP1) or peripheral blood mononuclear cells (PBMC) were measured after spike protein stimulation for 24 h by quantitative RT-PCR. The protein levels of interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the conditional medium were examined by enzyme-linked immunosorbent assay (ELISA). The siLILRB2 was transferred into CD33+ myeloid cells purified from human peripheral blood with Lipofectamine 3000 reagents. The knockdown efficiency was detected 24 h after transfection by flow cytometric analysis. The difference in the protein levels of IL-6 between the control cells and LILRB2-knocked-down cells after spike protein treatment was evaluated by ELISA. Results ·The study established a transfection system with 293T cells by which the SARS-CoV-2 S-ECD could be secreted to supernatants with normal biological activities. The interaction and the binding of spike protein with LILRB2 were evaluated by a co-immunoprecipitation assay and flow cytometric analysis, respectively. The mRNA expression levels of IL-6, IL-8, arginase 1 and IL-2 in THP1 cells were significantly up-regulated 24 h after spike protein treatment compared to the control cells (all P<0.05). Consistently, the mRNA levels of IL-6, transforming growth factor-β (TGF-β), IL-8, IL-10 and IL-1β in PBMC were notably increased after spike protein stimulation (all P<0.05). In addition, spike protein could also induce the release of IL-6 and IL-1β in PBMC as measured by ELISA (all P<0.05). More importantly, spike protein was able to increase the secretion of IL-1β and IL-6 by CD33+ myeloid cells 24 h after treatment (both P<0.05). LILRB2-overexpressing THP1 cells produced more IL-6 24 h after treatment with spike protein than the control cells (P<0.05). Two siRNAs could efficiently down-regulate the expression of LILRB2 in CD33+ cells as evaluated by flow cytometric analysis. Consistently, spike protein had no effect on the IL-6 secretion to supernatant from LILRB2-knockdown CD33+ myeloid cells. Conclusion ·SARS-CoV-2 can induce cytokine release syndrome by inflammatory factors, such as IL-6 and IL-1β, released by myeloid cells through spike protein binding to LILRB2.

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    MicroRNA-30b-5p inhibits autophagy in ovarian granulosa cells in polycystic ovary syndrome rats by targeting Atg5
    WANG Xuemin, WANG Yanan, NIU Aiqin, YE Ying, LI Fei
    Journal of Shanghai Jiao Tong University (Medical Science)   
    Online available: 18 January 2023

    Comparison of the root coverage and esthetic outcomes of 3 different techniques for gingival recession
    SUN Wentao, SUN Mengjun, XIE Yufeng, SHU Rong
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (11): 1550-1556.   DOI: 10.3969/j.issn.1674-8115.2022.11.005
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    Objective ·To evaluate the outcomes of connective tissue graft (CTG) combined with 3 different techniques for gingiva recession (GR) including envelope technique, tunnel technique (TUN) and vestibular incision subperiosteal tunnel access (VISTA), and analyze the differences of root coverage and esthetic outcomes of the 3 techniques. Methods ·A total of 87 patients who visited the Department of Periodontology, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from January 2020 to December 2021 with a total of 324 GRs were enrolled in this study. All GRs were treated with one of the 3 techniques. The patients′ periodontal conditions were examined at baseline and 6 months after surgery. The root coverage esthetic score (RES) and mucosal scarring index (MSI) were evaluated by 2 periodontists 6 months after surgery. The differences of keratinized gingiva (KG) and GR at baseline and 6 months after surgery were compared by using t-test. Analysis of variance was used to compare the differences of percentage of root coverage (PRC), RES and MSI of different techniques, the same technique in different regions, and different techniques in each region. Results ·In this study, KG increased by (1.49±1.36) mm, and there was a significant difference between each technique (P=0.002). GR decreased by (2.37±1.37) mm, and there was a significant difference between each technique (P=0.000). The mean PRC was (87.7±27.1)%, which was significantly different between each technique (P=0.003). The percentage of complete root coverage (PCRC) was 74.0%, and there was significant difference among the 3 techniques (P=0.000). There were significant differences in RES in different regions between envelope+CTG and VISTA+CTG (Penvelope=0.003, PVISTA=0.000). There was a significant difference in MSI of different regions in VISTA+CTG (P=0.000). Among the 3 techniques, only PRC had differences in the lower anterior teeth (P=0.011); there was a significant difference in RES between lower anterior teeth and lower posterior teeth (PLA=0.001,PLP=0.034), the RES of lower anterior teeth treated with TUN+CTG was higher, and the RES of lower posterior teeth treated with TUN+CTG and VISTA+CTG was higher; there were significant differences in MSI in each region (PUA=0.011, PUP=0.000, PLA=0.003, PLA=0.001). Conclusion ·All the 3 techniques are capable of reducing GR and widening KG. The root coverage and esthetic outcomes of TUN+CTG are superior to the other 2 techniques if the operator′s experience is not considered.

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    Reflection and exploration of digital chronic disease management based on the proactive health index
    GAO Xiang, LI Xiaoguang, ZHOU Liang, WANG Hui
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (2): 137-142.   DOI: 10.3969/j.issn.1674-8115.2023.02.001
    Abstract559)   HTML55)    PDF(pc) (1672KB)(608)       Save

    The disease burden caused by chronic non-communicable diseases continues to grow, with profound implications for public health and socio-economic development. The traditional health management of chronic diseases lacks diagnostic criteria and reasonable intervention time, and the bottleneck of the lack of residents' initiative is increasingly prominent. The construction of proactive health index (PHI) is expected to be an effective means to improve the health management of chronic diseases. As the world enters a critical period of digital transformation, China's health strategy has made clear that technological innovation and information technology should play a leading role in maintaining people's health, and digital health brings strategic opportunities for the development of chronic disease health management. In the context of the development of digital chronic disease prevention and control, this study analyzes the main bottlenecks existing in China's chronic disease health management, clarifies the importance of establishing diagnostic criteria for chronic disease health management, proposes the concept of PHI, and introduces the construction of PHI to solve the key problems of chronic disease health management. The application scenarios of PHI are deployed and prospected from the government side, the family physician side and the public side, in order to provide ideas for improving residents' health management initiative and enhancing the effectiveness of chronic disease health management.

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    Mediating effects of neuroticism and immature defense on relationship between childhood trauma and obsessive-compulsive symptoms in patients with obsessive-compulsive disorder
    ZHAO Qing, GU Wenjie, WANG Zhen
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1315-1322.   DOI: 10.3969/j.issn.1674-8115.2022.09.019
    Abstract546)   HTML46)    PDF(pc) (1913KB)(275)       Save

    Objective ·To explore the characteristics of childhood trauma, personality traits and defense mechanism in the patients with obsessive-compulsive disorder (OCD), and investigate the mediating effects of personality traits and defense style on the relationship between childhood trauma and obsessive-compulsive symptoms in the OCD patients. Methods ·Totally 113 patients with OCD who met the criteria of Diagnostic and Statistical Manual of Mental Disorders-5 (DMS-5), and 66 age- and gender-matched health controls with similar education level distribution were selected. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to evaluate the severity of obsessive-compulsive symptoms. Childhood Trauma Questionnaire (CTQ) was used to evaluate the childhood trauma experience. NEO Five-Factor Inventory (NEO-FFI) was used to measure the personality traits. Defense Style Questionnaire (DSQ) was used to evaluate the defense style. The correlations among childhood experience, obsessive-compulsive symptoms, personality traits and defense style as well as mediating role of personality traits and defense style between childhood trauma and obsessive-compulsive symptoms were analyzed. Results ·Compared with the health controls, the OCD patients showed higher scores of emotional abuse [8 (5, 25) points vs 6 (5, 22) points, P<0.05] and immature defense [(4.65±1.01) points vs (3.60±0.99) points, P<0.05]. In the OCD patients, the scores of emotional abuse (r=0.211, P<0.05) and immature defense (r=0.274, P<0.05) were positively correlated with the total scores of Y-BOCS, and the neuroticism scores of NEO-FFI were positively correlated with the total scores of Y-BOCS (r=0.468, P<0.05). The pathway analysis showed the indirect effect from emotional abuse to Y-BOCS via immature defense was 0.088 (95%CI 0.003?0.173, P<0.05). The immature defense played a completely mediated role, and indirect effect from emotional abuse to immature defense via neuroticism was 0.117 (95%CI 0.014?0.219, P<0.05). Conclusion ·Compared with healthy people, OCD patients have experienced more emotional and physical childhood trauma, and have abnormal personality traits of neuroticism, extraversion and conscientiousness. They tend to use immature defense mechanisms. The emotional abuse has an impact on immature defense via neuroticism, and finally affect the obsessive-compulsive symptoms.

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