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Li Zhao,1 Tuo Zhang,2 Xunliang Li,3 Li Chen,1 Shenglin Zhou,1 Zhaoli Meng,1 Wei Fang,1 Jianle Xu,4 Jicheng Zhang,1 Man Chen1,2 1Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Critical Care Medicine, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, People’s Republic of China; 3Department of Intensive Care Unit, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, People’s Republic of China; 4Department of Statistics and Medical Records Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Jicheng Zhang; Man Chen, Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Weiqi Road, Jinan, Shandong, 250021, People’s Republic of China, Email zhangjicheng2023@126.com; chenman_slyy@163.comPurpose: Sepsis-associated acute kidney injury (S-AKI) is associated with increased morbidity and mortality. We aimed to develop a nomogram for predicting the risk of S-AKI patients.Patients and Methods: We collected data from septic patients admitted to the Provincial Hospital Affiliated with Shandong First Medical University from January 2019 to September 2022. Septic patients were divided into two groups based on the occurrence of AKI. A nomogram was developed by multiple logistic regression analyses. The performance of the nomogram was evaluated using C-statistics, calibration curves, and decision curve analysis (DCA). The validation cohort contained 70 patients between December 2022, and March 2023 in the same hospital.Results: 198 septic patients were enrolled in the training cohort. Multivariate logistic regression analysis showed that neutrophil gelatinase-associated lipocalin (NGAL), platelet-to-lymphocyte ratio (PLR), and vasopressor use were independent risk factors for S-AKI. A nomogram was developed based on these factors. C-statistics for the training and validation cohorts were respectively 0.873 (95% CI 0.825– 0.921) and 0.826 (95% CI 0.727– 0.924), indicating high prediction accuracy. The calibration curves showed good concordance. DCA revealed that the nomogram was of great clinical value.Conclusion: The nomogram presents early and effective prediction for the S-AKI patients, and provides optimal intervention to improve patient outcomes.Keywords: sepsis, acute kidney injury, neutrophil gelatinase-associated lipocalin, platelet-to-lymphocyte ratio, vasopressor use, nomogram

Hao Hong,1,* Suya Zhou,2,* Junyao Zheng,3 Haimin Shi,3 Yue Chen,4 Ming Li3 1Department of Intensive Care Unit, The First Affiliated Hospital of Soochow University, Soochow, Suzhou, People’s Republic of China; 2Laboratory Nephrology, Jinshan hospital of Fudan University, Shanghai, People’s Republic of China; 3Laboratory Nephrology, The First Affiliated Hospital of Soochow University, Soochow, Suzhou, People’s Republic of China; 4Laboratory Nephrology, The First People’s Hospital of Kunshan, Soochow, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming Li, Email 1925924373@qq.comPurpose: The aim of this study was to investigate the changes of different metabolites in the body fluids of non-dialysis patients with chronic kidney disease (CKD) using a metabolomics approach. The goal was to identify early biomarkers of CKD progression through metabolic pathway analysis.Patients and Methods: Plasma samples from 47 patients with stages 1– 4 CKD not requiring dialysis and 30 healthy controls were analyzed by liquid chromatography-mass spectrometry (LC-MS). Using multivariate data analysis, specifically a partially orthogonal least squares discriminant analysis model (OPLS-DA), we investigated metabolic differences between different stages of CKD. The sensitivity and specificity of the analysis were evaluated using the Area Under Curve (AUC) method. Furthermore, the metabolic pathways were analyzed using the Met PA database.Results: Plasma samples from CKD patients and controls were successfully differentiated using an OPLS-DA model. Initially, twenty-five compounds were identified as potential plasma metabolic markers for distinguishing CKD patients from healthy controls. Among these, six compounds (ADMA, D-Ornithine, Kynurenine, Kynurenic acid, 5-Hydroxyindoleacetic acid, and Gluconic acid) were found to be associated with CKD progression It has been found to be associated with the progression of CKD. Changes in metabolic pathways associated with CKD progression include arginine and ornithine metabolism, tryptophan metabolism, and the pentose phosphate pathway.Conclusion: By analyzing the metabolic pathways of different metabolites, we have identified the significant impact of CKD progression. The main metabolic pathways involved are Arginine and Ornithine metabolism, Tryptophan metabolism, and Pentose phosphate pathway. ADMA, D-Ornithine, L-Kynurenine, Kynurenic acid, 5-Hydroxyindoleacetic acid, and Gluconic acid could serve as potential early biomarkers for CKD progression. These findings have important implications for the early intervention and treatment of CKD, as well as for further research into the underlying mechanisms of its pathogenesis.Keywords: arginine and ornithine metabolism, tryptophan metabolism, pentose phosphate pathway, biomarkers

Hao Hong,1 Junyao Zheng,2 Haimin Shi,2 Suya Zhou,3 Yue Chen,4 Ming Li2 1Department of Intensive Care Unit, The First Affiliated Hospital of Soochow University, Soochow, People’s Republic of China; 2Laboratory Nephrology, The First Affiliated Hospital of Soochow University, Soochow, People’s Republic of China; 3Laboratory Nephrology, Jinshan Hospital of Fudan University, Shanghai, People’s Republic of China; 4Laboratory Nephrology, The First People’s Hospital of Kunshan, Soochow, People’s Republic of ChinaCorrespondence: Ming Li, Email 1925924373@qq.comPurpose: Changes in inflammation, immunity, and nutritional status can promote the development of chronic kidney disease (CKD), and the Naples prognostic score (NPS) reflects changes in these three general clinical parameters. Indoleamine 2.3-dioxygenase (IDO) can block the function of inflammatory cells and inhibit the production of inflammatory cytokines. We examined use of the NPS and IDO activity to predict early-stage CKD.Patients and Methods: Clinical and demographic parameters and the NPS were recorded for 47 CKD patients and 30 healthy controls. A one-way ANOVA or the rank sum test was used to compare variables in the different groups. Spearman or Pearson correlation coefficients were calculated, and logistic regression was used to identify significant factors. Receiver operating characteristic (ROC) analysis was also performed.Results: The NPS had a positive correlation with plasma IDO activity and IDO activity was lowest in controls, and increased with CKD stage. ROC analysis indicated that NPS had an area under the curve (AUC) of 0.779 when comparing controls with all CKD patients. A prediction model for CKD (− 4.847 + [1.234 × NPS] + [6.160 × plasma IDO activity]) demonstrated significant differences between controls and patients with early-stage CKD, and for patients with different stages of CKD. This model had AUC values of 0.885 (control vs CKD1– 4), 0.876 (control vs CKD2), 0.818 (CKD2 vs CKD3), and 0.758 (CKD3 vs CKD4).Conclusion: A prediction model based on the NPS and IDO provided good to excellent predictions of early-stage CKD.Keywords: inflammation, immune, nutrition, score, metabolomic, kynurenine pathway

Hao Hong,1,&ast; Junyao Zheng,2,&ast; Haimin Shi,2 Suya Zhou,3 Yue Chen,4 Ming Li2 1Intensive Care Unit, the First Affiliated Hospital of Soochow University, Soochow, People’s Republic of China; 2Laboratory Nephrology, the First Affiliated Hospital of Soochow University, Soochow, People’s Republic of China; 3Laboratory Nephrology, Jinshan Hospital of Fudan University, Shanghai, People’s Republic of China; 4Laboratory Nephrology, the First People’s Hospital of Kunshan, Soochow, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Li, Email 1925924373@qq.comPurpose: We aimed to explore changes in plasma and urine indole lactic acid (ILA) levels and the relationship between inflammation and ILA in chronic kidney disease (CKD) patients and healthy people.Patients and Methods: Forty-seven CKD patients and 30 healthy individuals were included in this study. One-way ANOVA was used for variables with normal distribution and homogeneous variance. A rank-sum test was performed for non-normally distributed variables. Correlation analyses were performed using Pearson’s or Spearman correlation analyses. Independent relationship between patients and CKD was analyzed using ordinal and binary logistic regressions. Receiver operating characteristic (ROC) curve was used.Results: Plasma and urine ILA levels were positively correlated (r = 0.51, P < 0.01). Plasma ILA was positively correlated with BMI, age, creatinine, BUN, triglycerides, and uric acid and negatively correlated with hemoglobin levels. Urine ILA levels were positively correlated with age, creatinine, BUN, and uric acid and negatively correlated with hemoglobin and albumin levels. Ordered logistic regression analysis showed that CKD was significantly correlated with plasma ILA (OR=4.49, P

Mengwen Feng,1 Min Huang,2 Yuanyuan Fan,1 Genyan Liu,3 Suming Zhou,2 Jing Zhou2 1Department of Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Geriatric Intensive Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Jing Zhou, Department of Geriatric Intensive Care Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of China, Email zhoujing1364@jsph.org.cnPurpose: Elizabethkingia spp. infections have recently increased, and they are difficult to treat because of intrinsic antimicrobial resistance. This study aimed to investigate the clinical characteristics of patients with pulmonary infection with Elizabethkingia spp. and reveal the risk factors for infection and death.Patients and Methods: In this retrospective case–control study, patients were divided into infection and control groups based on the bacterial identification results. Patients in the infection group were further divided into survival and death groups according to their hospital outcomes. Clinical characteristics between different groups were compared. We further analyzed antimicrobial susceptibility testing results of the isolated strains.Results: A total of the 316 patients were divided into infection (n = 79), 23 of whom died, and control (n = 237) groups. Multivariate logistic regression analysis showed that glucocorticoid consumption (OR: 2.35; 95% CI: 1.14– 4.81; P = 0.02), endotracheal intubation (OR: 3.74; 95% CI: 1.62– 8.64; P = 0.002), and colistin exposure (OR: 2.50; 95% CI: 1.01– 6.29; P = 0.046) were significantly associated with pulmonary infection with Elizabethkingia spp. Advanced age (OR: 1.07, 95% CI: 1.00– 1.15; P = 0.046), high acute physiology and chronic health evaluation (APACHE) II score (OR: 1.21; 95% CI: 1.01– 1.45; P = 0.037), and low albumin level (OR: 0.73, 95% CI: 0.56– 0.96; P = 0.025) were significantly associated with in-hospital mortality of infected patients. Elizabethkingia spp. was highly resistant to cephalosporins, carbapenems, macrolides, and aminoglycoside, and was sensitive to fluoroquinolones, minocycline, and co-trimoxazole in vitro.Conclusion: Glucocorticoid consumption, tracheal intubation, and colistin exposure were associated with pulmonary infection with Elizabethkingia spp. for critically ill patients. Patients with advanced age, high APACHE II score, and low albumin level had higher risk of death from infection.Keywords: Elizabethkingia spp, intensive care unit, infection, mortality, antimicrobial susceptibility testing

Mianxian Li,1,&ast; Shuru Zhou,2,&ast; Zexiong Feng,1,&ast; Chi Zhang1 1Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2The Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chi Zhang, Email zhangchi13@suda.edu.cnObjective: Coronary artery disease (CAD) and type 2 diabetes (T2DM) are closely associated with increased rate of death. C1q/TNF-related protein 6 (CTRP6) is a novel adipocytokine which plays an important role in glucose and lipid metabolism. Little is known about the function of CTRP6 in CAD and T2DM patients. Herein, we aimed to study the association of CTRP6 level with CAD and T2DM.Methods: This study included 51 CAD, 44 CAD+T2DM and 65 non-CAD+T2DM patients from Affiliated Aoyang Hospital of Jiangsu University. Serum CTRP6 concentrations were detected by ELISA. Multiple logistic regression was used to analyze the association of serum CTRP6 with CAD and T2DM.Results: Serum CTRP6 concentrations were significantly lower in CAD patients than controls. However, there is no significant statistical difference between CAD+T2DM patients and non-CAD+T2DM patients. Serum CTRP6 was negatively correlated with low-density lipoprotein cholesterol (LDL-C) (ρ=− 0.2769, p=0.028) in controls. Serum CTRP6 was positively correlated with age (ρ=0.4121, p=0.0027), systolic blood pressure (SBP) (ρ=0.4012, p=0.0035), Creatinine (ρ=0.3295, p=0.0194), uric acid (UA) (ρ=0.3386, p=0.0162), and left ventricular end diastolic diameter (LVD) (ρ=0.4277, p=0.0042) and negatively correlated with ejection fraction (EF) (ρ=− 0.3237, p=0.0342) in CAD patients. Serum CTRP6 was negatively correlated with high-density lipoprotein cholesterol (HDL-C) (ρ=− 0.3164, p=0.0387) in CAD+T2DM patients. Multiple logistic regression showed that the decrease of CTRP6 was significantly related to the increased prevalence of CAD. What is more, CTRP6 increased prevalence of T2DM in CAD patients.Conclusion: Lower serum CTRP6 could be a risk factor of CAD. However, higher circulating CTRP6 associated with the increased prevalence of T2DM in CAD patients.Keywords: CTRP6, coronary artery disease, type 2 diabetes, adipokine, CTRP, risk factor

Zhuhua Jin,1,2 Lei Zhu,3 Shuping Zhou,2,4 Chao Lu2,4 1Department of Information Management, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, Anhui Province, People’s Republic of China; 2School of Economics and Management, Anhui University of Science and Technology, Huainan, 232001, People’s Republic of China; 3Department of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, Anhui Province, People’s Republic of China; 4First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, Anhui Province, People’s Republic of ChinaCorrespondence: Lei Zhu, Department of Neurology, Department of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, Anhui Province, People’s Republic of China, Email salimai@126.com Chao Lu, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, Anhui Province, People’s Republic of China, Email 765385306@qq.comBackground: Post-stroke Fatigue (PSF) after Intracerebral Hemorrhage (ICH) is a long-term symptom in stroke survivors. However, the pathogenesis of PSF remains inadequately understood and sufficient evidence-based treatments are lacking. Mobile health (mHealth) technology offers a promising approach to expanding access to high-quality and culturally tailored evidence-based mental care.Aim: This study examined the role of mHealth called iHealth in the management of PSF after ICH.Methods: A total of 225 patients diagnosed with intracerebral hemorrhage (ICH) were included in the study and randomly assigned to either the Mobile Health Intervention Group (mHI Group) or the non-Mobile Health Intervention Group (non-mHI). The management involved the utilization of a digital healthcare application named iHealth, which incorporated digital questionnaires, fatigue scale tests, and online videos for the purpose of administering the Patient Fatigue Reporting Measurement Information System (PFRMIS) short form as part of the initial patient assessment following ICH. The study was conducted remotely via video conferencing over a 12-week period in mHI Group, with fatigue assessments being conducted 3 months post-ICH onset in two groups.Results: Following the administration of PSF by iHealth, Univariate Logistic analyses indicated a significant association between fatigue and the type of activity, with patients who were sedentary or did nothing experiencing higher levels of fatigue (β=2.332, p< 0.001; β=2.517, p< 0.001). Multivariate Logistic analyses demonstrated a positive association between the intensity of physical activity and decreased emotional well-being and family support, as well as increased fatigue. (p=0.001, p=0.002, p=0.001). The FSS results demonstrated a significantly reduced incidence of PSF in the MHI group in comparison to non-mHI group following the conclusion of the programme. (13.1% vs 40%, p< 0.001).Conclusion: This study explored the effectiveness of the iHealth app for PSF following ICH, indicating that iHealth is a clinically valuable tool that warrants further dissemination.Keywords: post-stroke fatigue, mobile health intervention, fatigue severity scale, intracerebral hemorrhage, iHealth

Haohua Yuan,1 Huan Gui,1 Shuanghui Chen,1 Lan Zhu,1 Chenglv Wang,1 Qianyu Jing,2 Hang Lv,1 Quan Wan,2 Shuyi Wang,1 Shengwen Zhou,1 Xiaodong Ren,1 Yingjie Nie,1,3 Linzhao Li1 1Medical College, Guizhou University, Guizhou Province, 550025, People’s Republic of China; 2School of Preclinical Medicine of Zunyi Medical University, Zunyi, Guizhou Province, 563000, People’s Republic of China; 3NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, 550002, People’s Republic of ChinaCorrespondence: Yingjie Nie; Linzhao Li, Medical College of Guizhou University, Guiyang, Guizhou Province, 550025, People’s Republic of China, Tel +86-085188274013; +86-085188274016, Email nienyj@hotmail.com; lzli@gzu.edu.cnPurpose: This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-β-CD).Methods: R848-loaded PLGA nanoparticles modified with 2-HP-β-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo.Results: The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-β-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival.Conclusion: The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.Keywords: R848, 2-HP-β-CD, anti-TNFR2, TIME, immunotherapy

Guodong Yang,1– 3 Shuang Zhou,4 Yue Feng,5 Jiaran Lang,1– 3 Yaxin Chen,1– 3 Huipeng Ren1– 3 1Mental Health Center, Hebei Medical University and Hebei Technical Innovation Center for Mental Health Assessment and Intervention, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 3Department of Psychiatry, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 4The Sixth People’s Hospital of Hebei Province, Baoding, Hebei, 071000, People’s Republic of China; 5Maternity & Child Care Center of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of ChinaCorrespondence: Huipeng Ren, The First Hospital of Hebei Medical University, 89 Donggang Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email renhuipeng@126.comPurpose: In clinical work, it has been found that the prevalence of hyperuricemia (HUA) is significantly higher in younger patients with psychiatric disorders, but there are few studies in this area. The present study aims to evaluate the prevalence of HUA and the relationship between the HUA and age in hospitalized patients with psychiatric disorders in the real world, and to provide a theoretical basis for clinical staff to pay attention to the metabolic indicators of younger patients and for future related studies.Methods: This is a cross-sectional evaluation of a cohort of 1761 patients with psychiatric disorders of hospitalized. The categories of disorders designed for study included: Depression, Bipolar disorder, Schizophrenia, Anxiety, Obsessive-Compulsive disorder, Acute and transient psychotic disorder, Dissociative(conversion) disorders, Conduct disorders and Tic disorders. In addition, based on age, the participants are stratified into three groups. The authors used Kruskal–Wallis tests, chi-square tests, and multiple linear logistic regression to verify the relationship between HUA and age among hospitalized patients with psychiatric disorders.Results: Overall, the estimated prevalence of HUA was 35.4%. The prevalence of HUA was significantly higher in individuals with 17 years and under compared to those with 45 years and above (P < 0.001). After adjusting for confounders, the prevalence of HUA remained higher at 17 years and under than at 45 years and above. Bipolar disorder can lead to an increased prevalence of HUA (P< 0.05).Conclusion: The prevalence of HUA was higher in hospitalized patients with psychiatric disorders, and the prevalence was inversely proportional to age.Keywords: hyperuricemia, uric acid, age, psychiatric disorders, bipolar disorder

Xiaohong Chen,1,&ast; Shiqi Zhou,2,&ast; Lin Yang,1 Qianqian Zhong,1 Hongguang Liu,3 Yongjian Zhang,1 Hanyi Yu,2 Yongjiang Cai1 1Center of Health Management, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2School of Future Technology, South China University of Technology, Guangzhou, People’s Republic of China; 3Center of Health Management, Huazhong University of Science and Technology Union Hospital (Nanshan Hospital), Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongjiang Cai, Center of Health Management, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China, Email caiyj2000@sina.cn Hanyi Yu, School of Future Technology, South China University of Technology, Guangzhou, People’s Republic of China, Email yuhanyi@scut.edu.cnPurpose: The purpose of this study is to explore the independent-influencing factors from normal people to prediabetes and from prediabetes to diabetes and use different prediction models to build diabetes prediction models.Methods: The original data in this retrospective study are collected from the participants who took physical examinations in the Health Management Center of Peking University Shenzhen Hospital. Regression analysis is individually applied between the populations of normal and prediabetes, as well as the populations of prediabetes and diabetes, for feature selection. Afterward,the independent influencing factors mentioned above are used as predictive factors to construct a prediction model.Results: Selecting physical examination indicators for training different ML models through univariate and multivariate logistic regression, the study finds Age, PRO, TP, and ALT are four independent risk factors for normal people to develop prediabetes, and GLB and HDL.C are two independent protective factors, while logistic regression performs best on the testing set (Acc: 0.76, F-measure: 0.74, AUC: 0.78). We also find Age, Gender, BMI, SBP, U.GLU, PRO, ALT, and TG are independent risk factors for prediabetes people to diabetes, and AST is an independent protective factor, while logistic regression performs best on the testing set (Acc: 0.86, F-measure: 0.84, AUC: 0.74).Conclusion: The discussion of the clinical relationships between these indicators and diabetes supports the interpretability of our feature selection. Among four prediction models, the logistic regression model achieved the best performance on the testing set.Keywords: prediabetes, prediction model, physical examination, machine learning, regression analysis

Jianqiu Yang,1,2 Chunyu Yuan,1 Shengru Zhou,1 Zhicheng Teng,2 Min Li1 1Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University), Suzhou, People’s Republic of China; 2Suzhou Medical College of Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Min Li, Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University), No. 9, Chongwen Road, Suzhou, 215100, People’s Republic of China, Tel +86-18936140383, Email lm@suda.edu.cnAbstract: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, a rare immune-mediated inflammatory disease, poses diagnostic and therapeutic challenges owing to its multi-system involvement, high heterogeneity, and lack of specific laboratory tests. Additionally, lacking evidence-based treatment recommendations, with the primary approach focusing on symptomatic relief. Herein, we report the case of a 32-year-old Chinese woman who presented with recurrent, generalized multiple osteoarticular pain lasting over one year and skin erythema pustulosis for 11 months. Traditional treatments, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and other traditional approaches, yielded no significant effects. Despite the prior use of adalimumab and acitretin capsules, the treatment remained unsatisfying, especially regarding the skin lesions. Considering the complex pathogenesis of SAPHO syndrome, the patient was orally administered baricitinib (2 mg), a Janus kinase (JAK) inhibitor, twice daily. A notable improvement in both skin lesions and osteoarticular pain was observed within two weeks of treatment initiation. Subsequently, the dosage of baricitinib was halved and continued for an additional three months, during which regular follow-ups revealed neither disease recurrence nor adverse effects. Collectively, the successful treatment of refractory SAPHO syndrome with baricitinib presents a promising implication for addressing the therapeutic challenges of this rare autoimmune condition, offering a potential breakthrough in managing its complex manifestations.Keywords: SAPHO syndrome, autoinflammatory conditions, therapeutic challenges, baricitinib

Siyuan Zhou,1,2 Xiaojie Hu,1,2 Yunfei Wang,1,2 Wenting Fei,2 Yuqin Sheng,2 Huafa Que1,2 1Department of Traditional Chinese Surgery, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Longhua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Huafa Que, Department of Traditional Chinese Surgery, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 725, Wanping South Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 18917763260, Email huafaque@126.comObjective: Diabetic foot ulcer (DFU) frequently leads to infections, with infected DFUs being a common cause of amputation. Infection by methicillin-resistant Staphylococcus aureus (MRSA) notably increases the necessity for amputation and surgical debridement in affected individuals. Consequently, determining the prevalence and trends of MRSA in patients with DFU is of critical importance. This study aimed to assess the global prevalence and to identify trends in the occurrence of MRSA in tissue or wound swab samples from DFU patients.Methods: We conducted a comprehensive literature search across PubMed, Embase, Scopus, and Ovid, spanning from the inception of these databases to July 2023, imposing no language restrictions. The inclusion criteria required that the studies report on 30 or more patients with DFU. Additionally, we categorized our analysis based on geographic region, publication date, and the economic status of the patient’s domicile. Our primary endpoint was to ascertain the prevalence of MRSA in DFUs. This systematic review has been registered at (https://www.crd.york.ac.uk/prospero/), with the identifier CRD 42023444360.Results: Our analysis encompassed 40 studies involving 12,924 patients across 20 countries. We found that the overall prevalence of MRSA in DFU was 17% (95% Confidence Interval [CI] 0.14– 0.20). Regional prevalence varied significantly: in South America, it was 61% (95% CI 0.46– 0.76), in North America 20% (95% CI 0.12– 0.27), in Europe 19% (95% CI 0.14– 0.25), in Africa 13% (95% CI 0.06– 0.20), and in other subgroups 11% (95% CI 0.08– 0.15). The prevalence of MRSA in DFUs also differed according to the economic status of the countries: 19% (95% CI 0.15– 0.23) in high-income countries, 24% (95% CI 0.1– 0.37) in upper-middle-income countries, 11% (95% CI 0.07– 0.15) in lower-middle-income countries, and 20% (95% CI 0.13– 0.27) in low-income countries. Notably, there has been a decline in MRSA prevalence, from 25% before 2010 to 9% thereafter.Conclusion: This meta-analysis reveals a decreasing yet still significant global prevalence of MRSA in DFUs. This trend has important implications for antimicrobial resistance and underscores the need for developing targeted programs focusing on infection prevention and exploring alternative therapeutic strategies.Keywords: diabetic foot ulcers, global prevalence, epidemiological trends, systematic review, meta-analysis

Wenhua Yu,1,&ast; Shuodi Zhou,1,&ast; Yu Zhou2 1School of Mathematics and Statistics, Shandong Normal University, Jinan, Shandong, 250014, People’s Republic of China; 2Department of Mathematics, London School of Economics and Political Science, London, WC2A 2AE, UK&ast;These authors contributed equally to this workCorrespondence: Shuodi Zhou, School of Mathematics and Statistics, Shandong Normal University, Jinan, Shandong, People’s Republic of China, Email shuodzhou123@163.comPurpose: Research has demonstrated a strong correlation between mathematics self-efficacy and math performance. Middle school children are increasingly receiving solution-focused brief therapy (SFBT), which is a type of psychotherapy. The study intends to use SFBT intervention to improve mathematics self-efficacy of students and to determine whether SFBT intervention was effective. To examine whether Rasch model can be used to evaluate students’ mathematics self-efficacy.Methods: This study intends to use Radar chart, Rasch model, Line chart to measure the variations of mathematics self-efficacy of three 8th graders (n=3) during SFBT intervention.Results: Radar chart and Rasch model demonstrated a general increment in the mathematics self-efficacy of two pupils, while another one decreased. Additionally, three students showed a decline in their mathematics self-efficacy on particular mathematical problems using a line chart.Conclusion: Overall, students with varied degrees of self-efficacy in math benefited from SFBT interventions, which partially supports the usefulness of SFBT as a tool for assessing students’ mathematics self-efficacy. It supported that Rasch model can reflected the changes in students’ mathematics self-efficacy. This study provides guidance for measuring the improvement of students’ academic self-efficacy through SFBT intervention using Rasch model.Keywords: mathematics self-efficacy, solution-focused brief therapy intervention, radar chart, wright map

Wenjun Liang,1 Angela TH Kwan,2 Huifang Ye,3 Mohammad Mofatteh,4 Mingzhu Feng,1 Jack Wellington,5 Pingzhong Fu,6 Wenlong Wei,1 Yu Sun,1 Jianhui Huang,7 Jie Luo,7 Yimin Chen,1 Shuiquan Yang,1 Sijie Zhou7 1Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People’s Hospital, Foshan, People’s Republic of China; 2Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 3Department of Pharmacy, Foshan Sanshui District People’s Hospital, Foshan, People’s Republic of China; 4School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, United Kingdom; 5School of Medicine, Cardiff University, Cardiff, United Kingdom; 6Department of Radiology, Foshan Sanshui District People’s Hospital, Foshan, Guangdong Province, People’s Republic of China; 7Department of Surgery of Cerebrovascular Diseases, First People’s Hospital of Foshan, Foshan, Guangdong Province, People’s Republic of ChinaCorrespondence: Shuiquan Yang, Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People’s Hospital, Foshan, Guangdong Province, 528100, People’s Republic of China, Email yangshuiquan1969@126.com Sijie Zhou, Department of Neurosurgery, First People’s Hospital of Foshan, Foshan, Guangdong Province, 528000, People’s Republic of China, Email zhousijie91@163.comPurpose: In this study, we aimed to determine whether post-Alberta Stroke Project Early CT Changes Score (post-ASPECTS) in anterior stroke and post-(posterior circulation) PC-ASPECTS in posterior stroke on CT can predict post-endovascular thrombectomy (EVT) functional outcomes among patients with acute ischemic stroke (AIS) after EVT.Patients and Methods: A total of 247 consecutive patients aged 18 and over receiving EVT for LVO-related AIS were recruited into a prospective database. The data was retrospectively analyzed between March 2019 and February 2022 from two comprehensive tertiary care stroke centers: Foshan Sanshui District People’s Hospital and First People’s Hospital of Foshan in China. Patient parameters included EVT within 24 hr of symptom onset, premorbid modified Rankin scale (mRS) ≤ 2, presence of distal and terminal cerebral blood vessel occlusion, and subsequent 24– 72-hr post-stroke onset CT scan. Univariate comparisons were performed using the Fisher’s exact test or χ2 test for categorical variables and the Mann–Whitney U-test for continuous variables. Logistic regression analysis was performed to further analyze for adjusting for confounding factors. A p-value of ≤ 0.05 was statistically significant.Results: Overall, 236 individuals with 196 anterior circulation ischemic strokes and 40 posterior strokes of basilar artery occlusion were examined. Post-ASPECTS in anterior stroke and post-pc-ASPECTS as strong positive markers of favorable outcome at 90 days post-EVT; and lower rates of inpatient mortality/hospice discharge, 90-day mortality, and 90-day poor outcome were observed. Moreover, patients in the post-ASPECTS ≥ 7 cohort experienced shorter door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), and last known normal-to-puncture time (LKNPT).Conclusion: Post-ASPECTS ≥ 7 in anterior circulation AIS and post-pc-ASPECTS ≥ 7 in posterior circulation can serve as strong prognostic markers of functional outcome after EVT.Keywords: endovascular therapy, thrombectomy, large vessel occlusion, cerebral ischemic stroke, ASPECTS

Xuejun Tan,1 Yukun Xu,1 Sirui Zhou,1 Mingyue Pan,1 Yue Cao,1 Xiuping Cai,2 Qing Zhao,1,2,&ast; Kewei Zhao1,2,&ast; 1The Third Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Guangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment of Osteoporosis, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kewei Zhao; Qing Zhao, Department of Laboratory Medicine, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, 261 Longxi Avenue, Liwan District, Guangzhou, Guangdong, People’s Republic of China, Tel +86-13711355225 ; +86-18825144487, Email zkw2011@gzucm.edu.cn; zhaoqing900116@126.comAbstract: All humans are universally affected by inflammatory diseases, and there is an urgent need to identify new anti-inflammatory drugs with good therapeutic benefits and minimal side effects to the organism. Recently, it has been found that plant-derived vesicle-like nanoparticles (PDVLNs) have good biocompatibility, with their active ingredients exhibiting good therapeutic effects on inflammation. They can also be used as drug carriers for targeted delivery of anti-inflammatory drugs. Therefore, PDVLNs represent a popular research area for novel anti-inflammatory drugs. This paper details the origin, biological functions, isolation and purification, and identification of PDVLNs, as well as the therapeutic effects of their intrinsic bioactive components on inflammatory diseases. It also introduces their targets as drug carriers to facilitate the development and application of PDVLNs anti-inflammatory drugs.Keywords: plant, vesicle-like nanoparticles, inflammation, inflammatory diseases

Shaodan Zhou,1 Yishuang Wen,1 Chao Liu,1 Jian Zhong,1 Manli Liang,1 Yu Wu,2 Sirao Lv,1 Zhuowei Gong,1 Dayuan Lao,1 Taiyan Li,1 Ting Lu,1 Jingqun Tang,1 Xuean Mo,1 Wen Huang1 1Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2University of Pittsburgh School of Medicine, Pittsburgh, PA, USACorrespondence: Wen Huang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-771-5356504, Fax +86-771-5350031, Email hwen1229@163.comPurpose: With the adjustment of prevention strategies in December 2022, coronavirus disease 2019 (COVID-19) became widely prevalent in China. This study is aimed to describe the clinical characteristics of myasthenia gravis (MG) patients with COVID-19 and identify risk factors of exacerbation in MG patients with COVID-19 in Guangxi.Patients and Methods: A total of 489 MG patients and 587 control subjects in Guangxi during the COVID-19 pandemic were enrolled in this case–control study. After contacting the participants, the clinical data of MG patients and the control group were analyzed. The clinical characteristics of MG patients with COVID-19 were described. Multivariable logistic regression analysis was used for discovering independent risk factors of MG exacerbation in the patients with MG and COVID-19.Results: A total of 311 (75.30%) MG patients and 428 (72.91%) control subjects were infected with COVID-19, and 64.31% of MG patients with COVID-19 were women. The median age at the time of interview was 41 (IQR: 28, 54) years old, and median onset age was 36 (IQR: 24, 51), both of which were lower than those in MG patients without COVID-19. MG duration was 24 (IQR: 9, 72) months. About 44.69% of patients were generalized MG (GMG). About 11.90% of MG patients with COVID-19 showed severe COVID-19 symptoms and the duration of symptomatic COVID-19 was 9.57 ± 6.79 days, higher than those in the control group. About 35.69% MG patients with immunosuppressive drugs were infected with COVID-19, which is higher than those in the non-infected MG patients (21.57%). A total of 120 (38.59%) MG patients with COVID-19 had comorbidities. About 21 (20.19%) of the 104 MG patients without vaccination showed severe COVID-19 symptoms. Multivariable logistic regression analysis showed that baseline MG activities of daily living profile (MG-ADL, OR 1.280, 95% CI: 1.010– 1.621, p = 0.041), duration of COVID-19 (OR 1.158, 95% CI: 1.100– 1.220, p < 0.001), GMG (OR 2.331, 95% CI: 1.228, 4.426, p = 0.010), and lack of COVID vaccination (OR 2.075, 95% CI: 1.152, 3.738, p = 0.015) were independent factors of exacerbation in MG patients with COVID-19.Conclusion: MG patients with immunosuppressive drugs, younger onset, longer MG duration, or comorbidities are more susceptible to COVID-19. The baseline MG-ADL, duration of symptomatic COVID-19, GMG, and lack of COVID-19 vaccination are independent risk factors of exacerbation in MG patients with COVID-19.Keywords: myasthenia gravis, COVID-19, exacerbation, vaccination, clinical characteristics

Xiaoyun Gao,&ast; Moxi Chen,&ast; Penghao Liu, Shenyuan Zhou, Sai Kong, Junfeng Zhang, Jun Cao Department of Anesthesiology, Shanghai Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Cao, Department of Anesthesiology, Shanghai Sixth People’s Hospital, No. 600, Yishan Road, Shanghai, 200233, People’s Republic of China, Tel +86 18930173661, Email dr_caojun@sina.comBackground: A novel ultrasound-guided paravertebral block, the edge laminar block (ELB) was reported recently. However, it was unclear how effective ELB was in comparison with traditional blocking methods. We conducted a trial to compare the analgesic efficacy of ELB with the thoracic paravertebral block (TPVB) and the retrolaminar block (RLB) in patients undergoing video-assisted thoracic surgery (VATS).Methods: We identified 90 patients who were scheduled for VATS and randomly assigned them to three groups: ELB group (Group E), TPVB group (Group T), and RLB group (Group R). Each group underwent ELB, TPVB, and RLB, respectively, under ultrasound guidance before general anesthesia induction. All patients received post-operative routine analgesia protocol. Our primary outcome was the extent of dermatomal sensory loss on the midclavicular, midaxillary, and scapular lines, measured using a pinprick 15 minutes after the nerve block. Secondary outcomes included the intraoperative dose of sufentanil, the numerical rating scale (NRS) scores assessed in the post-anesthesia care unit (PACU) and at 6, 12, and 24 hours post-operatively, and pethidine administrated as analgesic rescue dose.Results: The percentages of nerve block range reaching the midclavicular line, midaxillary line, and scapular line in Group E were 96.7%, 93.3%, 93.3%, and 60% in Group T and 30%, 56.7%, and 96.7% in Group R, respectively. Group E had wider dermatomal sensory loss on the midclavicular line and midaxillary line compared to Group R (P

Yunxia Huang,1,&ast; Yi Guo,2,&ast; Qin Xiao,3,&ast; Shuyu Liang,2 Qiang Yu,4 Lang Qian,1 Jin Zhou,1 Jian Le,1 Yuchen Pei,5 Lei Wang,4 Cai Chang,1 Sheng Chen,4 Shichong Zhou1 1Department of Ultrasonography, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Department of Radiology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China; 3Department of Electronic Engineering, Fudan University and Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai, Shanghai, People’s Republic of China; 4Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China; 5Precision Cancer Medical Center Affiliated to Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shichong Zhou, Department of Ultrasonography, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 21-64175590, Email sczhou@hotmail.com Sheng Chen, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 21-64175590, Email 0456177@fudan.edu.cnPurpose: The emergence of genomic targeted therapy has improved the prospects of treatment for breast cancer (BC). However, genetic testing relies on invasive and sophisticated procedures.Patients and Methods: Here, we performed ultrasound (US) and target sequencing to unravel the possible association between US radiomics features and somatic mutations in TNBC (n=83) and non-TNBC (n=83) patients. Least absolute shrinkage and selection operator (Lasso) were utilized to perform radiomic feature selection. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was utilized to identify the signaling pathways associated with radiomic features.Results: Thirteen differently represented radiomic features were identified in TNBC and non-TNBC, including tumor shape, textual, and intensity features. The US radiomic–gene pairs were differently exhibited between TNBC and non-TNBC. Further investigation with KEGG verified radiomic–pathway (ie, JAK-STAT, MAPK, Ras, Wnt, microRNAs in cancer, PI3K-Akt) associations in TNBC and non-TNBC.Conclusion: The pivotal network provided the connections of US radiogenomic signature and target sequencing for non-invasive genetic assessment of precise BC treatment.Keywords: triple-negative breast cancer, radiomics, somatic mutation, signaling pathway

Qianqian Zhou,1 Shengru Zhou,1 Huizi Xiong,1 Jianqiu Yang,1 Ziliang Yang,2 Naihui Zhou,2 Jinzhu Mao,2 Min Li1,2 1Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), Suzhou, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Min Li, Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), No. 9, Chongwen Road, Suzhou, 215123, People’s Republic of China, Tel +86-18936140383, Email lm@suda.edu.cnIntroduction: Psoriasis is an immune-mediated chronic inflammatory skin disease. As our understanding of the pathogenesis of psoriasis has improved, biologic agents have become increasingly important in the treatment of psoriasis. However, the use of biologic agents is associated with cutaneous side effects. A new type of side effect called paradoxical reactions is an emerging threat arising from the increasing use of biologic agents.Case: Here, we present a case of paradoxical skin reactions – pyoderma gangrenosum (PG) and eczema – induced by biologic therapy. The case was successfully and eventually treated with baricitinib.Discussion: PG is a rare inflammatory disease characterised by painful and necrotic ulcerations containing neutrophils. It has been associated with autoimmune diseases such as inflammatory bowel disease (IBD). TNF (tumor necrosis factor) -α inhibitors can effectively treat refractory PG, while IL (interleukin) − 17A inhibitors may worsen IBD symptoms. The cause of PG in this case was believed to be secukinumab, not adalimumab. The patient was diagnosed with eczematous dermatitis due to TNF-α inhibitors, and baricitinib was added to treat eczematous dermatitis.Conclusion: Paradoxical reactions are unpredictable events that may occur during treatment with biologics at anytime. They need further research in order to formulate personalised treatment.Keywords: biology drugs, pyoderma gangrenosum, eczema, adalimumab, secukinumab, baricitinib

Wenzhe Zhao,1 Haiqin Zhu,1 Xiaoqing Zhao,1 Xinyi Wu,1 Fei Sun,1 Meng Pan,1,&ast; Shengru Zhou2,&ast; 1Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), Suzhou, 215123, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengru Zhou, Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University, (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), No. 9, Chongwen Road, Suzhou, 215123, People’s Republic of China, Tel +86-17717453465, Fax +86-2164669691, Email zhoushengru1989@foxmail.comPurpose: Direct immunofluorescence (DIF) on frozen sections (DIF-F) plays a key role in the identification and differential diagnosis of bullous dermatoses, which are a group of critical autoimmune diseases that include pemphigus, bullous pemphigoid (BP), and epidermolysis bullosa acquisita (EBA). However, this technique requires specialized laboratory equipment conditions, sample acquisition and sample preservation. In this study, the application value of DIF on paraffin-embedded tissue sections (DIF-P) detecting IgG using heat-induced antigen retrieval (HIAR) in the diagnosis of bullous dermatosis was explored.Patients and Methods: Samples from 12 patients with pemphigus vulgaris (PV), 10 patients with pemphigus foliaceus (PF), 17 patients with BP, and 4 patients with EBA were retrospectively studied for DIF-P IgG detection. Formalin-fixed, paraffin-embedded tissue (FFPE) was used, and the antigen retrieval method used in the experiment was HIAR. All patients were diagnosed with the autoimmune bullous disease (AIBD) based on clinical presentation, histopathology, DIF-F, and enzyme-linked immunosorbent assay (ELISA).Results: Intercellular staining for IgG in the epidermis was successful in paraffin-embedded tissue sections in 11 of 12 PV samples and in all 10 PF samples. IgG at the basement membrane zone (BMZ) was not detected by immunofluorescent staining in 17 BP samples and 4 EBA samples.Conclusion: The detection of IgG by DIF-P using HIAR can be used for the diagnosis of pemphigus as an alternative method to DIF-F.Keywords: pemphigus, bullous dermatoses, direct immunofluorescence, IgG, paraffin-embedded section, heat-induced antigen retrieval

Yiming Cheng,1 Ying Ye,1 Allison Gaudy,1 Atalanta Ghosh,2 Yongjun Xue,3 Alice Wang,1 Simon Zhou,1 Yan Li1 1Clinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, Princeton, NJ, USA; 2Global Biometrics and Data Sciences, Bristol Myers Squibb, Princeton, NJ, USA; 3Nonclinical Research & Development, Bristol Myers Squibb, Princeton, NJ, USACorrespondence: Yan Li, Clinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, 556 Morris Ave, Summit, Princeton, NJ, 07901, USA, Tel +1 908-481-6203, Email Yan.Li@bms.comIntroduction: Iberdomide, a novel cereblon modulator (CELMoD®), is currently under clinical investigation for hematology indications. To evaluate the influence of hepatic impairment on the pharmacokinetics (PK) of iberdomide and its major active metabolite M12, a phase 1, multicenter, open-label study was conducted in healthy subjects and subjects with mild, moderate, and severe hepatic impairment.Methods: Forty subjects were enrolled in the study and divided into five groups based on hepatic function. 1 mg iberdomide was administered and plasma samples were collected to evaluate the pharmacokinetics of iberdomide and M12.Results: After a single dose of iberdomide (1 mg), mean iberdomide Cmax (maximum observed concentration) and AUC (area under the concentration-time curve) exposure were generally comparable between hepatic impairment (HI) subjects (severe, moderate and mild) and their respective matched normal controls. Mean Cmax and AUC exposure of the metabolite M12 were generally comparable between mild HI and matched normal subjects. However, mean Cmax of the M12 was 30% and 65% lower and AUC was 57% and 63% lower in moderate and severe HI subjects as compared to their respective matched normal controls. However, given the relatively low M12 exposure as compared to its parent drug, the observed differences were not considered clinically meaningful.Conclusion: In summary, 1 mg single oral dose of iberdomide was generally well-tolerated. HI (mild, moderate or severe) had no clinically relevant impact on iberdomide PK and therefore, no dose adjustment is warranted.Keywords: hepatic impairment, iberdomide, pharmacokinetics

Hong Liao,1,&ast; Shixin Zhou,2,&ast; Si Chen,3 Jun Li,3 Zongqi Zhang,3 Ling Meng,3 Qiliang Liu,4 Yuan Wu,3 Yuanqiao He,5– 7 Ming Li3 1Department of Medicine, The Eighth Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China; 2School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Oncology, Wuhan Pulmonary Hospital, Wuhan, Hubei, People’s Republic of China; 4Department of Pathology, Wuhan Pulmonary Hospital, Wuhan, Hubei, People’s Republic of China; 5Department of Laboratory Animal Science, Nanchang University, Nanchang, People’s Republic of China; 6Jiangxi Province Key Laboratory of Laboratory Animal, Nanchang, People’s Republic of China; 7Nanchang Royo Biotech Co, Ltd, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Li, Department of Oncology, Wuhan Pulmonary Hospital, No. 28 Baofeng Road, Qiaokou District, Wuhan City, Hubei Province, 430030, People’s Republic of China, Tel +86-13971222216, Email drliming1992@outlook.com Yuanqiao He, Department of Laboratory Animal Science, Nanchang University, No. 999, Xuefu Road, Nanchang, Jiangxi, 330031, People’s Republic of China, Tel +791-83968063, Email heyuanqiao@ncu.edu.cnPurpose: Non-small-cell lung cancer (NSCLC) comprises approximately 80% of all lung malignancies. The 5-year survival rate of patients with advanced lung cancer who lost their chances of surgery is approximately 15%. Suitable animal models are important in screening individualized treatment plans for patients with lung cancer, evaluating the pre-clinical efficacy of new drugs, and conducting basic research.Patients and Methods: In this study, we collected malignant pleural effusion (MPE) samples from 31 patients with NSCLC, successfully constructed 11 NSCLC patient-derived xenografts (PDXs), and analyzed the factors affecting their successful establishment. Primary PDX tumors were characterized using histological analysis, immunohistochemistry, short tandem repeat (STR) profiling, and cytogenetic analysis.Results: The PDXs preserved the histopathology and protein expression pattern of parental tumors. STR analysis revealed the PDX tissue and a tumor tissue of the same individual origin. Statistical analysis showed that the survival time of patients reflected the malignant degree of MPEs to a certain extent, thus affecting the establishment of PDXs. However, the age, gender, and clinical and biochemical indicators of the patients did not affect the establishment of PDX models.Conclusion: These data suggest that the established NSCLC PDXs preserved the molecular characteristics of primary lung cancer and can serve as a new tool to elucidate the pathogenesis of tumors, explore new treatment methods, and conduct the research and development of new drugs for tumors.Keywords: PDX, translational model, short tandem repeat profiling, cytogenetic analysis, survival time

The Isa smelting furnace discharges the matte and slag in the same tapping hole. As a result, an electric furnace needs to clean the slag. In the present study, the copper slag cleaning in an electric furnace, particularly the separation of the matte from the slag during the reduction process, was investigated. For Fe3O4 to FeO, the foaming slag in the melt disappeared when the Fe3O4 content was less than 10%. With the formation of the metallic iron, the foaming slag formed again, hindering the sedimentation of the matte. When the anthracite dosage increased to 2.61%, the copper content in the slag increased to 9.46%. The microstructure of the slag and the existence of the metallic iron found in the slag were analyzed in detail. The results obtained in this study provide a theoretical basis for the reasonable control of the transformation of Fe3O4 during the copper slag cleaning.

Suizi Zhou,1,2,&ast; Yitong Liu,1,2,&ast; Yueying Yang,1 Hongming Huang,1 Qianhui Qiu1 1Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore&ast;These authors contributed equally to this workCorrespondence: Qianhui Qiu, Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China, Email qiuqianhui@hotmail.comPurpose: This study aimed to investigate whether the impaired ciliary length and aberrant ciliary ultrastructure marker, dynein axonemal intermediate chain 1 (DNAI1), are important pathological characteristics in nasal mucosa from patients with allergic rhinitis (AR).Patients and Methods: Biopsies were taken from the inferior turbinate (IT) of controls (n = 20) and patients with AR (n = 20). The ciliary length and the DNAI1 location patterns were assessed by using immunofluorescent staining. Three patterns of DNAI1 localization were defined using a semi-quantitative scoring system: normal (N), partial (P) and absence (A). Every individual section was assigned a score between 0 and 2 in each high-power field (5 fields per sample). The score of 0 = pattern N > 70%; 1 = patterns N + P > 70%; and 2 = pattern A ≥ 30%. The receiver operating characteristic (ROC) curve was used to evaluate the predicted value of DNAI1 score for AR.Results: The ciliary length was reduced by 33.3% in patients with AR compared with controls (P < 0.0001). The higher DNAI1 score was found in the AR group, with a median (first and third quartile) of 0.9 (0.4 and 1.08), which was 0.1 (0 and 0.76) in the control group (P = 0.0071). The ROC of DNAI1 was calculated based on the area under the curve of 0.74 (P = 0.0094). The cutoff value of ROC was 0.5833, with a sensitivity and specificity of 70%.Conclusion: These results suggested that the shorter ciliary length and aberrant localization of DNAI1 are potentially important pathological characteristics of the allergic nasal mucosa. The aberrant localization of DNAI1 may provide a novel candidate target for clinical management of AR.Keywords: allergic rhinitis, cilia length, DNAI1, biomarker, ciliated marker

Yan Zhang,1 Wenjie Li,1 Xiaomin Tian,1 Ruanyang Sun,1 Shidan Zhou,2 Ling Jia,1 Jian Sun,1,3,4 Xiao-Ping Liao,1,3,4 Ya-Hong Liu,1,3,4 Yang Yu1,3,4 1Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, People’s Republic of China; 2Intensive Care Unit, Huizhou Municipal Central Hospital, Huizhou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Microbial Safety and Health, Guangdong Institute of Microbiology, Guangdong Academy of Science, Guangzhou, People’s Republic of China; 4Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, People’s Republic of ChinaCorrespondence: Yang Yu, Email graceyyu@scau.edu.cnObjective: Carbapenem-resistant Enterobacteriaceae (CRE) have become an increasingly common cause of healthcare-related infections and present a serious challenge to clinical treatment. This study examined the phenotypic, genotypic characterization, clinical, and microbiological data of CRE in the Huizhou Municipal Central Hospital.Methods: We conducted a phenotypic susceptibility evaluation and whole genome sequence analysis for 52 CRE strains isolated from 37 patients and 2 medical device-related samples during 2013– 2017 to characterize risk factors, antimicrobial resistance profiles, dominant clones and hospital transmission.Results: Long-term hospitalization, treatment time with antibiotics and use of invasive devices were linked to the risk of CRE infection. The carbapenem resistance genes (CRGs) we found included blaNDM (82.7%), blaIMP (19.2%) and blaKPC (3.8%), Escherichia coli (44.2%) and Klebsiella pneumoniae (44.2%) were the dominant species we identified, and the type of CRG carried by isolates was highly correlated with species. The coexistence of CRGs with a variety of other antibiotic resistance genes leads to an increased prevalence of high resistance levels for CRE to β-lactams and other antibiotic classes such as aminoglycosides and fluoroquinolones. These isolates were sensitive only to colistin and tigecycline. In addition to this, we observed significantly genomic diversity of CRE isolates in this hospital. Importantly, we found that long-term transmission of multiple CRE clones had occurred at this hospital between various wards.Conclusion: Evaluating and improving the current infection control strategies may be necessary, and reducing nosocomial transmission remains the primary control element for CRE infections in China.Keywords: carbapenem-resistant Enterobacteriaceae, bacteremia, carbapenem resistance genes, nosocomial transmission

Bingxin Song,1 Shishi Zhou,2 Chenghui Li,2 Hongjuan Zheng,2 Xia Zhang,2 Xiayun Jin,2 Jianfei Fu,2 Huixian Hu1 1Department of Medical Hematology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang Province, People’s Republic of China; 2Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang Province, People’s Republic of ChinaCorrespondence: Jianfei Fu, Department of Medical Oncology, Zhejiang University Jinhua Hospital, 351 Mingyue Road, Jinhua, 321000, Zhejiang Province, People’s Republic of China, Fax +86-579-82552856, Email 11218276@zju.edu.cn Huixian Hu, Department of Medical Hematology, Zhejiang University Jinhua Hospital, 351 Mingyue Road, Jinhua, Zhejiang Province, 321000, People’s Republic of China, Fax +86-579-82136611, Email huhuixian@zju.edu.cnObjective: Chemotherapy-induced thrombocytopenia (CIT) can lead to chemotherapy dose delay or reduction, and even serious bleeding. This study aimed to develop a CIT-predicting model based on the laboratory indices of cancer patients undergoing chemotherapy.Material and Methods: From Jun 1, 2017 to Dec 30, 2021, a total of 2043 patients who had received 7676 cycles of chemotherapy were retrospectively enrolled. A logistic regression analysis was performed to identify predictive factors, on the basis of which a nomogram model for predicting CIT was established. A bootstrapping technique was applied for internal validation. A generalized additive mixed model (GAMM) was constructed to analyze the trends in the changes of aspartate aminotransferase (AST), ratio of AST to alanine transaminase (ALT) (AST/ALT ratio), and platelet (PLT) count in patients with solid tumors. P values ≤ 0.05 were considered statistically significant.Results: The patient-based incidence of CIT was 20.51% and the cycle-based incidence was 10.01%. The multivariate analysis showed that AST level, AST/ALT ratio, and total bilirubin (Tbil), white blood cell (WBC), platelet (PLT), hemoglobin (Hb) levels were significantly associated with the risk of CIT. The GAMM analysis showed that PLT level was inversely associated with AST/ALT ratio and AST level, more significantly with AST/ALT ratio. And both exhibited statistically predictive abilities for CIT. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.793, a sensitivity of 0.543 and a specificity of 0.930.Conclusion: The AST/ALT ratio was inversely associated with the CIT risk in cancer patients. The GAMM model based on laboratory indices presented a high accuracy in predicting the risk of CIT, and a potential to be translated into clinical management.Keywords: chemotherapy-induced thrombocytopenia, solid tumors, AST/ALT-ratio, prediction model

Zhanjie Li,1 Ying Zhang,2 Weihong Zhang,1 Yongxiang Zhang,1 Suming Zhou,3 Wensen Chen,1 Yun Liu4,5 1Department of Infection Control, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Infection Control, Lianshui County People’s Hospital, Huaian, People’s Republic of China; 3Department of Geriatric Critical Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Information, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 5Department of Medical Informatics, School of BioMedical Engineering and Informatics, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Wensen Chen, Department of Infection Control, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China, Tel +86-13809049855, Email wensenchen@njmu.edu.cn Yun Liu, Department of Information, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guang Zhou Road, Nanjing, People’s Republic of China, Tel +86-18805152008, Email liuyun@njmu.edu.cnObjective: To analyze the infection and distribution of multidrug-resistant organisms (MDRO) in different clinical specimens, thereby providing a reference for clinical diagnosis and treatment and prevention and control.Patient and Methods: 2314 strains of MDRO isolated from clinical specimens in the First Affiliated Hospital of Nanjing Medical University from January to December 2020. MDRO were collected by Information System. The detection rate of MDRO, infection rate, the proportion of infection, and detection rate of MDRO infection in different specimens were analyzed.Results: The top three specimens in the detection rate of MDRO were BALF (60.71%), sputum (33.68%), and blood (28.79%). The top three specimens in the proportion of MDRO infection were blood (97.74), other sterile body fluids (90.35%), and BALF (90.20%). The top three specimens in the MDRO infection rate were BALF (9.75%), sputum (3.07%), and secretions (2.90%). The top three specimens in the detection rate of MDRO infection were sputum (0.63‰), other sterile body fluids (0.13‰), and secretions (0.11‰).Conclusion: The detection and infection distribution of MDRO vary greatly in different specimens. The submission of sterile body fluids for examination should be strengthened and the standard of sample collection should be highlighted.Keywords: different specimens, MDRO, detection rate, infection, sterile body fluids

Wenyan Peng,1,&ast; Xiuying Jiang,1,&ast; Lei Zhu,2,&ast; Xiaofeng Li,3,&ast; Qizhi Zhou,4,&ast; Ying Jie,5 Zhipeng You,6 Miaoqin Wu,7 Xiuming Jin,8 Xiaoyi Li,9 Shiyou Zhou1 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, People’s Republic of China; 2Henan Provincial People’s Hospital, Henan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450003, People’s Republic of China; 3Department of Ophthalmology, Chengdu Aier Eye Hospital, Sichuan, People’s Republic of China; 4Department of Ophthalmology, Chongqing Aier Eye Hospital, Chongqing, People’s Republic of China; 5Department of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 7Department of Ophthalmology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 8Department of Ophthalmology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 9Zhaoke Ophthalmology Ltd, Guangzhou, 511458, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiyou Zhou, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, People’s Republic of China, Tel +8620-6661-5460 ; +86-13829709097, Fax +8620-87333271, Email zhoushiy@mail.sysu.edu.cnPurpose: To confirm the efficacy and safety of a novel ophthalmic cyclosporine A gel (CyclAGel, 0.05% CsA) in treating patients with moderate-to-severe dry eye disease (DED).Patients and Methods: The COSMO trial was a randomized, multicenter, double-masked, vehicle-controlled, phase III trial. Patients with moderate-to-severe DED were enrolled in 37 hospitals in China between November 2020 and April 2021. Eligible patients were randomized 1:1 to receive CyclAGel 0.05% or vehicle eye drops once nightly (QD). The primary endpoint was the proportion of subjects with at least a 1-point improvement in ICSS at day 84. Treatment-emergent adverse events (TEAEs) were recorded.Results: The full analysis set (FAS) included 315 and 312 participants in the CyclAGel and vehicle groups, respectively. The primary efficacy endpoint was achieved. The proportion of subjects with at least a 1-point improvement in ICSS from baseline to day 84 was significantly higher in the CyclAGel group than in the vehicle group (73.7% [232/315] vs 53.2% [166/312], P< 0.0001). Significant improvements relative to the vehicle were also observed in the ICSS and Oxford scale scoring of corneal and conjunctival fluorescein staining at day 14, 42, and 84. The Schirmer tear test results were significantly higher in the CyclAGel group than in the vehicle group on days 14 and 84 (all P< 0.05). The CyclAGel 0.05% was well tolerated, and the TEAEs were mostly mild. The most frequent treatment-related TEAE was eye pain (6.9% vs 1.6% in the CyclAGel and vehicle groups, respectively). No serious treatment-related TEAEs were reported.Conclusion: Clinically and statistically significant improvements in ICSS, tear production, and symptoms were observed in participants administered CyclAGel 0.05% QD for moderate-to-severe DED. CyclAGel 0.05% QD is a new effective, safe, and well-tolerated therapeutic option that might bring additional benefits of convenience and compliance as a once-A-day treatment for DED.Keywords: dry eye disease, cyclosporine, ophthalmic gel, corneal staining, dryness score

Hao Hong,1 Suya Zhou,2 Haimin Shi,3 Ming Li3 1Intensive Care Unit, The First Affiliated Hospital of Soochow University, Soochow, People’s Republic of China; 2Laboratory Nephrology, Department of Nephrology, Jinshan Hospital of Fudan University, Shanghai, People’s Republic of China; 3Laboratory Nephrology, The First Affiliated Hospital of Soochow University, Soochow, People’s Republic of ChinaCorrespondence: Ming Li, Tel +86 13656237709, Fax +0512-67972681, Email szdrli@163.comPurpose: Our aim was to determine the relationship between plasma and urine indoleamine 2.3-dioxygenase (IDO) activity and stage of chronic kidney disease (CKD).Patients and Methods: Demographic and clinical parameters, including plasma and urine IDO activity, were recorded in 47 CKD patients and 30 controls. One-way ANOVA with the least significant difference method was used to compare means of variables that had normal distributions and homogeneous variance. Variables with non-normal distributions were log-transformed and compared using the rank sum test Pearson or Spearman correlation coefficients were determined. Binary logistic regression and ordinal logistic regression were used to identify independently significant factors. Receiver operating characteristic (ROC) analysis was performed.Results: The control group had higher levels of hemoglobin and albumin and lower levels of creatinine and blood urea nitrogen (BUN; all P< 0.01). The level of highly sensitive C reactive protein (hs-CRP) increased as CKD stage increased (P

Chunyu Yuan,1,&ast; Dongmei Deng,2,&ast; Jianqiu Yang,1 Simeng Liu,3 Qihong Qian,4 Min Chen,1 Shengru Zhou,1 Yujiang Li,5 Min Li1,4 1Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), Suzhou Ctiy, Jiangsu, People’s Republic of China; 2Health Management Center, The Fifth People’s Hospital of Hainan Province, Haikou Ctiy, Hainan, People’s Republic of China; 3Department of Dermatology, Aerospace Center Hospital, Beijing Ctiy, People’s Republic of China; 4Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou Ctiy, Jiangsu, People’s Republic of China; 5Department of Dermatology, Sanmenxia Central Hospital, Sanmenxia Ctiy, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yujiang Li, Department of Dermatology, Sanmenxia Central Hospital, Middle Road of Yaoshan, Hubin District, Sanmenxia, Henan, 472000, People’s Republic of China, Tel +86-13525857005, Email 294161298@qq.com Min Li, Department of Dermatology, the First Affiliated Hospital of Soochow University, No. 188 Shizi Road, Gusu District, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-18936140383, Email lmpfdoctor@163.comPurpose: Dyskeratosis congenita (DC) is an inherited telomere biology disorder characterized clinically by mucocutaneous triad of reticulate hyperpigmentation, nail changes and oral leukoplakia. Bone marrow failure, pulmonary fibrosis and malignancies are the mainly life-threatening causes. There are X-linked recessive, autosomal dominant and autosomal recessive patterns of DC. DKC1 is the most common pathogenic mutation gene responsible for X-linked DC, and it encodes a protein, dyskerin, which is a component of telomerase holoenzyme complex essential for telomere maintenance. Patients with DC have very short telomeres, but the precise pathogenic mechanism remains unclear. This study aimed to identify the causative mutations in the DKC1 gene in three Chinese families with the X-linked form of DC.Patients and Methods: Three Chinese families with DC were included in this study. Whole exome sequencing and Sanger sequencing were performed to clarify the mutation of DKC1 gene. Measurement of relative telomere length through qPCR. Predictions of protein structure and function were performed using bioinformatics tools, including I-TASSER, Polyphen-2 and SIFT.Results: There were four males with DC and a female carrier in three Chinese pedigrees. The novel mutation c.92A>C (p. Q31P) and the missense mutation c.1058C>T (p. A353V) in DKC1 were identified. Both mutations locally changed the structure of dyskerin. Variant Q31P and A353V were predicted to have “deleterious” and “natural” effects on the function of dyskerin, respectively.Conclusion: The novel variant and missense variant detected in the DKC1 gene improve our understanding of DC and broaden the mutation spectrum of the DKC1 gene.Keywords: dyskeratosis congenita, mucocutaneous triad, DKC1 gene, mutation

Hui Han,1– 3,&ast; Ming Chen,2,&ast; Zhenyu Li,2,&ast; Siqi Zhou,2 Yingbin Wu,3 Jian Wei1 1Department of Sports Medicine and Joint Orthopedics, Liuzhou People’s Hospital, Liuzhou, Guangxi, People’s Republic of China; 2Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Orthopedic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Wei, Department of Sports Medicine and Joint Orthopedics, Liuzhou People’s Hospital, Liuzhou, Guangxi, People’s Republic of China, Tel +86-13669663233, Email wei198206@163.comPurpose: Osteoarthritis (OA) is an age-related degenerative disease associated with enhanced degradation of extracellular matrix (ECM) and decreased autophagy. Our study is aimed to explore how corosolic acid (CRA) affect cartilage ECM metabolism and the potential mechanism.Methods: Rat chondrocytes were pretreated with different concentrations of CRA (0, 2.5, 5, and 10 μM), and were stimulated with IL-1β (10ng/mL) for 24 h, subsequently. RT-qPCR, Western blot, and immunofluorescence were used to detect the expression of genes related to ECM metabolism and explore the potential molecular mechanism. The effect of CRA on articular cartilage was observed in the surgically induced OA rat model with the method of Safranin O/Fast green and immunohistochemical staining.Results: Results showed that CRA reversed the IL-1β-induced degradation of aggrecan and type II collagen and the high expression of MMP13 and ADAMTS5. Mechanistically, CRA enhanced autophagy through inhibiting the classical PI3K/AKT/mTOR signaling pathway. Furthermore, inhibition of autophagy partly abolished the protective effects of CRA on ECM synthesis in IL-1β-treated chondrocytes. Correspondingly, the protective effect of CRA was also confirmed in a rat OA model.Conclusion: Herein, we demonstrate that CRA can enhance autophagy by inhibiting PI3K/AKT/mTOR signaling pathway, prevent IL-1β-induced cartilage ECM degradation, and may be a potentially applicable candidate for the treatment of OA.Keywords: osteoarthritis, corosolic acid, autophagy, extracellular matrix, PI3K/AKT/mTOR signaling

Pulin Li,1,&ast; Xiaojuan Chen,2,&ast; Sijing Zhou,3,&ast; Xingyuan Xia,1 Enze Wang,1 Rui Han,1 Daxiong Zeng,4,5 Guanghe Fei,1 Ran Wang1 1Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Infectious Diseases, Hefei Second People’s Hospital, Hefei, People’s Republic of China; 3Department of Occupational Medicine, Hefei Third Clinical College of Anhui Medical University, Hefei, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Suzhou Dushu Lake Hospital, Suzhou, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanghe Fei; Ran Wang, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China, Tel/Fax +86 -551-62922913, Email guanghefei@hotmail.com; wangran@ahmu.edu.cnIntroduction: Lung adenocarcinoma (LUAD) is the most common type of lung cancer. DEP domain-containing 1 B (DEPDC1B) is involved in the development of several cancers; however, its role in LUAD is unknown. Therefore, we aimed to determine the biological function and prognostic value of DEPDC1B in LUAD.Material and Methods: We analyzed the correlation between DEPDC1B expression and the clinical features of LUAD and lung squamous cell carcinoma (LUSC). Survival was evaluated by generating Kaplan–Meier curves, which were used to analyze the relationship between DEPDC1B expression and prognosis in LUAD and LUSC. DEPDC1B expression in tumor and normal tissues from patients with LUAD and LUSC was determined using immunohistochemistry, and its clinical significance was analyzed. Finally, the correlation between the expression and biological function of DEPDC1B in LUAD was examined.Results: Our findings revealed that DEPDC1B expression was higher in tumor tissues than that in normal tissues from patients with LUAD and LUSC (P < 0.001). These results were confirmed in clinical samples from patients using immunohistochemistry. Analysis of a dataset from The Cancer Genome Atlas (TCGA) showed that high DEPDC1B expression was associated with poor prognosis only in patients with LUAD (P < 0.001). Similarly, high DEPDC1B expression was related to shorter overall survival (OS) and progression-free interval (PFI) in patients with LUAD. These associations were not observed in LUSC. Functional enrichment analysis suggested that DEPDC1B promoted tumor development in LUAD by regulating the cell cycle.Conclusion: High DEPDC1B expression predicts poor prognosis in patients with LUAD. Thus, DEPDC1B has potential as a therapeutic target for LUAD.Graphical Abstract: Keywords: DEP domain-containing 1B, lung adenocarcinoma, prognosis, immunohistochemistry, bioinformatics

Yu Wang,1 Jiong Tang,2 Su Zhou,3 Tian-Tian Liang,1 Fang-Fang Wang,4 Hong Ning1 1Department of Pharmacy, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, People’s Republic of China; 2Department of Pharmacy, Sichuan Second Hospital of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Department of Pharmacy, Sichuan GEM Flower Hospital, Chengdu, People’s Republic of China; 4Department of Pharmacy, Emeishan People’s Hospital, Emeishan, People’s Republic of ChinaCorrespondence: Hong Ning, Department of Pharmacy, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 12 Changjia Alley, Jingzhong Street, Mianyang, 621000, People’s Republic of China, Tel +86-0816-2242469, Email NingHong555@126.comBackground: Rifaximin, a rifamycin antibiotic, is widely used to treat infectious diarrhea but not commonly used in H. pylori eradication. With its potential advantages of the agent, some studies were conducted on this topic. The aim of this study is to assess effectiveness and safety of rifaximin-containing regimens and to evaluate whether they are alternative choices for H. pylori eradication.Methods: Scientific databases including PubMed, EMbase and Cochrane Library were used to identify clinical trials on rifaximin-containing regimens published from January 2000 to October 2021. Review Manager 5.4 and STATA12 were adopted for the systematic review.Results: In this study, totally 1025 patients were included from 3 randomized controlled and 9 single-arm studies. It showed that the differences in effectiveness and safety between rifaximin-containing and first-line regimens were not statistically significant in randomized controlled trials. However, the results of the single-arm trials indicated that the eradication and adverse drug reaction rate varied suggesting data instability (r=38.1%-85.4%, rADR 0.00– 67.5% by ITT analysis). Among them, the eradication rate of pediatric patients (r=85.4% by ITT analysis) was higher than that of adult patients (r=38.1– 74.5% by ITT analysis). Meanwhile, in all adult subgroups (triple or quadruple, with or without amoxicillin, different duration and rifaximin dose), the results did not show sufficient effectiveness as all the eradication rates did not meet the minimum ideal or ideal target.Conclusion: Taken together, rifaximin-containing regimens should not be recommended for H. pylori eradication as they cannot achieve the eradication rate desired.Keywords: rifaximin, Helicobacter pylori, effectiveness and safety, systematic review

Yue-Ying Yang,1,2,&ast; Jing Liu,2,&ast; Yi-Tong Liu,3,4 Hsiao-Hui Ong,2 Qian-Min Chen,2,4 Ce-Belle Chen,5 Mark Thong,6 Xinni Xu,6 Sui-Zi Zhou,3,4 Qian-Hui Qiu,3,4 De-Yun Wang2 1Department of Otolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Otolaryngology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 3Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 4The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 5Centre for Ion Beam Applications, Department of Physics, National University of Singapore, Singapore; 6Department of Otolaryngology-Head and Neck Surgery, National University Hospital, National University Health System, Singapore&ast;These authors contributed equally to this workCorrespondence: Qian-Hui Qiu, Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Road II, Guangzhou, 510080, People’s Republic of China, Tel +86 20 83827812, Email qiuqianhui@hotmail.com De-Yun Wang, Department of Otolaryngology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, NUHS Tower Block, 1E Kent Ridge Road, 119228, Singapore, Tel + 65 6772 5373/5370/5371, Fax +65 6775 3820, Email entwdy@nus.edu.sgPurpose: Radiotherapy (RT) is the mainstay treatment for head and neck cancers. However, chronic and recurrent upper respiratory tract infections and inflammation have been commonly reported in patients post-RT. The underlying mechanisms remain poorly understood.Method and Materials: We used a well-established model of human nasal epithelial cells (hNECs) that forms a pseudostratified layer in the air-liquid interface (ALI) and exposed it to single or repeated moderate dose γ-irradiation (1Gy). We assessed the DNA damage and evaluated the biological properties of hNECs at different time points post-RT. Further, we explored the host immunity alterations in irradiated hNECs with polyinosinic-polycytidylic acid sodium salt (poly [I:C]) and lipopolysaccharides (LPS).Results: IR induced DNA double strand breaks (DSBs) and triggered DNA damage response in hNECs. Repeated IR significantly reduced basal cell proliferation with low expression of p63/KRT5 and Ki67, induced cilia loss and inhibited mucus secretion. In addition, IR decreased ZO-1 expression and caused a significant decline in the transepithelial electrical resistance (TEER). Moreover, hyperreactive response against pathogen invasion and disrupted epithelial host defense can be observed in hNECs exposed to repeated IR.Conclusion: Our study suggests that IR induced prolonged structural and functional impairments of hNECs may contribute to patients post-RT with increased risk of developing chronic and recurrent upper respiratory tract infection and inflammation.Keywords: human nasal epithelial cells, irradiation, DNA double strand breaks, epithelial barrier, host defense

Yun Hong,1,&ast; Da-Peng Dai,2,&ast; Jian-Ping Cai,2 Shuang-Hu Wang,3 Yi-Ran Wang,1,4 Fang-Ling Zhao,2,4 Shan Zhou,2 Quan Zhou,3 Pei-Wu Geng,3 Yun-Fang Zhou,3 Xue Xu,1 Ji-Hua Shi,1 Qing-Feng Luo1 1Department of Gastroenterology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 2The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, 100730, People’s Republic of China; 3Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui, 323020, People’s Republic of China; 4Peking University Fifth School of Clinical Medicine, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing-Feng Luo, Department of Gastroenterology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Tel + 86 138 1151 9095, Email luoqf2000@126.comPurpose: To study the potential drug–drug interactions between simvastatin and vonoprazan and to provide the scientific basis for rational use of them in clinical practice.Methods: An incubation system was established with rat liver microsomes, and the main metabolite of vonoprazan M-I was detected by UPLC-MS/MS. The IC50 value of simvastatin was then calculated and its inhibitory mechanism against vonoprazan was also analyzed. Twelve SD rats were randomly divided into 2 groups, then they were given simvastatin or saline for 2 weeks continuously. On the day of the experiment, both groups were intragastrically administered with vonoprazan once, followed by the collection of blood at different time points. Then the plasma concentration of vonoprazan and M-I in rats were detected by UPLC-MS/MS.Results: In vitro experiments revealed that simvastatin could inhibit the metabolism of vonoprazan, and its inhibition type belonged to the mixed non-competitive and competitive inhibition model. In vivo experiments in rats demonstrated that the area under concentration time curve (AUC) of vonoprazan was decreased but the clearance (CLz/F) of it was increased in the simvastatin administrated group, as compared to those of the control group. However, M-I in simvastatin treated group exhibited the higher AUC and lower CLz/F values compared to those in the control group. These data indicated that multiple doses of simvastatin administration could reduce the plasma concentration of vonoprazan and accelerate its metabolic rate in rats.Conclusion: Simvastatin could inhibit the metabolism of vonoprazan in vitro but multiple doses of simvastatin exhibited the opposite effect In vivo. Altogether, our data indicated that an interaction existed between simvastatin and vonoprazan and additional cares might be taken when they were co-administrated in clinic.Keywords: vonoprazan, simvastatin, drug–drug interactions, liquid chromatography-tandem mass spectrometry, rat liver microsomes

Lieve T van Egmond,1,&ast; Elisa MS Meth,1,&ast; Shervin Bukhari,1 Joachim Engström,1 Maria Ilemosoglou,1 Jasmin Annica Keller,1 Shiyang Zhou,1 Helgi B Schiöth,2 Christian Benedict3 1Department of Surgical Sciences (Sleep Science Laboratory), Uppsala University, Uppsala, Sweden; 2Department of Surgical Sciences, Functional Pharmacology, Uppsala University, Uppsala, Sweden; 3Department of Pharmaceutical Biosciences, Molecular Neuropharmacology (Sleep Science Laboratory), Uppsala University, Uppsala, 751 24, Sweden&ast;These authors contributed equally to this workCorrespondence: Lieve T van Egmond, Department of Surgical Sciences (Sleep Science Laboratory), Uppsala University, Husargatan 3, Box 593, Uppsala, 751 24, Sweden, Tel +46 18-4714123, Email lieve.van.egmond@neuro.uu.seBackground: Acute sleep loss increases the brain’s reactivity toward positive and negative affective stimuli. Thus, despite well-known reduced attention due to acute sleep loss, we hypothesized that humans would gaze longer on happy, angry, and fearful faces than neutral faces when sleep-deprived. We also examined if facial expressions are differently perceived after acute sleep loss.Methods: In the present, within-subjects study, 45 young adults participated in one night of total sleep deprivation and one night with an 8-hour sleep opportunity. On the morning after each night, an eye tracker was used to measure participants’ time spent fixating images of happy, angry, fearful, and neutral faces. Participants also evaluated faces’ attractiveness, trustworthiness, and healthiness on a 100-mm visual analog scale.Results: Following sleep loss, participants struggled more fixating the faces than after sleep. The decrease in total fixation duration ranged from 6.3% to 10.6% after sleep loss (P< 0.001). Contrary to our hypothesis, the reduction in total fixation duration occurred irrespective of the displayed emotion (P=0.235 for sleep&ast;emotion interaction) and was also present for the upper (P< 0.001) but not the lower part of the faces (except for the lower part of angry faces). Overall, faces were evaluated as less trustworthy (− 2.6 mm) and attractive (− 3.6 mm) after sleep loss (p< 0.05).Discussion: Facial expressions are crucial for social interactions. Thus, spending less time fixating on faces after acute sleep loss may come along with several problems for social interactions, eg, inaccurate and delayed judgment of the emotional state of others. In addition, more negative social impressions of others may lead to social withdrawal in sleep-deprived humans.Keywords: sleep deprivation, sleep, eye-tracking, gaze, faces, emotions

Shi Zhou, Xing-Hu Zhang, Yuan Zhang, Ge Gong, Xiang Yang, Wen-Hui Wan Department of Geriatrics, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, Jiangsu, People’s Republic of ChinaCorrespondence: Wen-Hui Wan, Department of Geriatrics, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, Jiangsu, People’s Republic of China, Tel/Fax +86 25 80862433, Email wanwhnj@sina.comPurpose: The age-adjusted Charlson comorbidity index (ACCI) is a useful measure of comorbidity to standardize the evaluation of elderly patients and has been reported to predict mortality in various cancers. To our best knowledge, no studies have examined the relationship between the ACCI and survival of elderly patients with cancer. Therefore, the primary objective of this study was to investigate the relationship between the ACCI and survival of elderly patients with cancer.Patients and Methods: A total of 64 elderly patients (> 80 years) with cancer between 2011 and 2021 were enrolled in this study. According to the ACCI, the age-adjusted comorbidity index was calculated by weighting individual comorbidities; patients with ACCI< 11 were considered the low-ACCI group, whereas those with ACCI≥ 11 were considered the high-ACCI group. The correlations between the ACCI score and survival outcomes were statistically analyzed.Results: There was a significant difference in overall survival (OS) and progression-free survival (PFS) between the high-ACCI group and the low-ACCI group (P< 0.001). The median OS time of the high-ACCI group and the low-ACCI group were 13.9 (10.5– 22.0) months and 51.9 (34.1– 84.0) months, respectively. The 2-, 3-, and 5-year survival rates of the high-ACCI group were 28.1%, 18.8%, and 4.2%, respectively, whereas the 2-, 3-, and 5-year survival rates of the low-ACCI group were 77.3%, 66.4%, and 39.1%, respectively. Multivariate analysis showed that ACCI was independently associated with OS (HR=1.402, 95% CI: 1.226– 1.604, P < 0.05) and PFS (HR=1.353, 95% CI: 1.085– 1.688, P = 0.0073).Conclusion: The ACCI score is a significant independent predictor of prognosis in elderly patients with cancer.Keywords: age-adjusted Charlson comorbidity index, comorbidity, elderly cancer patients, prognosis

Jun Deng, Shifa Zhou, Zhiwen Wang, Genbo Huang, Jingjun Zeng, Xiujiang Li Department of Emergency Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Xiujiang Li, Department of Emergency Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, People’s Republic of China, Tel/Fax +86-791-8869-2540, Email xiujiang_li@email.ncu.edu.cnBackground: Limited evidence and contradictory results have been reported regarding the impact of tumor site on lymph node metastasis (LNM) and prognosis in T1 stage adenocarcinoma (AC). We aimed to compare two anatomic locations in terms of LNM and prognosis using a comprehensive statistical analysis of a large population.Methods: The Surveillance, Epidemiology, and End Results (SEER) database and our center (First Affiliated Hospital of Nanchang University) were used to extract patient information. Univariate and multivariate logistic or Cox regression and propensity score matching were used to explore the association between LNM/survival and tumor site.Results: Information for 12,404 patients, including 9655 colonic AC and 2749 rectal AC patients, was extracted from the SEER database. The 516 AC patients included 184 colonic and 332 rectal AC patients from our center. Multivariate logistic regression analysis revealed a correlation between LNM and tumor site (colon vs rectum, odds ratio [OR] =1.52, 95% CI, 1.349– 1.714, P< 0.001). Additionally, we found that younger age, T1b stage, poor differentiation, and lymphatic invasion were risk factors for LNM. After adjusting for confounding factors by PSM, we found that the location of the rectum remained a higher risk factor for LNM. However, we found that patients diagnosed with rectal AC had a prognosis similar to that of patients diagnosed with colonic AC, which was demonstrated by the analysis of SEER data and data from our center.Conclusion: T1-stage rectal AC may have a higher risk of LNM than colonic AC, while rectal AC has a prognosis similar to that of colonic AC.Keywords: colorectal adenocarcinoma, anatomic location, SEER, lymph node metastasis, survival

Jiankai Mao,1,&ast; Chaoyue Wang,2,3,&ast; Chao Teng,4,&ast; Mengpu Wang,2,3 Siyao Zhou,2 Ke Zhao,2 Xiangming Ye,5 Yijia Wang6 1Tongde Hospital of Zhejiang Province, Hangzhou, People’s Republic of China; 2Department of Psychiatry, School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 4The 4th Clinical College of Zhejiang Chinese Medicine University, Hangzhou, People’s Republic of China; 5Zhejiang Provincial People’s Hospital, Hangzhou, People’s Republic of China; 6Wenzhou Seventh People’s Hospital, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangming Ye; Yijia Wang, Email yexmdr@126.com; wyj202188@126.comIntroduction: The COVID-19 is a highly contagious disease belonging to the family of coronaviruses which can affect a great deal of people shortly. As a devastating event in the world, many people suffer the PTSD from this severe disease. The aim of study is to explore the prevalence and severity of post-traumatic stress disorder (PTSD) symptoms, and discuss the possible factors among the general public in China after the COVID-19 epidemic outbreak.Methods: This is a cross-sectional study. We used the self-designed demographic questionnaire and the Posttraumatic Stress Checklist-Civilian Version (PCL-C) of Chinese version as our screening tools to investigate 4872 subjects living in the communities in China from Nov. 8th, 2020 to Dec. 8th, 2020.Results: Finally, we received 3705 effective respondents. The response rates of the questionnaire can reach 76.97 percentage. Peculiarly, the prevalence of PTSD mild and severe symptoms after the COVID-19 epidemic outbreak was 53.2%. Mild PTSD symptoms accounted for 24.9%, and severe PTSD symptoms (scores above 38) accounted for 28.3%. PCL-C mean scores were 41.4± 14.7. The females accounted for 67.7% of the total samples. Participants’ mean age was 30.5± 11.2 years old. The PCL-C gross scores of females were all higher than males in four subject groups. Meantime, gender and age made differences not only in total PCL-C points but also in the four aspects of PCL-C (P< 0.001). The middle-aged group (ages from 45 to 60) got the lowest scores among the four groups.Conclusion: COVID-19 brought tremendous psychological pressure on the public in many ways, including people’s work, social contact, study, and daily life. Results of our research discover that symptoms of the PTSD are severe, including the re-experiencing, avoidance/numbing, flashbacks, and hyper-arousal. Actions should be taken at society level to prevent and protect individuals from PTSD suffering. Special attention should be paid to females and young people. Further studies should be conducted to explore the dynamic and other risk and protection factors to prevent PTSD.Keywords: COVID-19, post-traumatic stress symptoms, mental health, age, female

Zhidong Liu,1 Miao Wang,1 Chunbo Zhang,2 Shigao Zhou,1 Guang Ji3 1Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 2School of Pharmacy, Nanchang University, Nanchang, Jiangxi, 330031, People’s Republic of China; 3Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of ChinaCorrespondence: Guang Ji, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai, 200032, People’s Republic of China, Tel +86 18156416071, Fax +86 21-64385700, Email jiliver@vip.sina.comAbstract: Ceruloplasmin (CP) is a multicopper oxidase and antioxidant that is mainly produced in the liver. CP not only plays a crucial role in the metabolic balance of copper and iron through its oxidase function but also exhibits antioxidant activity. In addition, CP is an acute-phase protein. In addition to being associated with aceruloplasminemia and neurodegenerative diseases such as Wilson’s disease, Alzheimer’s disease, and Parkinson’s disease, CP also plays an important role in metabolic diseases, which are caused by metabolic disorders and vigorous metabolism, mainly including diabetes, obesity, hyperlipidemia, etc. Based on the physiological functions of CP, we provide an overview of the association of type 2 diabetes, obesity, hyperlipidemia, coronary heart disease, CP oxidative stress, inflammation, and metabolism of copper and iron. Studies have shown that metabolic diseases are closely related to systemic inflammation, oxidative stress, and disorders of copper and iron metabolism. Therefore, we conclude that CP, which can reduce the formation of free radicals in tissues, can be induced during inflammation and infection, and can correct the metabolic disorder of copper and iron, has protective and diagnostic effects on metabolic diseases.Keywords: ceruloplasmin, physiological function, iron, oxidative stress, inflammatory state, metabolic disease

Chengliang Yuan, Meifang Huang, Huilin Wang, Wei Jiang, Cuiyun Su, Shaozhang Zhou Department of Respiratory Oncology, Guangxi Medical University Affiliated Tumor Hospital, Nanning City, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of ChinaCorrespondence: Shaozhang Zhou; Cuiyun SuDepartment of Respiratory Oncology, Guangxi Medical University Affiliated Tumor Hospital, Nanning City, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Tel +86-0771-5320761; +86-0771-5334955, Fax +86-0771-5300613, Email zhoushaozhang@gxmu.edu.cn; 503893236@qq.comPurpose: PD-1 inhibitors have been routinely used to treat advanced non-small cell lung cancer (NSCLC) and have significantly improved clinical outcomes. In this study, we aimed to explore the influence of pretreatment fibrinogen-albumin ratio (FAR) on treatment response and survival in advanced NSCLC patients treated with first-line anti-PD-1 therapy plus platinum-based combination chemotherapy.Patients and Methods: A total of 91 patients with advanced NSCLC were included in the study. All patients received at least two cycles of systemic first-line anti-PD-1 therapy plus platinum-based combination chemotherapy. Receiver operating characteristics analysis was performed to determine the optimal cutoff values of FAR. Univariate and multivariate analyses were used to identify independent prognostic factors, and the Kaplan–Meier method was used to estimate survival curves.Results: Multivariate logistic regression analysis showed that N stage (N2-3) and high FAR (≥ 0.175, optimal cutoff value) were independent predictors for objective response rate (P = 0.0002, P = 0.0005, respectively). Multivariate Cox regression analysis of progression-free survival and overall survival showed that high FAR (≥ 0.145) was independent prognostic factors (P = 0.0061, P = 0.0024, respectively). Progression-free survival and overall survival were significantly shorter in the high FAR (≥ 0.145) group than those in the low FAR (< 0.145) group (P = 0.0024, P = 0.0024, respectively).Conclusion: Pretreatment FAR was an independent predictor for treatment response and independent prognostic factors in advanced NSCLC patients treated with first-line anti-PD-1 therapy plus platinum-based combination chemotherapy.Keywords: non-small cell lung cancer, serum albumin, plasma fibrinogen, immunotherapy, prognosis

Peiqi Zhao,1,&ast; Yuanlin Xu,2,&ast; Wei Ji,3 Lanfang Li,1 Lihua Qiu,1 Shiyong Zhou,1 Zhengzi Qian,1 Huilai Zhang1 1Department of Lymphoma, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People’s Republic of China; 2Department of Lymphatic Comprehensive Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 3Public Laboratory, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peiqi Zhao; Huilai ZhangDepartment of Lymphoma, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People’s Republic of ChinaTel +86-22-23340123Email peiqizhao@126.com; zhanghltch@163.comPurpose: Cancer vaccines are a promising therapeutic approach in cancer immunotherapy and can inhibit tumor growth and prevent tumor recurrence and metastasis by activating a sustained antitumor immunoprotective effect. However, the therapeutic effect of cancer vaccines is severely weakened by the low immunogenicity of cancer antigens and the immunosuppressive microenvironment in tumor tissues.Methods: Here, we report a novel hybrid membrane nanovaccine, composed of mesoporous silica nanoparticle as a delivery carrier, hybrid cell membranes obtained from dendritic cells and cancer cells, and R837 as an immune adjuvant (R837@HM-NPs). We investigated the anti-tumor, tumor recurrence and metastasis prevention abilities of R837@HM-NPs and their mechanisms of action through a series of in vivo and ex vivo experiments.Results: R837@HM-NPs not only provide effective antigenic stimulation but are also a durable supply of the immune adjuvant R837. In addition, R837@HM-NPs promote antigen endocytosis into dendritic cells via various receptor-mediated pathways. Compared with HM-NPs or R837@HM-NPs, R837@HM-NPs in combination with an immune checkpoint blockade showed stronger antitumor immune responses in inhibiting tumor growth, thus eliminating established tumors, and rejecting re-challenged tumors by regulating the immunosuppressive microenvironment and immunological memory effect.Conclusion: These findings suggest that the hybrid membrane nanovaccine in combination with immune checkpoint blockade is a powerful strategy to enhance antitumor immunotherapy without concerns of systemic toxicity.Keywords: hybrid membrane, immune checkpoint blockade, immunotherapy, mesoporous silica nanoparticle, nanovaccine

Zhou S, Cui Y, Yu D, Liang J, Zhang M, Ye W. Onco Targets Ther. 2017;10:2527–2538. The Editor and Publisher of OncoTargets and Therapy are retracting the published article. Concerns were raised regarding the duplication of western blot images and an investigation found duplicated images in Figures 3 and 6. Specifically, The image in Figure 3D, TE10, c-caspase-3, has been duplicated with the same image from Figure 6C, TE10, c-PARP. The image in Figure 3D, TE10, c-PARP has been duplicated with the same image from Figure 3D, TE11, c-PARP. The image in Figure 3D, TE10/miR-381(+), c-caspase-3, has been duplicated with the same image from Figure 3D, TE11/miR-NC(-), Total PARP. The image in Figure 3D, TE11, Total PARP, has been duplicated with the same image from Figure 6C, TE11, Total caspase-3. The image from Figure 6C, TE10/shXIAP(+), c-PARP has been duplicated with the same image from Figure 6C, TE11/shcontrol(-), Total caspase-3. The authors cooperated with the investigation but were unable to provide a satisfactory explanation regarding the duplicated images and were unable to verify the published work. Therefore, the Editor and Publisher are retracting the article and the authors have been notified. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Binbin Zhang,1,&ast; Aiqun Xu,2,&ast; Dong Wu,1,&ast; Wanli Xia,3,&ast; Pulin Li,1 Enze Wang,1 Rui Han,1 Peng Sun,1 Sijing Zhou,4,5 Ran Wang1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Department of General Medicine, Hefei Second People’s Hospital, Hefei, Anhui Province, People’s Republic of China; 3Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 4Hefei Third Clinical College of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 5Hefei Prevention and Treatment Center for Occupational Diseases, Hefei, Anhui Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sijing ZhouHefei Prevention and Treatment Center for Occupational Diseases, Hefei, 230022, People’s Republic of ChinaTel/Fax +86 551-63672040Email zhousijing@yeah.netRan WangDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China, Tel/Fax +86-551-6292-2914Email ranwangtjmu@hotmail.comPurpose: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. The mechanisms underlying NSCLC initiation and progression require further investigation. The purpose of this study was to investigate the role of ADP ribosylation factor-like GTPase 14 (ARL14) related to the progression of NSCLC.Patients and Methods: We analyzed the correlation between clinical characteristics and ARL14 expression using data from The Cancer Genome Atlas (TCGA). Kaplan–Meier analysis was conducted to evaluate the prognostic value of ARL14 in NSCLC. Functions of ARL14 were identified by enrichment analysis. The relationship between ARL14 expression and immune cell infiltration was also studied. Furthermore, ARL14 expression was examined using immunohistochemistry, and its clinical significance was analyzed in 120 patients with NSCLC.Results: Our study revealed that the expression level of ARL14 in patients with NSCLC was higher than that in normal tissues. Using TCGA data, higher ARL14 expression in lung adenocarcinoma was associated with residual tumor (P = 0.017), while it was associated with age (P = 0.003) and N stage (P = 0.009) in lung squamous cell carcinoma. Similar results were obtained from 120 patients with NSCLC. High ARL14 expression was associated with poor overall survival and progression-free survival in NSCLC. Multivariate analysis revealed that ARL14 was an independent risk factor for patients with NSCLC. Functional enrichment analysis indicated that ARL14 was related to the occurrence and development of tumors.Conclusion: Increased ARL14 expression was considerably correlated with poor survival in NSCLC, and it might be a promising prognostic biomarker for NSCLC.Keywords: ADP ribosylation factor-like GTPase 14, non-small cell lung cancer, prognosis, immunohistochemistry, bioinformatics

Lei Zhu,1 Chuanqing Yu,1 Shuping Zhou,2 Min Xue,1 Jie Chen,3 Meijun Wu,4 Shuyang Dong,1 Guanmin Huang,5 Yueyue Chang,1 Mei Zhang1 1Department of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, 232007, People’s Republic of China; 2Department of Gastroenterology, First Affiliated Hospital of Anhui University of Science and Technology,First People’s Hospital of Huainan, Huainan, 232007, People’s Republic of China; 3Department of Neurosurgery, General Hospital of Huainan Oriental Hospital Group, Huainan, 232007, People’s Republic of China; 4Department of Comprehensive Health Care, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, People’s Republic of China; 5Department of Neurosurgery, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, 232007, People’s Republic of ChinaCorrespondence: Chuanqing Yu; Mei ZhangDepartment of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, 203 Huaibin Road, Huainan, 232007, Anhui Province, People’s Republic of ChinaTel +86-18949669880; +86-18949669978Email yuchuanqin1967@126.com; hnzhangmei2008@126.comObjective: The proteoglycan versican (VCAN) plays an important role in extracellular matrix (ECM) assembly, and diminished maintenance of the ECM has been increasingly regarded as an important factor in the development of intracranial aneurysms (IAs). Previous studies have revealed that single-nucleotide polymorphisms (SNPs) of the VCAN gene are associated with susceptibility to IAs in European or Japanese populations. However, the association between IA susceptibility and VCAN SNPs in the Eastern Chinese population remains unclear. This study aimed to investigate the associations of the SNPs rs251124, rs2287926, and rs173686 with IA susceptibility in the Eastern Chinese population.Methods: A total of 162 patients with IA and 182 controls were enrolled in this study. The study was conducted between January 2017 and December 2020. SNP genotyping for rs251124, rs2287926, and rs173686 was performed using Kompetitive Allele Specific PCR (KASP) after DNA extraction. The SNP data were analysed with CFX Manager Software version 3.1 (Bio-Rad).Results: rs251124 and rs173686 were significantly associated with susceptibility to IA. The frequency of rs251124-TT in IA was higher than in controls (OR =1.26, 95% CI: 1.07– 1.49; P< 0.01), and its risk mainly came from the T allele. Furthermore, logistic regression analysis showed that the T/T genotype and T allele of rs251124 were independent risk factors for IA (OR=1.726, 95% CI: 1.136– 2.263; P=0.011). Moreover, the G/G genotype and G allele of rs173686 were associated with increased IA susceptibility (OR=2.52, 95% CI: 1.261– 5.037; P=0.009).Conclusion: The SNPs rs251124 and rs173686 were strongly associated with genetic susceptibility to IA in the Eastern Chinese population; however, no such association was found in the SNP rs2287926 of VCAN. Our findings suggest that the VCAN gene is an IA susceptible gene that should be further studied as a screening marker for IAs.Keywords: intracranial aneurysm, susceptibility, VCAN gene, Eastern Chinese population, SNP

Meihong Yu,1,2 Kaixuan Li,3 Shishuang Zhou,4 Hanyu Wang,1,2 Meixian Le,1,2 Chen Li,1,2 Deliang Liu,1,2 Yuyong Tan1,2 1Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Research Center of Digestive Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 4Department of Nursing Administration, Army Military Medical University, Chongqing, 400038, People’s Republic of ChinaCorrespondence: Yuyong TanDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, No. 139 Middle Renmin Road, Changsha, Hunan, 410011, People’s Republic of ChinaTel +86-15116280621Fax +86-731-85533525Email tanyuyong@csu.edu.cnKaixuan LiDepartment of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of ChinaTel +86 15580027242Email lkxxgz@csu.edu.cnPurpose: Sharp-pointed FBs with both sides embedded in the duodenal wall are rare. Compared with smooth edged FBs, sharp objects are more likely to be associated with significant adverse events, when penetrating the wall of the digestive tract. The clinical features of patients who experienced sharp-pointed FBs embedded in both sides of the duodenum were retrospectively analyzed, as were the efficacy and safety of endoscopic removal of these FBs.Patients and Methods: This retrospective study included 21 adults with both sides of sharp-pointed FBs embedded into the duodenal wall who were admitted to the Second Xiangya Hospital in China between January 1, 1996, and May 31, 2021. Data associated with the endoscopic removal of these FBs were collected from the electronic medical record system (EMRS) of the hospital.Results: The incidence rate of duodenal total FBs and FBs embedded in both sides was 8.87% and 1.03%, respectively. The success rate of endoscopic treatment was 100.00% in 124 patients without embedded duodenal FBs and 97.14% in 35 patients with one side embedded duodenal FBs. Of the 21 patients with FBs embedded in both sides of the duodenal wall, endoscopic removal was successful in 85.71% of patients, whereas 14.29% required surgery. FBs removed from these patients included toothpicks in 12; needles in 3; jujube pits in 2; and a chopstick, dentures, fish bones, and chicken bones in one each. Most of these 21 FBs were located in the bulb and descending duodenum, followed by the third part of duodenum.Conclusion: Sharp-edged FBs with both sides embedded in the duodenal wall are rare. Endoscopic removal may be considered as a feasible, safe, and effective method of removing sharp-pointed FBs with both sides embedded in the duodenal wall. And if endoscopic removal is unsuccessful, surgical management can be a secondary option.Keywords: adult, duodenum, endoscopic removal, foreign bodies, surgical operation

Nan Wang,1,2 Hongshan Ge,1 Shu Zhou1 1Department of Obstetrics and Gynecology, Taizhou People’s Hospital, Taizhou, Jiangsu Province, People’s Republic of China; 2Department of Graduate College, Dalian Medical University, Dalian, Liaoning Province, People’s Republic of ChinaCorrespondence: Hongshan Ge Email dafeng76@126.comBackground: The World Health Organization (WHO) has defined Unexplained Recurrent Spontaneous Abortion (URSA) as three and more consecutive miscarriages before the 20th week of gestation. To date, empiric therapy for patients with unexplained recurrent pregnancy loss (URPL) is not precise. Studies have shown that URSAs are associated with Th1/Th2 and Th17/Treg immune imbalances at the maternal-fetal interface. The immunosuppressant cyclosporine A (CsA) is widely used in patients with organ transplantation or autoimmune diseases, and it has a good safety profile in pregnant women. However, high-quality evidence for CsA treatment of URSAs is lacking. Our purpose with this study is to evaluate the efficacy and safety of CsA for improving pregnancy outcomes in patients with URSAs and to explore the role of CsA in regulating the immune balance.Methods/Design: We expect to officially initiate our study at the Taizhou People’s Hospital in March 2022. We defined the live birth rate as the primary outcome, and the secondary outcomes include the rates of successful pregnancy, miscarriage, pregnancy complications, and adverse pregnancy outcomes, and newborn birth weights. Patients who meet URSA eligibility criteria will be randomized in a 1:1 ratio into either a study group receiving CsA 2 weeks after fertilization or a control group receiving placebo at 2 weeks after fertilization (the women in both groups will receive the relevant treatment for 6 months). In addition, we will collect peripheral blood samples of the participants before and after the treatments, and we will isolate mononuclear cells and measure cytokine levels (IFN-γ, TNF-α, IL-2, IL-10, IL-6, IL-4) and Th1/Th2, Th17/Treg ratios.Discussion: This is the first randomized controlled trial to evaluate the clinical and immunomodulatory effects of CsA on the pregnancy outcomes of women with URSA and our results will provide evidence to evaluate the use of CsA as a treatment for women with URSAs.Keywords: cyclosporine A, live birth rate, recurrent abortion of unknown cause, Th1, Th2

Zhenghua Liu, Shize Yang, Siyu Zhou, Shiyao Dong, Jiang Du Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning Province, People’s Republic of ChinaCorrespondence: Jiang DuDepartment of Thoracic Surgery, The First Affiliated Hospital of China Medical University, No. 155 North Nanjing Street, Heping District, Shenyang, Liaoning Province, People’s Republic of ChinaTel/Fax +86-24-961200Email dujiang02116@163.comPurpose: Lung adenocarcinoma (LUAD) is a most common malignant tumor, even worse for diseases with relatively poor prognosis. Non-coding RNAs have the potential to be biomarkers for the prognosis of various cancers. LncRNA DRAIC and miR-3940-3p have been screened as dysregulated RNAs in LUAD. The clinical significance and biological function of lncRNA DRAIC and miR-3940-3p in LUAD were assessed in this study.Patients and Methods: A total of 122 cases of LUAD patients with complete clinical information were enrolled. The expression levels of lncRNA DRAIC and miR-3940-3p were determined via RT-qPCR in LUAD tissues and cells. The relationship between lncRNA DRAIC or miR-3940-3p expression and the clinicopathological features of patients was analyzed based on the Pearson Chi-square test. For the prognostic value, the Kaplan–Meier plot and multi-variate Cox proportional regression analysis were introduced. Finally, the effect of lnc DRAIC and miR-3940-3p on the LUAD cellular function was investigated by CCK-8 and Transwell assay.Results: lnc DRAIC was upregulated in LUAD tissues and cells, but miR-3940-3p was downregulated. Both of them showed significant associations with and TNM stage, lymph node metastasis, and a poor prognosis. Lnc-DRAIC and miR-3940-3p have the potential as independent prognostic factors for LUAD. Furthermore, the inhibition of lnc DRAIC can inhibit cell proliferation, migration, and invasion of LUAD partly as a ceRNA of miR-3940-3p.Conclusion: lncRNA DRAIC/miR-3940-3p axis may be involved in the progression of LUAD and can be developed to promising prognostic factors, which may provide new insights into the treatment of LUAD.Keywords: lung adenocarcinoma, lncRNA DRAIC, miR-3940-3p, progression, prognosis

Jianhong Ji,1,&ast; Li Wang,2,&ast; Haiyang Guan,2 Yaqiong Jiang,1 Sanlian Zhou,2 Junhua Sheng,3 Lihua Wang4 1Intensive Care Unit, The Second Affiliated Hospital of Nantong University, Nantong, People’s Republic of China; 2Department of Emergency, The Second Affiliated Hospital of Nantong University, Nantong, People’s Republic of China; 3Department of Medical, The Second Affiliated Hospital of Nantong University, Nantong, People’s Republic of China; 4Department of Nursing, The Second Affiliated Hospital of Nantong University, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihua WangDepartment of Nursing, The Second Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of ChinaTel +86 13815219995Email lihua_wangdr@outlook.comObjective: This study was designed to verify the effect of group random quality control on the first aid ability of ward doctors and nurses with regard to the resuscitation of patients with in-hospital cardiac arrest (IHCA).Methods: The first aid quality control team of our hospital was established in December 2018, when the number, qualifications, organizational structure, quality control methods, and responsibilities of the team and team members were determined. The baseline data and assessment results of examinees, the rates of return of spontaneous circulation (ROSC), and the discharge survival rate of IHCA patients in 2019 and 2020 were compared.Results: There were no significant differences in the baseline data of examinees at each stage (p > 0.05). As time went on, the results of the four practical examinations were significantly improved (pairwise comparison, p < 0.05). The number of problems in examinations was significantly higher for physicians than for nurses. After guidance in department relearning, the incidence of related problems was significantly reduced, but the mastery of the frequency and depth of extracorporeal cardiac compression were not always up to standard. The proportion of critically ill patients and the incidence of IHCA in the hospital in 2020 was higher than in 2019 (p < 0.05), and the ROSC rate was also significantly higher than it was in 2019 (p < 0.05), but the difference in the survival rate at discharge was not statistically significant (p > 0.05).Conclusion: Group random quality control meets the needs of IHCA emergencies, and it can improve the first aid skills and organizational coordination of doctors and nurses on the ward through continuous discovery and problem solving so that the ultimate goal of improving the success rate of resuscitation can be achieved.Keywords: in-hospital cardiac arrest, cardiopulmonary resuscitation, quality control, patient outcomes, survival, ability

Zhan-jie Li,1,&ast; Ke-wei Wang,2,&ast; Bo Liu,1 Feng Zang,1 Yu Zhang,3 Wei-hong Zhang,1 Su-ming Zhou,4 Yong-xiang Zhang1 1Department of Infection Control, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China; 2Institute of Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, Wuxi, 214062, Jiangsu, People’s Republic of China; 3Department of Infection Management, the Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, People’s Republic of China; 4Department of Geriatric Critical Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong-xiang ZhangDepartment of Infection Control, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People’s Republic of ChinaTel +86-025-68306917; +86-13951951616Email Yongxiang216021ICU@163.comSu-ming ZhouDepartment of Geriatric Critical Medicine, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People’s Republic of ChinaEmail zhousmco@aliyun.comBackground: To analyze the distribution and source of MDROs infection in the ICUs and to provide a basis for formulating more effective prevention and control programs for MDROs.Methods: A retrospective investigation was conducted on MDROs infection in 8 ICUs of a large tertiary hospital from July 2013 to June 2019. A total of 2629 strains of MDROs isolated from 1701 inpatients were selected for analysis. The MDROs of the 8 ICUs were divided into two types of four categories according to source: out-of-hospital (out-of-hospital transfer and community acquisition) and in-hospital (in-hospital transfer and department acquisition) infections.Results: CRAB (41.84%) and CRE (35.07%) accounted for the majority of the infecting MDROs. The detection rates of MRSA, CRAB, CRPA and CRE were 61.24%, 83.75%, 43.01% and 30.15%, respectively. The top three infection sites of MDROs were the lower respiratory tract (81.10%), blood (6.70%) and abdominal cavity (5.80%). The out-of-hospital and in-hospital infection rates of MDROs were 50.51% and 49.49%, respectively; the out-of-hospital infection rates for MRSA, CRAB, CRPA and CRE were 43.56%, 55.91, 64.44% and 44.58%, respectively. The proportions of MRSA, CRAB, CRPA and CRE infections contracted in the department were 40.98%, 36.27%, 25.56% and 46.62%, respectively. There was a statistically significant difference between comprehensive ICU and specialized ICU wards as sources for CRAB infections (P < 0.001).Conclusion: The main source of MDROs in the ICU is not the hospital itself entirely. It is particularly important to strengthen the identification of MDRO sources and implement more effective and accurate infection prevention and control measures.Keywords: MDRO, intensive care unit, ICU, source