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Qi Wu,1,* Kexin Liu,2,* Ruijuan Hou,1 Xingxing Wu,3 Xiaoyu Ruan,4 Mao Wang,5 Zhiting Sun,6 Lingchang Meng,6 Guoliang Dai,7 Changyin Li,7 Jing Wu,1,6 Genglin Mu6 1Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China; 2Department of Gastroenterology, The 981th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Chengde, Hebei, 067000, People’s Republic of China; 3Department of Gastroenterology, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, 450053, People’s Republic of China; 4Internal Medicine Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 5Ethics Committee, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 6Institute of Chinese Medicine of Nanjing University, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China; 7Clinical Pharmacology Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Wu, Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Institute of Chinese Medicine of Nanjing University, 321, Zhongshan Road, Nanjing, Jiangsu, People’s Republic of China, Tel +86 13451825475, Email wujing@njucm.edu.cnPurpose: Inflammatory bowel disease (IBD) is a serious disease that affects the metabolism and inflammatory responses of human beings. From the perspective of traditional Chinese medicine, damp-heat syndrome is one of the main syndromes of IBD. Rhizoma Paridis, also known as the root of Paris polyphylla, a well-known herbal medicine used in China, is used to treat IBD with damp-heat syndrome (IBD-DH). However, uncertainty still exists regarding the underlying mechanisms and the impact of Rhizoma Paridis on IBD-DH.Methods: The rats in the model (DAT) and medication administration (Rhizoma Paridis total saponins (RPTS) and Pennogenin (PN)) groups were given a high temperature and high humidity environment, high fat and high sugar diet combined with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish the model of experimental colitis of damp-heat type, and the normal control group (RNC) rats were given a normal diet at normal temperature and humidity. Damp-heat control group (DNC) was set with the same condition as DAT without TNBS. Hematoxylin-Eosin (HE) staining was used to observe the histopathological morphology of the rat colorectum. The expression of the metabolism-related genes (Phospholipase A2 (sPLA2, cPLA2), and phosphatidylethanolamine N-methyltransferase (PEMT)) was assessed by using real-time quantitative PCR analysis (RT–qPCR). And the levels of the metabolism-related proteins (sPLA2, cPLA2), S100A8/9, Arg-1, and cytokines were detected by enzyme-linked immunosorbent assay (ELISA) kit. To investigate lipids and amino acids which closely associated with the IBD and IBD-DH, lipid pseudotargeted metabolomics with UHPLC-TQ/MS analysis method, as well as targeted quantitative amino acid analysis were performed.Results: Our data showed that RPTS (50 mg/kg) and PN (20 mg/kg) significantly ameliorated the severity of TNBS-induced colitis and downregulated the levels of circulating proinflammatory cytokines. Compared with RNC group, lipid pseudotargeted metabolomics demonstrated that glycerophospholipids, sphingolipids, carnitine, and glycerolipids were the four most perturbed lipid classes, and amino acids targeted metabolomics demonstrated that serine, N-acetylneuraminic acid, histidine, proline, taurine, and kynurenine changed significantly in DAT group . Correlation analyses showed tight associations between most of differential metabolites and proinflammatory cytokines. RPTS and PN both regulated glycerophospholipid metabolism and sphingolipid metabolism. However, both of them did not have a significant effect on amino acid modulation. RPTS and PN potentially regulated sPLA2, cPLA2, and PEMT.Conclusion: These results showed that RPTS (50 mg/kg) and PN (20 mg/kg) effectively alleviated rats’ colitis of damp-heat type, affected cytokines, and altered lipid metabolism without significant modulation on amino acid metabolism.Keywords: inflammatory bowel disease, lipid pseudotargeted metabolomics, amino acids targeted metabolomics, Rhizoma Paridis saponins, cytokines

Ganzhe Xu,1 Guoyu Dai,2 Zhongli Huang,3 Qiunong Guan,2 Caigan Du,2 Xiaoming Xu4 1Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Department of Biomedical Engineering, Guoke Ningbo Life Science and Health Industry Research Institute, Ningbo, Zhejiang, People’s Republic of China; 3Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Urology, Ningbo No. 2 Hospital, Ningbo, Zhejiang, People’s Republic of ChinaCorrespondence: Caigan Du, Department of Biomedical Engineering, Guoke Ningbo Life Science and Health Industry Research Institute, Ningbo, Zhejiang, People’s Republic of China, Email ducaigan@ucas.ac.cn Xiaoming Xu, Department of Urology, Ningbo No. 2 hospital, Ningbo, Zhejiang, People’s Republic of China, Email xiaomingxu6@sohu.comAbstract: Benign prostatic hyperplasia (BPH) mainly causes lower urinary tract symptoms in ageing men, but its exact etiology and pathogenesis have not been established. The objective of this review was to design an update on the advances of human BPH research. We undertook a literature search for identifying studies of the roles of sex hormones (androgens and estrogens) in the onset and development of human BPH using the Pubmed database. In literature, many studies have indicated that ageing and obesity are the factors for preceding the onset of BPH. No evidence for the role of testosterone (T) or dihydrotestosterone (DHT) is found in BPH initiation. Since BPH exclusively occurs in the transitional zone (TZ) surrounding the urethra, it is postulated that years of exposure to uncharacterized urinary toxins could disrupt the homeostasis of the stroma and/or epithelium of this prostatic zone that are typically occurring in ageing men. After cellular damage and subsequent inflammation generated, the intraprostatic DHT produced mainly from T by 5α-reductase promotes BPH development. Further, estrogens could take part in the nodular proliferation of stromal cells in some BPH patients. The confounding of BPH may attenuate the development of prostate tumor in the TZ. In conclusion, evidence in literature suggests that androgens are not etiological factors for BPH, and intraprostatic DHT along with chronic inflammation are mainly responsible for nodular proliferation of stromal and/or epithelial cells in prostatic TZ. The urinary factors for the etiology of BPH and BPH as a prediction of PCa progression still need further investigation.Keywords: benign prostatic hyperplasia, tissue homeostasis, etiology, nodular proliferation, stroma, epithelium, androgens, steroid sex hormones

Ying Zhang,1,* Xinxin Wang,1,* Xiaoqiao Sang,1,* Zhou Zhou,1 Guangrong Dai,1 Xiaobao Zhang1,2 1Department of Anesthesiology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, People’s Republic of China; 2The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaobao Zhang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 6 Zhenhua East Road, Lianyungang, Jiangsu, People’s Republic of China, Email hotdog100@163.comPurpose: Post-induction hypotension (PIH) is a common clinical phenomenon linked to increased morbidity and mortality in various non-cardiac surgeries. Patients with surgery in the afternoon may have preoperative hypovolemia caused by prolonged fasting and dehydration, which increases the risk of hypotension during the induction period. However, studies on the fluid therapy in early morning combating PIH remain inadequate. Therefore, we aimed to investigate the influence of prophylactic high-volume fluid in the early morning of the operation day on the incidence of PIH during non-cardiac surgery after noon.Patients and Methods: We reviewed the medical records of patients who underwent non-cardiac surgery after noon between October 2021 and October 2022. The patients were divided into two groups based on whether they received a substantial volume of intravenous fluid (high-volume group) or not (low-volume group) in the early morning of the surgery day. We investigated the incidence of PIH and intraoperative hypotension (IOH) as well as the accumulated duration of PIH in the first 15 minutes. In total, 550 patients were included in the analysis.Results: After propensity score matching, the incidence of PIH was 39.7% in the high-volume group and 54.1% in the low-volume group. Multivariate logistic regression analysis showed that patients in the high-volume group had lower incidence of hypotension after induction compared with the low-volume group (odds ratio, 0.55; 95% CI, 0.34– 0.89; p = 0.016). The high-volume fluid infusion in the preoperative morning was significantly correlated with the decreased duration of PIH (p = 0.013), but no statistical difference was observed for the occurrence of IOH between the two groups (p = 0.075).Conclusion: The fluid therapy of more than or equal to 1000 mL in the early morning of the surgery day was associated with a decreased incidence of PIH compared with the low-volume group in patients undergoing non-cardiac surgery after noon.Keywords: anesthesia induction, hypotension, fluid optimization, preoperative rehydration, hemodynamic instability

Chunmei Yang,1,* Xiaoling Che,1,* Yu Zhang,2 Didi Gu,1 Guidong Dai,1 Jian Shu,1 Lu Yang1 1Department of Radiology, The Affiliated Hospital of Southwest Medical University, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan Province, People’s Republic of China; 2Department of Radiology, The First People’s Hospital of Yibin, Yibin, 644000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Shu; Lu Yang, Department of Radiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, People’s Republic of China, Tel +86 0830-18980253083 ; +86 0830-2504762, Email shujiannc@163.com; yanglu@swmu.edu.cnBackground: Development of versatile nanoplatform still remains a great challenge due to multistep synthesis and complicated compositions. Therefore, it is significant to develop a facile method to synthesize a nanocomposite to achieve multimodal imaging and even imaging-guided cancer therapeutics.Methods and Results: In our study, hyaluronic acid-functionalized iron (II) tungstate nanoparticles (HA-FeWO4 NPs) were successfully synthesized as a versatile nanoplatform by a facile one-pot hydrothermal procedure. The formed multifunctional HA-FeWO4 NPs were investigated via a series of characterization techniques, which demonstrated good biocompatibility, excellent dispersion, low cytotoxicity, active tumor-targeting ability and high photothermal efficiency. Furthermore, tumor was clearly visualized by HA-FeWO4 NPs with multimodal imaging of infrared thermal imaging, magnetic resonance imaging, computed tomography imaging in 4T1 tumor bearing mice. More importantly, HA-FeWO4 could achieve multimodal imaging-guided photothermal therapy of 4T1 tumors.Conclusion: The constructed HA-FeWO4 NPs have great potential as ideal nanotheranostic agents for multimodal imaging and even imaging-guided cancer theranostics in biological systems.Keywords: theranostics, multimodal imaging, photothermal therapy, diagnostic imaging, nanomedicine

Superconducting materials exhibiting topological properties are emerging as an exciting platform to realize fundamentally new excitations from topological quantum states of matter. In this letter, we explore the possibility of a field-free platform for generating Majorana zero energy excitations by depositing magnetic Fe impurities on the surface of candidate topological superconductors, LiFeAs and PbTaSe2. We use scanning tunneling microscopy to probe localized states induced at the Fe adatoms on the atomic scale and at sub-Kelvin temperatures. We find that each Fe adatom generates a striking zero-energy bound state inside the superconducting gap, which do not split in magnetic fields up to 8 T, underlining a nontrivial topological origin. Our findings point to magnetic Fe adatoms evaporated on bulk superconductors with topological surface states for exploring Majorana zero modes and quantum information science under field-free conditions.

GuiYing Dai,1,* JunYu Wang,1 FengLi Gao,2 WenHong Liu,1 Ping Li,1 Bing Wei,1 Jun Yang1,* 1Emergency Medicine Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, & Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing, People’s Republic of China; 2Nursing Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Yang, Emergency Medicine Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, & Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing, People’s Republic of China, Tel +86-13581846750, Fax +86-51718170, Email yangjun26@sina.comPurpose: To investigate the nursing prediction value of Barthel score, sequential organ failure assessment (SOFA) score and D-dimer on non-ST-elevation myocardial infarction (NSTEMI) inpatients.Methods: The clinical data of 358 NSTEMI patients admitted to the emergency department were analyzed using logistic regression equation and a ROC curve was drawn. The area under ROC curve (AUC) of different indicators was compared. A COX regression model was created, and a survival curve was drawn.Results: There were significant differences in age, D-dimer, WBC, NT-proBNP, EF (%), BI score, MEWS score, and SOFA score between the 28-day death group and the survival group (P

Hong Wang,1,&ast; Tao Yang,2,&ast; Xiaodan Yu,3,&ast; Zhihong Chen,4 Yajuan Ran,5 Jiajia Wang,6 Guangming Dai,1 Huojin Deng,7 Xinglong Li,8 Tao Zhu8 1Respiratory Medicine, First People’s Hospital of Suining City, Suining, 629000, Sichuan, People’s Republic of China; 2Thoracic Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 3Respiratory Medicine, Fifth People’s Hospital of Chengdu, Chengdu, 610000, Sichuan, People’s Republic of China; 4Respiratory Medicine, Zhongshan Hospital of Fudan University, Shanghai, 20032, People’s Republic of China; 5Pharmacy Department, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 6Rheumatology Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 7Respiratory Medicine, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510280, People’s Republic of China; 8Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Zhu, Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China, Tel +86 23 63693094, Email zhutao063020@163.comBackground/Purpose: A patient’s length of hospital stay (LHS) is associated with the severity and outcome of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Therefore, identification of patients with prolonged LHS at an early stage can potentially reduce the risk of adverse events and treatment costs in patients with AECOPD. Therefore, this study aimed to explore the independent predictors of prolonged LHS in AECOPD patients.Patients and Methods: This multicenter cross-sectional study was conducted at two tertiary hospitals between January 2019 and August 2020. Demographic data, underlying diseases, symptoms, and laboratory findings were collected. Univariate analysis was used to identify variables with significant differences. A collinearity diagnostic was applied to the selected variables before the establishment of the regression model. Ordinal logistic regression was performed to explore the independent risk factors for prolonged LHS in patients with AECOPD.Results: In total, 598 patients with AECOPD were screened. Finally, the LHS of 111, 218, and 100 patients was < 7, 7– 10, and ≥ 11 days, respectively. Significant differences in the 12 variables were found in the univariate analysis. Because collinearities among white blood cells (WBC), neutrophils (NS), and NS% were observed, WBC and NS% were excluded. Subsequently, an ordinal logistic regression model identified that rates of hypertension and chronic cor pulmonale (CCP), neutrophil–lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR) were independent predictors of prolonged LHS in AECOPD patients.Conclusion: Collectively, our results showed that inflammatory status, hypertension, and CCP were independently associated with LHS in patients with AECOPD. These data indicate that early and appropriate administration of antibiotics and anti-inflammatory drugs is essential for reducing LHS. Hypertension and CCP were independent predictors of worse outcomes in patients with AECOPD. Therefore, advanced management and care should be provided to AECOPD patients with hypertension and/or CCP on admission.Keywords: acute exacerbation of chronic obstructive pulmonary disease, chronic cor pulmonale, erythrocyte sedimentation rate, hypertension, length of hospital stay, neutrophil–lymphocyte ratio

Gaosai Dai,1 Yupeng Yang,2 Shuhao Liu,3 Huantao Liu1 1Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Department of Thyroid and Breast Surgery, Jinan Zhangqiu District Hospital of TCM, Jinan, Shandong, 250200, People’s Republic of China; 3Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Huantao LiuDepartment of Breast Surgery, Qilu Hospital of Shandong University, Wenhuaxi Road 107, Jinan, Shandong, 250012, People’s Republic of ChinaEmail liuhuantao3l@163.comBackground: Hypoxia is an important process that involved in the tumor microenvironment. In addition, hypoxic tumor cell-derived exosomes could promote tumor growth and angiogenesis. Thus, we aimed to investigate whether exosomes could regulate tumor development and progression under hypoxia in breast cancer.Methods: The level of SNHG1 in hypoxic breast cancer cells and exosomes derived from hypoxic breast cancer cells was determined by real-time qPCR assay. Bioinformatics prediction and dual-luciferase reporter assays were used to determine the interaction between SNHG1, miR-216b-5p and JAK2.Results: We found that comparing with exosomes derived from normoxia breast cancer cells, exosomes derived from hypoxic breast cancer cells could promote the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs). In addition, SNHG1 level was significantly upregulated in exosomes derived from hypoxic breast cancer cells. Moreover, exosome-mediated delivery of SNHG1 siRNA3 markedly reversed the effects of exosome-mediated delivery of SNHG1 on HUVECs. Mechanically, SNHG1 could increase the level of JAK2 by competitively binding to miR-216b-5p. Additionally, exosome-mediated delivery of SNHG1 was found to promote breast cancer growth in vivo.Conclusion: Collectively, our study revealed that exosomal SNHG1 from hypoxic breast cancer cells could promote tumor angiogenesis and growth via regulating miR-216b-5p/JAK2 axis, suggesting that SNHG1 may serve as a potential therapeutic target for breast cancer.Keywords: breast cancer, exosomes, tumor microenvironment, hypoxia, long noncoding RNAs

Yulan Yan,1,&ast; Chunmei Yang,1,&ast; Guidong Dai,1 Yu Zhang,1 Guojian Tu,1 Yuwei Li,2 Lu Yang,1 Jian Shu1 1Department of Radiology, The Affiliated Hospital of Southwest Medical University, and Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan Province, People’s Republic of China; 2Department of Interventional Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Yang; Jian ShuDepartment of Radiology, The Affiliated Hospital of Southwest Medical University, and Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan Province, People’s Republic of ChinaTel +86 830-2504762; +86 18980253083Email yangluchem@qq.com; shujiannc@163.comBackground: Development of new long-circulating contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI) of different biological systems still remains a great challenge. Here, we report the synthesis of folic acid (FA)-targeted CuFeSe2 nano-contrast agent for CT and MRI imaging in vitro and in vivo.Methods and Results: In our study, CuFeSe2 was fabricated through a facile and green aqueous reaction and then further aminated through silanization. The amine-functionalized CuFeSe2-NH2 nanoparticles enable the covalent conjugation of folate-conjugated polyethylene glycol (FA-PEG-COOH) as a targeting ligand onto their surface, which could improve the dispersion and endue the targetability of nanoparticles, respectively. The formed multifunctional CuFeSe2-PEG-FA nanoparticles were characterized via different techniques, which exhibited outstanding dispersion, good biocompatibility and excellent FA-targeted capability. Meanwhile, the nanoparticles were quite safe in the given concentration range as confirmed by in vitro and in vivo toxicity assay. Importantly, CuFeSe2-PEG-FA nanoparticles were successfully applied in CT/MRI dual-modality imaging in vitro and in vivo, which showed a better imaging performance and targeted capability.Conclusion: Therefore, the constructed CuFeSe2-PEG-FA nanoparticles have a great potential as an efficient contrast agent for dual-modality imaging of different biological systems.Keywords: CuFeSe2 nanoparticles, magnetic resonance imaging, computed tomography imaging, dual-modality imaging, folic acid

Guohua Dai, Shuzhong Li, Chuqiang Yin, Yuanliang Sun, Derong Xu, Zhongying Wang, Liangrui Luan, Jianwen Hou, Ting Wang Affiliated Hospital of Qingdao University, Qingdao 266003, People’s Republic of ChinaCorrespondence: Ting Wang Tel +86 18661809505Email wangting20@hotmail.comObjective: In the present study, we aimed to describe the clinical features, diagnosis, treatment, and prognosis of spinal epidural abscess (SEA).Methods: The complete clinical data of 11 SEA patients who were treated in our hospital system from January 2015 to June 2018 were retrospectively analyzed. Moreover, the clinical features, diagnosis, treatment, and prognosis of 642 SEA cases collected from the foreign literature from 2010 to 2019 were also investigated.Results: Among our 11 SEA patients, nine cases had purulent inflammation, two cases had tuberculosis, two cases had infection caused by Staphylococcus aureus, one case had infection caused by Streptococcus constellatus, one case had infection caused by Klebsiella pneumoniae, five cases showed negative bacterial culture, and two cases had Mycobacterium tuberculosis. All 11 cases showed focal spinal pain, eight cases exhibited neurological deficits, and six cases experienced fever. Nine of the 11 cases involved the lumbosacral spine, one case involved the thoracic spine, and one case involved the cervical spine. Eight patients had a longer course of disease (> 2 weeks), all 11 patients had vertebral osteomyelitis, and nine patients had intervertebral discitis. One patient had motor dysfunction of arms and legs, one patient had lower limb motor dysfunction, one patient had limb numbness, one patient experienced relapse after the conservative treatment, and one patient experienced relapse after the surgical treatment. The follow-up time was 15– 24 months.Conclusion: The classic diagnosis of triads (focal spine pain, neurological deficit, and fever) was less specific for SEA. MRI examination, blood culture, tissue culture, and biopsy could be used for the diagnosis for SEA. Suppuritis was a common cause of SEA. Early detection, early diagnosis and early treatment, as well as the selection of the most suitable treatment regimen based on comprehensive evaluation, played crucial roles in a better prognosis of SEA. There was no statistically significant difference in terms of the general condition, diagnosis, treatment and prognosis between the patients with negative and positive culture results (P> 0.05). For SEA patient with negative culture, antibiotic treatment should be used empirically.Keywords: epidural abscess, clinical features, diagnosis and treatment, prognosis

Shijing Liao,1,* Yapeng Zhang,1,* Xuanhe Pan,1 Feizhou Zhu,2 Congyuan Jiang,3 Qianqian Liu,2 Zhongyi Cheng,4 Gan Dai,1 Guojun Wu,1 Linqian Wang,5 Liyu Chen1 1Department of Medical Microbiology, School of Basic Medical Sciences, Central South University, Changsha 410013, China; 2Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, Changsha 410013, China; 3Hunan Anson Biotechnology Co., Ltd., Changsha 410008, China; 4Jingjie PTM BioLab Co., Ltd., Hangzhou Economic and Technological Development Area, Hangzhou 310018, China; 5Department of Clinical Laboratory, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China *These authors contributed equally to this work Background: The threat of drug-resistant Pseudomonas aeruginosa requires great efforts to develop highly effective and safe bactericide. Objective: This study aimed to investigate the antibacterial activity and mechanism of silver nanoparticles (AgNPs) against multidrug-resistant P. aeruginosa. Methods: The antimicrobial effect of AgNPs on clinical isolates of resistant P. aeruginosa was assessed by minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). In multidrug-resistant P. aeruginosa, the alterations of morphology and structure were observed by the transmission electron microscopy (TEM); the differentially expressed proteins were analyzed by quantitative proteomics; the production of reactive oxygen species (ROS) was assayed by H2DCF-DA staining; the activity of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) was chemically measured and the apoptosis-like effect was determined by flow cytometry. Results: Antimicrobial tests revealed that AgNPs had highly bactericidal effect on the drug-resistant or multidrug-resistant P. aeruginosa with the MIC range of 1.406–5.625 µg/mL and the MBC range of 2.813–5.625 µg/mL. TEM showed that AgNPs could enter the multidrug-resistant bacteria and impair their morphology and structure. The proteomics quantified that, in the AgNP-treated bacteria, the levels of SOD, CAT, and POD, such as alkyl hydroperoxide reductase and organic hydroperoxide resistance protein, were obviously high, as well as the significant upregulation of low oxygen regulatory oxidases, including cbb3-type cytochrome c oxidase subunit P2, N2, and O2. Further results confirmed the excessive production of ROS. The antioxidants, reduced glutathione and ascorbic acid, partially antagonized the antibacterial action of AgNPs. The apoptosis-like rate of AgNP-treated bacteria was remarkably higher than that of the untreated bacteria (P