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Xiangan Gong,1,2 Qian Zhao,1,2 Huimin Zhang,1,2 Rui Liu,1,2 Jie Wu,1,2 Nanxin Zhang,3 Yuanxian Zou,1,2 Wen Zhao,1,2 Ran Huo,1,2,4 Rongtao Cui1– 4 1Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China; 4Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Rongtao Cui, Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +86 18653170822, Email cuirt1986@outlook.comAbstract: Pathological scarring results from aberrant cutaneous wound healing due to the overactivation of biological behaviors of human skin fibroblasts, characterized by local inordinate inflammation, excessive extracellular matrix and collagen deposition. Yet, its underlying pathogenesis opinions vary, which could be caused by increased local mechanical tension, enhanced and continuous inflammation, gene mutation, as well as cellular metabolic disorder, etc. Metabolic reprogramming is the process by which the metabolic pattern of cells undergoes a systematic adjustment and transformation to adapt to the changes of the external environment and meet the needs of their growth and differentiation. Therefore, the abnormality of metabolic reprogramming in cells within wounds and scars attaches great importance to scar formation. Mesenchymal stem cells-derived exosomes (MSC-Exo) are the extracellular vesicles that play an important role in tissue repair, cancer treatment as well as immune and metabolic regulation. However, there is not a systematic work to detail the relevant studies. Herein, we gave a comprehensive summary of the existing research on three main metabolisms, including glycometabolism, lipid metabolism and amino acid metabolism, and MSC-Exo regulating metabolic reprogramming in wound healing and scar formation for further research reference.Keywords: mesenchymal stem cells-derived exosomes, metabolic reprogramming, scar, wound healing, fibroblast

Yuan Wang, Xiaoyu Song, Ru Cui, Xinlin Luo, Juntian Dong, Hanqi Wang, Chengcheng Song, Yifa Zhou, Sisi Cui Engineering Research Center of Glycoconjugates, Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun, 130024, People’s Republic of ChinaCorrespondence: Sisi Cui, Engineering Research Center of Glycoconjugates of Ministry of Education, Jilin Provincial Key Laboratory on Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun, 130024, People’s Republic of China, Email cuiss100@nenu.edu.cnPurpose: Conventional oral formulations for inflammatory bowel disease (IBD) treatment are less than satisfactory, due to the poor controllability of drug release and lack of specificity to the inflammation sites in the gastrointestinal (GI) tract. To overcome these limitations, we developed a multiple carbohydrate-based nanosystem with pH/ROS dual responsibility and charge-mediated targeting ability for IBD-specific drug delivery.Methods: In view of the overproduction of ROS and overexpression of cationic proteins in the inflammatory colon, the designed nanosystem was composed of oxidation-sensitive cyclodextrin (OX-CD), chitosan (CS) and pectin (AHP). OX-CD was utilized to load dexamethasone (DM) by the solvent evaporation method. CS and AHP with opposite charges were sequentially coated onto OX-CD to generate the nanosystems by the electrostatic self-assembly method. The physicochemical properties, stability, dual-sensitive drug release behavior, cytotoxicity, cellular uptake and anti-inflammatory activity were investigated in vitro. In vivo bio-distribution and therapeutic efficacy of the nanosystem were further evaluated in the ulcerative colitis (UC) mice.Results: The obtained AHP/CS/OX-CD-DM nanosystem (ACOC-DM) could maintain stability under the GI pH environments, and release drug in the inflammatory colon with pH/ROS sensitivity. Dual polysaccharide-coated ACOC-DM exhibited higher cellular uptake and anti-inflammatory efficacy in macrophages than single polysaccharide-coated CS/OX-CD-DM nanosystem (COC-DM). Orally administrated ACOC-DM could enhance inflammation targeting ability and therapeutic efficacy of DM in the UC mice.Conclusion: This carbohydrate-based nanosystem with pH/ROS dual sensitivity and inflammation targeting capacity may serve as a safe and versatile nanoplatform for IBD therapy. Keywords: PH/ROS sensitivity, pectin, chitosan, oxidation-sensitive cyclodextrin, inflammation targeting, oral delivery

Huimin Zhang,1,* Chengyu Zang,1,2,* Wen Zhao,1 Linfeng Zhang,1 Rui Liu,1 Zhang Feng,1 Jie Wu,1 Rongtao Cui1– 3 1Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Shandong University, Jinan, People’s Republic of China; 3Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rongtao Cui, Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +86 18653170822, Email cuirt1986@outlook.comBackground: Mesenchymal stem cell-derived exosomes (MSC-exo) have been shown to have significant potential in wound healing and scar relief processes. According to reports, TNFSF13 and HSPG2 are associated with various fibrotic diseases. The aim of this study is to investigate how TNFSF13 and HSPG2 affect the formation of hypertrophic scar (HS) and the mechanism by which exosomes regulate HS.Methods: Immunohistochemistry, qRT-PCR, Western blot, and immunofluorescence were performed to measure TNFSF13 expression in HS skin tissues and hypertrophic scar fibroblast (HSF). HSF were treated with recombinant TNFSF13 protein and TNFSF13 siRNAs to probe the effect of TNFSF13 on the activity of HSF. The CCK-8, EdU, Transwell, and Western blot were used to investigate the role of TNFSF13 in viability, proliferation and inflammation. The influence of MSC-exo on the proliferation and function of HSF was determined by scratch and Western blot.Results: TNFSF13 was dramatically up-regulated in HS skin tissues and HSF. Recombinant TNFSF13 protein increased cell viability, proliferation, migration, fibrosis, inflammation, and the binding between TNFSF13 and HSPG2 of HSF. The opposite results were obtained in TNFSF13 siRNAs transferred HSF. Furthermore, TNFSF13 activated the nuclear factor-κB (NF-κB) signaling pathway. Silencing of HSPG2 and inhibition of NF-κB remarkably eliminated the promoting effects of TNFSF13 on cell viability, proliferation, migration, fibrosis and inflammation of HSF. MSC-exo reduced α-SMA and COL1A1 inhibited the proliferation and migration of HSF by inhibiting TNFSF13 and HSPG2.Conclusion: TNFSF13 activates NF-κB signaling pathway by interacting with HSPG2, which regulates the proliferation, migration, fibrosis and inflammatory response of HSF. Through the above mechanisms, knocking out TNFSF13 can inhibit the proliferation, migration, fibrosis and inflammatory response of HSF, whereas MSC-exo could reverse this process. These results suggest that MSC-exo alleviates HS by inhibiting the fibroblasts via TNFSF-13/HSPG2 signaling pathway.Keywords: TNFSF13, HSPG2, hypertrophic scar(HS), MSC-exo, fibroblasts

Wen Zhao,1,2,* Huimin Zhang,1,2,* Rui Liu,1,2 Rongtao Cui1– 3 1Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 3Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rongtao Cui, Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +86 18653170822, Email cuirt1986@outlook.comAbstract: Pathological scars are the result of over-repair and excessive tissue proliferation of the skin injury. It may cause serious dysfunction, resulting in psychological and physiological burdens on the patients. Currently, mesenchymal stem cells-derived exosomes (MSC-Exo) displayed a promising therapeutic effect on wound repair and scar attenuation. But the regulatory mechanisms are opinions vary. In view of inflammation has long been proven as the initial factor of wound healing and scarring, and the unique immunomodulation mechanism of MSC-Exo, the utilization of MSC-Exo may be promising therapeutic for pathological scars. However, different immune cells function differently during wound repair and scar formation. The immunoregulatory mechanism of MSC-Exo would differ among different immune cells and molecules. Herein, this review gave a comprehensive summary of MSC-Exo immunomodulating different immune cells in wound healing and scar formation to provide basic theoretical references and therapeutic exploration of inflammatory wound healing and pathological scars.Keywords: exosomes, inflammation, immune cells, immunoregulation, scars

Wen Zhao,1 Rui Zhang,1 Chengyu Zang,1 Linfeng Zhang,1 Ran Zhao,1 Qiuchen Li,1 Zhanjie Yang,1 Zhang Feng,1 Wei Zhang,1 Rongtao Cui1,2 1Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Rongtao Cui, Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +86 18653170822, Email cuirt1986@outlook.comIntroduction: The therapies of using exosomes derived from mesenchymal stem cells (MSC-Exo) for wound healing and scar attenuation and micro RNAs (miRNAs) for regulation of genes by translational inhibition and mRNA destabilization obtained great achievements. Silent information regulator 1 (SIRT1) is the silent information, which has an intricate role in many biological processes. However, the effects of SIRT1 and miR-138-5p loaded in MSC-Exo on pathological scars remain unclear.Methods: MSC-Exo was isolated and identified by ultracentrifugation, transmission electron microscopy, nanoparticle size measuring instrument and Western blot assays. The relationship between SIRT1 and miR-138-5p was verified by a double-luciferase reporter assay. Cell Counting Kit-8, &Tgr;ranswell, scratch, and Western blot assays were used to evaluate the proliferation and migration of human skin fibroblasts (HSFs), and the protein expression of SIRT1, NF-κB, α-SMA and TGF-β 1 in HSFs, respectively. Flow cytometry was used to assess the apoptosis and cell cycle of HSFs affected by SIRT1.Results: Our study demonstrated that miR-138-5p loaded in MSC-Exo could attenuate proliferation, migration and protein expression of HSFs-derived NF-κB, α-SMA, and TGF-β 1 by targeting to SIRT1 gene, which confirmed the potential effects of MSC-Exo in alleviating pathological scars by performing as a miRNA’s delivery vehicle.Conclusion: Exosomes derived from MSCs acting as a delivery vehicle to deliver miR-138-5p can downregulate SIRT1 to inhibit the growth and protein expression of HSFs and attenuate pathological scars.Keywords: mesenchymal stem cell-derived exosomes, miR-138-5p, SIRT1, human skin fibroblasts, pathological scars

Wei Huang,1,2,* Jinyong Zhang,3,* Shiyi Liu,1 Chunxia Hu,1 Min Zhang,1 Shumin Cheng,1 Huijuan Yu,1,2 Manling Zheng,1 Jinsong Wu,2 Yuemei Lu,2 Quanming Zou,3 Ruiqin Cui1 1Bacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China; 2Department of Clinical Microbiology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China; 3National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Quanming Zou; Ruiqin Cui, Email qmzou2007@163.com; screening_sz@163.comBackground: The use of antibiotic adjuvants is a complementary strategy to the development of new antibiotics. The essential role of the ArnA dehydrogenase domain (ArnA_DH) in the addition of 4-amino-L-arabinose (L-Ara4N) to lipid A makes it a potential target in polymyxin adjuvant design.Purpose: This study aimed to identify a dehydrogenase inhibitor that enhances the antibacterial effect of polymyxin B (PB) and to further understand the mechanism of this drug combination.Methods: A susceptible K. pneumoniae strain, ATCC13883, was used to screen a dehydrogenase inhibitor library based on 3-(4,5)-dimethylthiazol(-z-y1)-2,5-diphenyltetrazolium bromide (MTT) and chequerboard assays. The protein- and cell-based effects of disulfiram (DSF) on ArnA activity were assessed, and the transcription levels of genes in the arn operon were evaluated by quantitative real-time polymerase chain reaction (qRT–PCR). Lipid A was isolated, and a structural analysis was performed. The cell wall function was evaluated through membrane integrity and bacterial viability assays. The in vivo antibacterial activity was evaluated using a mouse pulmonary infection model.Results: We screened a dehydrogenase inhibitor library and found that the anti-alcoholism drug DSF significantly enhanced the antibacterial activity of PB in vitro and in vivo. The protein-based enzyme activity assay showed that DSF exerted no direct effect on the dehydrogenase activity of ArnA. Treatment with the combination of DSF and PB but not with PB alone decreased both the transcription level of genes in the arn operon and the modification level of lipid A. DSF also strengthened the disruption of the cell membrane integrity of PB. Moreover, the enhanced PB antibacterial activity was effective against clinical PB-resistant strains.Conclusion: We identified a new drug combination that can be used to reduce the necessary dosage of PB and overcome PB resistance, and this drug combination has good prospects for clinical application.Keywords: polymyxins, antibiotic adjuvants, antibacterial, cell membrane

Rongli Cui,* Zhiqiang Song,* Baojun Suo, Xueli Tian, Yan Xue, Lingmei Meng, Zhanyue Niu, Zhu Jin, Hejun Zhang, Liya Zhou Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liya ZhouDepartment of Gastroenterology, Peking University Third Hospital, 49 Road Garden, Haidian District, Beijing, 100191, People’s Republic of ChinaTel +86-13911827827Fax +86-10-82265021Email zhouliya123456@163.comBackground: It has not been fully confirmed whether the detection of Helicobacter pylori resistance gene mutation can replace antibiotic drug sensitivity test to guide the clinical individualized treatment. Therefore, we have studied this aspect and discussed the application value of antibiotic sensitivity gene test.Materials and Methods: The biopsy specimen of gastric mucosa from the patients examined by endoscopy and positive for rapid urease test were collected continuously for histopathological analysis, H. pylori culture, antibiotic drug sensitivity test (E-test drug sensitivity test), and antibiotic sensitivity gene test (high-throughput nucleotide sequencing). The participants received triple plus bismuth solution eradication treatment (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, twice daily for 14 days) for follow-up, and the eradication effect was determined.Results: The 551/602 subjects, who met the inclusion criteria, were subjected to culture for H. pylori and antibiotic drug sensitivity determination; among them 506 were cultured successfully. The results showed that the resistance rates of H. pylori were 38.9% for clarithromycin and 31.0% for levofloxacin. In 489 H. pylori strains, the mutations were detected in clarithromycin and levofloxacin resistance genes, indicating the genotype resistance. The resistance genes of clarithromycin and levofloxacin were consistent with phenotype resistance with respect to sensitivity (81.2% and 69.7% for clarithromycin and levofloxacin, respectively) and specificity (88.9% and 93.7% for clarithromycin and levofloxacin, respectively). The eradication rate of H. pylori in the clarithromycin-resistant group was significantly lower than that in the sensitive group (ITT: 52.1% vs 85.0%, P < 0.001).Conclusion: A correlation was established between the resistance genes of clarithromycin and levofloxacin and their phenotypic resistance and clinical efficacy. The detection of H. pylori resistance genes has a good clinical application prospect.Keywords: Helicobacter pylori, drug resistance, clarithromycin, levofloxacin, mutation, high-throughput nucleotide sequencing

Jun Sha,1,2 Dandan Cao,1,2 Rui Cui,1,2 Lu Xia,1,2 Xin Hua,1,2 Yuan Lu,1,2 Shuhua Han1 1Department of Respiratory Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing City, Jiangsu Province, People’s Republic of China; 2Medicine Department of Southeast University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Shuhua HanDepartment of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar (UOG), P.O. box 196, Gondar, EthiopiaTel +251-918-192721Email abty12@gmail.comIntroduction: Mannose, a major monosaccharide component of N-glycans, involves in the glycometabolism of human body. Recently, mannose has been shown to suppress tumor growth through enhancing chemosensitivity and reducing the activity of mannose phosphate isomerase (MPI). However, it is largely unknown whether mannose exerts effects on non-small cell lung cancer (NSCLC).Materials and Methods: First, a mannose IC50 assay was conducted to find a suitable concentration of mannose for cell experiments. Then, vitro studies including CCK-8 assay, scratch wound healing assay, and TUNEL assay were performed to evaluate the effects of mannose on A549 cells, and an animal model was established to evaluate the antitumoural effect of mannose on NSCLC in vivo. Finally, immunohistochemistry was done to detect the expression of MPI by Rabbit Anti-MPI.Results: In this study, a concentration of mannose, 15mM, was used to explore the suppressive effect of mannose on A549 cells. CCK-8 assay demonstrated that mannose significantly inhibited the proliferation of A549 cells and enhanced the anti-tumor efficacy of carboplatin. Wound healing assay showed that mannose inhibits the migration of A549 cells, and mannose-induced migration inhibition was more efficient in A549 cells treated with carboplatin. TUNEL assay demonstrated that mannose significantly enhanced the efficacy of carboplatin to promote apoptosis treated by mannose (15mM) or carboplatin. The results of animal experiments revealed that the size and weight of tumors derived from A549 cells treated with mannose were smaller than those derived from control cells, and co-treatment with mannose and carboplatin had most efficient inhibition on tumor growth. MPI expression detection showed that the expression level of MPI in the stage Tis (tumor in situ) was the highest, while the stage IV has the lowest.Discussion: Collectively, our findings suggest that mannose inhibited cell proliferation and migration, promoted cell apoptosis and enhanced the efficacy of carboplatin in lung adenocarcinoma. Preliminary results showed that mannose had less side effect on health. In the future, mannose may be a potential candidate drug for adjuvant therapy of lung adenocarcinoma.Keywords: mannose, NSCLC, cancer

Qiuyang Deng,1,* Jinyong Zhang,2,* Min Zhang,1 Zhou Liu,3 Yuxin Zhong,1 Shiyi Liu,1 Ruiqin Cui,1 Yun Shi,2 Hao Zeng,2 Xiyao Yang,3 Chuchu Lin,4 Yutian Luo,5 Huaisheng Chen,5 Weiyuan Wu,6 Jinsong Wu,6 Tianle Zhang,7 Yuemei Lu,6 Xueyan Liu,5 Quanming Zou,2 Wei Huang1 1Bacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of China; 2National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing, People’s Republic of China; 3Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Department of Nosocomial Infection Control, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of China; 5Intensive Care Unit, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of China; 6Department of Clinical Microbiology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of China; 7Guangdong Medical University, Dongguan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei HuangBacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of ChinaTel +86 7522942513Fax +86 7522942514Email whuang_sz@163.comQuanming Zou National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical PharmacyCollege of Pharmacy, Army Medical University, Chongqing 400038, People’s Republic of ChinaTel/Fax +86 2368752316Email qmzou2007@163.comObjective: We aimed to establish a tool for rapid identification of KL49 Acinetobacter baumannii.Methods: Based on the capsular polysaccharide (CPS) synthesis genes database, we investigated the distribution of K locus type 49 (KL49) genes in other KL types and established a rapid identification method for KL49. We collected 61 clinical carbapenem-resistant A. baumannii (CRAB) strains, identified KL49 by gtr100 detection, and used whole genome sequencing (WGS) for verification. A mouse pneumonia model was used to confirm the hypervirulence phenotype. We tested the presence of gtr100 gene in 165 CRAB strains from three provinces in China and evaluated the correlation of gtr100 carrying CRAB infection with mortality.Results: The gtr100 gene is the CPS synthesis gene found only in KL49. We screened out nine WGS-validated KL49 strains from 61 CRAB clinical strains using polymerase chain reaction (PCR) to detect the gtr100 gene. The survival rates of KL49 strains were significantly lower than nonKL49 strains in a mouse pneumonia model. The survival rates of LAC-4 gtr100 knockout strain decreased significantly. Analysis of phylogenetics showed the worldwide spread of KL49 A. baumannii. Infection of gtr100 carrying CRAB is an independent risk for mortality (OR, 10.76; 95%CI: 3.08– 37.55; p< 0.001).Conclusion: The hypervirulence phenotype of KL49 CRAB and the association with mortality highlight the urgent need for implementing control measures. The rapid identification assay has the potential to facilitate early medical intervention and worldwide surveillance.Keywords: Acinetobacter baumannii, hypervirulent, K locus, Kaptive, mortality

Ran Cui,1,* Ludi Yang,2,* Yiwei Wang,2,* Ming Zhong,3 Minhao Yu,3 Bo Chen1 1Department of Hepatopancreatobiliary Surgery, East Hospital Affiliated Tongji University, Tongji University School of Medicine, Shanghai 200120, Mainland China; 2State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai 200240, Mainland China; 3Department of Gastrointestinal Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, Mainland China*These authors contributed equally to this workCorrespondence: Bo ChenDepartment of Hepatopancreatobiliary Surgery, East Hospital Affiliated Tongji University, Tongji University School of Medicine, 1800 Yuntai Road, Shanghai, Mainland ChinaEmail chenbo7349@sohu.comMinhao YuDepartment of Gastrointestinal Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, Mainland ChinaEmail fishmeangood@163.comObjective: Colorectal cancer is one of the most common malignant tumors worldwide. ASXL2 is an enhancer of the trithorax and polycomb genes, which have been proven to act in many tumor types. The role of ASXL2 in the occurrence and development of tumors has been extensively studied in recent years. However, the relationship between ASXL2 and the prognosis of CRC is still unclear.Materials and Methods: In this study, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot analysis and immunohistochemistry (IHC) were used to examine the expression of ASXL2 in CRC tissues. Cells were transfected with siRNAs or lentivirus to regulate the expression of ASXL2. The effects of ASXL2 on the proliferation of CRC cells were determined by CCK8 assay.Results: This study demonstrated that ASXL2 was significantly more highly expressed in CRC specimens than in normal adjacent tissues. The upregulation of ASXL2 was related to advanced clinical stage. Patients who exhibited high expression levels of ASXL2 had poorer overall survival, whereas those with low expression of ASXL2 survived longer. Multivariate Cox regression analysis revealed that ASXL2 expression could be considered an independent prognostic factor for CRC. Inhibition or overexpression of ASXL2 markedly influenced the proliferation of CRC cells.Conclusion: These results showed that ASXL2 could induce cell proliferation, which was associated with poor prognosis of CRC patients, suggesting that ASXL2 might be a new therapeutic target for CRC.Keywords: ASXL2, colorectal cancer, cell proliferation, prognosis marker

Soyeon Bang,1 Junhong Li,2 Meiqin Zhang,3 Renjie Cui,3 Xingwen Wu,4 Zhaochen Xin,1 Duan Ma,3,5 Jin Zhang,3 Hongwei Zhang1 1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Urology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China; 3Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 4Department of Dentistry, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Children’s Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Hongwei ZhangDepartment of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of ChinaTel +86-13681973106Fax +86 21-64038472Email zhang.hongwei@zs-hospital.sh.cnDuan MaKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, 130 Dong an Road, Xuhui District, Shanghai 200032, People’s Republic of ChinaTel +86-13916126452Fax +86 21-54237441Email duanma@shmu.edu.cnBackground: Krüppel-like factor 16 (KLF16), a member of the KLF family, is involved in metabolism and regulation of the endocrine system and has emerging roles in tumor progression. However, the expression of KLF16 and its role in breast cancer are elusive.Methods: We investigated the expression and prognostic value of KLFs in breast cancer using data acquired from the TCGA BRCA dataset and the Kaplan–Meier plotter dataset. The protein levels of KLF16 in breast specimens were detected by immunohistochemistry (IHC). KLF16 silencing using shRNAs was performed to explore the effects of KLF16 on breast cancer cell growth, migration, and invasion. The expression of EMT markers in cells manipulated for KLF16 expression was assessed by Western blotting.Results: Using publicly available dataset and specimens from breast cancer patients, we found that the expression levels of KLF16 were significantly higher in tumor tissues and that high levels of KLF16 were associated with poor prognosis in breast cancer patients. Moreover, KLF16 expression levels had relation to several clinicopathological parameters of breast cancer, including the molecular subtype and histological grade. Importantly, knockdown of KLF16 dramatically suppressed cell proliferation both in vitro and in vivo. Also, KLF16 deletion impaired migration, and invasion in breast cancer cells, and suppressed epithelial–mesenchymal transition (EMT).Conclusion: Our results suggest that KLF16 has important oncogenic functions in breast cancer and that the expression levels of KLF16 are associated with prognosis in breast cancer patients. Our findings also suggest that KLF16 is involved in proliferation, migration, and invasion in breast cancer cells. Thus, KLF16 might be a promising prognostic marker and a therapeutic target for breast cancer.Keywords: breast cancer, EMT, Krüppel-like factor 16, metastasis, proliferation

Ruili Jiao,1,2,* Shipeng Sun,3,* Xiaoqiong Gao,1 Ran Cui,1 Guangming Cao,1 Huali Wei,4 Shuzhen Wang,1 Zhenyu Zhang,1 Huimin Bai1 1Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, People’s Republic of China; 2Department of Obstetrics and Gynecology, Maternal and Child Health Hospital, Beijing, People’s Republic of China; 3Clinical Laboratories, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Department of Obstetrics and Gynecology, Emergency General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huimin Bai; Zhenyu Zhang Email bhmdoctor@sina.com; zhenyuzhang@ccmu.edu.cnObjective: This study tried to evaluate whether 8% polyethylene glycol (PEG) 6000 precipitation combined with differential ultracentrifugation (PPDU) was an efficient and practical method for the enrichment and purification of extracellular vesicles (EVs) derived from the culture supernatant of human ovarian cancer cell line A2780 and from body fluids of patients with high-grade serous carcinoma (HGSC).Methods: PPDU was used to enrich and purify the EVs derived from body fluids of patients with HSGC and cell culture supernatant of subclones of human ovarian cancer cell line A2780 with high/low invasive capacity (named as A-H/A-L, respectively). Transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA) were used to identificate the EVs size and distribution. Western blots (WB) were used to detect the expression of CD9, CD63, Alix and Calnexin. The high-purity EVs derived from the cell culture supernatant of A-H/A-L were detected by the protein profile. Expression of integrins (ITGs) αV, β 1 and β 3 in the EVs derived from body fluids of HGSC patients was also evaluated.Results: The diameter of EVs was about 30– 260 nm observed under the TEM. Under the NTA identification, the peak size of EVs was ranged from 70 to 159nm. EVs derived from different specimens did not significantly differ in mean size and peak size. Presence of CD9, CD63 and Alix and absence of Calnexin were confirmed in the EVs. The protein concentrations of EVs’ sample extracted from A-H/A-L cell culture supernatant were 0.36μg/μL and 0.20μg/μL, respectively. The total amount of protein obtained from 300ul EVs was 108.02ug and 61.44ug, respectively. Totally, 2397 peptides and 952 proteins were identified by isobaric tags for relative and absolute quantitation (ITRAQ). The expression of ITGαV, β 1, and β 3 in the EVs from plasma and ascites of HGSC patients was significantly higher than the control group (plasma: all P< 0.0001; ascites: P=0.036, 0.001 and 0.004, respectively). The expression level of ITGαV and β 1 in EVs of HGSC’s ascites was significantly higher than that in plasma (P= 0.004, 0.001, respectively). The expression of ITGβ 3 was also slightly elevated in EVs-derived HGSC patients’ ascites (P=0.492).Conclusion: PPDU was an efficient and practical method to enrich EVs from body fluids and cell culture supernatant. The characteristic expression of ITGαV, β 1 and β 3 in ascites and plasma EVs of patients with HGSC provided useful information on the development of EVs in HGSC.Keywords: EVs, PEG6000 precipitation, HGSC, body fluids, cell culture supernatant

Rui Cui,1,2 Xiao-hui Wang,3 Chao Ma,4 Tong Liu,5 Zhi-gang Cheng,1 Zhi-yu Han,1 Fang-yi Liu,1 Xiao-ling Yu,1 Jie Yu,1,* Ping Liang1,* 1Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China; 2Department of Ultrasonography, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, People’s Republic of China; 3Department of Ultrasonography, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, People’s Republic of China; 4Department of Ultrasonography, Qiqihaer Hospital of Chinese Medicine, Qiqihaer 161000, People’s Republic of China; 5Department of Ultrasonography, Hebei Chest Hospital, Shijiazhuang 050000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ping Liang; Jie YuDepartment of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, People’s Republic of ChinaTel +86-10-66939530Fax +86-10-68161218Email liangping301@hotmail.com; yu-jie301@hotmail.comPurpose: To compare overall survival (OS) and progression-free survival (PFS) between microwave ablation (MWA) and transarterial chemoembolization (TACE) for solitary hepatocellular carcinoma (HCC) smaller than 5 cm.Methods: Patients with solitary HCC smaller than 5cm who initially underwent MWA or TACE were identified in Chinese PLA General Hospital from June 2010 to October 2015. Propensity score matching (PSM) was performed with a 1:1 matching protocol. OS and PFS were compared by using the log-rank test. After matching, subgroup analysis based on tumor size (≤3cm/3.1–5cm) was also conducted. Prognostic factors for OS and PFS were assessed with Cox proportional hazard regression model.Results: A total of 202 patients (MWA, n=120; TACE, n=82) were identified. After matching, 116 patients were included (58 patients for each treatment group). MWA provided significantly better OS and PFS than TACE for both the entire cohort (OS, P

Dandan Cao,1,2 Jun Sha,1,2 Rui Cui,1,2 Shuhua Han1 1Department of Pulmonary Medicine, Zhongda Hospital, School of Medicine, South-East University, Nanjing, Jiangsu, People’s Republic of China; 2Medicine Department of Southeast University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Shuhua HanDepartment of Pulmonary Medicine, Zhongda Hospital, Ding Jia Qiao No. 87, Nanjing, Jiangsu 210009, People’s Republic of ChinaEmail hanshuhua0922@126.comAbstract: The concept of spread through air spaces (STAS) has been described as a new form of invasion in the lung in the 2015 WHO classification of Lung Tumors, namely invasion through alveolar spaces. STAS is a prognostic factor independent of growth pattern and tumor stage, and it is also an independent risk factor for unfavorable prognosis of stage I lung adenocarcinoma (ADC) and stage I lung squamous cell carcinoma (SCC). The pathological characteristics are different between ADC and SCC. STAS is not reported as routine, so setting a unified pathological reading standard, and hunting for STAS as a regular reading process is urgently advocated. We write this review to investigate the research progress of STAS and its effects on the prognosis of lung cancer.Keywords: lung cancer, STAS, pathological characteristics, prognosis

Miaomiao Li*, Tao Guo*, Ran Cui, Ying Feng, Huimin Bai, Zhenyu ZhangDepartment of Obstetrics and Gynecology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workObjectives: This study aimed to identify potential prognostic factors for patients with complex atypical hyperplasia (CAH) or early-stage endometrial cancer (EC) who received progestin therapy to spare fertility and, thus, improve the management of this patient group.Materials and methods: The PubMed, PMC, EMBASE, Web of Science, and Cochrane databases were searched for correlational studies published in English. Studies that evaluated the prognosis of patients with CAH or early-stage EC were pooled for a systematic review and meta-analysis.Results: In total, 31 eligible studies, including 8 prospective and 23 retrospective studies involving 1099 patients, were included in this analysis. The most commonly used progestin agents were medroxyprogesterone acetate (MPA, 47.0%) and megestrol acetate (MA, 25.5%). The total complete response (CR) rate was 75.8% (833/1099), and the median time to CR with first-line progestin therapy was 6 months. In total, 294 (26.8%) patients who achieved CR became pregnant spontaneously (28 cases) or through assisted reproductive technology (127 cases). During the median follow-up of 39 months, 245 (22.3%) women developed recurrence. Only one patient (0.09%) died of the disease. The meta-analysis showed that compared to a BMI

Xuanxuan Dai,1,* Junru Zhang,2,* Guilong Guo,1 Yuepiao Cai,3 Ri Cui,3 Changtian Yin,1 Weidong Liu,3 Rajamanickam Vinothkumar,3 Tingting Zhang,3 Guang Liang,3 Xiaohua Zhang1 1Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; 2College of Pharmacy, Binzhou Medical University, Yantai, Shandong 264003, China; 3Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China *These authors contributed equally to this work Introduction: Targeted therapies using epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR mutations, leading to the approval of gefitinib and erlotinib as standard first-line clinical treatment. Inevitably, a considerable proportion of patients develop resistance to EGFR-TKIs due to the acquisition of secondary mutations within EGFR. Therefore, alternative strategies to target NSCLC are desperately needed. Materials and methods: In this study, we have evaluated the effect of a reactive oxygen species (ROS)-inducing agent WZ35, a mono-carbonyl analog of curcumin, to target an inherent biological property of cancer cells, increased oxidative stress. To study whether WZ35 can inhibit NSCLC tumorigenesis, we used gefitinib- and erlotinib-resistant cell line H1975.Results: In this study, we show that WZ35 treatment dramatically decreases cell viability and induces apoptosis in H1975 cells through the generation of ROS. We also found that the ­antitumor activity of WZ35 involved ROS-mediated activation of the endoplasmic reticulum stress pathway and mitochondrial dysfunction. Furthermore, WZ35 significantly inhibited H1975 xenograft tumor growth through the inhibition of cell proliferation and induction of apoptosis. Discussion: These findings show that WZ35 may be a promising candidate for the treatment of EGFR-TKI-resistant NSCLC. Keywords: epidermal growth factor receptor, reactive oxygen species, mono-carbonyl analog of curcumin, ER stress, mitochondrial dysfunction, apoptosis, NSCLC

Wei-Juan Zeng,1 Chun-Wei Peng,1 Jing-Ping Yuan,1 Ran Cui,2 Yan Li11Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan, People’s Republic of China; 2Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education) and College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, People’s Republic of China Purpose: The aims of this study are to establish a new method for simultaneously detecting the interactions between cancer cells and immunocytes in malignant ascites (MA) and to propose a new model for MA classification.Methods: A quantum dot (QD)-based multiplexed imaging technique was developed for simultaneous in situ imaging of cancer cells, lymphocytes, and macrophages. This method was first validated in gastric cancer tissues, and then was applied to MA samples from 20 patients with peritoneal carcinomatosis from gastrointestinal and gynecological origins. The staining features of MA and the interactions between cancer cells and immunocytes in the ascites were further analyzed and correlated with clinical features.Results: The QD-based multiplexed imaging technique was able to simultaneously show gastric cancer cells, infiltrating macrophages, and lymphocytes in tumor tissue, and the technique revealed the distinctive features of the cancer tumor microenvironment. When this multiplexed imaging protocol was applied to MA cytology, different features of the interactions and quantitative relations between cancer cells and immunocytes were observed. On the basis of these features, MA could be classified into immunocyte-dominant type, immunocyte-reactive type, cancer cell-dominant type, and cell deletion type; the four categories were statistically different in terms of the ratio of cancer cells to immunocytes (P

This paper describes GCAM v5.1, an open source model that represents the linkages between energy, water, land, climate, and economic systems. GCAM is a market equilibrium model, is global in scope, and operates from 1990 to 2100 in 5-year time steps. It can be used to examine, for example, how changes in population, income, or technology cost might alter crop production, energy demand, or water withdrawals, or how changes in one region's demand for energy affect energy, water, and land in other regions. This paper describes the model, including its assumptions, inputs, and outputs. We then use 11 scenarios, varying the socioeconomic and climate policy assumptions, to illustrate the results from the model. The resulting scenarios demonstrate a wide range of potential future energy, water, and land uses. We compare the results from GCAM v5.1 to historical data and to future scenario simulations from earlier versions of GCAM and from other models. Finally, we provide information on how to obtain the model.

Geoelectric fields produced by time‐varying magnetic fields during geomagnetic storms can result in potentially damaging geomagnetically induced currents (GICs) in long conductors at the Earth's surface. GICs can pose a significant risk to the integrity of grounded electrical infrastructure, particularly high‐voltage transformers. In this study, an inferred GIC is calculated using an augmented differential magnetometer measurement (DMM) technique on a 500 kV transmission line in central Alberta and is validated using a proximal transformer neutral‐to‐ground (TNG) current measurement by AltaLink L.P. using a Hall probe at a transformer substation. This research outlines a custom‐built and innovative DMM design by which both DMM sensors deployed around a power line measure the background geomagnetic disturbance (GMD) field and the magnetic field generated locally by the GIC. We show how this modified approach provides two independent estimates for GIC derived using only ΔBy or ΔBz, the magnetic field components perpendicular to the line carrying GIC. Results for a geomagnetic storm on 12 Oct 2021 show contemporaneous peaks in the TNG current and the DMM‐inferred GIC. The two data sets have similar waveforms and are within the same order of magnitude. The background GMD is reconstructed using DMM and shows excellent correlation to the measured GMD at the permanent Canadian Array for Real‐time Investigations of Magnetic Activity magnetic station at Ministik Lake, approximately 48.5 km away. Based on the results presented here, we verify the added utility value of DMM for temporary deployments for assessing GIC risk in electrical power grids. Plain Language Summary: During geomagnetic storms, changes in the Earth's magnetic field can result in geomagnetically induced currents (GICs) that travel through conductive structures at the Earth's surface, such as power lines. GICs are near‐DC currents that can be harmful to electrical infrastructure. In this study, we built and tested an augmented differential magnetometer measurement (DMM) setup where sensors placed around the high‐voltage power line could measure the natural magnetic field disturbances and the magnetic field fluctuations caused by GICs. Using the differential measurement in the components of the magnetic field perpendicular to the power line, two estimates for GIC were calculated during the geomagnetic storm on 12 October 2021, on a 500 kV transmission line in Alberta, Canada, and then compared to the Hall probe GIC data from a nearby AltaLink transformer substation. The results show that the inferred GICs from the DMM matched well with the Hall probe current measurements in waveform and amplitude. Also, the background magnetic disturbance measured by the DMM closely matched the background magnetic field measured at a permanent magnetic station about 48.5 km away. Based on these findings, we conclude that DMM could be useful for temporary deployments to assess GIC risk in electrical power grids. Key Points: An alternative configuration for the differential magnetometer measurement (DMM) method for monitoring geomagnetically induced currents (GICs) is presentedThis augmented DMM technique provides two independent component‐wise measurements of GICsThe inferred GIC is compared and validated against transformer neutral‐to‐ground current data from Alberta's electrical power grid [ABSTRACT FROM AUTHOR]

Group B Streptococcus (GBS) is a major member of the Gram-positive Streptococcus family, which occupies a dominant position in the infection spectrum of newborns and young infants. GBS infections occurring 0‒6 days after birth are called GBS early-onset disease (GBS-EOD), and those occurring 7‒89 days are called GBS late-onset disease (GBS-LOD). With the use of intrapartum antibiotic prophylaxis, the incidence of neonatal GBS-EOD has declined without a notable impact on GBS-LOD, which brings great pressure and challenge to clinical diagnosis and nursing work. However, the specific mechanisms by which GBS transmission triggers illness in newborns and young infants are not fully elucidated. Some factors, such as maternal GBS colonization, maternal characteristics (age, weight and ethnicity), preterm birth, GBS infection in multiple births, and exposure to human immunodeficiency virus, have been identified as risk factors for GBS-LOD. To prevent maternal and infant GBS infection, some measures, such as vaccination of pregnant women, gut microbiota regulation and lactoferrin supplementation, are developing. In addition, strengthening maternal health care and health education, along with some other conventional infection control strategies (including enhancing hand hygiene awareness among caregivers and making good disinfection of the environment and equipment) is also effective in the prevention of GBS-LOD. This review elaborates the prevalence, transmission, risk factors and prevention of GBS-LOD in infants, aiming to improve the understanding and clinical practice ability of the medical staff.

C21H18BrO3P, monoclinic, P21/c (no. 14), a = 20.2890(9) Å, b = 5.9736(2) Å, c = 16.1577(8) Å, β = 105.371(2)°, V = 1888.24(14) Å3, Z = 4, R gt(F) = 0.1359, wR ref(F 2) = 0.1414, T = 298.00 K.

In order to study the motion characteristics of the prosthesis, a three‐dimensional model of the test platform was established, and the corresponding control scheme was designed according to this model. For the lower limb prosthesis test platform, a fuzzy proportion‐integration‐differentiation (PID) control model was created. Second, the matlab modules were used to construct the virtual model, and the goal function's control research was conducted. Finally, a virtual model was created, and the outcomes were studied, in order to assess the differences between the control results of proportional‐integral‐differential controller and fuzzy proportional‐integral‐differential controller. The results verify that the test platform using fuzzy proportional‐integral‐differential controller is capable of greater stability. The lower limb prosthetic knee joint test platform was built, and the corresponding experimental research was carried out on the motion of the lower limb prosthetic knee joint. The experimental data showed that the angle error of the hip joint was within 2° when the normal human gait was walking on the ground. The error of the joint angle does not exceed 3°. The prosthesis can clearly better mimic the angles of the hip and knee joints. [ABSTRACT FROM AUTHOR]

The nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome is an inflammatory protein complex, and can participate into the inflammatory response. Upon activation, these inflammasomes can lead to Caspase-1 activation, thereby inducing a cascade of inflammatory factor activation and further cell pyroptosis. Excessive activation of inflammasomes will induce the overexpression of inflammatory factors, persistently triggering immune dysregulation and inflammatory chain reactions, even causing severe damage. The recent studies have confirmed a close association between retinal diseases, such as diabetic retinopathy(DR), retinal ischemia-reperfusion injury(RIRI), and proliferative vitreoretinopathy(PVR)with immune dysregulation and inflammatory responses, which is serving as crucial factors in the progression of retinal diseases. This article reviews the NLRP3 inflammasome signaling pathway and its role in the occurrence and development of retinal diseases, in order to provide new ideas for the pathogenesis and prevention of retinal diseases.

To meet the growing demand for integrated monitoring of complex power grid equipment, it is necessary to improve the situational awareness model of power transformers. The model is expected to assist monitoring personnel in timely identifying transformers with deteriorating trends among massive and discrete monitoring information, and to make responses in advance. However, the current transformer state awareness technology generally has the problem of single data source and poor timeliness, and still requires monitoring personnel to make artificial analysis and prediction in combination with telemetry information, which cannot fully meet the requirements of power grid equipment monitoring. This paper is based on multi-source data fusion technology, through associating and mining transformer alarm information, equipment maintenance records and power transmission and transformation online monitoring data, to extract the dimension features of transformer operation situation assessment. By constructing a multi-layer perceptron model, a transformer state transition model based on the principle of Markov chain is established, which can predict possible defects 2 h in advance and achieve good results, and determine the transformer state early warning index, providing sufficient time for monitoring personnel to deploy transformer operation and maintenance work in advance. Finally, the effectiveness of the method proposed in this paper is proved by the case of transformer crisis state in a city substation, and the method proposed in this paper has important significance for transformer state early warning.