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SIRT2 regulates macrophage chemotaxis by de-modifying histone H4K8 lactylation SONG Wenting, TAO Yue, PAN Yi, MO Xi, CAO Qing Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (8): 1008-1016.   DOI: 10.3969/j.issn.1674-8115.2023.08.008 Abstract （573）   HTML （49）    PDF（pc） （4083KB）（390）       Knowledge map    Save Objective ·To explore the regulatory role of silent information regulator 2 (SIRT2) in modulating the immune phenotype of macrophages after infection by removing the lactylation at H4K8 site of histone and the corresponding mechanism. Methods ·Human THP-1 leukemia cells were induced by phorbol 12-myristate 13-acetate (PMA) and stimulated by lipopolysaccharide (LPS) to establish a macrophage infection model. Macrophages without LPS treatment (pTHP-1) were set as the control (CTRL) group, and macrophages with LPS treatment were set as the infected (LPS) group. Western blotting was used to detect the level of histone modification and SIRT2 protein in macrophages. RT-qPCR was used to detect the expression level of glycolytic key enzymes [phosphofructokinase liver type (PFKL), lactate dehydrogenase A (LDHA)] and modulators genes hypoxia inducible factor 1α (HIF-1α), and the expression level of Sirtuin genes and HDAC genes between the two groups. Transwell was used to detect the ability of macrophage chemotaxis. Lentivirus packaging and cell infection were used to construct SIRT2 overexpression cell line. The interaction analysis method of RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) was used to analyze the difference and pathway enrichment of the genes specifically bound to H4K8 lactylation (H4K8la). Results ·Compared to the CTRL group, macrophage glycolysis was upregulated and the level of H4K8la was significantly increased in the LPS group (P<0.05), while the level of lactylation in other sites remained unchanged. Among all known enzymes with deacetylation modification function, only SIRT2 showed a significant decrease after LPS treatment (P<0.05), and overexpression of SIRT2 could significantly inhibit the level of H4K8la modification, while the level of H4K8ac remained unchanged (P>0.05). The interactive analysis of ChIP-seq and RNA-seq revealed that chemotaxis-related genes were regulated by H4K8la, and macrophage chemotaxis ability significantly decreased after the overexpression of SIRT2 and downregulation of H4K8la (P<0.05). Conclusion ·SIRT2 can change the expression of target genes related to chemotaxis by removing H4K8la modification, thereby reducing the chemotaxis ability of macrophages. Targeting SIRT2 and H4K8la modification may help control inflammation mediated by macrophages. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （559）   HTML （21）    PDF（pc） （1837KB）（148）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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Construction of Shanghai Diabetes Clinical Database and real-world study XUE Yanbin, QI Jiying, ZHANG Zizheng, JING Renjie, SUN Wen, YAO Huayan, HE Ping, CUI Bin, NING Guang Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (9): 1145-1152.   DOI: 10.3969/j.issn.1674-8115.2023.09.008 Abstract （458）   HTML （20）    PDF（pc） （3298KB）（427）       Knowledge map    Save Objective ·To construct a clinical database of diabetes in Shanghai, mine the value of clinical data, and carry out real-world study. Methods ·The data were extracted from Shanghai Link Healthcare Database. All original clinical data have undergone standard processes such as desensitization, encryption, cleaning, standardization, information extraction and structuring, and clinical data were analyzed by the method of medical statistics or machine learning according to different research contents. Results ·The database has imported the clinical data of 150 million visits and treatment records of 2.12 million diabetic patients in 37 municipal hospitals over a ten-year period from 2013 to 2022. The overall analysis showed the basic characteristics and development trends of all aspects of diabetes disease in real-world settings, the potential risks of diabetes are discovered by constructing retrospective cohort, and the inherent patterns of the disease are revealed by using machine learning methods such as cluster analysis and network analysis. Conclusion ·The establishment of Shanghai Diabetes Clinical Database can not only summarize and show the clinical status of diabetes, but also obtain more scientific achievements with realistic clinical value by real-world clinical data study. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （431）   HTML （24）    PDF（pc） （1743KB）（134）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （418）   HTML （30）    PDF（pc） （2669KB）（255）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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Research progress on the neural circuit of pain emotion mediated by amygdala MA CUI, YE Yujuan, YAN Xingke Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (10): 1304-1310.   DOI: 10.3969/j.issn.1674-8115.2023.10.012 Abstract （392）   HTML （22）    PDF（pc） （1243KB）（259）       Knowledge map    Save The occurrence of pain emotion is closely related to the functional and structural changes of specific central nervous circuit. When pain is accompanied by depression, anxiety, pain aversion memory and other emotional states, it activates or inhibits different neural circuits. The amygdala (AMY) of the limbic system participates in the regulation of pain, anxiety, depression, aversive memory and other emotions, and has extensive connections with brain nuclei related to pain and emotion, jointly regulating pain, anxiety, depression, aversive memory and other responses. This article summarizes the main circuits related to pain emotions mediated by AMY. It is concluded that the neural circuits related to depression include central amygdala → parafascicular nucleus of thalamus (CeA GABA → PF Glu), dorsal raphe nucleus → central amygdala (DRN 5-HT → CeA SOM), central amygdala → ventrolateral periaqueductal gray (CeA GABA → vlPAG GABA). Nerve circuits related to anxiety include ventral tegmental area → central amygdala (VTA→CeADA), locus coeruleus → basolateral amygdala (LCNE→BLA). The neural circuit related to pain aversion memory is lateral parabrachial nucleus → central amygdala (lPBN CGRP→CeA CGRP). Among them, activating the CeA GABA→PF Glu circuit can lead to depression accompanied by pain, activating the CeA GABA→vlPAG GABA circuit can alleviate pain sensitivity caused by depression, and activating the DRN 5-HT→CeA SOM circuit can alleviate pain perception and depressive emotions; activating the VTA→CeA DA loop can alleviate pain sensitivity and anxiety like behavior, inhibiting LC NE→BLA loop can alleviate anxiety caused by pain; activating the lPBN CGRP→CeA CGRP loop can generate pain aversion memory. Reference | Related Articles | Metrics

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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 Abstract （369）   HTML （29）    PDF（pc） （1399KB）（269）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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Review of role of fatty acid binding protein -4 in obesity -associated tumors WU Ruifang, FENG Ming, MENG Jian Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (10): 1311-1316.   DOI: 10.3969/j.issn.1674-8115.2023.10.013 Abstract （342）   HTML （25）    PDF（pc） （1265KB）（212）       Knowledge map    Save Obesity is one of the major factors threatening human health. Excessive fat accumulation not only has detrimental effects on human metabolism and cardiovascular system, but also is highly correlated to the incidence and mortality of various tumors. Fatty acid binding protein-4 (FABP4) is a small molecule protein mainly expressed in adipocytes and macrophages, and is responsible for participating in fatty acid transport and lipid response. It has been found that FABP4 levels are not only associated with body fat content, but also aberrantly expressed in various obesity-associated tumor cells and tumor microenvironment, which is closely related to obesity-associated carcinogenesis, metastasis, recurrence and patient prognosis. Since FABP4 expression varies in different types of obesity-associated tumors, suggesting a complex role of FABP4 in tumorigenesis. Based on this, this article reviews different roles of FABP4 in multiple obesity-associated tumors. Reference | Related Articles | Metrics

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Research progress in the role of gut microbiota in the pathogenesis and treatment of IgA nephropathy LI Junru, OUYANG Yan, XIE Jingyuan Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (8): 1044-1048.   DOI: 10.3969/j.issn.1674-8115.2023.08.013 Abstract （339）   HTML （37）    PDF（pc） （1212KB）（249）       Knowledge map    Save As the most common form of glomerulonephritis worldwide, IgA nephropathy (IgAN) is characterized by the diffuse deposition of immune complexes formed by glycosylation-deficient IgA1 (Gd-IgA1) and its specific antibodies (Gd-IgA1-IgG) in the glomerular mesangium. Although the mechanisms of Gd-IgA1 production are still unknown, there is accumulating evidence that Gd-IgA1-producing plasma cells are primarily derived from gut-associated lymphoid tissue, giving rise to the "gut-kidney axis" theory. Further research has discovered that gut microbiota may be involved in IgAN development and progression, and that several interventions to regulate gut microbiota, such as probiotics, fecal microbiota transplantation, and intestinal immunity modulation, may be used in the treatment of IgAN. In patients with IgAN, targeted-release formulation-budesonide has been shown to reduce urinary protein levels and delay kidney progression. Gut microbiota has promising potential as a preventive, diagnostic and therapeutic target for IgAN, and further research is needed. Reference | Related Articles | Metrics

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Expert consensus on postoperative rehabilitation nursing of patients with head and neck cancer GU Fen, WANG Yueping, YANG Wenyu, ZHAO Xiaomei, TANG Yan, SHEN Shukun, MAO Yan, ZHANG Jinfeng, WU Yifan, ZHANG Yuanyuan, YANG Yue, ZHANG Jianchun, YU Hong, WANG Lan, HAO Guihua, HOU Lili Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (10): 1289-1296.   DOI: 10.3969/j.issn.1674-8115.2023.10.010 Abstract （313）   HTML （23）    PDF（pc） （1380KB）（285）       Knowledge map    Save The location and size of tumors, treatment methods and prognosis of patients with head and neck cancer can seriously affect their oral function and neck activity, thereby affecting daily activities such as eating, speech and upper limb movement. Early rehabilitation after head and neck cancer surgery can accelerate functional recovery, alleviate discomfort symptoms, improve quality of life, and reduce unnecessary rehabilitation or treatment measures. Developing a clinical rehabilitation nursing pathway for head and neck cancer, forming personalized rehabilitation plans, and conducting early and effective nursing interventions are currently one of the key points of clinical work for patients with head and neck cancer. At present, domestic and foreign guidelines or consensus pays less attention to the impairments of speech function, chewing and swallowing function, neck and shoulder function etc., and lacks a systematic and comprehensive rehabilitation nursing guide or consensus to provide practical guidance for the care of patients with head and neck cancer. Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine organized relevant experts from Beijing, Shanghai, Sichuan, Shaanxi, Zhejiang and Anhui to draft Expert consensus on postoperative rehabilitation nursing of patients with head and neck cancer basing on previous literature and clinical nursing skills and experiences, of which the aim is to provide guidance for those patients in the aspects of oral care, nutritional support, flap donor area care, care after tracheotomy, chewing and swallowing rehabilitation, speech function rehabilitation, neck and shoulder function rehabilitation, restricted mouth opening rehabilitation, risk identification and prevention and follow-up. Reference | Related Articles | Metrics

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Study on the significance and mechanism of ASGR1 in hepatocellular carcinoma LI Qianyu, GUO Wenyun, QIAN Yifei, LI Songling, ZHU Zijun, LIU Yanfeng Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (9): 1107-1114.   DOI: 10.3969/j.issn.1674-8115.2023.09.005 Abstract （311）   HTML （17）    PDF（pc） （6113KB）（304）       Knowledge map    Save Objective ·To explore the significance and mechanism of asialoglycoprotein receptor 1 (ASGR1) in hepatocellular carcinoma. Methods ·The expression of ASGR1 in patients with liver cancer in The Cancer Genome Atlas (TCGA) database was analyzed by R language and the related survival curves were drawn. The Human Protein Atlas (HPA) database was used to obtain the immunohistochemistry (IHC) data of normal human liver tissue and liver cancer tissue to analyze the protein expression of ASGR1. By using the hydrodynamic tail vein injection (HTVI) delivery method, Asgr1 was knocked out in the liver of fully immune mice to explore its tumorigenic function invivo. Gene knockout efficiency was verified by Western blotting (WB). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and correlation analysis were performed by using R language. The GSEA hallmark correlation pathway analysis was performed by using Gene Set Enrichment Analysis (GSEA) software. The expression level of key genes of glycolysis in mouse liver cancer tissue was verified by quantitative real-time PCR (qPCR). Results ·ASGR1 was significantly low-expressed in liver cancer tissue, and the low expression of ASGR1 in liver cancer patients was associated with poorer overall survival (OS), disease-free interval (DFI), progression-free interval (PFI), and disease-specific survival (DSS). The higher the degree of tumor grade, the lower the expression level of ASGR1 in patients with liver cancer. Immunohistochemistry showed that the protein expression of ASGR1 in normal human liver tissue was significantly higher than that in liver cancer tissue. In an immunocompetent mouse model of hepatocellular carcinoma, knockout of endogenous Asgr1 in mice increased the size and number of tumor nodules in liver tissue. In the TCGA database, patients with liver cancer in the ASGR1 low-expression group were enriched in multiple cancer and metabolic pathways. The expression of ASGR1 was negatively correlated with some key genes of glycolysis. The level of glycolysis in liver cancer tissues of mice in the Asgr1 knockout group was higher than that in the control group. It was suggested that the low expression of ASGR1 be likely to promote the growth and development of liver cancer and strengthen metabolic reprogramming to promote the anabolic development of tumors. Conclusion ·The expression of ASGR1 is significantly reduced in patients with liver cancer, which is positively correlated with the prognosis of patients. Knocking out Asgr1 in mice can promote the occurrence and development of hepatocellular carcinoma. ASGR1 can be used as a potential biomarker for poor prognosis of liver cancer and a new target for potential treatment. Table and Figures | Reference | Related Articles | Metrics

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Analysis of m 6A methylation expression profiles in liver tissue of high -fat diet -induced mouse models of NAFLD LIU Junjun, LU Sumei, ZHANG Bingyang, LI Yongqing, MA Wanshan Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (10): 1227-1235.   DOI: 10.3969/j.issn.1674-8115.2023.10.002 Abstract （298）   HTML （25）    PDF（pc） （3120KB）（204）       Knowledge map    Save Objective ·To detect the differences in m6A methylation modification and gene expression of liver tissue mRNA in high-fat diet-induced mouse models of non-alcoholic fatty liver disease (NAFLD) using microarray technology. Methods ·The NAFLD models were established in 6-8 weeks old male C57BL/6J mice fed with high-fat chow for 16 weeks (high-fat group, n=10). The basal group (n=10) was given 10% fat diet. Hematoxylin-eosin (H-E) staining was used to assess the histopathological changes in liver tissue and to determine the success of the NAFLD models. The changes of mRNA m6A methylation and expression levels in the liver tissues of the two groups were detected by using methylated RNA immunoprecipitation (MeRIP) and microarray expression profiling. Results ·The livers of the mice in the basal group were bright red with few fat deposits, while the livers of the mice in the high-fat group were yellowish with diffuse infiltration and fusion of lipid droplets in the hepatocytes by H-E staining, suggesting that the high-fat diet-induced NAFLD models were successfully constructed. The results of the MeRIP-microarray showed that the m6A methylation levels of 320 genes in the livers of mice in the high-fat group were significantly altered compared with those in the basal group (P<0.05 and fold change>1.5), of which 108 genes were up-regulated and 212 genes were down-regulated. Genes with significant differences in m6A methylation levels between the two groups were intersected with those with differentially expressed mRNAs, and 163 genes were found to have significant differences in both m6A methylation level and mRNA expression level. Conclusion ·The change in m6A modification of liver tissue mRNA in the high-fat diet-induced mouse models of NAFLD is significant and the change is associated with the gene expression of mRNA. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （286）   HTML （20）    PDF（pc） （2014KB）（352）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （275）   HTML （20）    PDF（pc） （1283KB）（173）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （272）   HTML （32）    PDF（pc） （1360KB）（264）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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Study on factors influencing social network service addiction among junior college students based on problem behavior theory WANG Suping, TANG Hua, ZHOU Dong, CAI Yong, GONG Ruijie Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (8): 955-962.   DOI: 10.3969/j.issn.1674-8115.2023.08.002 Abstract （269）   HTML （32）    PDF（pc） （1846KB）（394）       Knowledge map    Save Objective ·To construct a structural equation model based on problem behavior theory to conduct a study on social network addiction among junior college students. Methods ·A cross-sectional questionnaire survey was conducted in a college in Shanghai. Logistic regression analysis was used to analyze the effects of gender, grade, study pressure, self-esteem, loneliness, depression, entrapment, defeat, interpersonal needs, perceived social support, smoking, alcohol, exercise, and academic achievement on social network service addiction. Based on the problem behavior theory, the structural equation model was used to construct a theoretical framework model of social network service addiction of junior college students. Results ·60.31% of the total 980 participants had social network service addiction. The univariate Logistic regression results showed that depression, self-esteem, loneliness, frustration, drowsiness, social support, interpersonal needs, exercise, and academic performance had a significant impact on social network addiction. The structural equation model fitted well [S－Bχ2/df=8.03, goodness-of-fit index (GFI)=0.924, comparative fit index (CFI)=0.909, Tucker-Lewis index (TLI)=0.872, root mean square error of approximation (RMSEA)=0.096, standardized root mean square residual (SRMR)=0.070], suggesting the mutual influence between the personality system and the perceived environment system, between the personality system and the behavioral system, and between the perceived environment system and the behavior system interact (β=1.018, P=0.000; β=0.218, P=0.003; β=0.268, P=0.000). The influence of personality system and behavior system on social network service addiction was not statistically significant, while the perceived environment system had a significant positive impact on social network service addiction (β=0.481, P=0.001). Conclusion ·Personality system and behavior system indirectly affect social network service addiction by influencing perceived environment system, and perceived environment system directly affects social network service addiction. For the problem of social network addiction among lower grade college students, it is necessary to fully respect the characteristics of college students, and work together from three levels of the system to reduce the risk of social network addiction among college students. Table and Figures | Reference | Related Articles | Metrics

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Research progress of the role of non-canonical Wnt signaling pathway in ovarian cancer and its potential therapeutic implications ZHOU Wanzhen, TENG Yincheng Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (8): 1056-1063.   DOI: 10.3969/j.issn.1674-8115.2023.08.015 Abstract （262）   HTML （28）    PDF（pc） （1663KB）（257）       Knowledge map    Save Ovarian cancer is a malignant tumor of the female reproductive system with the highest mortality, and involves the aberrant regulation of multiple molecular signaling pathways. As a highly conserved molecular pathway, Wnt signaling pathway plays an important role in embryonic development, tissue homeostasis, and tumorigenesis. Wnt signaling pathway includes canonical Wnt/β-catenin pathway and non-canonical pathway, and the latter mainly includes Wnt/planar cell polarity (Wnt/PCP) pathway and Wnt/Ca2+ pathway. Previous studies have mainly focused on the relationship between the canonical Wnt pathway and tumor progression. Recently, the non-canonical Wnt pathway has gradually received attention, and related researches have enriched the understanding of the non-canonical Wnt pathway in physiological and pathological processes such as tissue development and tumorigenesis. The existing studies suggest that the nonclassical Wnt pathway is abnormally regulated in ovarian cancer and is closely related to the staging and prognosis of ovarian cancer. Non-classical Wnt pathway plays an important role in many biological processes such as proliferation, migration and invasion of ovarian cancer cells, and the changes of this pathway are also related to chemotherapy resistance of ovarian cancer. This article reviews the role of the non-canonical Wnt pathway in ovarian cancer, and discusses the research progress of targeted therapy based on the non-canonical Wnt pathway, aiming to provide new ideas for the development of novel targeted drugs. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （262）   HTML （26）    PDF（pc） （13112KB）（104）       Knowledge map    Save 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). Table and Figures | Reference | Related Articles | Metrics

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

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Effect of Piezo1 on osteogenic differentiation of mouse bone marrow mesenchymal stem cells C3H10T1/2 based on CRISPR/Cas9 GAO Xin, YANG Yiling, HUANG Xiangru, DAI Qinggang, JIANG Lingyong Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (9): 1080-1088.   DOI: 10.3969/j.issn.1674-8115.2023.09.002 Abstract （258）   HTML （17）    PDF（pc） （3275KB）（552）       Knowledge map    Save Objective ·To investigate the effect of Piezo1 on osteogenic differentiation of mouse mesenchymal stem cells C3H10T1/2 cell line based on CRISPR/Cas9 system that can achieve stable gene knockout. Methods ·According to the principle of CRISPR/Cas9 target design principle, two single guide RNAs (sgRNAs) were designed to construct lentivirus expressing Cas9 and lentivirus expressing sgRNA by using Lenti-Cas9-GFP and Lenti-U6-sgRNA-mCherry vectors. After the C3H101/2 cells were transfected with two types of lentiviruses, flow cytometry was used to screen mCherry- and GFP-positive cells. The monoclonal cells were selected, and amplified by PCR and agarose gel electrophoresis, and finally the monoclonal cell line with Piezo1 gene fragment knocked out was obtained. Sequencing, quantitative realtime PCR (qPCR) and immunofluorescence were performed to verify the the knockout efficiency of the constructed Piezol knockout C3H10T1/2 cells (CPK). CCK-8 assay was used to detect the effect of knocking out Piezo1 on cell proliferation; in vitro osteogenic induction differentiation was performed on successfully constructed Piezo1 gene knockout cells, and alkaline phosphatase (ALP) staining and alizarin red staining were used to investigate the effect of Piezo1 on osteogenic ability. Results ·Positive clone was obtained in bacterial fluid of monoclonal cell lines with Piezol knocked out after PCR amplification and agarose gel electrophoresis. Sequencing analysis showed that a stop condon TGA was produced in exon 4 of Piezo1 gene in advance, so that the protein could not be translated correctly. qPCR verified that Piezo1 gene in CPK was inhibited at mRNA level; Immunofluorescence showed that the knockout efficiency of Piezo1 gene in CPK was high, which basically hindered the expression of Piezo1 in cells. CCK-8 assay showed that the cell proliferation ability decreased after knocking out Piezo1 (P<0.05); The results of ALP staining and alizarin red staining showed that the osteogenic ability of cells decreased after knocking out Piezo1(P<0.05). The mRNA expression levels of osteogenetic-related genes such as α 1 type Ⅰ collagen (Col1a1), Runt-related transcription factor 2 (Runx-2), osterix (Osx) and alkaline phosphatase (Alp) in CPK decreased significantly (all P<0.05). Conclusion ·Piezo1 knockout C3H10T1/2 cells based on CRISPR/Cas9 system is constructed successfully and the osteogenic activity of stable Piezo1 knockout cell line is hindered significantly. Table and Figures | Reference | Related Articles | Metrics