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Ling Duan,1 Wenhui Guo,1 Shuo Yin,1 Shoubo Yang,1 Jie Liu,2 Yunyun Duan,3 Gehong Dong,4 Wenbin Li,1 Feng Chen1 1Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 3Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 4Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of ChinaCorrespondence: Wenbin Li; Feng Chen, Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Nansihuan Road, Beijing, 100070, People’s Republic of China, Tel +86-10-59975034, Email liwenbin@ccmu.edu.cn; chenfeng406@sina.comPurpose: To investigate the prognostic significance of pan-immune-inflammation value (PIV) and PILE score (based on PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)) in patients with primary central nervous system lymphoma (PCNSL).Patients and Methods: A total of 109 patients were enrolled. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE score was incorporated based on PIV, LDH levels, and ECOG PS. The Kaplan–Meier curves and Cox hazards regression models were applied for survival analyses. The relationship between PIV, PILE, and therapeutic response was examined.Results: Baseline high PIV was significantly associated with worse overall survival (OS) in univariate (HR 3.990, 95% CI 1.778– 8.954, p < 0.001) and multivariate (HR 3.047, 95% CI 1.175– 7.897, p = 0.022) analyses. High PIV was also associated with worse progression-free survival (PFS) in univariate (HR 2.121, 95% CI 1.075– 4.186, p = 0.030) but not significant in multivariate analyses. PIV outperformed other systemic inflammation parameters. The patients in the high PILE group (PILE score 2– 3) had worse OS (p = 0.008) and PFS (p < 0.001) compared to the low PILE group (PILE score 0– 1). PILE was independently associated with therapeutic response to initial treatment (OR 0.17, 95% CI 0.05– 0.46; p < 0.001).Conclusion: High PIV and PILE were correlated with worse clinical outcomes in PCNSL patients, indicating that PIV and PILE might be a powerful predictor of prognosis and a potential predictive indicator for therapeutic response in PCNSL.Keywords: primary central nervous system lymphoma, pan-immune inflammation value, PILE score, prognosis

Huiqian Guo,1,2,&ast; Jing Luo,1,3,&ast; Suming Chen,1 Ting Yu,4 Xiaofei Mu,4 Fangzhou Chen,4 Xiuhui Lu,4 Jiaqi He,4 Yali Zheng,4 Chunmei Bao,2 Peng Wang,4 Zhe Yin,4 Boan Li1– 3 1Department of Clinical Laboratory, the Fifth Medical Center of PLA General Hospital, Beijing, 100039, People’s Republic of China; 2School of Medical Laboratory, Weifang Medical University, Weifang, 261053, People’s Republic of China; 3Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 4State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Boan Li, Department of Clinical Laboratory, the Fifth Medical Center of PLA General Hospital, Beijing, 100039, People’s Republic of China, Email lba@263.net Zhe Yin, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China, Email jerry9yin@163.comPurpose: To investigate the genetic diversity of IncG plasmids, we have proposed a typing scheme based on replicon repA and performed comparative genomic analysis of five IncG plasmids from China.Methods: p30860-KPC, p116965-KPC, pA1705-KPC, pA1706-KPC and pNY5520-KPC total in five IncG plasmids from clinical isolates of Pseudomonas and Enterobacteriaceae, respectively, were fully sequenced and were compared with the previously collected reference plasmid p10265-KPC.Results: Based on phylogeny, IncG-type plasmids are divided into IncG-I to IncG-VIII, the five plasmids belong to IncG-VIII. A detailed sequence comparison was then presented that the IncG plasmid involved accessory region I (Tn 5563a/b/c/d/e), accessory region II (ISpa19), and accessory region III (blaKPC-2-region). Expect for the pNY5520-KPC, the rest of the plasmids had the same backbone structure as the reference one. Within the plasmids, insertion sequences Tn 5563d and Tn 5563e were identified, a novel unknown insertion region was found in Tn 5563b/c/d/e. In addition, Tn 6376b and Tn 6376c were newly designated in the study.Conclusion: The data presented here including a typing scheme and detailed genetic comparison which provide an insight into the diversification and evolution history of IncG plasmids.Keywords: IncG plasmids, blaKPC-2, phylogenetic tree, multidrug resistance, mobile elements

Jiaqi He,1,&ast; Xiuhui Lu,2,&ast; Chenchen Yuan,1 Yali Zheng,2 Fangzhou Chen,2 Jing Luo,2 Kejiao Ma,2 Fan Yang,2 Peng Wang,2 Dongsheng Zhou,2 Li Wang,1 Zhe Yin2 1Department of Clinical Laboratory, The First Affiliated Hospital of Henan University, Kaifeng, 475000, People’s Republic of China; 2State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wang, Department of Clinical Laboratory, The First Affiliated Hospital of Henan University, Kaifeng, 475000, People’s Republic of China, Email wangli851217@163.com Zhe Yin, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China, Email jerry9yin@163.comPurpose: Pseudomonas aeruginosa is a common causative bacteria in nosocomial infections. This study aims to describe the structure and evolutionary characteristics of mobile genetic elements (MGEs) carrying antibiotic resistance genes (ARGs) from P. aeruginosa and to conduct bioinformatics and comparative genomic analysis to provide a deeper understanding of the genetic characteristics and diversity of MGEs in P. aeruginosa.Methods: Fifteen clinical isolates of P. aeruginosa from China were collected and sequenced in this study, and 15 novel MGEs were identified. Together with four MGEs from GenBank, a total of 19 MGEs were used to perform detailed modular structure dissection and sequence comparison. Then, the biological experiments were carried out to verify the biological characteristics of these isolates and MEGs.Results: The novel MGEs identified in this study displayed diversification in modular structures, which showed complex mosaic natures. The seven types of 19 MGEs included in this study were divided into three groups: i) novel MGEs (firstly identified in this study): four IncpSE5381-aadB plasmids and three Tn 7495-related integrative and mobilizable elements (IMEs); ii) newly defined MGEs (firstly designated in this study, but with previously determined sequences): four Tn 7665-related IMEs; iii) novel transposons with reference prototypes identified in this study: two Tn 6417-related integrative and conjugative elements (ICEs), two IS-based transposition units, two Tn 501-related unit transposons, two Tn 1403-related unit transposons. At least 36 ARGs involved in resistance to 11 different classes of antimicrobials and heavy metals were identified. Additionally, three novel blaOXA variants were identified. Antimicrobial susceptibility testing showed that these variants were resistant to some β-lactamase antibiotics and blaOXA-1204 was additionally resistant to cephalosporins.Conclusion: The continuous evolution of ARG-carrying MGEs during transmission, leading to the emergence of novel MGEs or ARGs, which facilitates the spread of antibiotic resistance in P. aeruginosa and enhances the diversity of transmission modes of bacterial resistance.Keywords: Pseudomonas aeruginosa, genome sequencing, mobile genetic elements, antimicrobial resistance, OXA

Yongxu Lin,1,2 Yaling Liu,3 Qiuyan Lin,1,2 Mingrong Wang,1,2 Pingying Jiang,1,2 Kaiyi Mao,1,2 Fenglin Chen,1,2 Jian Ding,3 Dan Li1,2 1Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 2Fujian Clinical Research Center for Digestive System Tumors and Upper Gastrointestinal Diseases, Fuzhou, People’s Republic of China; 3Department of Gastroenterology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of ChinaCorrespondence: Dan Li, No. 29 Xinquan Road, Fuzhou, 350001, People’s Republic of China, Email doctorlidan99@fjmu.edu.cn Jian Ding, No. 20 Chazhong Road, Fuzhou, 350005, People’s Republic of China, Email docdingjian@163.comPurpose: Early detection of hyperlipidemic acute pancreatitis (HLAP) with exacerbation tendency is crucial for clinical decision-making and improving prognosis. The aim of this study was to establish a reliable model for the early prediction of HLAP severity.Patients and Methods: A total of 225 patients with first-episode HLAP who were admitted to Fujian Medical University Union Hospital from June 2012 to June 2023 were included. Patients were divided into mild acute pancreatitis (MAP) or moderate-severe acute pancreatitis and severe acute pancreatitis (MSAP+SAP) groups. Independent predictors for progression to MSAP or SAP were identified through univariate analysis and least absolute shrinkage and selection operator regression. A nomogram was established through multivariate logistic regression analysis to predict this progression. The calibration, receiver operating characteristic(ROC), and clinical decision curves were employed to evaluate the model’s consistency, differentiation, and clinical applicability. Clinical data of 93 patients with first-episode HLAP who were admitted to the First Affiliated Hospital of Fujian Medical University from October 2015 to October 2022 were collected for external validation.Results: White blood cell count, lactate dehydrogenase, albumin, serum creatinine, serum calcium, D-Dimer were identified as independent predictors for progression to MSAP or SAP in patients with HLAP and used to establish a predictive nomogram. The internally verified Harrell consistency index (C-index) was 0.908 (95% CI 0.867– 0.948) and the externally verified C-index was 0.950 (95% CI 0.910– 0.990). The calibration, ROC, and clinical decision curves showed this nomogram’s good predictive ability.Conclusion: We have established a nomogram that can help identify HLAP patients who are likely to develop MSAP or SAP at an early stage, with high discrimination and accuracy.Keywords: early prediction, nomogram, hyperlipidemic acute pancreatitis, risk factor, prognosis

Yong Zhou, Zhen Wang, Fei Chen, Ying-Xia Xiong, Wei Wang, Jun-Min Huang, Wei Fang Department of Emergency, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of ChinaCorrespondence: Zhen Wang, Department of Emergency, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, People’s Republic of China, Tel +86 10 63926250, Fax +86 10 63925651, Email wangzhen@bjsjth.cnObjective: Our aim was to highlight the clinical characteristics and determine the risk factors associated with severe and non-severe COVID-19 infection.Study Method: A retrospective review was conducted on clinical data obtained from patients with COVID-19 infection, admitted to the emergency department between November 2022 and January 2023. Total of 1684 participants were categorized into severe (312 cases,18.53%) and non-severe (1,372 cases,81.47%) cohorts. Logistic regression was utilized for multivariate analysis, with a P-value less than 0.05 signifying a significant difference between the groups.Results: The study consisted of 952 males (56.53%) and 732 females (43.47%) participants. The age distribution ranged from 18 to 93 years in both cohorts. There were statistically significant differences between the clinical symptoms of the severe and non-severe cohorts (P < 0.05). According to the multivariate statistical analysis, patients with more pronounced clinical manifestations had significantly elevated values related to age(P < 0.05), diabetes(P < 0.01), hypertension(P < 0.01), C-reactive protein (CRP) (P < 0.05), and lactate dehydrogenase (LDH) (P < 0.01) as compared to those presenting with milder symptoms.Conclusion: The primary clinical presentations in both the cohorts were mostly similar. Predominant factors contributing to the severity of COVID-19 infection were age, diabetes, hypertension, elevated CRP levels, and increased LDH.Keywords: clinical manifestations, COVID-19, risk factors

Sijin Wu,1 Zhongli Chen,1 Yuan Gao,1 Songren Shu,2 Feng Chen,1 Ying Wu,1 Yan Dai,1 Shu Zhang,1 Keping Chen1 1Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Cardiovascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Keping Chen, Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Email chenkeping@263.netBackground: The diagnosis of cardiac syncope remains a challenge. This study sought to develop and validate a diagnostic model for the early identification of individuals likely to have a cardiac cause.Methods: 877 syncope patients with a determined cause were retrospectively enrolled at a tertiary heart center. They were randomly divided into the training set and validation set at a 7:3 ratio. We analyzed the demographic information, medical history, laboratory tests, electrocardiogram, and echocardiogram by the least absolute shrinkage and selection operator (LASSO) regression for selection of key features. Then a multivariable logistic regression analysis was performed to identify independent predictors and construct a diagnostic model. The receiver operating characteristic curves, area under the curve (AUC), calibration curves, and decision curve analysis were used to evaluate the predictive accuracy and clinical value of this nomogram.Results: Five independent predictors for cardiac syncope were selected: BMI (OR 1.088; 95% CI 1.022– 1.158; P =0.008), chest symptoms preceding syncope (OR 5.251; 95% CI 3.326– 8.288; P < 0.001), logarithmic NT-proBNP (OR 1.463; 95% CI 1.240– 1.727; P < 0.001), left ventricular ejection fraction (OR 0.940; 95% CI 0.908– 0.973; P < 0.001), and abnormal electrocardiogram (OR 6.171; 95% CI 3.966– 9.600; P < 0.001). Subsequently, a nomogram based on a multivariate logistic regression model was developed and validated, yielding AUC of 0.873 (95% CI 0.845– 0.902) and 0.856 (95% CI 0.809– 0.903), respectively. The calibration curves showcased the nomogram’s reasonable calibration, and the decision curve analysis demonstrated good clinical utility.Conclusion: A diagnostic tool providing individualized probability predictions for cardiac syncope was developed and validated, which may potentially serve as an effective tool to facilitate early identification of such patients.Keywords: cardiac syncope, syncope, diagnosis, nomogram, prediction model

Zhiliang Zhang,1,&ast; Zhongxiang Ding,2,&ast; Fenyang Chen,2 Rui Hua,3 Jiaojiao Wu,3 Zhefan Shen,2 Feng Shi,3 Xiufang Xu1 1School of Medical Imaging, Hangzhou Medical College, Hangzhou, People’s Republic of China; 2Department of Radiology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Shi; Xiufang Xu, Email feng.shi@uii-ai.com; 1996033011@hmc.edu.cnBackground: Cerebral small vessel disease lacks specific clinical manifestations, and extraction of valuable features from multimodal images is expected to improve its diagnostic accuracy. In this study, we used deep learning techniques to segment cerebral small vessel disease imaging markers in multimodal magnetic resonance images and analyze them with clinical risk factors.Methods and results: We recruited 211 lacunar stroke patients and 83 control patients. The patients’ cerebral small vessel disease markers were automatically segmented using a V-shaped bottleneck network, and the number and volume were calculated after manual correction. The segmentation results of the V-shaped bottleneck network for white matter hyperintensity and recent small subcortical infarction were in high agreement with the ground truth (DSC> 0.90). In small lesion segmentation, cerebral microbleed (average recall=0.778; average precision=0.758) and perivascular spaces (average recall=0.953; average precision=0.923) were superior to lacunar infarct (average recall=0.339; average precision=0.432) in recall and precision. Binary logistic regression analysis showed that age, systolic blood pressure, and total cerebral small vessel disease load score were independent risk factors for lacunar stroke (P< 0.05). Ordered logistic regression analysis showed age was positively correlated with cerebral small vessel disease load score and total cholesterol was negatively correlated with cerebral small vessel disease score (P< 0.05).Conclusion: Lacunar stroke patients exhibited higher cerebral small vessel disease imaging markers, and age, systolic blood pressure, and total cerebral small vessel disease score were independent risk factors for lacunar stroke patients. V-shaped bottleneck network segmentation network based on multimodal deep learning can segment and quantify various cerebral small vessel disease lesions to some extent.Keywords: lacunar stroke, cerebral small vessel disease, imaging markers, deep learning, quantification, image segmentation, clinical risk factors

Chenhao Xing,1 Yamin Lu,2 Guangxia Liu,2 Fang Chen,2 Zhan Hou,2 Yiwen Zhang2 1Graduate School of Hebei North University, Hebei North University, Zhangjiakou, Hebei, People’s Republic of China; 2Department of Nuclear Medicine, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Yamin Lu, Department of Nuclear Medicine, Hebei General Hospital, Shijiazhuang, 050051, People’s Republic of China, Tel +86 15833956939, Email xyluyamin@163.comObjective: The purpose of the study was to investigate the expression levels and correlation of inflammatory factors such as miR-377-3p and TGF-β in patients with diabetic kidney disease (DKD), and to investigate the regulatory mechanism of transfection of miR-377-3p on the inflammatory response of HK-2 cell induced by high glucose.Methods: According to UACR, patients were divided into normal albuminuria group (Con, n = 29), microalbuminuria group (Micro, n = 31) and macroalbuminuria group (Macro, n = 30), analyzed the correlation and influencing factors between DKD and inflammatory factor. HK-2 cells were randomly divided into four groups: normal control group (NC), high glucose group (HG), miR-377-3p overexpression group (MIN), and miR-377-3p inhibition group (IN). After transfection of miR-377-3p mimics and inhibitors, the contents of TGF-β, IL-6 and IL-18 were detected by RT-PCR and Western blot.Results: The levels of miR-377-3p, TGF-β, IL-6 and IL-18 in both Micro group and Macro group were significantly higher than those in Con group (P < 0.05); Pearson correlation analysis showed that miR-377-3p was positively correlated with UACR, TG, TGF-β, IL-6 and IL-18, and negatively correlated with GFR (P < 0.05). Cell experiment: RT-PCR and Western blot results showed that miR-377-3p, TGF-β, IL-6 and IL-18 in HG group were significantly higher than those in NC group (P < 0.05). After transfection with miR-377-3p inhibitor, the levels of miR-377-3p, TGF-β, IL-6 and IL-18 in IN group were significantly decreased compared with HG group and MIN group.Conclusion: miR-377-3p expression was elevated both in serum of DKD patients and in HK-2 cells with high glucose induced injury, overexpression of miR-377-3p exacerbates the damage to HK-2 cells and promotes the progression of DKD. Silencing miR-377-3p can potentially regulate the levels of inflammatory factors in HK-2 cells by targeting downregulation of TGF-β expression, thereby mitigating the damage to HK-2 cells and delaying the development of diabetic kidney disease.Keywords: miR-377-3p, transforming growth factor beta, interleukin 6, interleukin 18, renal tubular epithelial cells

Ming Zhang,1,&ast; Feng Chen,2,&ast; Shaoguang Feng,3,&ast; Xu Liu,4 Zhen Wang,5 Nan Shen,6 Lingjian Meng,7 Dongsheng Zhu,1 Zhitao Zhu8 1Department of Pediatric Surgery, The First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 2Department of Pediatric, Luodian Hospital, Shanghai, People’s Republic of China; 3Department of Pediatric Surgery, The Children’s Hospital of Hangzhou, Hangzhou, People’s Republic of China; 4Department of Pediatric Surgery, The Children’s Hospital of Xuzhou, Xuzhou, People’s Republic of China; 5Department of Pediatric, the Maternal and Child Health Hospital of Zibo, Zibo, People’s Republic of China; 6Department of Pediatrics, Suqian Hospital Affiliated to Xuzhou Medical University, Suqian, People’s Republic of China; 7Department of Pediatrics, Hospital Affiliated to Xuzhou Medical University, Xuzhou, People’s Republic of China; 8Department of Radiology, The Second People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhitao Zhu; Dongsheng Zhu, Email zhuzhitao621@126.com; zhudongsheng@tmu.edu.cnObjective: To investigate the role of FBLN5in renal clear cell carcinoma (KIRC), in particular on the tumor’s immune microenvironment, including children and young adults.Methods: FBLN5 expression in tumor and normal samples was explored using SangerBox, TIMER2.0, GEPIA, UALCAN, HPA databases. The Linkedomics database was used to obtain FBLN5 co-expressed genes in KIRC tissue. SangerBox was also used to estimate immune infiltration of FBLN5 in KIRC. The Kaplan-Meier plotter was used to investigate the survival effects of FBLN5 expression in the presence of immune infiltration. We then collected 48 cases from 7 hospitals over a-20 year period to calculate the impact of FBLN5 on the prognosis of children and young adults with KIRC.Results: FBLN5 expression was significantly reduced in KIRC tissue compared to normal adjacent tissue. FBLN5 was potentially involved in the immune-related biological processes. In addition, FBLN5 expression has been linked to a number of immune checkpoints, cytokines, chemokines and chemokine receptors in KIRC. At the same time, the expression of FBLN5 affected the survival rates differently in KIRC patients with high or low levels of immune infiltration. High expression of FBLN5 in children and young adults with KIRC was associated with a favorable prognosis.Conclusion: This study shed light on the potential of FBLN5 as a prognostic marker in children and young adults with KIRC and as an immune-related target for clinical treatment.Keywords: FBLN5, immune microenvironment, prognostic biomarker, kidney cancer, children

Shan Niu,1,&ast; Xiaoxiao Yin,1,&ast; Bing Pan,2 Haotian Chen,1 Chunxiao Dai,3 Chunnan Tong,4 Fang Chen,2 Xiuqin Feng1 1Nursing Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Psychiatry, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Clinical Psychology, Affiliated Hangzhou First People’s Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Psychiatry, The Second Hospital of Jinhua, Jinhua, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuqin FengNursing Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, Zhejiang, People’s Republic of China, Email fengxiuqin@zju.edu.cnBackground: Non-suicidal self-injury (NSSI) and depression often co-occur among adolescents with more severe clinical symptoms. This study examined the network structures of NSSI and depressive symptoms in adolescents.Methods: Participants were recruited in the psychiatric outpatient clinics of three tertiary hospitals between April 10 and July 10, 2023. All participants been already found with self-injury behaviors in outpatient when enrolled. NSSI diagnostic criteria and Patient Health Questionnaire-9 (PHQ-9) were utilized to collect NSSI and depressive symptoms separately. We performed a network analysis to visualize the correlation between each symptom and to identify core and bridging symptoms in comorbidities.Results: A total of 248 patients were enrolled in the study, with a mean age of 15.48 (SD = 1.62). Based on the PHQ-9 scores and grades, our results showed that the incidence of depression in adolescents with non-suicidal self-injury behavior was relatively high (N=235, 94.76%), with the majority having severe depression. The network analysis revealed that nodes D-6 “feeling bad, failing or letting yourself or your family down”, D-1 “little interest or pleasure” and D-4 “feeling tired” were the most vital and most central symptoms. The most crucial bridging symptom is the node NSSI-8 “frequent thinking about self-injury”, which connects the NSSI to the depression comorbid network.Conclusion: This study offers a significant symptom-level conceptualization of the association between NSSI and depressive symptoms in a clinical sample of adolescents, which not only enhances our understanding of the comorbid but also identifies potential treatment targets to prevent and treat comorbidity between adolescent NSSI and depression.Keywords: non-suicidal self-injury, depression, comorbidity network, bridge symptoms, network analysis

Ju J, Wang N, Wang J, Wu F, Ge J, Chen F. Drug Des Devel Ther. 2018;12:997-1008. At the request of the authors, the Editor and Publisher of the journal Drug Design, Development and Therapy have retracted the published article. Following publication of the article, the authors raised concerns about the duplication of images from Figure 2 with those from an unrelated article and the duplication of images within Figure 8. Specifically, Images from Figure 2B, MDA-MB-453 and MDA-MB-231, have been duplicated with the same images for Figure 2F and 3I from Dong SR, Ju XL, Yang WZ. STAT5A reprograms fatty acid metabolism and promotes tumorigenesis of gastric cancer cells. Eur Rev Med Pharmacol Sci. 2019;23(19):8360-8370. https://doi.org/10.26355/eurrev_201910_19147. Images for Figure 8, FL-/siRNA+ and FL+/siRNA-, 0 h; FL-/siRNA- and FL-/siRNA+, 12 h; FL-/siRNA-, 24 h and FL-/siRNA+, 48 h; and FL-/siRNA-, 48 h and FL+/siRNA-, 24 h, have been duplicated. The corresponding author was cooperative and responded to our queries but was unable to provide a satisfactory explanation for how the images came to be duplicated or provide satisfactory original data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the authors requested to retract the article and the Publisher and Editor agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Jinpeng Xu,1 Guomei Tian,2 Jingran He,1 Fangmin Deng,1 Fangting Chen,1 Qi Shi,1 Jian Liu,1 Hongyu Zhang,1 Ting Zhang,1 Qunhong Wu,1 Zheng Kang1 1School of Health Management, Harbin Medical University, Harbin, People’s Republic of China; 2Department of Nuclear Medicine, the Fourth Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaCorrespondence: Zheng Kang, School of Health Management, Harbin Medical University, Harbin, People’s Republic of China, Email kangzheng@hrbmu.edu.cnPurpose: To understand the public’s self-willingness to report medical insurance fraud and their expectations on others, to provide a reference for the government to do a good job in medical insurance anti-fraud.Methods: Data were obtained from a questionnaire survey of 846 respondents in China. Descriptive statistical analyses and multinomial logistic regression were used to analyze the different subjective attitudes of the public toward different subjects when faced with medical insurance fraud and the influencing factors.Results: 511 (60.40%) respondents were willing to report medical insurance fraud, while 739 (87.35%) respondents expected others to report it. 485 (57.33%) respondents were willing and expected others to report medical insurance fraud, followed by those who were not willing but expected others to report it (254, 30.02%). Compared to those who were unwilling to report themselves and did not want others to report, those who believe their reporting is useless (OR=3.13, 95% CI=1.15– 8.33) and those who fear for their safety after reporting (OR=2.96, 95% CI=1.66– 5.26) were more likely to expect others to report. Self-reporting willingness was stronger among the public who were satisfied with the government’s protective measures for the safety of whistleblowers (OR=4.43, 95% CI=1.38– 14.17). The public who believe that both themselves and others have responsibilities to report medical insurance fraud were willing to report and expect others to do the same.Conclusion: The public had a “self-avoidance” and “other-reliance” mentality in medical insurance anti-fraud. The free-rider mentality, lack of empathy, concerns about own risk after reporting, and the interference of decentralized responsibility were important factors contributing to this public mentality. At this stage, the government should prevent the public’s “collective indifference” in medical insurance anti-fraud efforts. Improving the safety and protection of whistleblowers and making everyone feel more responsible and valued may be effective incentives to enhance the public’s willingness to report.Keywords: medical insurance, anti-fraud, whistleblower, subjective attitudes

Limin Jia,1 Yanfeng Wang,2 Wenyuan Zhang,3 Yulian Lin,1 Fang Chen,1 Yixiao Wan,1 Xin Fu4,5 1Department of Cardiothoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, 317000, People’s Republic of China; 2Department of Geriatrics, Taizhou Central Hospital (Taizhou University Hospital) of Zhejiang, Taizhou, Zhejiang, 318000, People’s Republic of China; 3Department of ICU, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, 317000, People’s Republic of China; 4Department of Radiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, 317000, People’s Republic of China; 5Department of Radiology, Enze Hospital, Taizhou Enze Medical Center (Group), Taizhou, Zhejiang, 318000, People’s Republic of ChinaCorrespondence: Xin Fu, Department of Radiology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, No. 150 Ximen Street, Linhai City, Taizhou, Zhejiang, 317000, People’s Republic of China, Tel + 86-0576-85120120, Email fux005ing@126.comBackground and Purpose: To explore the feasibility of the modified blood collection method in pre-deposit autotransfusion in patients undergoing thoracotomy surgery.Methods: This double-blinded randomised controlled trial enrolled 92 patients from the cardiothoracic surgery department from February 2019 to October 2020.Results: Compared with the conventional blood collection method, the modified blood collection method avoided blood overflow from the oblique plane of the needle (χ2 = 61.986, P < 0.01) and reduced the diameter of the bruising area after 24 hours (χ2 = 24.611, P < 0.01). Furthermore, due to optimising the blood collection method, diastolic blood pressure reduced slightly before and after blood collection (t = 2.036, P < 0.05), and patients in the test group had less pain (based on the numerical rating score) (t = 5.556, P < 0.01). Meanwhile, the time required to collect 400 mL of blood was shortened (t = 17.744, p < 0.01).Conclusion: An improved blood collection method can enhance the blood donation experience, avoid blood spillage, lessen pain and reduce adverse reactions. This may be of great significance in ensuring blood quality and the safety of subsequent transfusions.Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT05539846.Keywords: pre-deposit autotransfusion, extracorporeal circulation, open heart surgery

Several investigations have demonstrated the association of MTSS1 with left ventricular (LV) structure and function. A recently published study has even revealed that rs35006907 was associated with both MTSS1 expression and the risk of dilated cardiomyopathy (DCM).

Haoran Ding,&ast; Guoqi Zhu,&ast; Hao Lin, Jiapeng Chu, Deqiang Yuan, Yi’an Yao, Yanhua Gao, Fei Chen, Xuebo Liu Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Chen; Xuebo Liu, Email riverapt@126.com; lxb70@hotmail.comBackground: The risk of acute myocardial infarction (AMI) is elevated in patients with systemic lupus erythematosus (SLE), and it is of great clinical value to identify potential molecular mechanisms and diagnostic markers of AMI associated with SLE by analyzing public database data and transcriptome sequencing data.Methods: AMI and SLE-related sequencing datasets GSE62646, GSE60993, GSE50772 and GSE81622 were downloaded from the Gene Expression Omnibus (GEO) database and divided into prediction and validation cohorts. To identify the key genes associated with AMI related to SLE, WGCNA and DEGs analysis were performed for the prediction and validation cohorts, respectively. The related signaling pathways were identified by GO/KEGG enrichment analysis. Peripheral blood mononuclear cells (PBMCs) from patients with AMI were collected for transcriptome sequencing to validate the expression of key genes in patients with AMI. Least absolute shrinkage and selection operator (LASSO) regression analysis was applied to screen diagnostic biomarkers. The diagnostic efficacy of biomarkers was validated by ROC analysis, and the CIBERSORTx platform was used to analyze the composition of immune cells in AMI and SLE.Results: A total of 108 genes closely related to AMI and SLE were identified in the prediction cohort, and GO/KEGG analysis showed significantly enriched signaling pathways. The results of differential analysis in validation cohort were consistent with them. By transcriptional sequencing of PBMCs from peripheral blood of AMI patients, combined with the results of prediction and validation cohort analysis, seven genes were finally screened out. LASSO analysis finally identifies DYSF, LRG1 and CSF3R as diagnostic biomarkers of SLE-related-AMI. CIBERSORTx analysis revealed that the biomarkers were highly correlated with neutrophils.Conclusion: Neutrophil degranulation and NETs formation play important roles in SLE-related AMI, and DYSF, LRG1 and CSF3R were identified as important diagnostic markers for the development and progression of SLE-related AMI.Keywords: myocardial infarction, systemic lupus erythematosus, WGCNA, DEGs, RNA-seq, neutrophil

Hao Zhang, Fan Chen Department of Traditional Chinese Medicine, People’s Hospital of Dongxihu District, Wuhan, Hubei, 430040, People’s Republic of ChinaCorrespondence: Fan Chen, Department of Traditional Chinese Medicine, People’s Hospital of Dongxihu District, No. 48, Jinbei First Road, Jinghe Street, Wuhan, Hubei, 430040, People’s Republic of China, Tel +86 15972944985, Email chenfancf79@126.comObjective: To explore the efficacy of electroacupuncture (EA) with sparse-dense wave form on the improvement of facial nerve edema, facial spasm, and repair of nerve injury in patients with acute facial paralysis.Methods: This study enrolled 100 patients who were treated for acute facial paralysis in People’s Hospital of Dongxihu District from December 2019 to December 2020. They were randomly divided into the control group (continuous wave) and the sparse-dense wave group (sparse-dense wave), following by being intervened by EA with different wave forms. Then the facial disability index (FDI) score, serum levels of immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) in the two groups were evaluated.Results: The total effectiveness rate (98.00% and 86.00%, respectively; P < 0.05) and the recovery rate of facial spasm (76.00% and 56.00%, respectively; P< 0.05) in the sparse-dense wave group was both significantly higher than that of the control group. After treatment, the scores of physical functions of patients in both groups increased (P < 0.05), the scores of social/well-being dysfunctions decreased (P < 0.05). Besides, the levels of serum IgA, IgG, and IgM in both groups decreased (P < 0.05), and the serum levels in the sparse-dense wave group were significantly lower than the control group (P < 0.05).Conclusion: EA intervention with sparse-dense wave form is effective for patients with acute facial paralysis, in that it effectively reduced the occurrence of facial spasm and promoted the improvement of edema and repair of nerve injury.Keywords: acute phase, electroacupuncture, EA, facial spasm, nerve edema, nerve injury repair, peripheral facial paralysis, sparse-dense wave

Xiao-Ru Liang,1,&ast; Yan-Fei Liu,1,&ast; Feng Chen,2 Zhi-Xia Zhou,3 Li-Jie Zhang,1 Zhi-Juan Lin1 1Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Weifang Medical University, Weifang, People’s Republic of China; 2Department of General Surgery, Weifang Traditional Chinese Hospital, Weifang, Shandong, People’s Republic of China; 3Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Juan Lin; Li-Jie Zhang, Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Weifang Medical University, Weifang, People’s Republic of China, Tel +86-536-8462530, Email eva1949@163.com; zhanglj@wfmc.edu.cnAbstract: Long non-coding RNAs (lncRNAs) are non-coding RNAs (ncRNAs) longer than 200nt. They have complex biological functions and take part in multiple fundamental biological processes, such as cell proliferation, differentiation, survival and apoptosis. Recent studies suggest that lncRNAs modulate critical regulatory proteins involved in cancer cell cycle, such as cyclin, cell cycle protein-dependent kinases (CDK) and cell cycle protein-dependent kinase inhibitors (CKI) through different mechanisms. To clarify the role of lncRNAs in the regulation of cell cycle will provide new ideas for design of antitumor therapies which intervene with the cell cycle progression. In this paper, we review the recent studies about the controlling of lncRNAs on cell cycle related proteins such as cyclin, CDK and CKI in different cancers. We further outline the different mechanisms involved in this regulation and describe the emerging role of cell cycle-related lncRNAs in cancer diagnosis and therapy.Keywords: cyclin, cyclin-CDK, CDK inhibitors, lncRNA

Danfeng Yu, Fengfeng Jiang, Wei Xu, Pingyou He, Feng Chen, Xiaobo Liu, Xiang Bao Department of Neurosurgery, Jinhua Municipal Central Hospital, Jinhua, 321000, People’s Republic of ChinaCorrespondence: Xiang Bao, Department of Neurosurgery, Jinhua Municipal Central Hospital, Jinhua, 321000, People’s Republic of China, Email 18257012012@163.comBackground: Resolvin D1 (RvD1) possesses anti-inflammatory properties and may be neuroprotective. This study was designed to ascertain the potential role of serum RvD1 in the evaluation of aSAH severity and prognosis of human aneurysmal subarachnoid hemorrhage (aSAH).Methods: In this prospective observational study, serum RvD1 levels were measured in 123 patients with aSAH and in 123 healthy volunteers. Six-month neurological function was assessed using extended Glasgow outcome scale (GOSE). A prognostic prediction model was appraised using a series of evaluative tools, such as a nomogram, receiver operating characteristic (ROC) curve, decision curve, calibration curve, restricted cubic spline, and Hosmer-Lemeshow goodness of fit statistics.Results: Serum RvD1 levels were markedly lower in patients than in controls (median, 0.54 versus 1.47 ng/mL; P< 0.001). Serum RvD1 levels were independently correlated with Hunt-Hess scores (beta, − 0.154; 95% confidence interval [CI], − 0.198--0.109; VIF, 1.769; P=0.001), modified Fisher scores (beta, − 0.066; 95% CI, − 0.125--0.006; VIF, 1.567; P=0.031) and 6-month GOSE scores (beta, 1.864; 95% CI, 0.759– 2.970; VIF, 1.911; P=0.001) and were independently predictive of a poor prognosis (GOSE scores of 1– 4) (odds ratio, 0.137; 95% CI, 0.023– 0.817; P=0.029). Serum RvD1 levels significantly distinguished the risk of a worse prognosis, with an area under the ROC curve of 0.750 (95% CI, 0.664– 0.824). Using the Youden method, serum RvD1 levels < 0.6 ng/mL was effective in predicting worse prognosis with 84.1% sensitivity and 62.0% specificity. Moreover, the model containing serum RvD1 levels, Hunt-Hess scores and modified Fisher scores was efficient, reliable and beneficial in prognostic prediction using a series of the afore-mentioned evaluative tools.Conclusion: A decline in serum RvD1 levels following aSAH is closely correlated with illness severity and independently predicts a worse outcome in patients with aSAH, implying that serum RvD1, as a prognostic biomarker of aSAH, may be of clinical value in aSAH.Keywords: aneurysm, subarachnoid hemorrhage, resolvin D1, prognosis, severity

Xiaotian Shi, Shan Wang, Jieqiong Hu, Fei Chen, Heng Zhang, Yifan Yang, Xv Li, Qing Ma Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Qing Ma, Email maqing3@163.comObjective: Determine the relationship of renal function with frailty using different formulas for estimated glomerular filtration rate (eGFR).Methods: Individuals who were 60-years-old or more (n=507) were recruited from August 2020 to June 2021, and the FRAIL scale was used to classify them as non-frail or frail. The three equations used to compute the eGFR were based on serum creatinine (eGFRcr), cystatin C (eGFRcys), or SCr+CysC (eGFRcr-cys). Renal function was classified using eGFR and defined as normal (≥ 90 mL/min/1.73m2), mild damage (59– 89 mL/min/1.73m2), or moderate damage (≤ 60 mL/min/1.73m2). The relationship of frailty with renal function was analyzed. A subset of participants (n=358) was used to analyze changes in eGFR from 1 January 2012 to 31 December 2021 according to frailty and using the different eGFR equations.Results: There were significant differences between the eGFRcr-cys and eGFRcr values in the frail group (P< 0.05), but not the non-frail group; however, the differences between the eGFRcr-cys and eGFRcys values were significant in the frail and non-frail groups (P< 0.001). Based on each eGFR equation, the prevalence of frailty increased as eGFR decreased (P< 0.001), but there was no significant relationship after adjusting for age or the age-adjusted Charlson co-morbidity index. There were temporal declines in eGFR in all three frailty groups (robust, pre-frail, and frail), especially in the frail group (2.226 mL/min/1.73m2 per year; P< 0.001).Conclusion: For older individuals who are frail, the eGFRcr value may not provide accurate estimates of renal function. Frailty is associated with a rapid decline in kidney function.Keywords: elderly, frailty, kidney function, serum creatinine, cystatin C

Fang Chen,&ast; Fan Feng,&ast; Dianping You, Yinghui Guo, Shuo Yang, Tong Zhao, Suzhen Sun,&ast; Le Wang&ast; Institute of Pediatric Research, Children’s Hospital of Hebei Province, Shijiazhuang, 050031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Le Wang, Institute of Pediatric Research, Children’s Hospital of Hebei Province, 133 Jianhua South Street, Shijiazhuang, Hebei Province, 050031, People’s Republic of China, Tel +86-0311-85911389, Email luka_wl@163.comBackground: Febrile seizures (FS) are a common cause of paediatric emergencies, but research on their aetiology and epidemiology are limited. The aim of this study was to investigate the prevalence of central nervous system (CNS) pathogenic infections in patients with FS-associated hospitalization.Methods: A prospective observational study was conducted in children under 16 years of age with FS-associated hospitalization. Demographic, clinical and laboratory data were recorded. Multiplex-PCR was performed on cerebrospinal fluid (CSF) samples for nine viruses, nine bacteria and one fungus.Results: A total of 119 children were enrolled between June 2021 and June 2022. Of these, 83.2% had a final diagnosis of FS (69.7%) or FS plus (13.4%). In addition, epilepsy and encephalitis/meningitis were also found in 16.8% (20/119). Seven pathogens were identified from 9 CSF samples (7.6%), including viruses (EV, EBV, HHV-6) and bacteria (H. influenzae, S. pneumoniae, M. tuberculosis, S. putrefaciens). There were no significant clinical or laboratory differences between children who tested positive or negative for pathogens in the CSF, except for the presentation of herpes pharyngitis. Children with encephalitis/meningitis had longer hospital stays compared with those diagnosed with FS at discharge; abnormal EEG findings were significantly more common in patients with epilepsy.Conclusion: FS-associated hospitalized children may have viral or bacterial intracranial infections. Pathogen testing of CSF is an important basis for timely antibiotic or antiviral therapy when clinical and laboratory findings make FS indistinguishable from other CNS disorders.Keywords: febrile seizure, children, CSF, infection

Feifei Chen,1,2 Rohaya Abdullah2 1Department of College English, Zhejiang Yuexiu University, Shaoxing, Zhejiang, People’s Republic of China; 2School of Educational Studies, Universiti Sains Malaysia (USM), Penang, MalaysiaCorrespondence: Feifei Chen, Zhejiang Yuexiu University, Shaoxing, Zhejiang, People’s Republic of China, Tel +8013957567140, Email chenfeifei@student.usm.myBackgrounds and Aims: Though EFL teachers now generally hold an equity-oriented mindset, they are often blamed for not implementing equitable practices in the actual teaching. The contributing factors causing cognition-practice inconsistency should be recognized and highlighted to ensure equitable teaching. Therefore, by taking an interpretative qualitative approach, this study explored in-depth the contributing factors that caused the mismatch between EFL teachers’ equity-oriented cognition and practices.Methods: We adopted classroom observation and stimulated recall interviews with 10 university teachers to examine the contributing factors that lead to cognition-practice inconsistency.Results: Our results showed two experiential factors (unpleasant schooling experiences and limited effective training) and five contextual factors (unfavorable student factors, inharmonious classroom climate, toxic school contexts, equity-deficient education system, and negative social cultures) mediated the relationship between teachers’ equity-oriented cognition and practices.Conclusion: The findings shed light on an association between influential factors and teachers’ equity-oriented cognition-practice mismatch. Moreover, an equity-oriented teaching framework was thus proposed to help eliminate the constraining effect of these factors.Keywords: educational equity, English as a Foreign Language, EFL, contributing factors, cognition-practice inconsistency

Xiaoyu Wu,1,&ast; Danfei Ji,1,&ast; Zefan Wang,1,&ast; Wenhua Yu,2 Quan Du,2 Wei Hu,3 Yongke Zheng,3 Xiaoqiao Dong,2 Fanghui Chen4 1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Neurosurgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Intensive Care Unit, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Emergency Department, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqiao Dong; Fanghui Chen, Email dxqhyy@163.com; wangxiaoleihzsy@163.comBackground: NADPH oxidase 2 (NOX2) is highly expressed in injured brain tissues. We determined serum NOX2 levels of aneurysmal subarachnoid hemorrhage (aSAH) patients and further investigated correlation of serum NOX2 levels with disease severity, delayed cerebral ischemia (DCI) plus prognosis after aSAH.Methods: Serum NOX2 levels were measured in 123 aSAH patients and 123 healthy controls. World Federation of Neurological Surgeons scale (WFNS) score and modified Fisher (mFisher) score were utilized to assess disease severity. Modified Rankin scale (mRS) score was used to evaluate the clinical prognosis at 90 days after aSAH. Relations of serum NOX2 levels to DCI and 90-day poor prognosis (mRS score of 3– 6) were analyzed using multivariate analysis. Receiver operating characteristic curve (ROC) was built to evaluate the prognostic predictive capability.Results: Serum NOX2 levels in aSAH patients, compared with healthy controls, were significantly increased, and were independently correlated with WFNS score, mFisher score and post-stroke 90-day mRS score. Patients with poor prognosis or DCI had significantly higher serum NOX2 levels than other remainders, and serum NOX2 levels independently predicted 90-day poor prognosis and DCI. Serum NOX2 had high prognosis and DCI predictive abilities, and their areas under ROC curve were similar to those of WFNS score and mFisher score.Conclusion: Serum NOX2 levels are significantly associated with hemorrhage severity, poor 90-day prognosis and DCI in aSAH patients. Hence, complement NOX2 may serve as a potential prognostic biomarker after aSAH.Keywords: NADPH oxidase 2, biomarker, aneurysmal subarachnoid hemorrhage, disease severity, delayed cerebral ischemia, prognosis

Yuanyuan Peng,1 Yan Xu,1 Liping Yue,1 Fanglei Chen,1 Jie Wang,2 Guozhen Sun2,3 1Department of Nursing, School of International Medical Technology, Sanda University, Shanghai, People’s Republic of China; 2Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3School of Nursing, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Guozhen Sun, Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China; School of Nursing, Nanjing Medical University, Nanjing, People’s Republic of China, Tel +86 13851769549, Fax +86 25 6830348, Email gzsun100@126.comBackground: In the fight against heart failure (HF), informal caregivers are an indispensable part of the team. As a protective factor against stress, resilience can help to enhance caregivers’ psychological adaptation and ultimately increase the quality of care during the HF caregiving period. Recognizing its predictors and exploring how these variables interact could promote tailored strategies to enhancing caregivers’ resilience of HF patients. Thus, this study aimed to identify promoting and risk factors of resilience in informal caregivers of HF patients from the Chinese context and to understand the interactions between these factors and resilience.Methods: This cross-sectional study was conducted from December, 2020 to March, 2022 among 210 caregivers in Nanjing, China. The General Information Questionnaire, the Connor-Davidson Resilience Scale, the General Self-Efficacy Scale, the Perceived Social Support Scale, the Positive and Negative Affect Scale, the Simplified Coping Style Questionnaire and the Family Hardiness Index were used in this survey. Data were analysed with Pearson’s correlation analysis, the multiple linear regression model and the structural equation modeling (SEM).Results: The resilience of 210 Chinese HF caregivers was at the moderate and higher level (66.40± 15.08). The SEM had a good fit (root mean square error of approximation=0.047, comparative fit index=0.994, Tucker-Lewis index=0.987). Perceived social support (β=0.390, P< 0.001), positive coping style (β=0.159, P=0.019) and self-efficacy (β=0.332, P< 0.001) had positive direct effects on resilience among HF caregivers, separately. Both perceived social support (β=0.04, P< 0.001) and self-efficacy (β=0.07, P< 0.001) indirectly influenced resilience through positive coping style.Conclusion: We recommended that multi-dimensional and greater social support, higher self-efficacy and especially, positive coping strategies should be offered or encouraged during the caregiving period, which may contribute to enhancing HF caregivers’ resilience.Keywords: heart failure, caregivers, resilience, influencing factors, structural equation model, positive coping style, mediator

Fangyan Chen,1 Yabo Ge,1,2 Wenjun Xu,1 Junshuai Yu,1 Yiwen Zhang,1 Xingjian Xu,1 Shuqiong Zhang1 1Institute of Child Development, Jinhua Polytechnic, Jinhua, People’s Republic of China; 2College of Teacher Education, Zhejiang Normal University, Jinhua, People’s Republic of ChinaCorrespondence: Shuqiong Zhang, Institute of Child Development, Jinhua Polytechnic, 1188 Wuzhou Road, Jinhua, Zhejiang Province, 321007, People’s Republic of China, Email 20050507@jhc.edu.cnIntroduction: Kindergarten teachers who empathize with toddlers experience a great risk of burnout and emotional disturbance. This is referred to as compassion fatigue, in which teachers’ empathy experience is reduced. This study proposed a moderated mediation model to identify the risks of compassion fatigue and its protective factors for developing evidence-based clinical interventions.Methods: In this cross-sectional study, self-report measures were administered to 1049 kindergarten teachers to observe their mindsets toward children, motivation for teacher empathy, job stress, social support, and compassion fatigue. The PROCESS macro (SPSS 23.0) was used to assess the moderated mediation model.Results: The results demonstrated that motivation for teacher empathy mediated the negative relationship between kindergarten teachers’ mindsets toward children and compassion fatigue. Moreover, job stress and social support moderated the relationship between kindergarten teachers’ mindsets toward children and motivation for teacher empathy. However, this effect was not observed in the negative relationship between kindergarten teachers’ mindsets toward children and compassion fatigue.Conclusion: The proposed moderated mediation model was found to be valid. Furthermore, the study findings have practical implications for developing evidence-based interventions for addressing kindergarten teachers’ compassion fatigue.Keywords: compassion fatigue, mindsets toward children, empathic motivation, kindergarten teachers

Zheng J, Shao Y, Jiang Y, et al. Cancer Manag Res. 2019;11:5231–5242. We, the Editors and Publisher of Cancer Management and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 2, 3 and 4. Specifically, The images for Figure 2A, Control, 30µg/ml, and 90µg/ml have been duplicated with images from Figure 4D, +-0, -+0, -+90 and +-90, respectively. The graph for Figure 3B has been duplicated with the graph for Figure 4G. When approached for an explanation, the authors were cooperative but were unable to provide a sufficient explanation for the image duplication or provide sufficient original data for their study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors do not agree with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Ya-Hui Hu,1 Gui-Zhou Li,1,2 Jia-Yi Long,1,2 Qing-Yan Yang,1,2 Yong Zhang,1 Feng Chen,1 Yong-Ren Wang3 1Department of Pharmacy, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 3Department of Hematology and Oncology, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yong-Ren Wang, Children’s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, 210008, People’s Republic of China, Email wangyongren@gmail.comAbstract: Vincristine-induced peripheral neuropathy (VIPN) is a common adverse effect of vincristine (VCR) for which there is no preventative or curative treatment. Here, we report a case of a patient suffering from severe VCR-related neurotoxicity. To explore the possible causes of severe VIPN in this patient, a set of genes involved in VCR metabolism, transport or are related to the cytoskeleton, microtubules, and inherited neurological diseases gene polymorphisms were examined via pharmacogenetic analyses. The genotyping results revealed the presence of a complex pattern of polymorphisms in CYP3A5, ABCC2, SYNE2, BAHD1, NPSR1, MTNR1B, CEP72, miR-4481 and miR-3117. A comprehensive understanding of all the pharmacogenetic risk factors for VIPN may explain the occurrence of severe neurotoxicity in our patient. This case brings to light the potential importance of pharmacogenetic testing in clinical practice. It also exemplifies the importance of developing early-detection strategies to optimize treatment regimens through prior risk stratification while reducing adverse drug reactions and personalizing therapy.Keywords: vincristine, peripheral neuropathy, pharmacogenetics, toxicity, polymorphisms, precision medicine

Yitong Zheng,1,&ast; Guoshu Yin,1,&ast; Fu Chen,2 Ling Lin,3,4 Yongsong Chen1 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 2Department of Nutrition, The First Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 3Department of Rheumatology and Immunology, The First Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 4Department of Rheumatology, Shantou University Medical College, Shantou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Lin, Department of Rheumatology and Immunology, The First Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China, Tel +86-0754-88258290, Fax +86-0754-88259850, Email llinc@163.net Yongsong Chen, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China, Tel +86-0754-88258290, Fax +86-0754-88259850, Email yongsongchen@126.comPurpose: To use the triglyceride glucose (TyG) index to evaluate insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS) and to explore alternative indicators for early identification of IR.Patients and Methods: This study included 114 patients with PCOS and 61 healthy volunteers. Pearson or Spearman correlations were calculated to compare the association between the TyG index and triglyceride glucose body mass index (TyG-BMI) with homeostatic model assessment for IR (HOMA-IR), homeostasis model assessment for β-cell function (HOMA-β), quantitative insulin sensitivity check index (QUICKI), and fasting glucose-to-insulin ratio (FG-IR). The receiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of the TyG index and TyG-BMI in identifying IR (defined as HOMA-IR ≥ 2.5) in patients with PCOS.Results: Correlation analyses revealed that the TyG index of the PCOS group was positively correlated with HOMA-IR (r=0.515, P< 0.01) and HOMA-β (r=0.348, P< 0.01), but negatively correlated with QUICKI (r=− 0.532, P< 0.01) and FG-IR (r=− 0.394, P< 0.01). The ROC curve of IR defined by HOMA-IR showed that the AUC value of TyG-BMI was the highest, at 0.796 (95% confidence interval (CI): 0.710– 0.866, P< 0.001) when the cut-off point was 191.53, with 85.3% sensitivity and 73.9% specificity values. For the TyG index, the AUC was 0.781 (95% CI: 0.693– 0.853, P< 0.001) when 8.51 was the cut-off point, with a sensitivity of 63.2% and specificity of 87.0%.Conclusion: This study found that the TyG index and TyG-BMI performed better than traditional lipid ratios, such as triglycerides/high density lipoprotein cholesterol (TG/HDL-C), in predicting IR and may be used as markers of IR in Chinese patients with PCOS.Keywords: triglyceride glucose body mass index, triglycerides/high density lipoprotein cholesterol, quantitative insulin sensitivity check index, fasting glucose-to-insulin ratio

Jun Wang,1 Yue-Tao Zhao,2,3 Meng-Jiao Sun,1 Feng Chen,3 Hong-Li Guo3 1Department of Hematology and Oncology, Children’s Hospital of Nanjing Medical University, Nanjing, 210008, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China; 3Pharmaceutical Sciences Research Center, Department of Pharmacy, Children’s Hospital of Nanjing Medical University, Nanjing, 210008, People’s Republic of ChinaCorrespondence: Hong-Li Guo, Children’s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, 210008, People’s Republic of China, Email guomomohl@163.comAbstract: High-dose methotrexate (HDMTX) is a pivotal component of the chemotherapeutic regimens of osteosarcoma. However, the use of HDMTX is limited by an increased risk of dose-dependent toxicity. It is thought that the plasma levels and therapy-related toxicity of MTX could be associated with single nucleotide polymorphisms (SNPs) within MTX metabolism pathway genes. Here, we report a case of a paediatric osteosarcoma girl with delayed MTX excretion who was successfully managed using supportive measures and continuous veno-venous haemodiafiltration. We further identified the cause that could account for delayed elimination by genotyping analysis. The results showed that variations have been found in SLCO1B1, SLC19A1, ABCB1 and MTHFR, all those were reported to have a strong association with delayed elimination of MTX in clinical studies. After comprehensive consideration of genotype and clinical phenotype, the second course of HDMTX was administered to this patient at a half reduced dose. We also performed a literature review to summarize the pharmacogenetic factors that influence HDMTX pharmacokinetics or MTX-related adverse effects in osteosarcoma patients. It is suggested that the potential risk of delayed MTX elimination is worthy of clinical attention, and the implementation of genotyping should be considered to ensure therapeutic safety.Graphical Abstract: Keywords: high-dose methotrexate, osteosarcoma, delayed excretion, single nucleotide polymorphisms

Ping Li,1,&ast; Junjie Peng,1,&ast; Guangxi Chen,1,2,&ast; Fangying Chen,1,3 Yongchun Shen,1 Lin Liu,4 Lei Chen1 1Laboratory of Pulmonary Diseases and Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China; 2Department of Sleep Medicine, Jiujiang First People’s Hospital, Jiujiang, People’s Republic of China; 3Department of Tuberculosis, the Third People’s Hospital of Tibet Autonomous Region, Lhasa, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, 363 Hospital, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Chen, Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China, Email lchens@126.com Lin Liu, Department of Respiratory and Critical Care Medicine, 363 Hospital, Chengdu, People’s Republic of China, Email lliniu@126.comPurpose: DNA methylation, a major epigenetic modification, has been documented to play an important role in chronic obstructive pulmonary disease (COPD). In this study, we aimed to profile the DNA methylation patterns in a mouse model of airway inflammation induced by cigarette smoke (CS), a foremost risk factor of COPD.Material and Methods: To establish a model of airway inflammation, wild-type mice were exposed to mainstream CS or room air for 2 hours twice daily, 6 days per week for consecutive 4 weeks. Lung tissues of the mice were collected for genome-wide DNA methylation analysis by liquid hybridization capture-based bisulfite sequencing, which were used for intersection analysis with gene expression by cDNA microarray to identify candidate methylated genes. Then, functional enrichment analyses with protein–protein interaction (PPI) network regarding these genes were conducted to explore the potential mechanisms.Results: After 4-week CS exposure, the level of DNA methylation accompanied by a subacute airway inflammation was markedly enhanced, and 2002 differentially methylated genes (DMGs) were annotated, including 565 DMGs contained methylations in gene promoters, which were used for intersection with the differentially expressed genes. Then, 135 candidate methylated genes were further selected by the intersection, among which 58 genes with functional methylated modification were finally identified. Further analyses revealed candidate methylated genes were significantly enriched in a complicated network of signals and processes, including interleukins, toll-like receptors, T-cells differentiation, oxidative stress, mast cells activation, stem cells proliferation, etc., as well as the 58 functional methylated genes were partially located at key positions in PPI network, especially CXCL1, DDX58 and JAK3.Conclusion: This study suggests CS exposure significantly enhances DNA methylated level, and the potential functional methylated genes are closely related to complicated inflammatory-immune responses, which may provide some new experimental evidence in understanding the epigenetic mechanisms of CS-induced airway inflammation in COPD.Keywords: chronic obstructive pulmonary disease, airway inflammation, cigarette smoke, DNA methylation, liquid hybridization capture-based bisulfite sequencing

Yi Li, Hui Dong, Yudi Dong, Qiaoyuan Wu, Ni Jiang, Qing Luo, Fang Chen Department of Cancer Research Laboratory, Department of Pathology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of ChinaCorrespondence: Qing Luo; Fang Chen, Department of Cancer Research Laboratory, Department of Pathology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, Guizhou, 563003, People’s Republic of China, Tel +85128608074, Email zlsysluoqing@163.com; 819448232@qq.comObjective: The purpose of this study was to explore the expression and distribution of tumor-infiltrating immune cells (TIICs) and their relationship with recurrence and metastasis of nasopharyngeal carcinoma (NPC).Methods: The gene expression profiles of NPC were downloaded from GEO database (GSE53819 and GSE64634). The abundance of TIICs in NPC samples was calculated by the CIBERSORT algorithm, and TIICs with higher expression were screened in NPC. Then, we performed immunohistochemistry experiments to evaluate the expression of selected TIICs in 94 NPC samples from the Affiliated Hospital of Zunyi Medical University. We further explored the relationship between TIICs and recurrence and metastasis of NPC.Results: The results based on the GEO database showed that the expression of CD8 T cells, NK cells, macrophages and plasma cells was higher than that in normal tissues. Immunohistochemistry results showed that CD8 T cells, NK cells, macrophages and plasma cells were mainly expressed in the stroma, and the expression of CD8 T cells and NK cells in the stroma of patients without recurrence or metastasis was significantly higher than that in patients with recurrence or metastasis of NPC. Kaplan–Meier analysis showed that patients with high CD8 T cells and high NK cells expression in the stroma had favorable recurrence or metastasis-free survival and overall survival (P< 0.05). Univariate and multivariate Cox analyses indicated that CD8 T cells and NK cells in the stroma were independent factors for the recurrence or metastasis of NPC.Conclusion: The expression of CD8 T cells, NK cells, macrophages and plasma cells is significantly higher than that in normal tissues. Among them, the expression of CD8 T cells and NK cells is closely related to the recurrence and metastasis of NPC. They are independent factors affecting the recurrence and metastasis of NPC.Keywords: TIICs, nasopharyngeal carcinoma, recurrence and metastasis, CD8 T cells, NK cells

Hongxiang Wei,1,&ast; Fei Chen,1,&ast; Jinyuan Chen,2,&ast; Huangfeng Lin,1 Shenglin Wang,1 Yunqing Wang,1 Chaoyang Wu,1 Jianhua Lin,1 Guangxian Zhong1 1Department of Orthopaedics, Fujian Institute of Orthopaedics, the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 2The Centralab, the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangxian Zhong; Jianhua Lin, Tel/Fax +86 591 87981029, Email zhongguangxian@163.com; jianhual@126.comPurpose: The objective of this study was to investigate the antitumor activity, targeting capability, and mechanism of the developed nanodrug consisting of doxorubicin and exosome (Exo-Dox) derived from mesenchymal stem cells in vitro and in vivo.Methods: The exosomes were isolated with Exosome Isolation Kit, and the Exo-Dox was prepared by mixing exosome with Dox-HCl, desalinizing with triethylamine and then dialyzing against PBS overnight. The exosome and Exo-Dox were examined by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). The antitumor activity, targeting capability, and mechanism of the developed Exo-Dox were evaluated by cell viability assay, histological and immunofluorescence analysis and in vivo imaging system.Results: NTA results showed the size of the exosomes had increased from 141.6 nm to 178.1 nm after loading with doxorubicin. Compared with free Dox, the Exo-Dox exhibited higher cytotoxicity against osteosarcoma MG63 cells, HOS cells, and 143B cells than free Dox, the half-maximal inhibitory concentrations (IC50) of Dox, Exo-Dox were calculated to be 0.178 and 0.078 μg mL− 1 in MG63 cells, 0.294 and 0.109μg mL− 1 in HOS cells, 0.315 and 0.123 μg mL− 1 in 143B cells, respectively. The in vivo imaging showed that MSC derived Exo could serve as a highly efficient delivery vehicle for targeted drug delivery. The immunohistochemistry and histology analysis indicated that compared with the free Dox group, the Ki67-positive cells and cardiotoxicity in Exo-Dox group were significantly decreased.Conclusion: Our results suggested that MSC-derived Exo could be excellent nanocarriers used to deliver chemotherapeutic drug Dox specifically and efficiently in osteosarcoma, resulting in enhanced toxicity against osteosarcoma and less toxicity in heart tissue. We further demonstrated the targeting capability of Exo was due to the chemotaxis of MSC-derived exosomes to osteosarcoma cells via SDF1-CXCR4 axis.Keywords: targeted therapy, exosome, doxorubicin, osteosarcoma, nanocarrier

Li Zhu,1– 3,&ast; Jin Li,4,5,&ast; Junchi Xu,4,5 Fan Chen,2,3 Xunxun Wu,2,3 Chuanwu Zhu1– 3 1Department of Infectious Diseases, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Hepatology, the Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Department of Hepatology, the Fifth People’s Hospital of Suzhou, Suzhou, Jiangsu, People’s Republic of China; 4Central Laboratory, the Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 5Central Laboratory, the Fifth People’s Hospital of Suzhou, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuanwu Zhu, Department of Infectious Diseases, the Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou, 215004, People’s Republic of China, Email zhuchw@126.comIntroduction: The adaptive immune response may reflect the immunomodulatory efficacy during peginterferon alfa-2a (PEG-IFN α-2a) treatment in chronic hepatitis B (CHB) patients. We evaluated the predictive efficiency of T-cell subsets on patient’s response to PEG-IFN α-2a treatment.Methods: The proportions of CD8+PD-1+, CD8+Tim-3+ and CD4+CD25high T-cells were measured at baseline and week 52 in CHB patients who underwent PEG-IFN α-2a treatment. The proportions of T-cell subsets were compared among different responders and non-responders (determined by biochemical, serological, and virological responses).Results: The baseline proportions of the three T-cell subsets were significantly higher in CHB patients (65 cases) than in healthy controls (28 cases), while the proportions declined significantly after 52 weeks of PEG-IFN treatment. Responders (ALT < 40 IU/L, 89.2% [58/65]; HBV DNA < 2.7 log10 IU/ml, 66.2% [43/65]; and HBeAg seroconversion [SR], 53.9% [35/65]) experienced more pronounced declines in the proportion of T-cell subsets compared to non-responders. In particular, the baseline proportions of CD4+CD25high T-cells displayed significant difference between SR and non-SR groups. The stepwise logistic regression analysis identified that CD4+CD25high T-cells combined with baseline HBV DNA and ALT can predict SR and CR (ALT < 40 IU/L, HBV DNA < 2.7 log10 IU/mL and HBeAg seroconversion) after 52 weeks of PEG-IFN treatment with high accuracy.Conclusion: PEG-IFN therapy induces significant declines in the proportion of some key T-cell subsets in HBeAg-positive patients. The model constructed with CD4+CD25high T-cells combined with ATL and HBV DNA may help to predict the efficacy of PEG-IFN α-2a therapy.Keywords: PEG-IFN α-2a, chronic hepatitis B, clinical response, HBeAg seroconversion, T-cell subsets

Feng-jia Chen,1,2,&ast; Li-juan Du,1,2,&ast; Zhimin Zeng,1,2,&ast; Xin-yan Huang,1,2 Chang-yi Xu,1,2 Wei-ping Tan,1,2 Can-mao Xie,1,2 Yu-xia Liang,1,2 Yu-biao Guo1,2 1Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 2Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu-biao Guo; Yu-xia Liang, Tel +86 20 8775 5766, Email guoyb@mail.sysu.edu.cn; liangyx69@mail.sysu.edu.cnPurpose: PTPRH inhibits EGFR activity directly in cancer patients and activated EGFR induces goblet cell hyperplasia and mucus hypersecretion in asthma. However, the function of PTPRH in asthma remains unknown. The purpose of this study was to access the association of PTPRH with asthma and its underlying mechanism.Patients and Methods: We examined the PTPRH level in asthma patients (n = 108) and healthy controls (n = 35), and analyzed the correlations between PTPRH and asthma-related indicators. Human bronchial epithelial cell (HBECs) transfected with PTPRH and asthma mouse model were set up to investigate the function of PTPRH.Results: The expression of PTPRH was significantly increased and correlated with pulmonary function parameters, including airway obstruction, and T-helper2 (Th2) associated markers in asthma patients. PTPRH increased in the house dust mite (HDM)-induced asthmatic mice, while Th2 airway inflammation and Muc5ac suppressed when treated with PTPRH. Accordingly, PTPRH expression was markedly increased in IL-13-stimulated HBECs but PTPRH over-expression suppressed MUC5AC. Moreover, HBECs transfected with over-expressed PTPRH inhibited the phosphorylation of EGFR, ERK1/2 and AKT, while induced against PTPRH in HBECs dephosphorylated of EGFR, ERK1/2 and AKT.Conclusion: PTPRH reduces MUC5AC secretion to alleviate airway obstruction in asthma via potential phosphorylating of EGFR/ERK1/2/AKT signaling pathway, which may provide possible therapeutic implications for asthma.Keywords: asthma, PTPRH, human bronchial epithelial cells, EGFR/ERK1/2/AKT, MUC5AC

Shifu Li, Wengui Tao, Zheng Huang, Langchao Yan, Bo Chen, Chudai Zeng, Fenghua Chen Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Fenghua Chen, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of China, Email xyswcfh@csu.edu.cnBackground: Brain arteriovenous malformations (bAVM) are abnormal vascular lesions characterized by direct connections between arteries and veins without an intervening capillary bed. The primary goal for brain AVM treatment is to prevent rupture and hemorrhage; however, the underlying molecular mechanisms are still unknown.Methods: We constructed venous hypertension (VH) rat model with end-to-end anastomosis of the proximal left common carotid artery and the left distal external jugular vein. Thirty-eight adult rats were randomly assigned to four groups: the 0-week (n=5), the 1-week VH group (n=12), the 3-week VH group (n=9), and the 6-week VH group (n=12). We measured the hemodynamics and diameter of the arterialized veins. An RNA sequencing of arterialized veins was conducted, followed by comprehensive bioinformatics analysis to identify key genes and biological pathways involved in VH progression. The candidate genes from RNA-Seq were validated by RT-qPCR and immunostaining in human tissues.Results: We observed high-flow and low resistance characteristics in VH models. A total of 317 upregulated and 258 downregulated common genes were consistently differentially expressed during VH progression. Thirteen co-expression modules were obtained by WGCNA analysis, and 4 key modules were identified. Thirteen genes: Adamts8, Adamtsl3, Spon2, Adamtsl2, Chad, Itga7, Comp, Itga8, Bmp6, Fst, Smad6, Smad7, Grem1, and Nog with differential expressions were identified using the density of maximum neighborhood component (DMNC) algorithm in Cytohubba. The expression of five potential genes (Adamts8, Adamtsl3, Spon2, Adamtsl2, Itga8) were increased in RT-qPCR, while in human bAVM tissue, the protein levels of Adamtsl2 and Itga8 were significant elevated and Spon2 and Adamtsl3 were decreased.Conclusion: The identified gene networks of Adamtsl3, Spon2, Adamtsl2, and Itga8 provided key genes for further intervention.Graphical Abstarct: Keywords: WGCNA, xCells, focal adhesion, vascular microenvironment, bioinformatics

Fang Chen,1,2,&ast; Han Zhong,1,&ast; Tengjiao Yang,3 Chuan Shen,2 Yuxiao Deng,4 Longzhi Han,2 Xiaosong Chen,2 Haomin Zhang,5 Yongbing Qian2 1Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Pharmacy, The Third People’s Hospital of Henan Province, Zhengzhou, People’s Republic of China; 4Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 5Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haomin ZhangDepartment of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Tel +86-21-68383715Email zhanghaomin@renji.comYongbing QianDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Tel +86-21-68383715Email qianyb79@hotmail.comBackground: Ceftazidime-avibactam (CZA) has been approved in vitro activity against carbapenem-resistant K. pneumoniae (CRKP), but the experience for the treatment of CRKP in liver transplantation (LT) recipients was limited, and previous data on its efficacy in this setting are lacking.Methods: LT recipients with CRKP infection who received CZA treatment were reviewed retrospectively, microbiological and clinical response, adverse events were also assessed. The primary outcome was 30-day mortality after CZA administration.Results: CZA was used in 21 LT recipients (including 4 pediatric patients) with CRKP infections after failure with other antimicrobials. CZA was administered as monotherapy in 4 patients. Median time from the onset of CRKP infection until the initiation of CZA treatment was 2 days (IQR, 1– 6.5), and the median treatment duration was 12 days (IQR, 8.5– 18.5). The mortality at 14 days, 30 days and all-cause was 28.6%, 38.1% and 42.9%, respectively. In adult patients, clinical response of 14 days and 30 days was 70.6% (12/17) and 58.8% (10/17), respectively, while in pediatric patients the 14-day and 30-day clinical response were both 75%, respectively. The relapse rate during the treatment developed in 3 patients after 30 days with the cessation of CZA monotherapy. CZA resistance was not detected in any case and 3 (3/21, 14.3%) patients developed acute kidney injury related to uncontrolled infection.Conclusion: CZA shows promising results, even in monotherapy, for the treatment of patients with severe infections due to carbapenem-resistant K. pneumoniae among LT recipients. The emergence of resistance to CZA was not observed.Keywords: carbapenem-resistant Klebsiella pneumoniae, ceftazidime-avibactam, liver transplantation, intra-abdominal infection, pneumonia

Zhiquan Hu,1,&ast; Jingjing Li,2,&ast; Chunguang Yang,1 Fen Chen,3 Zhihua Wang,1 Ping Lei,4 Guanxin Shen4 1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunguang YangDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Road, Wuhan, 430030, People’s Republic of ChinaTel +86-13871084024Fax +86-27-83663460Email cgyang-hust@hotmail.comFen ChenDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaEmail 54113447@qq.comBackground: COVID-19 outbreak began in Wuhan and pandemics occur. Although SARS-CoV-2-specific immunoglobulins have been detected in serum of COVID-19 patients, their dynamics and association with outcomes have not been fully characterized.Methods: This retrospective cohort study investigated the association between SARS-CoV-2-specific immunoglobulins and clinical outcomes of COVID-19 patients. We recruited 137 participants who were diagnosed with COVID-19 in four wards of the Tongji Hospital in Wuhan, China. Among the 137 participants, 81 patients were recovered, 23 patients died, and 33 patients remained hospitalized by the end of the study. SARS-CoV-2-specific immunoglobulins were analyzed by chemiluminescence assays. Laboratory and radiological characteristics, and clinical outcomes were compared between the recovered group and the deceased group. Furthermore, a matched cohort study was conducted in which each non-survivor was matched to two recovered patients of similar age.Results: SARS-CoV-2-specific IgM levels peaked in the fourth week after the onset of COVID-19, while serum IgG levels rose earlier and remained high up to the eighth week. In the age-matched cohort study, the serum IgM, but not IgG levels, were higher among the non-survivors than in the recovered group (P = 0.006). The area under the ROC curve for the IgM and IgG levels was 0.702 (95% CI: 0.560– 0.845, P = 0.006) and 0.596 (95% confidence interval: 0.449– 0.744, P = 0.194), respectively. We also showed that patients with COVID-19 who had high IgM or IgG levels (stratified according to best cut-off) exhibited significantly lower overall survival (Kaplan–Meier survival curves, P < 0.05).Discussion: These results indicate the association between immunoglobulins and outcome in patients with COVID-19 and demonstrated that elevated serum IgM levels could indicate poor outcomes in patients with COVID-19. Further, the information about the profile of SARS-CoV-2-specific IgGs may be useful for the future epidemiological investigations of COVID-19 therapies.Keywords: SARS-CoV-2, COVID-19, immunoglobulin, prognosis, antibodies, IgM, IgG, diagnosis

Dongbei Li,1 Fangman Chen,2 Cheng Cheng,1 Haijun Li,3,&ast; Xudong Wei1,&ast; 1Department of Hematology, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou City, Henan Province, People’s Republic of China; 2School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xudong Wei; Haijun Li Email xudongwei@zzu.edu.cn; navylizz@sina.comPurpose: Photodynamic therapy (PDT) with spatiotemporal controlled and noninvasive advantages has obtained growing attention in cancer treatment. Nevertheless, PDT still suffers from self-aggregation-induced photosensitizer quenching and reactive oxygen species (ROS) scavenging in cancer cells with abundant glutathione (GSH) pools, leading to insufficient performance.Methods: In this study, we develop a versatile nanocarrier (SSNs) with a disulfide-bond-bridged silica framework for enhanced photo-immunotherapy. Such SSNs spatially confine photosensitizers Ce6 in the matrix to prevent self-aggregation. Under the high GSH level of cancer cells, the disulfide-bond-bridged framework was degradable and triggered the exposure of photosensitizers to oxygen, accelerating the ROS generation during PDT. In addition, GSH depletion via the break of the disulfide-bond increased the ROS level, together resulting in efficient tumor killing outcomes with a considerable immunogenic cell death effect in vitro. Importantly, the SSNs@Ce6 accumulated in the tumor site and exhibited enhanced PDT efficacy with low systemic toxicity in vivo.Results: The GEN-loaded nanoplatform (Ag-MONs@GEN) showed glutathione-responsive matrix degradation, resulting in the simultaneous controlled release of GEN and silver ions. Ag-MONs@GEN exhibited excellent anti-bacterial activities than Ag-MONs and GEN alone, especially enhancing synergetic effects against four antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Moreover, Ag-MONs@GEN showed good biocompatibility on L929 and HUVECS.Conclusion: Notably, SSNs@Ce6-mediated PDT completely eradicated 4T1 tumors when combined with the PD-1 checkpoint blockade. Overall, the confinement of photosensitizers in a biodegradable disulfide-bridged-framework provides a promising strategy to unleash the potential of photosensitizers in PDT, especially in combined cancer photo-immunotherapy.Keywords: photodynamic therapy, glutathione depletion, photosensitizer confinement, degradation, cancer immunotherapy

Zhimin Su,1,2 Linbin Lu,1 Fuyu Chen,3 Jianhui Chen,4 Xiong Chen1 1Department of Oncology, 900th Hospital of PLA, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350024, People’s Republic of China; 2Department of Medical Oncology, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, 361015, People’s Republic of China; 3Department of Substation Maintenance Center, State Grid Quanzhou Electric Power Supply Company, Quanzhou, 362000, People’s Republic of China; 4Department of Urology, Fujian Medical University Union Hospital, Fuzhou, 350024, People’s Republic of ChinaCorrespondence: Xiong ChenDepartment of Oncology, 900th Hospital of PLA, Fuzong Clinical Medical College of Fujian Medical University, 156 North Xierhuan Road, Fuzhou, 350024, People’s Republic of ChinaEmail cxiongzpc@fjmu.edu.cnIntroduction: Sunitinib-induced diarrhea seriously affects the prognosis of patients with metastatic renal cell carcinoma (mRCC) and reduces their quality of life. We aim to explore and find the relationship between sunitinib-induced diarrhea and gut microbiota.Methods: Feces were collected from 31 mRCC patients receiving sunitinib treatment. To characterize the feces gut microbiome profiles of patients, the V3-V4 region of 16S rRNA sequencing was carried out in this study.Results: Gut microbial diversity was decreased both in the severe diarrhea group and in the sunitinib-post group. The microbial composition with higher abundance of Bacteroides (mucus degrading bacteria) and lower abundance of Faecalibacterium, Oscillospira, Ruminococcaceae, Eubacterium and Coriobacteriaceae (butyrate-producing bacteria) were found in patients with diarrhea. Interestingly, the abundance of Actinobacteria was decreased in patients receiving sunitinib with severe diarrhea.Conclusion: This study reported an association between gut microbiota and sunitinib-induced diarrhea. Defects of the butyrate-producing bacteria and the increase in Bacteroides may be the physiological basis of sunitinib-induced diarrhea.Keywords: sunitinib-induced diarrhea, 16S rRNA sequencing, gut microbial diversity, butyrate-producing bacteria

Fang Chen,1,2,&ast; Yuan-Bing Liu,1,3,&ast; Bin-Jie Fu,1 Fa-Jin Lv,1 Zhi-Gang Chu1 1Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Radiology, Youyang Hospital, A Branch of The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Radiology, Qijiang People’s Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Gang ChuDepartment of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaTel +86 18723032809Fax +86 23 68811487Email chuzg0815@163.comPurpose: To investigate the clinical and computed tomography (CT) characteristics of pulmonary nodules caused by cryptococcal infection and gain a greater insight and understanding that will reduce misdiagnosis.Materials and Methods: A total of 47 patients with confirmed pulmonary cryptococcosis (PC) manifested as nodules were retrospectively enrolled from January 2013 to December 2020. The clinical and CT data of patients with single and multiple nodules were analyzed and compared with emphasis on exploring the characteristics of the solitary ones.Results: Among the 47 patients, single and multiple nodules were detected in 25 (53.2%) and 22 (46.8%) patients, respectively, with similar clinical characteristics. The diameter of solitary nodules was smaller than that of the largest ones of the multiple nodules (P = 0.000). Compared with multiple nodules, less solitary nodules were located in the subpleural zone (P = 0.031) and had a cavity or vacuole (P = 0.049). Regarding the solitary nodules, 22 (88.0%) and 3 (12.0%) were solid and subsolid, respectively. Eighteen (81.8%) solid solitary nodules exhibited either one of air bronchogram or vacuole, satellite lesions, and halo sign. Twenty-three (92.0%) of 25 patients with solitary nodules had follow-up CT data, and most of them had no changes (12, 52.1%) or increased in size and/or density (8, 34.8%), but only a few (3, 13.0%) decreased with or without anti-inflammatory therapy.Conclusion: The clinical characteristics of patients with solitary and multiple nodules caused by PC are similar. The solitary nodules are smaller, more scattered, but less necrotic than multiple ones. For solitary nodules with air bronchogram or vacuole, satellite lesions, or halo sign, PC should be considered as one of the differential diagnosis.Keywords: tomography, x-ray computed, pulmonary nodules, cryptococcosis

Jiangtao Yin,1,2,&ast; Wenjian Mao,1,&ast; Xiaojia Xiao,3 Xianqiang Yu,4 Baiqiang Li,5 Faxi Chen,5 Jiajia Lin,5 Jing Zhou,1 Jing Zhou,4 Zhihui Tong,5 Lu Ke,5 Weiqin Li1,5 1Department of Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Intensive Care Unit, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 3Department of Critical Care Medicine, Jinling Hospital of Southern Medical University, Nanjing, People’s Republic of China; 4Southeast University School of Medicine, Nanjing, People’s Republic of China; 5Department of Critical Care Medicine, Jinling Hospital, Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Ke; Weiqin LiDepartment of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 225001, People’s Republic of ChinaEmail ctgkelu@nju.edu.cn; njzy_pancrea@163.comObjective: Immunosuppression is common in patients with infected pancreatic necrosis (IPN) and associated with morbidity and mortality. This study aimed to investigate the impact of immune status on mortality and readmission after hospital discharge in patients with IPN-related sepsis.Methods: In this prospective observational study, eligible adult patients with IPN-related sepsis requiring ICU admission were included. Monocytic human leukocyte antigen DR (mHLA-DR), expression of regulatory T cells (Treg), and neutrophil CD88 (nCD88) were measured on the diagnosis of sepsis, ICU discharge, hospital discharge, and 15, 30, 60 days after hospital discharge. Logistic regression model was used to assess potential risk factors for readmission 60-days within the index discharge.Results: A total of 53 patients were included, 13 died during hospitalization and one withdrew the consent soon after discharge. Among the survivors, a tendency of immune recovery was observed during the consecutive follow-ups, evidenced by the increased expression of mHLA-DR. Sixteen patients (41.03%) were readmitted within 60 days after the index discharge. In the multivariable regression model, APACHE II score when sepsis was diagnosed > 9 and mHLA-DR at discharged < 14,591 AB/C were found to be independent risk factors affecting readmission.Conclusion: Immunosuppression is common in patients with IPN-related sepsis and can persist until two months after discharge. The compromised mHLA-DR level at discharge was associated with readmission within two months after discharge.Keywords: infected pancreatic necrosis, sepsis, immunosuppression, monocyte HLA-DR, readmissions

Jing Xu,1,&ast; Fengyuan Chen,1,&ast; Guoquan Wang,1,&ast; Bin Liu,2 Hang Song,1 Teng Ma2 1Department of Biochemistry and Molecular Biology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China; 2Department of Cellular and Molecular Biology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Teng Ma; Hang Song Email mateng82913@163.com; hangsong@ahtcm.edu.cnAbstract: G. lucidum has a long history of thousands of years in China and is closely related with the lives of the Chinese people. It is reported to cure various diseases due to its high nutritional value and wide range of uses. The fascinating effects of G. lucidum have tethered a multitude of efforts to explore its effective ingredients and supplement functions. At present, many cancer research studies have reported the G. lucidum polysaccharides (GLPs) and G. lucidum triterpenes (GLTs) as the main active ingredients in G. lucidum, which have shown positive effects on radiotherapy and chemotherapy. GLPs or GLTs treatment synergizes with radiotherapy and chemotherapy through multiple pathways, including oxidative stress, apoptosis, immune microenvironment, etc. Therefore, this review aims to analyze and summarize these complex molecules from G. lucidum in order to create more treatment options for cancer patients in the future.Keywords: GLP, GLTs, pharmacology, general structure, radiotherapy and chemotherapy

Yajie Zhu,1 Xiaoli Ge,1 Di Xie,1 Shangyuan Wang,1 Feng Chen,2 Shuming Pan1 1Department of Emergency Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of China; 2Division of Medical Microbiology, Department of Clinical Laboratory, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Shuming PanDepartment of Emergency Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai, 200092, People’s Republic of ChinaTel +862125076045Fax +862165030840Email panshuming@xinhuamed.com.cnFeng ChenDivision of Medical Microbiology, Department of Clinical Laboratory, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai, 200092, People’s Republic of ChinaTel +862125078999Fax +862165030840Email chenfeng@xinhuamed.com.cnBackground: Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are most often caused by bacterial pneumonia and characterized by severe dyspnea and high mortality. Knowledge about the lung injury effects of current clinical bacterial strains is lacking. The aim of this study was to investigate the ability of representative pathogenic bacteria isolated from patients to cause ALI/ARDS in mice and identify the major virulence factor.Methods: Seven major bacterial species were isolated from clinical sputum and unilaterally instilled into the mouse airway. A histology study was performed to determine the lung injury effect. Virulence genes were examined by PCR. Sequence types of P. aeruginosa strains were identified by MLST. LC-MS/MS was used to analysis the bacterial exoproducts proteome. LasB was purified through a DEAE-cellulose column, and its toxicity was tested both in vitro and in vivo.Results: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus agalactiae, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli were randomly separated and tested 3 times. Among them, gram-negative bacteria have much more potential to cause acute lung injury than gram-positive bacteria. However, P. aeruginosa is the only pathogen that induces diffuse alveolar damage, hemorrhage and hyaline membranes in the lungs of mice. The lung injury effect is associated with the excreted LasB elastase. Purified LasB recapitulated lung injury similar to P. aeruginosa infection in vivo. We found that this was due to the powerful degradation effect of LasB on the extracellular matrix of the lung and key proteins in the coagulation cascade without inducing obvious cellular apoptosis. We also report for the first time that LasB could induce DIC-like coagulopathy in vitro.Conclusion: P. aeruginosa strains are most capable of inducing ALI/ARDS in mice among major clinical pathogenic bacteria tested, and this ability is specifically attributed to their LasB production.Keywords: unilateral lung injury, LasB elastase, Pseudomonas aeruginosa, ALI/ARDS

Shuting Yang,1 Qian Zhang,1 Yifan Xu,1 Futeng Chen,1 Fangming Shen,1 Qin Zhang,1 He Liu,2 Yueying Zhang3 1Xuzhou Medical University, Xuzhou City, Jiangsu Province, People’s Republic of China; 2Department of Anesthesiology, The Affiliated Huzhou Hospital, Zhejiang University School of Medicine; Huzhou Central Hospital, Huzhou City, Zhejiang Province, People’s Republic of China; 3Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou City, Jiangsu Province, People’s Republic of ChinaCorrespondence: Yueying ZhangDepartment of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou City, Jiangsu Province, People’s Republic of ChinaTel +86 138 1531 0789Email zyy0218@126.comPurpose: To develop a risk prediction nomogram of postoperative sleep disturbance (PSD) in patients undergoing non-cardiac surgery.Patients and methods: Data on 881 consecutive patients who underwent non-cardiac surgery at the Affiliated Hospital of Xuzhou Medical University between June 2020 and April 2021 were prospectively collected. Of these, we randomly divided 881 non-cardiac patients into two groups, training cohort (n = 617) and validation cohort (n = 264) at the ratio of 7:3. Characteristic variables were selected based on the data of training cohort through least absolute shrinkage and selection operator (LASSO) regression. Multivariate logistic regression was used to identify the independent risk factors associated with PSD that then were incorporated into the nomogram. The predictive performance of the nomogram was measured by concordance index (C index), receiver operating characteristic (ROC) curve, and calibration with 1000 bootstrap samples to decrease the over-fit bias.Results: PSD was found in 443 of 617 patients (71.8%) and 190 of 264 patients (72.0%) in the training and validation cohorts, respectively. The perioperative risk factors associated with PSD were female sex, anxiety, dissatisfaction of ward environment, absence of combined regional nerve block, postoperative nausea and vomiting (PONV), the longer duration stayed in post anesthesia care unit (PACU), the higher dose of midazolam and sufentanil, the higher postoperative numeric rating score for pain (NRS) score. Incorporating these 9 factors, the nomogram achieved good concordance indexes of 0.82 (95% confidence interval [CI], 0.78– 0.85) and 0.80 (95% CI, 0.74– 0.85) in predicting PSD in the training and validation cohorts, respectively, and obtained well-fitted calibration curves. The sensitivity and specificity (95% CIs) of the nomogram were calculated, resulting in sensitivity of 74.0% (70.0– 78.2%) and 75.3% (68.4– 81.7%) and specificity of 79.3% (72.5– 85.2%) and 70.3% (58.4– 80.7%) for the training and validation cohorts, respectively. Patients who had a nomogram score of less than 262 or 262 or greater were considered to have low or high risks of PSD presence, respectively.Conclusion: The proposed nomogram achieved an optimal prediction of PSD in patients undergoing non-cardiac surgery. The risks for an individual patient to harbor PSD can be determined by this model, which can lead to a reasonable preventive and treatment measures.Keywords: postoperative sleep disturbance, surgery, LASSO regression analysis, nomogram

Minwei Zhang,1,2,&ast; Shuxuan Shao,1,2,&ast; Haitao Yue,1,2 Xin Wang,3 Wenrui Zhang,1,2 Fei Chen,1,2 Li Zheng,1,2 Jun Xing,1,2 Yanan Qin1,2 1College of Life Science & Technology, Xinjiang University, Urumqi, 830046, People’s Republic of China; 2Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, Urumqi, 830046, People’s Republic of China; 3The First Hospital of Jilin University, Changchun, 130061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanan Qin Email qingyalan12345@sina.comAbstract: In recent years, Au-based nanomaterials are widely used in nanomedicine and biosensors due to their excellent physical and chemical properties. However, these applications require Au NPs to have excellent stability in different environments, such as extreme pH, high temperature, high concentration ions, and various biomatrix. To meet the requirement of multiple applications, many synthetic substances and natural products are used to prepare highly stable Au NPs. Because of this, we aim at offering an update comprehensive summary of preparation high stability Au NPs. In addition, we discuss its application in nanomedicine. The contents of this review are based on a balanced combination of our studies and selected research studies done by worldwide academic groups. First, we address some critical methods for preparing highly stable Au NPs using polymers, including heterocyclic substances, polyethylene glycols, amines, and thiol, then pay attention to natural product progress Au NPs. Then, we sum up the stability of various Au NPs in different stored times, ions solution, pH, temperature, and biomatrix. Finally, the application of Au NPs in nanomedicine, such as drug delivery, bioimaging, photothermal therapy (PTT), clinical diagnosis, nanozyme, and radiotherapy (RT), was addressed concentratedly.Keywords: high stability Au NPs, polymer, natural product, resistance, nanomedicine

Duanfeng Jiang,1 Kaixuan Zhang,2 Yinghong Zhu,3 Yan Zhu,2 Lang Zou,2 Jian Hu,2 Yajuan Cui,4 Wen Zhou,3 Fangping Chen,1,2 Yanjuan He2 1Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, People’s Republic of China; 2Department of Hematology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 3Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, 410078, People’s Republic of China; 4Department of Hematology, the Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of ChinaCorrespondence: Yanjuan HeDepartment of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaTel +86 159 73130688Email 15973130688@163.comBackground: Lenalidomide, an immunomodulatory drug (IMiD), is an effective therapy for the treatment of multiple myeloma (MM). However, prolonged treatment may be accompanied by toxicity, second primary malignancies, and drug resistance. There is an inherent vulnerability in MM cells that high rates of immunoglobulin synthesis resulting in the high level of reactive oxygen species (ROS). This provides a therapeutic potential for MM.Materials and Methods: The intracellular ROS levels, H2O2 production and glutathione (GSH) levels were measured using detection kit. Cell viability was evaluated using cell-counting kit-8 (CCK-8) and soft agar colony formation assay. Apoptosis was determined in whole living cells using flow cytometry. Chidamide and its anti-myeloma efficacy in combination with lenalidomide were characterized in MM cell lines in vitro and in a mouse xenograft model. Moreover, Western blotting, immunofluorescence and immunohistochemical studies were performed.Results: ROS levels increased in a time- and dose-dependent manner with chidamide treatment. Moreover, the GSH levels were decreased and the mRNA level of SLC7A11 downregulated after chidamide treatment. The co-treatment with chidamide and lenalidomide increased apoptosis and proliferation inhibition, with combination index (CI) in the synergistic range (0.2– 0.5) using the Chou–Talalay method. The cooperative anti-myeloma efficacy was confirmed in the murine model, and immunohistochemical studies also supported this potentiation. Chidamide enhanced the effect of lenalidomide-induced degradation of IKZF1 and IKZF3 by elevating H2O2. In addition, co-treatment with chidamide and lenalidomide increased biomarkers of caspase and DNA damage.Conclusion: Elevated ROS production may constitute a potential biochemical basis for anti-myeloma effects of chidamide plus lenalidomide. The results of this study confirm the synergistic effect of chidamide and lenalidomide against MM and provide a promising therapeutic strategy for MM.Keywords: multiple myeloma, chidamide, lenalidomide, reactive oxygen species

Mou-chun Gong,&ast; Wei-qing Chen,&ast; Zhao-qing Jin, Jia Lyu, Li-hao Meng, Hai-yan wu, Fei-hua Chen Department of General Surgery, First People’s Hospital of Hangzhou Lin’an District, Hangzhou, Zhejiang, 311300, People’s Republic of China&ast;These authors contributed equally to this work.Correspondence: Fei-hua ChenDepartment of General Surgery, First People’s Hospital of Hangzhou Lin’an District, 548 Yijin Road, Street Jincheng, Hangzhou, Zhejiang, 311300, People’s Republic of ChinaEmail 13396510518@189.cnBackground: Topoisomerase 2-alpha (TOP2A) has been identified as a hub gene that played an important role in the initiation and progression of thyroid carcinoma (THCA). However, the exact function of TOP2A in papillary thyroid cancer (PTC) remained elusive. The current study aimed to evaluate the TOP2A expression, prognosis significance and key signaling pathways involved in PTC.Methods: We firstly evaluated the expression of TOP2A in PTC via UALCAN, cBioportal, HPA and LinkdedOmics databases. Genetic alteration of TOP2A in PTC was then explored in cBioportal. Prognostic impacts of TOP2A expression on disease-free survival (DFS) of PTC patients were subsequently evaluated using Kaplan–Meier plotter and Gepia databases. Taking gender, age, cancer stage, T, N and M stages into consideration, we compared survival difference between TOP2A high and low expression groups. KEGG pathway analysis in WebGestalt and GSEA analysis were further performed to reveal the potential TOP2A-associated signaling pathways involved in PTC. Finally, the upstream microRNAs of TOP2A were assessed using DIANA, TargetScan, miRDB and miRWALK database, followed by mechanism exploration of upstream microRNAs.Results: 1) The mRNA and protein of TOP2A were highly expressed in PTC tissue compared with normal thyroid tissue. TOP2A expression was associated with patient’s age, N stage and cancer stage (all P< 0.05). TOP2A protein was mainly localized to nucleoplasm. 2) Most of samples occurred the missense substitution, and mutation site was located at K1199E. Nucleotide mutations were mainly presented as G>A (35.29%). 3) TOP2A high expression significantly influenced the DFS of PTC patients (P=0.015). Restricted survival analysis showed that TOP2A high expression caused poorer DFS of female patients (P=0.003) and those with age < 60 years old (P=0.002), early clinical stage (P=0.012), N0 stage (P=0.002) or M0 stage (P=0.040). 4) Pathway analysis suggested that TOP2A positively participated in the cell cycle, oocyte meiosis and p53 signaling pathways (all P< 0.05) involved in thyroid cancer.Conclusion: The expression of TOP2A was higher in PTC tissue, which resulted in a worse DFS of patients with PTC. TOP2A might act as an effective therapeutic target for PTC treatment.Keywords: TOP2A, high expression, poor prognosis, pathway

Yilan Jin,1,&ast; Gaowa Jin,2,&ast; Jun Zhao,2 Caihong Jiang,2 Lanzhen Zhao,2 Ying Jiang,2 Feng Chen,2 Hui Li,2 Wenjuan Wang,2 Yungaowa Wu,2 Guang Liu,2 Xiaorong Li,2 Min Gu,2 Xiaomei Li,3 Quanfu Li2 1Ordos Clinical College, Inner Mongolia Medical University, Ordos, 017000, People’s Republic of China; 2Department of Medical Oncology, Ordos Central Hospital, Ordos, 017000, People’s Republic of China; 3Department of Medical Oncology, The General Hospital of the People’s Liberation Army, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Quanfu LiDepartment of Medical Oncology, Ordos Central Hospital, Ordos, 017000, People’s Republic of ChinaTel +86 477-8363279Fax +86 477-8363158Email li_qfedu@163.comXiaomei LiDepartment of Medical Oncology, The General Hospital of the People’s Liberation Army, Beijing, 100853, People’s Republic of ChinaTel +86 13501308592Email lixoamei@163.comObjective: The present study aims to investigate the correlation between the gene polymorphisms of the multidrug resistance protein 1 (ABCB1), the intron region of transcriptional factor (GTF2E1) and catechol-O-methyltransferase (COMT), dopamine receptor (DRD2), and the control of chemotherapy-induced nausea and vomiting (CINV) by olanzapine or aprepitant in a Chinese population under a fractionated cisplatin dosing pattern.Methods: Antiemetic treatment with 5 mg of olanzapine or aprepitant triplet therapy was conducted in 210 patients with malignancies receiving cisplatin multi-day chemotherapy. The general data on the patients were collected with the evaluation of the rate of complete protection (TP), complete remission (CR), complete control (TC), and time to first vomiting, the functional living index-emesis (FLIE) scale, and side effects in the acute and delayed phases. The DNA mass spectrometry detected the gene polymorphisms of ABCB1, GTF2E1, COMT, and DRD2, and the correlation with TP was analyzed.Results: 1) There were no statistically significant differences in the TP, CR, TC, time of first vomiting, and FLIE index at different phases between the 5mg of olanzapine group and the aprepitant group (P > 0.05). 2) The main side effect in the olanzapine group was drowsiness (P = 0.00), and in the aprepitant group was constipation (P = 0.02). 3) The distributions of each genotype were in the Hardy–Weinberg (H–W) equilibrium. Univariate analysis showed that in the olanzapine group, delayed-phase TP was correlated with the ABCB1 rs1045642 non-TT (P = 0.01) genotype.Conclusion: The present study revealed that females and the rs1045642TT genotype were independent risk factors for delayed-phase CINV in the northern Chinese population, which provided a scientific basis for subsequent CINV-related analysis of high-risk factors in Chinese patients.Keywords: chemotherapy-induced nausea and vomiting, cisplatin, multi-day chemotherapy, gene polymorphism

Haijun Li,1,&ast; Dongbei Li,2,&ast; Fangman Chen,3 Chao Yang,3 Xiaogai Li,1 Yuan Zhang,1 Chunlan Hua,1 Xiaoxu Ma,1 Xin Zhao,1 Dan Shao,3 Yingshuai Wang,4 Liang Ming1 1Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 2Department of Hematology, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450000, People’s Republic of China; 3Institutes for Life Sciences, School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 510630, People’s Republic of China; 4School of Life Science and Technology, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingshuai WangSchool of Life Science and Technology, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of ChinaEmail yingshuaiwang1987@163.comLiang MingDepartment of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaEmail mingliang3072@163.comPurpose: Antibiotic-resistant bacteria are pathogens that have emerged as a serious public health risk. Thus, there is an urgent need to develop a new generation of anti-bacterial materials to kill antibiotic-resistant bacteria.Methods: Nanosilver-decorated mesoporous organosilica nanoparticles (Ag-MONs) were fabricated for co-delivery of gentamicin (GEN) and nanosilver. After investigating the glutathione (GSH)-responsive matrix degradation and controlled release of both GEN and silver ions, the anti-bacterial activities of Ag-MONs@GEN were systematically determined against several antibiotic-susceptible and antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Furthermore, the cytotoxic profiles of Ag-MONs@GEN were evaluated.Results: The GEN-loaded nanoplatform (Ag-MONs@GEN) showed glutathione-responsive matrix degradation, resulting in the simultaneous controlled release of GEN and silver ions. Ag-MONs@GEN exhibited excellent anti-bacterial activities than Ag-MONs and GEN alone via inducing ROS generation, especially enhancing synergetic effects against four antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Moreover, the IC50 values of Ag-MONs@GEN in L929 and HUVECs cells were 313.6 ± 15.9 and 295.7 ± 12.3 μg/mL, respectively, which were much higher than their corresponding minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values.Conclusion: Our study advanced the development of Ag-MONs@GEN for the synergistic and safe treatment of antibiotic-resistant bacteria.Keywords: mesoporous organosilica nanoparticles, nanosilver, gentamicin, GSH-responsive release, antibiotics-resistant bacteria

Fengshou Chen, Jie Han, Bing Tang Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of ChinaCorrespondence: Bing Tang No. 155 Nangjing North Street, Shenyang, Liaoning Province, People’s Republic of ChinaTel +86 24 83283100Email tangbing527@126.comBackground: Immune-inflammatory mechanisms contribute greatly to the complex process leading to type A aortic dissection (TAAD). This study aims to explore immune infiltration and key immune-related genes in acute TAAD.Methods: ImmuCellAI algorithm was applied to analyze patterns of immune infiltration in TAAD samples and normal aortic vessel samples in the GSE153434 dataset. Differentially expressed genes (DEGs) were screened. Immune-related genes were obtained from overlapping DEGs of GSE153434 and immune genes of the ImmPort database. The hub genes were obtained based on the protein–protein interaction (PPI) network. The hub genes in TAAD were validated in the GSE52093 dataset. The correlation between the key immune-related genes and infiltrating immune cells was further analyzed.Results: In the study, the abundance of macrophages, neutrophils, natural killer T cells (NKT cells), natural regulatory T cells (nTreg), T-helper 17 cells (Th17 cells) and monocytes was increased in TAAD samples, whereas that of dendritic cells (DCs), CD4 T cells, central memory T cells (Tcm), mucosa associated invariant T cells (MAIT cells) and B cells was decreased. Interleukin 6 (IL-6), C-C motif chemokine ligand 2 (CCL2) and hepatocyte growth factor (HGF) were identified and validated in the GSE52093 dataset as the key immune-related genes. Furthermore, IL-6, CCL2 and HGF were correlated with different types of immune cells.Conclusion: In conclusion, several immune cells such as macrophages, neutrophils, NKT cells, and nTreg may be involved in the development of TAAD. IL-6, CCL2 and HGF were identified and validated as the key immune-related genes of TAAD via bioinformatics analyses. The key immune cells and immune-related genes have the potential to be developed as targets of prevention and immunotherapy for patients with TAAD.Keywords: acute type A aortic dissection, immune infiltration, ImmuCellAI, bioinformatics

Haimeng Yan,1 Donghua He,1 Weijia Huang,1 Fei Chen,1,2 Jingsong He,1 Zhen Cai,1,3,4 Yi Zhao1 1Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Hematology, Haining People’s Hospital, Haining, People’s Republic of China; 3Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 4Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou, 311121, People’s Republic of ChinaCorrespondence: Yi Zhao; Zhen CaiBone Marrow Transplantation Center, Zhejiang University School of Medicine, Qingchun Road 79, Hangzhou, 310009, People’s Republic of ChinaEmail zhaoyi999@zju.edu.cn; caiz@zju.edu.cnBackground: Acute promyelocytic leukemia differentiation syndrome (APL DS) is a common and severe complication seen in patients with APL treated with all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO). The presenting symptoms of APL DS are diverse, and rare symptoms are easy to be misdiagnosed. Therefore, it is very crucial to identify DS from uncommon signs to avoid delay in treatment.Case Presentation: Here, we report a patient of APL who developed severe abdominal pain during ATRA and ATO therapy, with increasing leukocyte count. Organic diseases were firstly excluded, and empiric treatment for DS was adopted. The abdominal pain was gradually relieved and the patient eventually achieved complete remission.Conclusion: This case history suggests that APL DS may manifest as severe abdominal pain, and the early identification of DS and immediate treatment could improve the prognosis of patients.Keywords: acute promyelocytic leukemia, all-trans-retinoic acid, arsenic trioxide, differentiation syndrome, abdominal pain, case report