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Ning Cui,1 Feng Ding2 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Feng Ding, Email dingfengkt@163.comBackground: Tumor-Node-Metastasis (TNM) stage of gastric cancer (GC) is one of the main factors affecting clinical outcome. The aim of this study was to explore the targets related to TNM stage of GC, and screening natural bioactive drug.Methods: RNA sequencing data of the TCGA-STAD cohort were downloaded from UCSC database. Genes associated with TNM staging were identified by weighted gene co-expression network analysis (WGCNA). Univariate Cox regression, least absolute shrinkage and selection operator (LASSO), extreme gradient boosting (Xgboost), random forest (RF) and cytohubba plug-in of cytoscope were applied to screen hub genes. Natural bioactive ingredients were available from the HERB database. Molecular docking was used to evaluate the binding activity of active ingredients to the hub protein. CCK-8, flow cytometry, transwell and Western blot assays were used to analyze the effects of diosgenin on GC cells.Results: 898 TNM-related genes were screened out through WGCNA. Three genes associated with GC progression/prognosis were identified, including nuclear receptor subfamily 3 group C member 2 (NR3C2), solute carrier family 1 member 5 (SLC1A5) and FAT atypical cadherin 1 (FAT1) based on the machine learning algorithms and hub co-expression network analysis. Diosgenin had good binding activity with SLC1A5. SLC1A5 was highly expressed in GC and was closely associated with tumor stage, overall survival and immune infiltration of GC patients. Diosgenin could inhibit cell viability and invasive ability, promote apoptosis and induce cell cycle arrest in G0/G1 phase. In addition, diosgenin promoted cleaved caspase 3 expression and inhibited Ki67, cyclin D1, p-S6K1, and SLC1A5 expression levels, while the mTORC1 activator (MHY1485) reversed this phenomenon.Conclusion: For the first time, this work reports diosgenin may inhibit the activation of mTORC1 signaling through targeting SLC1A5, thereby inhibiting the malignant behaviors of GC cells.Keywords: gastric cancer, weighted gene co-expression network analysis, diosgenin, molecular docking, diosgenin

Lihua Dai,1,* Zheqian Wu,1,* Liili Yin,1 Longjian Cheng,1 Qiang Zhou,2 Fei Ding1 1Department of Emergency, Shidong Hospital, ShangHai, People’s Republic of China; 2Department of General Surgery, Eighth People’s Hospital, ShangHai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Ding; Qiang Zhou, Email 10119038@qq.com; rabbit1264@163.comBackground: Upon uptake by stressed cells, functional mitochondria can perform their normal functions, ultimately enhancing the survival of host cells. However, despite the promising results of this approach, there is still a lack of understanding of the specific relationship between nerve cells and functional mitochondria.Methods: Functional mitochondria (F-Mito) were isolated from bone marrow-derived mesenchymal stem cells (BMSCs). The ability of microglia cells to internalize F-Mito was evaluated using a middle cerebral artery occlusion (MCAO) model in C57BL/6J mice and an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model. After OGD/R and F-Mito treatment, the temporal dynamics of intracellular reactive oxygen species (ROS) levels were examined.The relationship between ROS levels and F-Mito uptake was assessed at the individual cell level using MitoSOX, Mitotracker, and HIF-1α labeling.Results: Our findings indicate that microglia cells exhibit enhanced mitochondrial uptake compared to astrocytes. Furthermore, internalized F-Mito reduced ROS levels and HIF-1α levels. Importantly, we found that the ROS response in microglia cells following ischemia is a critical regulator of F-Mito internalization, and promoting autophagy in microglia cells might reduce the uptake of ROS and HIF-1α levels.Conclusion: It is verified that F-Mito derived from BMSCs play a protective role in ischemia-reperfusion injury, as their weakening reduces microglial cell activation and alleviates neuroinflammation.Keywords: neuroinflammation, ROS, stem cell, HIF-1α, ischemic stroke

Shengfang Bao, Hua Huang, Yingying Jin, Fei Ding, Zhen Yang, Xuemei Xu, Chenxi Liu, Xiqiong Han, Liping Wang, Jingyi Lu, Jiani Ma, Yanliang Jin Department of Rheumatology & Immunology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, People’s Republic of ChinaCorrespondence: Yanliang Jin, Email jinyanliang@scmc.com.cnAbstract: Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, benign, and self-limiting condition characterized by lymph node inflammation. While KFD is rarely associated with ocular manifestations, our case report highlights bilateral optic neuritis in a 13-year-old male patient with KFD. We also provide a comprehensive review of similar cases in the literature.Keywords: Kikuchi-Fujimoto disease, optic neuritis, neuromyelitis optica spectrum disorder, vision deficiency

Jiao Chen, Danmei Luo, Chengxia Sun, Xiaolan Sun, Changmao Dai, Xiaohong Hu, Liangqing Wu, Haiyan Lei, Fang Ding, Wei Chen, Xueping Li Geriatric Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Xueping Li, Chengdu University of Traditional Chinese Medicine, No. 37, Shier Bridge Road, Chengdu, Sichuan, People’s Republic of China, Tel +86-18380251086, Email 3173907@qq.comPurpose: Building and validating a clinical prediction model for novel coronavirus (COVID-19) re-positive cases in malnourished older adults.Patients and Methods: Malnourished older adults from January to May 2023 were retrospectively collected from the Department of Geriatrics of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. They were divided into a “non-re-positive” group and a “re-positive” group based on the number of COVID-19 infections, and into a training set and a validation set at a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify predictive factors for COVID-19 re-positivity in malnourished older adults, and a nomogram was constructed. Independent influencing factors were screened by multivariate logistic regression. The model’s goodness-of-fit, discrimination, calibration, and clinical impact were assessed by Hosmer-Lemeshow test, area under the curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CIC), respectively.Results: We included 347 cases, 243 in the training set, and 104 in the validation set. We screened 10 variables as factors influencing the outcome. By multivariate logistic regression analysis, preliminary identified protective factors, risk factors, and independent influencing factors that affect the re-positive outcome. We constructed a clinical prediction model for COVID-19 re-positivity in malnourished older adults. The Hosmer-Lemeshow test yielded χ2 =5.916, P =0.657; the AUC was 0.881; when the threshold probability was > 8%, using this model to predict whether malnourished older adults were re-positive for COVID-19 was more beneficial than implementing intervention programs for all patients; when the threshold was > 80%, the positive estimated value was closer to the actual number of cases.Conclusion: This model can help identify the risk of COVID-19 re-positivity in malnourished older adults early, facilitate early clinical decision-making and intervention, and have important implications for improving patient outcomes. We also expect more large-scale, multicenter studies to further validate, refine, and update this model.Keywords: malnutrition, COVID-19, re-positive, clinical prediction model

Danni Xue,1,* Binghai Sun,1,* Weijian Li,1 Hui Zhou,2 Fujun Ding,1 Weilong Xiao1,3 1School of Psychology, Zhejiang Normal University, Jinhua, 321004, People’s Republic of China; 2Jinhua Advanced Research Institute, Jinhua, Zhejiang, 321004, People’s Republic of China; 3Research Unit Occupational & Organizational Psychology and Professional Learning, KU Leuven, Leuven, 3000, Belgium*These authors contributed equally to this workCorrespondence: Fujun Ding, School of Psychology, Zhejiang Normal University, 688 Yingbin Road, Jinhua, 321004, People’s Republic of China, Email dfj201810100017@163.comBackground: Teacher burnout is characterized by emotional and physical exhaustion resulting from excessive work-related stress. Previous research based on traditional latent variable theory has revealed a significant negative relationship between TB and psychological capital (PsyCap). This study explored the complex symptoms of TB and the contact points of PsyCap in reducing TB using psychometric network analysis.Methods: A total of 3991 teachers completed the burnout subscale of the Professional Quality of Life and Psychological Capital Scale.Results: The results showed that: (a) In the TB network, the core symptoms displayed by teachers due to burnout are difficulty feeling “I am a very caring person”, “I am happy”, and “I am the person I always wanted to be”; (b) The TB-PsyCap network was closely connected, and the symptoms affected each other. PsyCap affected the TB network through “I feel optimistic and happy almost every day” and “I often feel that there is a future as a teacher”; (c) PsyCap’s bridge symptoms had a negative impact on TB, and PsyCap may reduce TB primarily through optimistic, hopeful dimensions.Conclusion and Implications: Psychometric network analysis helps us understand the complex symptoms of TB and the contact points of PsyCap in reducing TB. This study offers valuable insights into the prevention of, and intervention in, burnout within the teaching community.Keywords: teacher burnout, psychological capital, network analysis, network comparison

Bo Liu,1,2 Yan Li,2,3 Jinying Xiang,2,3 Yuehan Li,2,3 Mi Zhou,2,3 Yinying Ren,2,3 Zhou Fu,2,3 Fengxia Ding2,3 1Department of Cardiothoracic Surgery, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Pediatrics, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Respiratory Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Fengxia Ding, Department of Respiratory Medicine, Ministry of Education Key Laboratory of Child Development and Disorder, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children’s Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong Dis, Chongqing, 400014, People’s Republic of China, Tel +86-15178712548, Email 482613@hospital.cqmu.edu.cnObjective: This study aimed to investigate the role of pyroptosis in alveolar macrophages regarding the immune microenvironment of acute respiratory distress syndrome (ARDS) and its prognosis.Methods: ARDS Microarray data were downloaded from Gene Expression Omnibus (GEO). Support vector machine (SVM) and random forest (RF) models were applied to identify hub pyroptosis-related genes (PRGs) with prognostic significance in ARDS. RT-PCR was used to detect the relative expression of PRGs mRNA in alveolar macrophages of ARDS mice. Consensus clustering analysis was conducted based on the expression of the PRGs to identify pyroptosis modification patterns. Bioinformatic algorithms were used to study the immune traits and biological functions of the pyroptosis patterns. Finally, protein-protein interaction (PPI) networks were established to identify hub regulatory proteins with implications for the pyroptosis patterns.Results: In our study, a total of 12 PRGs with differential expression were obtained. Four hub PRGs, including GPX4, IL6, IL18 and NLRP3, were identified and proven to be predictive of ventilator-free days (VFDS) in ARDS patients. The AUC values of the 4 PRGs were 0.911 (GPX4), 0.879 (IL18), 0.851 (IL6) and 0.841 (NLRP3), respectively. In ARDS mice, GPX4 mRNA decreased significantly, while IL6, IL18, and NLRP3 mRNA increased. Functional analysis revealed that IL6 had the strongest positive correlation with the CCR pathway, while GPX4 exhibited the strongest negative correlation with the T co-inhibition pathway. Based on the expression of the 4 PRGs, three pyroptosis modification patterns representing different immune states were obtained, and pattern C might represent immune storm.Conclusion: The results showed that pyroptosis plays an important regulatory role in the immune microenvironment of ARDS. This finding provides new insights into the pathogenesis, diagnosis, and treatment of ARDS.Keywords: ARDS, macrophage, pyroptosis, immune, prognosis

Yumei Zhang,1,* Xin Li,1,* Suning Zhang,2 Wei Chen,3 Jianxin Lu,1 Yingxin Xie,1 Shengbin Wu,1 Feng Zhuang,1 Xiao Bi,1 Mingzi Chu,1 Feng Wang,1 Yemin Huang,1 Feng Ding,1 Chun Hu,1 Yu Pan1 1Division of Nephrology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Division of Emergency, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Division of Neurology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu Pan; Chun Hu, Division of Nephrology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201900, People’s Republic of China, Tel +86-021-56691101, Email panyu1980@163.com; spring_115@hotmail.comBackground: Since little is known about the acute kidney injury (AKI) in aging population infected with SARS-CoV-2 Omicron variant, we investigated the incidence, clinical features, risk factors and mid-term outcomes of AKI in hospitalized geriatric patients with and without COVID-19 and established a prediction model for mortality.Methods: A real-time data from the Shanghai Ninth People’s Hospital information system of inpatients with COVID-19 from 1 April 2022 to 30 June 2022 were extracted. Clinical spectrum, laboratory results, and clinical prognosis were included for the risk analyses. Moreover, Cox and Lasso regression analyses were applied to predict the 90-day death and a nomogram was established.Results: A total of 1607 SARS-CoV-2 infected patients were enrolled; hypertension was the most common comorbidity, followed by chronic cardiovascular disease, diabetes mellitus, and lung disease. Most of the participants were non-vaccinated and the mean age of patients was 82.6 years old (range, 60– 103 years). The AKI incidence was higher in relatively older patients (16.29% vs 3.63% in patients older than 80 years and 60 to 80 years, respectively). Linear regression models identified some variables associated with the incidence of AKI, such as older age, clinical spectrum, D-dimer level, number of comorbidities, baseline eGFR, and antibiotic or corticosteroid treatment. In this cohort, 11 patients died in-hospital and 21 patients died at 90-day follow-up. The predictive nomogram of 90-day death achieved a good C-index of 0.823 by using 5 predictor variables: ICU admission, D-dimer, peak of serum creatinine, rate of serum creatinine decline and white blood cell count (WBC).Conclusion: Older age, clinical spectrum, D-dimer level, number of comorbidities, baseline eGFR, and antibiotic or corticosteroid treatment are clinical risk factors for the incidence of AKI in geriatric COVID-19 patients. The prediction nomogram achieved an excellent performance at the prediction of 90-day mortality.Keywords: COVID-19, Omicron, acute kidney injury, aging, predictive nomogram

Rong Yu,1,&ast; Chuan Liu,1,&ast; Jixiang Zhang,1,&ast; Jiao Li,1,&ast; Shan Tian,2 Fugui Ding,1 Zhengru Liu,3 Ting Wang,4 Zhongchun Liu,5 Changqing Jiang,6 Jie Shi,7 Kaichun Wu,8 Weiguo Dong1 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 2Department of Infectious Diseases, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, People’s Republic of China; 3Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 4Department of Gastroenterology, First Affiliated Hospital of Hainan Medical College, Haikou, 570102, People’s Republic of China; 5Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 6Department of Clinical Psychology, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, People’s Republic of China; 7Department of Medical Psychology, Chinese People’s Liberation Army Rocket Army Characteristic Medical Center, Beijing, 100088, People’s Republic of China; 8Department of Gastroenterology, Xijing Hospital, Air Force Medical University, Xi’an, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiguo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Tel +86 027-88041911, Email dongweiguo@whu.edu.cn Kaichun Wu, Department of Gastroenterology, Xijing Hospital, Air Force Medical University, No. 127 West Changle Road, Xi’an, Shaanxi Province, 710032, People’s Republic of China, Tel +86 029-84771600, Email kaicwu@fmmu.edu.cnObjective: To explore the correlation between disease activity and anxiety, depression, sleep quality, and quality of life in patients with inflammatory bowel disease (IBD).Methods: The disease activity of IBD patients was evaluated by 66 gastroenterologists from 42 hospitals in 22 provinces in China from September 2021 to May 2022. Anxiety, depression, sleep quality and quality of life of IBD patients were investigated and statistically analyzed by different scales, including Generalized Anxiety Disorder 7-item Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Quality-of-Life Questionnaire (IBD-Q).Results: A total of 2478 IBD patients were included, of which 1532 (61.8%) were in active stage and 946 (38.2%) were in remission. The proportions of active IBD with anxiety, depression, sleep disturbance, and poor quality of life were 29.5%, 29.7%, 71.1%, and 50.1%, respectively, while the proportions of remission IBD with anxiety, depression, sleep disturbance, and poor quality of life were 19.1%, 24.4%, 69.3%, and 17.4%, respectively. IBD patients who also had anxiety, depression, sleep disturbances and poor quality of life had 80 cases (8.46%) in remission and 114 cases (7.44%) in active stage, with 54 cases (9.18%) in mild activity, 51 cases (6.95%) in moderate activity and 9 cases (4.49%) in severe activity. IBD patients with different disease activity levels differed in GAD-7 scores, PHQ-9 scores, PSQI scores, and IBD-Q scores (all P< 0.001). In IBD patients, anxiety, depression, and sleep disturbance, which interact with each other, can further aggravate their disease activity (all P< 0.001).Conclusion: Anxiety, depression, sleep disturbances, and quality of life are strongly correlated with disease activity in IBD patients, and IBD patients with psychological disturbances are most often in the active stage and have a poor quality of life.Keywords: inflammatory bowel disease, disease activity, anxiety, depression, sleep quality, quality of life, survey

Shengfang Bao,1,&ast; Jingyi Lu,1,&ast; Hua Huang,1 Ying-Ying Jin,1 Fei Ding,1 Zhen Yang,1 Xuemei Xu,1 Chenxi Liu,1 Xi Mo,2 Yanliang Jin1 1Department of Rheumatology & Immunology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi Mo; Yanliang Jin, Email xi.mo@shsmu.edu.cn; jinyanliang@scmc.com.cnObjective: To evaluate the risk of major infections in children with newly diagnosed childhood-onset systemic lupus erythematosus (cSLE).Methods: Predictors of major infections were identified by the multivariable logistic regression. Major infection free was defined as no major infection events within 6 months after the diagnosis of cSLE. The Kaplan–Meier survival plot was performed. A prediction model for major infection events was established and examined by receiver operating characteristic (ROC) curve analysis.Results: A total of 98 eligible patients were recorded in the medical charts. Sixty-three documented events of major infections were found in 60 (61.2%) cSLE patients. Furthermore, 90.5% (57/63) of infection events occurred within the first 6 months after the diagnosis of cSLE. The high SLEDAI (SLEDAI > 10), lupus nephritis and lymphocyte count < 0.8× 109/L were predictors for major infections. The CALL score (Children with high disease activity [SLEDAI > 10], lymphopenia, and LN) was defined by the number of predictors. Patients were then categorized into two groups: low-risk (score 0– 1) and high-risk (score 2– 3). Patients in the high-risk group had higher rates of the major infection occurrence than those in the low-risk group during the 6 months after the diagnosis of the cSLE (P< 0.001) (HR:14.10, 95% CI 8.43 to 23.59). The ROC curve analysis indicated that the CALL score was effective both in the whole cSLE cohort [area under the curve (AUC) = 0.89, 95% CI: 0.81– 0.97] and in the subgroup of lung infections (n = 35) (AUC = 0.79, 95% CI: 0.57– 0.99).Conclusion: High disease activity, LN and lymphopenia were predictors for major infections in newly diagnosed cSLE patients. Specific predictors help identify the cSLE patients with the high risk of major infections. The CALL score could be a useful tool to stratify cSLE patients in practice.Keywords: lupus, infection, pediatrics

Zhang L, Ding F. Onco Targets Ther. 2019;12:6577–6589. We, the Editors and Publisher of OncoTargets and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 3, 5 and 7 with images from other unrelated articles. Specifically, Images for Figure 3A, have been duplicated with images for Figure 4B from Guo H, Peng J, Hu J, et al. BAIAP2L2 promotes the proliferation, migration and invasion of osteosarcoma associated with the Wnt/β-catenin pathway. Journal of Bone Oncology. 2021;31:100393. https://doi.org/10.1016/j.jbo.2021.100393 and Figure 4D from Ding F, Lai J, Gao Y, et al. NEAT1/miR-23a-3p/KLF3: a novel regulatory axis in melanoma cancer progression. Cancer Cell Int. 2019;19:217. https://doi.org/10.1186/s12935-019-0927-6. The image for Figure 5A, BCAP-37, SiRNA+inhibitor, has been duplicated with the image for Figure 2C, Agomir-936 from Xu L, Li W, Shi Q, et al. MicroRNA‑936 inhibits the malignant phenotype of retinoblastoma by directly targeting HDAC9 and deactivating the PI3K/AKT pathway. Oncology Reports. 2020;43:635-645. https://doi.org/10.3892/or.2020.7456 (RETRACTED) and Figure 3e, p-XIST+miR-192 mimics, from Wang J, Yin G, Bian H, et al. LncRNA XIST upregulates TRIM25 via negatively regulating miR-192 in hepatitis B virus-related hepatocellular carcinoma. Mol Med. 2021;27:41. https://doi.org/10.1186/s10020-021-00278-3. Images for Figure 7A, have been duplicated with images for Figure 3E from Ouyang Y, Tang Y, Fu L, et al. Exosomes secreted by chronic hepatitis B patients with PNALT and liver inflammation grade ≥ A2 promoted the progression of liver cancer by transferring miR-25-3p to inhibit the co-expression of TCF21 and HHIP. Cell Prolif. 2020;53:e12833. https://doi.org/10.1111/cpr.12833; Figure 5B from Li H, Yao G, Zhai J, Hu D, Fan Y. LncRNA FTX Promotes Proliferation and Invasion of Gastric Cancer via miR-144/ZFX Axis. Onco Targets Ther. 2019;12:11701-11713. https://doi.org/10.2147/OTT.S220998 (RETRACTED) and Figure 5C from Teng L, Liu P, Song X, Wang H, Sun J, Yin Z. Long Non-Coding RNA Nuclear-Enriched Abundant Transcript 1 (NEAT1) Represses Proliferation of Trophoblast Cells in Rats with Preeclampsia via the MicroRNA-373/FLT1 Axis. Med Sci Monit. 2020;26:e927305. DOI: https://doi.org/10.12659/MSM.927305. The authors did not respond to our queries and were unable to provide an explanation for the duplicated images or provide data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Jing Tian,1,2 Fengqin Ding,3 Ruoya Wang,3 Gangfei Han,1 Jingjing Yan,3 Na Yuan,3 Yutao Du,3 Qinghua Han,1 Yanbo Zhang2– 4 1Department of Cardiology, the 1st Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Taiyuan, People’s Republic of China; 3Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 4Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of ChinaCorrespondence: Yanbo Zhang, Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China, Tel +86 3327518812, Email sxmuzyb@126.com Correspondence: Qinghua Han, Department of Cardiology, the 1st Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Tel +86 3100113031, Email syhqh@sohu.comPurpose: This study aimed to identify subgroups of chronic heart failure (CHF) patients with distinct trajectories of quality of life (QOL) and to identify baseline characteristics associated with the trajectories.Patients and methods: Two-year, prospective, cohort study including 315 patients with CHF was conducted from July 2017. Information on QOL assessed by CHF-patient-reported outcomes measure (CHF-PROM) was collected at baseline, 6, 12, 18, and 24 months. Demographic and clinical variables were recorded at baseline. Growth mixture model was used to identify distinct trajectories of CHF-PROM and its physical, psychological, social, and therapeutic domains. Single factor analysis was employed to assess the factors associated with development of CHF-PROM over time.Results: Two classes of overall score of CHF-PROM were identified: poorer (14.0%) and better (86.0%). Poorer class tended to be aged, have low diastolic blood pressure, have concomitant atrial fibrillation, diabetes, chronic obstructive pulmonary disease, cancers, and central nervous system diseases, and used nitrates. Three classes of physical scores were identified: unstable-poorer (5.2%), stable-poorer (29.4%) and better (65.4%). Age, NYHA grade, chronic obstructive pulmonary disease, combined with cancers and central nervous system diseases were related to the grouping. Poorer (8.6%) and better (91.4%) classes of psychological scores were identified. Poorer class tended to be female and had concomitant atrial fibrillation. Degenerate class (34.6%) and meliorate class (65.4%) of therapeutic scores were identified. Degenerate class tended to have concomitant chronic obstructive pulmonary disease and use less angiotensin converting enzyme inhibitors.Conclusion: We identified different classes with distinct trajectories of QOL that may help proper evaluate QOL and further improve its status for patients CHF.Keywords: patient-reported outcome, chronic heart failure, growth mixture model, dynamic trajectory

Fang Ding,1 Wenjing Liu,2 Huiqing Wang,3 Weiwei Wang,1 Caixia Yang1 1Department of Geriatrics, Hengshui People’s Hospital, Hengshui City, Hebei Province, People’s Republic of China; 2Department of Respiratory Medicine, Hengshui People’s Hospital, Hengshui City, Hebei Province, People’s Republic of China; 3Department of Intensive Care Medicine, Hengshui People’s Hospital, Hengshui City, Hebei Province, People’s Republic of ChinaCorrespondence: Fang Ding, Department of Geriatrics, Hengshui People’s Hospital, No. 180, Renmin East Road, TaoCheng District, Hengshui City, Hebei Province, 053000, People’s Republic of China, Tel +86 0318-2187239, Email dingfan99g@126.comObjective: To analyse the guiding value of procalcitonin (PCT) for the selection of ventilation switching points in sequential mechanical ventilation for patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and respiratory failure, and to provide a reference for the optimisation of mechanical ventilation for patients with COPD and respiratory failure.Methods: The study included 160 patients with an acute exacerbation of COPD complicated by respiratory failure who received sequential mechanical ventilation treatment. They were divided into two groups of 80 participants. The critical point of the pulmonary infection observation window (PIC) was used as the switching point for sequential mechanical ventilation treatment in the control group, and PCT clinical node was used as the switching point for sequential mechanical ventilation treatment in the observation group. The invasive ventilation time, non-invasive mechanical ventilation time, total mechanical ventilation time, intensive care unit (ICU) treatment time, complication rate and prognosis were compared for the two groups.Results: (1) There was no significant difference in the respiratory rate, heart rate, arterial systolic pressure, arterial oxygen partial pressure, arterial carbon dioxide partial pressure or pH value between the two groups after 1 day of treatment, and (2) invasive mechanical ventilation time, non-invasive mechanical ventilation time, total mechanical ventilation time, ICU treatment time and the incidence of complications were significantly different in the two groups (P = 0.0001).Conclusion: Detecting PCT can guide the selection of ventilation switching points in sequential mechanical ventilation therapy for patients with COPD with respiratory failure in the acute exacerbation stage, effectively reduce the misevaluation of PIC switching points so that patients can obtain stable criteria for judgement and effectively improve the efficiency and safety of mechanical ventilation treatment for patients in the acute exacerbation stage.Keywords: acute exacerbation of chronic obstructive pulmonary disease, respiratory failure, sequential mechanical ventilation, selection of ventilation mode switching point, procalcitonin, observation window of pulmonary infection, clinical value

Saiyue Deng,1 Quan Wang,2 Jingjing Fan,3 Xiaoyun Yang,3 Junhua Mei,4 Jiajia Lu,5 Guohua Chen,4 Yuan Yang,1 Wenhua Liu,6 Runsen Wang,7 Yujia Han,7 Rong Sheng,7 Wei Wang,1 Li Ba,1 Fengfei Ding1,8 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2School of Nursing, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, People’s Republic of China; 3Cardiac Unit, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 4Department of Neurology, Wuhan No.1 Hospital, Wuhan, 430022, People’s Republic of China; 5Cardiac Unit, Wuhan No.1 Hospital, Wuhan, 430022, People’s Republic of China; 6Department of Clinical Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, People’s Republic of China; 7Huawei Technologies Co, Shenzhen, People’s Republic of China; 8Department of Pharmacology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of ChinaCorrespondence: Fengfei Ding, Department of Pharmacology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 134 7625 5813, Email fengfei_ding@fudan.edu.cn Li Ba, Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Tel +86 136 0764 1809, Email bali2015@126.comPurpose: Heart rate variability (HRV) indices have been used as stress indicators. Rare studies investigated the associations of circadian rhythms of the HRV indices with the stress, mood, and sleep conditions in populations under stress.Methods: In total 257 female participants (203 shift workers and 54 non-shift workers) were included. All the participants completed a structured questionnaire to assess the stress, mood, and sleep conditions and performed 24-hour Holter electrocardiogram monitoring on the day away from shifts. Using epochs of 1-min or 5-min beat-to-beat intervals, the HRV indices (SDNN, RMSSD, LF, HF, LF/HF, and LFnu, SD1, SD2, SD1/SD2) were plotted as a function of time and fitted into cosine periodic curves, respectively. Three mathematical parameters based on the cosine periodic curves were extracted, MESOR (M, overall averages of the cosine curve), amplitude (A, amplitude of the peak of the cosine curve), and acrophase (θ, latency to the peak) to quantify the circadian rhythms of the HRV indices. Multivariable linear regression models were used to reveal the associations of these parameters with the clinical assessments of stress, mood, or sleep conditions, as well as with the 24-h averages of the HRV indices.Results: The parameters M and A of SDNN, RMSSD, LF, and HF, and θ of LF/HF and LFnu significantly differ between shift and non-shift workers. The parameter θ of LF/HF positively correlates with the severity of stress and anxiety. The parameter A of LF/HF and LFnu also positively correlates with daytime sleepiness and sleep fragmentation. In addition, the parameters M and A instead of θ of SDNN, RMSSD, LF, LF/HF, and LFnu significantly correlate with the 24-h averages of HRV indices.Conclusion: The circadian rhythms of the HRV indices over 24 hours can, to some extent, predict the severity of stress, emotion and sleep conditions in female populations under stress.Keywords: circadian rhythms, HRV indices, mental health, stress, sleepiness, fatigue, sleep fragmentation

Longjuan Cong,1 Yanhong Ju,2 Ling Gui,3 Bo Zhang,1 Fangyan Ding,3 Changqing Zou4 1Department of Social Medicine, College of Health Management, China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Section of Statistics, 4th People’s Hospital of Shenyang, Shenyang, Liaoning, People’s Republic of China; 3Department of Health Service Management, College of Health Management, China Medical University, Shenyang, Liaoning, People’s Republic of China; 4School of Health Humanities, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Changqing Zou Tel +86 189 0405 6411Email allan2003@vip.qq.comPurpose: Caregivers of stroke inpatients are at high risk of sleep disorder, which may lead to depressive symptoms. Self-efficacy has always been regarded as a protective factor against psychological disorders such as depressive symptoms. This study aims to investigate the sleep disorder and depressive symptoms of caregivers of stroke inpatients in China and explore the mediating effect of self-efficacy between sleep disorder and depressive symptoms among Chinese caregivers of stroke inpatients.Patients and Methods: In this cross-sectional study, a total of 305 caregivers who were hospitalized with stroke patients completed the PROMIS Sleep Disorder Short Form Scale, General Self-Efficacy Scale and Patient Health Questionnaire-9 in two general public hospitals in northeast and southeast China. A structural equation model with bootstrap method was performed to determine the mediation of self-efficacy between sleep disorder and depressive symptoms.Results: Among the participants, 55.4% of caregivers reported depressive symptoms. Sleep disorder and self-efficacy were significant predictors of depressive symptoms. The direct impact of sleep disorder on depressive symptoms was positive, and the path coefficient of sleep disorder with depressive symptoms was decreased from 0.45 to 0.38 (P < 0.01) after addition of self-efficacy in the model. This indicated that self-efficacy played as mediator.Conclusion: The caregivers of stroke inpatients were in poor physical and psychological health, and more than half of the caregivers (55.4%) suffered from depressive symptoms. Our research revealed the mediation of self-efficacy between sleep disorder and depressive symptoms, and emphasized the importance of enhancing self-efficacy to reduce depressive symptoms among caregivers of stroke inpatients. These results demonstrate that focusing on self-efficacy interventions can enhance mental health and reduce depressive symptoms effectively.Keywords: self-efficacy, sleep disorder, depressive symptoms, Chinese caregivers of stroke inpatients

Xiao Xie, Fangbao Ding, Haibo Xiao Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Fangbao Ding; Haibo XiaoDepartment of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai, 200092, People’s Republic of ChinaEmail dingfangbao@xinhuamed.com.cn; xiaohaibo@xinhuamed.com.cnBackground: Non-small cell lung cancer (NSCLC) is a subtype of lung cancer which seriously threatens the health of people. Circular RNAs (CircRNAs) are endogenous RNAs which have stable closed structure; they are known to be involved in tumorigenesis of NSCLC. Meanwhile, hsa_circ_0000729 was reported to be upregulated in NSCLC. Nevertheless, the function of hsa_circ_0000729 in NSCLC remains unclear.Methods: Western blot and RT-qPCR were performed to investigate protein and mRNA levels, respectively. CCK-8 assay was performed to test the cell viability and cell death was investigated by flow cytometry. NSCLC cell pyroptosis was observed by electron microscope. In addition, the migration and invasion of NSCLC cells were detected by wound healing and transwell assay. The relation among hsa_circ_0000729, miR-1281 and FOXO3 was explored by dual luciferase reporter assay and RNA pull-down.Results: Hsa_circ_0000729 was found to be upregulated in NSCLC cells, and hsa_circ_0000729 knockdown obviously suppressed the proliferation of NSCLC cells through inducing pyroptosis. In addition, silencing of hsa_circ_0000729 notably inhibited the invasion and migration of NSCLC cells. Meanwhile, hsa_circ_0000729 could bind with miR-1281, and FOXO3 was directly targeted by miR-1281. Moreover, the anti-tumor effect of hsa_circ_0000729 siRNAs on NSCLC was markedly reversed by miR-1281 antagomir. Furthermore, silencing of hsa_circ_0000729 inhibited the tumor growth of NSCLC in vivo.Conclusion: Knockdown of hsa_circ_0000729 inhibits the tumorigenesis of NSCLC through mediation of miR-1281/FOXO3 axis. Thus, hsa_circ_0000729 might be served as a crucial mediator in NSCLC.Keywords: hsa_circ_0000729, miR-1281, FOXO3, pyroptosis

Dong-Dong Duan,1 Hui Xie,1 Hua-Feng Shi,1 Wen-Wen Huang,1 Fan Ding,1 Jia-Kun Hong,1 Jun-Sheng Fan,1 Shou-Yong Hu,1 Qing-Wei Wang,1 Meng-Qiao Zhou2 1Department of Orthopedic Surgery, The First People’s Hospital of Jingmen, Jingmen, Hubei 448000, People’s Republic of China; 2Department of Cardiology, The First People’s Hospital of Jingmen, Jingmen, Hubei 448000, People’s Republic of ChinaCorrespondence: Meng-Qiao ZhouDepartment of Cardiology, The First People’s Hospital of Jingmen, 67 Xiangshan Avenue, Jingmen, Hubei 448000, People’s Republic of ChinaEmail dddan1120@163.comBackground: New evidence suggests that histidine triad nucleotide-binding protein 1 (Hint1) exerts a tumor suppressor effect in various human tumors, such as colorectal cancer and gastric cancer. However, it has not been reported whether Hint1 is involved in the occurrence and development of osteosarcoma (OS).Materials and Methods: The present study investigated the role of Hint1 in human OS cells by using cell lines, including 143B, U2OS, KHOS-240S, Saos-2 and MG-63. Cell proliferation and apoptosis were detected by flow cytometry.Results: The present result revealed that Hint1 is downregulated in these cell lines. The overexpression of Hint1 by adenovirus transfection in 143B and MG63 cell lines suppressed the proliferation and cell cycle, and increased the cell apoptosis. Mechanically, it was found that Hint1 downregulated the cyclin D1 expression via FOXO1 inhibition. Furthermore, FOXO1 overexpression in the 143B and MG63 cell lines significantly blurred the effects of Hint1 on cellular proliferation and apoptosis.Conclusion: The present study indicates that Hint1 inhibits the development of OS by regulating FoxO1-cyclin D1, suggesting that Hint1 may be a new method for the treatment of OS.Keywords: osteosarcoma, histidine triad nucleotide-binding protein 1, cell cycle, apoptosis, FOXO1

Yu Gong,1 Feng Ding,2 Yong Gu2 1Department of Internal Medicine, Division of Nephrology, Shanghai Municipal Eighth People’s Hospital, Shanghai, People’s Republic of China; 2Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Yu GongDepartment of Internal Medicine, Division of Nephrology, Shanghai Municipal Eighth People’s Hospital, 8 Caobao Road, Shanghai 200235, People’s Republic of ChinaTel +86 21 18930718612Email gyfd66@126.comBackground: Critically ill older patients with acute kidney injury (AKI), also referred to as acute renal failure, are associated with high in-hospital mortalities. Preexisting malnutrition is highly prevalent among AKI patients and increases in-hospital mortality rate. This study is to evaluate the predictive power of some serum nutritional related biomarkers predicting the 90 days in-hospital mortality of critically ill older patients with AKI.Methods: A prospective, observational study was conducted in a university teaching hospital. One hundred and five critically ill older patients with AKI aged 60–95 were enrolled and were divided into survival group (n=44) and non-survival group (n=61) in the light of their final outcomes. Receiver operating characteristic analyses (ROC) were performed to calculate the area under ROC curve (AUC). Sensitivity and specificity of in-hospital mortality prediction were calculated.Results: Significant differences were found between the survival group and non-survival group of critically ill older patients with AKI. AUC of low density lipoprotein (LDL) and albumin were 0.686 and 0.595, respectively. The asymptotic 95% confidence intervals of LDL and albumin were 0.524–0.820 and 0.488–0.696, respectively. Sensitivity of the 90 days in-hospital mortality prediction of LDL and albumin were 68.71% and 69.09%, respectively. Specificity of 90 days in-hospital mortality prediction of LDL and albumin were 69.23% and 50.0%, respectively.Conclusion: LDL and albumin did not have sufficient power to predict the 90 days in-hospital mortality of critically ill older patients with AKI. Further research on the association between malnutrition and poor prognosis of critically ill older patients with AKI is needed in the future.Trial registration: ClinicalTrials.gov identifier: NCT00953992.Keywords: critically ill older patients, acute kidney injury, mortality, nutritional related biomarker

Li Zhang, Fengping DingDepartment of Pathology, People’s Hospital of Xinchang County, Xinchang Affiliated Hospital of Wenzhou Medical University, Xinchang, Zhejiang, People’s Republic of ChinaCorrespondence: Li ZhangDepartment of Pathology, People’s Hospital of Xinchang County, Xinchang Affiliated Hospital of Wenzhou Medical University, 117 Gushan Middle Road, Nanming Street, Xinchang 312500, People’s Republic of ChinaTel +86 1 895 756 8155Email lizhang78@126.comPurpose: To detect the expression and function of circ_0008945 in breast cancer (BC) and to explore its potential molecular mechanisms in BC tumorigenesis.Materials and methods: We measured expression levels of circ_0008945, miR-338-3p and homeobox A3 (HOXA3) in BC tissue specimens and cells using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). We examined the effects of all three genes on BC cell proliferation using Cell Counting Kit-8 (CCK-8) and colony formation assays. We also performed a Transwell assay to assess the migratory and invasive ability of treated BC cells. BC cell apoptosis was assessed using flow cytometric (FCM) analysis; interaction between miR-338-3p and circ_0008945 or HOXA3 was verified by dual-luciferase reporter assay as well as by ribonucleic-acid (RNA) pulldown. Finally, we used an in vivo tumor growth assay to assess the role of circ_0008945 overexpression in BC tumor growth.Results: We found that circ_0008945 expression was significantly increased in both BC tissue specimens and cells. This increase was correlated with poor prognosis in BC patients. Knockdown of circ_0008945 inhibited BC cell proliferation, migration and invasion while promoting BC cell apoptosis in vitro. Overexpression of circ_0008945 remarkably promoted BC tumor growth in vivo. Mechanistically, circ_0008945 acted as a miRNA sponge for miR-338-3p and inhibited its expression in BC cells. Moreover, miR-338-3p targeted and inhibited HOXA3.Conclusion: We found that circ_0008945 acted as a BC oncogene by physically binding miR-338-3p, which further targeted and regulated HOXA3.Keywords: apoptosis, breast cancer, circ_0008945, miR-338-3p, proliferation

In the present paper, plasma surface alloying was implemented on powder metallurgy gears to improve its wear resistance based on double glow plasma surface metallurgy technology. A W-Mo alloy coating was obtained in the process. The morphology, microstructure and phase composition were investigated by SEM, EDS and XRD. The hardness was examined by Vickers hardness test and nanoindentation test. The tribological behavior of powder metallurgy gears before and after plasma surface alloying was evaluated on a ball-on-disc reciprocating sliding tribometer under dry sliding condition at room temperature. The results indicate that the W-Mo alloy coating is homogeneous without defects, which includes deposition layer and interdiffusion layer. The average microhardness of powder metallurgy gears before and after plasma surface alloying is 145.8 HV0.1 and 344.4 HV0.1, respectively; Nano hardness of deposition layer and interdiffusion layer is 5.76 GPa, 14.35 GPa, respectively. The specific wear rate of W-Mo alloy coating is lower than original PM gears. The wear mechanism of W-Mo alloy coating is slight adhesive wear. The W-Mo alloy coating prepared by double glow plasma surface alloying technology can effectively improve wear resistance of powder metallurgy gears.

Can Wang,1,2 Qing-ping Shi,1,2 Feng Ding,2 Xiao-dong Jiang,1,2 Wei Tang,3 Mei-Ling Yu,1,2 Jian-Hua Zhu2 1Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China; 2Faculty of Pharmacy, Bengbu Medical College, Bengbu, People’s Republic of China; 3Department of Pharmacy, Huaiyuan County Hospital of TCM in Anhui, Bengbu, People’s Republic of China Aim: To evaluate the factors influencing suspected hypersensitivity and adverse systemic reactions after Shuxuening injection and to provide innovative ideas and methods for the reevaluation of post-marketing safety of Shuxuening.Methods: This study used a prospective, nested case–control study design, combined with a prescription sequence analysis design method. It classified patients who exhibited trigger signals after administration of Shuxuening injection as suspected allergic patients and made comparisons with patients who did not report adverse effects to calculate the correlation between relevant risk factors and suspected allergic reactions. Randomized controlled studies and cohort studies of the adverse drug reaction (ADR) of Shuxuening were performed using a computer database. Data retrieval was carried out by the foundation governing the individual database. Meta-analysis was performed by using R3.2.3 software to evaluate the ADRs of Shuxuening.Results: The results of real-world study showed that administration of Shuxuening in combination with potassium aspartate and magnesium, atorvastatin calcium, Shengmai injection, pantoprazole sodium, or high-dose medication was a risk factor for suspected allergic reactions. Meta-analysis showed that the incidence of adverse events was 5.84% (95% CI 0.0499; 0.0674), and serious adverse reaction rate was 4.36% (95% CI 0.0188; 0.0760) when Shuxuening was used in combination with these drugs. The incidence of allergic reaction was also influenced by the vehicle, duration of treatment, single dose, and indicated vs off-label use.Conclusion: Risk factors for adverse reaction following the use of Shuxuening injection in patients are associated with a single dose, vehicle, type of disease, and combination with potassium aspartate, atorvastatin calcium, Shengmai injection, injection with pantoprazole sodium, and other drugs. Physicians should be careful to follow guidelines when administering this drug. We further propose that the unique methodology used in this study may be useful for reevaluation of the safety of other traditional Chinese medicines.Keywords: real-world study, evidence-based evaluation, Shuxuening injection, post-marketing safety reevaluation, allergic reaction

Yanpeng Zhang,1,2 Zhuocheng Li,2 Xiaolong He,1 Fanglin Ding,2 Weiqing Wu,2 Yong Luo,2 Bing Fan,2 Hong Cao1 1Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China; 2Laboratory Department of the First Affiliated Hospital of Shenzhen University, Shenzhen, 518000, China Purpose: Acinetobacter baumannii is an important pathogen in the nosocomial infections worldwide. Combining with carbapenemases, efflux pumps and outer membrane proteins (OMPs) have been thought to affect the development of carbapenem resistance in A. baumannii. This study aimed to investigate the contributions of different efflux pumps and OMPs in developing carbapenem resistance in a clinical isolate of A. baumannii and reveal the possible mechanism of overproduction of main efflux pumps. Patients and methods: In this study, an imipenem-susceptible clinical isolate was identified as A. baumannii and named SZE. Several common carbapenemases were detected by polymerase chain reaction (PCR). Imipenem-selected mutants were selected from SZE by serial subcultivations on Mueller–Hinton agar, and the minimum inhibitory concentration (MIC) was detected. Gene expressions of four families of efflux pumps, five OMPs, and blaOXA-51 were determined by reverse transcription quantitative PCR, and comparisons were made between SZE strain and the imipenem-selected mutants. The adeRS system in SZE and its mutant was sequenced and aligned. Results: Under consecutive imipenem-selected stress, the MIC to imipenem increased gradually from 0.125 μg/mL to 8 μg/mL. The effect of resistance inducement was almost neutralized when treated with an efflux pump inhibitor. The expression of efflux pumps, adeB, adeG, and adeJ, was increased by 6.9-, 4.0-, and 2.1-fold in mutants, respectively, compared to SZE. A single mutation (G to A) at position 58 was detected in the regulatory adeRS system and possibly upregulated the adeB expression, and then affected the carbapenem resistance in A. baumannii strains. Conclusion: In conclusion, under consecutive imipenem-selected stress in vitro, A. baumannii strain evolved the ability to reduce susceptibility to a variety of antimicrobials by overproduction of efflux pumps. Especially, the resistance-nodulation-cell division super family and a nucleotide mutant in adeRS regulating system caused the overexpression of adeABC. Keywords: Acinetobacter baumannii, efflux pump, multidrug resistance, imipenem, outer membrane protein

Ling Wang,1 Yanli An,2 Chenyan Yuan,3 Hao Zhang,2 Chen Liang,2 Fengan Ding,2 Qi Gao,1 Dongsheng Zhang4 1Department of Ultrasonography, Zhong Da Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China; 2Medical School, Southeast University, Nanjing, People’s Republic of China; 3Department of Clinical Laboratory, Zhong Da Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China; 4Jiangsu Key Laboratory for Biomaterials and Devices, Medical School, Southeast University, Nanjing, People’s Republic of China Background: Targeted delivery is a promising strategy to improve the diagnostic imaging and therapeutic effect of cancers. In this paper, novel cetuximab (C225)-conjugated, gemcitabine (GEM)-containing magnetic albumin nanospheres (C225-GEM/MANs) were fabricated and applied as a theranostic nanocarrier to conduct simultaneous targeting, magnetic resonance imaging (MRI), and double-targeted thermochemotherapy against pancreatic cancer cells. Methods: Fe3O4 nanoparticles (NPs) and GEM co-loaded albumin nanospheres (GEM/MANs) were prepared, and then C225 was further conjugated to synthesize C225-GEM/MANs. Their morphology, mean particle size, GEM encapsulation ratio, specific cell-binding ability, and thermal dynamic profiles were characterized. The effects of discriminating different EGFR-expressing pancreatic cancer cells (AsPC-1 and MIA PaCa-2) and monitoring cellular targeting effects were assessed by targeted MRI. Lastly, the antitumor efficiency of double/C225/magnetic-targeted and nontargeted thermochemotherapy was compared with chemotherapy alone using 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry (FCM) assay. Results: When treated with targeted nanospheres, AsPC-1 cells showed a significantly less intense MRI T2 signal than MIA PaCa-2 cells, while both cells had similar signal strength when incubated with nontargeted nanospheres. T2 signal intensity was significantly lower when magnetic and C225 targeting were combined, rather than used alone. The inhibitory and apoptotic rates of each thermochemotherapy group were significantly higher than those of the chemotherapy-alone groups. Additionally, both MTT and FCM analysis verified that double-targeted thermochemotherapy had the highest targeted killing efficiency among all groups. Conclusion: The C225-GEM/MANs can distinguish various EGFR-expressing live pancreatic cancer cells, monitor diverse cellular targeting effects using targeted MRI imaging, and efficiently mediate double-targeted thermochemotherapy against pancreatic cancer cells. Keywords: gemcitabine, Fe3O4 nanoparticles, theranostic nanocarrier

Fengan Ding,1 Yiping Li,1 Jing Liu,1 Lei Liu,1 Wenmin Yu,1 Zhi Wang,1 Haifeng Ni,2 Bicheng Liu,2 Pingsheng Chen1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Institute of Nephrology, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China Background: Gold nanoparticles (GNPs) can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.Results: Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM) to human renal proximal tubular cells (HK-2) by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM) treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the production of reactive oxygen species, the loss of mitochondrial membrane potential (ΔΨM), and an increase in apoptosis and autophagic cell death. Conclusion/significance: Our results demonstrate that renal tubular epithelial cells presented different responses under normoxic and hypoxic environments, which provide an important basis for understanding the risks associated with GNP use–especially for the potential GNP-related therapies in chronic kidney disease patients. Keywords: gold nanoparticles (GNPs), toxicity, autophagy, apoptosis

The Chronus Quantum (ChronusQ) software package is an open source (under the GNU General Public License v2) software infrastructure which targets the solution of challenging problems that arise in ab initio electronic structure theory. Special emphasis is placed on the consistent treatment of time dependence and spin in the electronic wave function, as well as the inclusion of relativistic effects in said treatments. In addition, ChronusQ provides support for the inclusion of uniform finite magnetic fields as external perturbations through the use of gauge-including atomic orbitals. ChronusQ is a parallel electronic structure code written in modern C++ which utilizes both message passing implementation and shared memory (OpenMP) parallelism. In addition to the examination of the current state of code base itself, a discussion regarding ongoing developments and developer contributions will also be provided. This article is categorized under: Software > Quantum Chemistry Electronic Structure Theory > Ab Initio Electronic Structure Methods Electronic Structure Theory > Density Functional Theory.