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Hongling Du,1– 3 Shunjie Zhang,1 Kezhu Yuan,4 Zhirui Yang,5 Mingquan Wu4 1Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Pharmacy, Sichuan Public Health Clinical Center, Chengdu, Sichuan, People’s Republic of China; 3State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 4Department of Pharmacy, Sichuan Orthopedic Hospital, Chengdu, Sichuan, People’s Republic of China; 5Department of Nuclear Medicine, Chengdu Second People’s Hospital, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Mingquan Wu, Department of Pharmacy, Sichuan Orthopedic Hospital, Chengdu, Sichuan, People’s Republic of China, Email 18782976939@163.comBackground: Rehmanniae Radix (RR) has received attention for its antithrombotic effect. However, few studies have independently explored the bioactive components responsible for its antithrombotic bioactivity and the potential mechanism. We aimed to reveal the antithrombotic mechanisms of RR by using metabolomics integrated with network pharmacology.Methods: A thrombosis model was established by intraperitoneal injection of type I carrageenan in rats, and antithrombotic function was evaluated at different doses of RR. Metabolomics was used to identify the differential metabolites in the serum. Network pharmacology was then applied to identify the potential targets for the antithrombotic activity of the RR. An integrated network of metabolomics and network pharmacology was constructed using Cytoscape. Finally, key targets were verified using molecular docking.Results: RR at 5.4 g/kg significantly alleviated the thrombosis. Thirteen potentially significant metabolites were involved in the therapeutic effects of RR against thrombosis, most of which were regulated for recovery after RR treatment. An integrated analysis of metabolomics and network pharmacology showed that the antithrombosis effect of RR was closely associated with the regulation of PLA2G2A, PTGS1, ALOX5, and CYP2C9. Molecular docking showed high affinity between the key targets and components of RR. We speculated that the components of RR, such as catalpol, ferulic acid methyl ester, and methyl 4-hydroxycinnamate, might act on key proteins, including PLA2G2A, PTGS1, and ALOX5, to exert antithrombosis effects.Conclusion: This study confirmed the antithrombotic effect of high-dose RR, revealed the antithrombotic mechanism and potential material basis, and laid the foundation for the antithrombotic clinical application of RR. Furthermore, it provides a successful case reference for screening natural herbal components and exploring their potential pharmacological mechanisms.Keywords: Rehmanniae radix, antithrombotic effects, metabolomics, network pharmacology

Yongcheng Yao,1,2 Jie Tang,3 Zhenzhen Li,1 Shuyan Chen,1 Haixia Du,1 Lingeng Lu4 1School of Mathematics and Statistics, Zhengzhou Normal University, Zhengzhou, Henan, People’s Republic of China; 2WorldPop, School of Geography and Environmental Science, University of Southampton, Southampton, UK; 3Library, Zhengzhou University of Technology, Zhengzhou, Henan, People’s Republic of China; 4Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale University, New Haven, CT, USACorrespondence: Yongcheng Yao, School of Mathematics and Statistics, Zhengzhou Normal University, Zhengzhou, Henan, 450044, People’s Republic of China, Email 806306944@qq.comObjective: COVID-19-related lockdown can lead to mental health problem, which displays heterogeneous between individuals. The aim of this study was to explore the association between mental health, social support and psychological capital state of professional staff with different personalities during the COVID-19 pandemic in China.Methods: A cross-section study was conducted via online survey using the questionnaires of General Health Questionnaire (GHQ-12), Multidimensional Scale of Perceived Social Support (MSPSS), Psychological Capital Questionnaire (PCQ), Eysenck Personality Questionnaire-Revision Short Scale of China (EPQ-RSC). A total of 626 employees were included. Multiple regression analysis was performed to investigate the association of psychological capital, perceived social support, EPQ-N and EPQ-E and their interactions in general mental health.Results: About 2.7% of professionals had mental health. The married had a higher mental health score than the single (P

Longdong Xu,1 Tingting Guo,2 Xihua Sheng,2 Huaping Du,2 Ying Tang2 1Department of Neurology, Changshu NO.5 People’s Hospital, Changshu, Jiangsu, 215500, People’s Republic of China; 2Department of Neurology, Suzhou Ninth People’s Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, Jiangsu, 215200, People’s Republic of ChinaCorrespondence: Ying Tang; Huaping Du, Department of Neurology, Suzhou Ninth People’s Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, No. 2666, Ludang Road, Wujiang District, Suzhou, Jiangsu, 215000, People’s Republic of China, Tel +86 512-82881179 ; +86 512-82885052, Email l5850213093@126.com; duhuaping226@126.comObjective: This study aims to investigate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) in patients with idiopathic facial nerve palsy.Methods: The clinical data of patients with idiopathic facial nerve palsy were retrospectively analyzed. After three months of follow-up, patients were divided into good prognosis and poor prognosis, and the correlation between NLR, CRP and idiopathic facial nerve palsy was analyzed.Results: Negative correlation of NLR with Portmann score in idiopathic facial nerve palsy (r=− 0.788, P< 0.05); In contrast to the group with poor prognosis, patients in good prognosis group had low levels of body mass index (BMI), NLR, and C-reactive protein (CRP), and high Portmann score (P< 0.05); Multivariate logistic regression analysis showed Portmann score (OR=1.268, 95% CI (1.005– 1.616)), NLR (OR=0.262, 95% CI (0.128– 0.533)) and CRP levels (OR=0.949, 95% CI (0.895– 0.989)) were risk factors of poor prognosis for patients with idiopathic facial nerve palsy. The area under the receiver operator characteristic (ROC) curve of NLR and CRP levels in predicting poor facial nerve function was 0.764 and 0.697, the specificity was 85.5% and 75.0%, and the sensitivity was 74. 0% and 76.0%, respectively. The ROC curve of the combined diagnosis was 0.829, the specificity was 80.7%, and the sensitivity was 82.0%.Conclusion: Elevated NLR and CRP are associated with a poor prognosis of idiopathic facial nerve palsy and can serve as an indicator for clinical prognosis, and can be widely used in clinical.Keywords: idiopathic facial nerve palsy, neutrophil-to-lymphocyte ratio, C-reactive protein, predictive value

Hao Du,1 Wentao Li,1 Xueyi Li,2 Zhiyuan Qiu,1 Jie Ding,2 Yi Zhang1 1Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Cultivation and Construction Site of the State Key Laboratory of Intelligent Imaging and Interventional Medicine, Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Jie Ding; Yi Zhang, Email dingjie711@seu.edu.cn; yizhangcir@126.comBackground: Poly-L-lactic acid (PLLA) stents have broad application prospects in the treatment of cardiovascular diseases due to their excellent mechanical properties and biodegradability. However, foreign body reactions caused by stent implantation remain a bottleneck that limits the clinical application of PLLA stents. To solve this problem, the biocompatibility of PLLA stents must be urgently improved. Albumin, the most abundant inert protein in the blood, possesses the ability to modify the surface of biomaterials, mitigating foreign body reactions—a phenomenon described as the “stealth effect”. In recent years, a strategy based on albumin camouflage has become a focal point in nanomedicine delivery and tissue engineering research. Therefore, albumin surface modification is anticipated to enhance the surface biological characteristics required for vascular stents. However, the therapeutic applicability of this modification has not been fully explored.Methods: Herein, a bionic albumin (PDA-BSA) coating was constructed on the surface of PLLA by a mussel-inspired surface modification technique using polydopamine (PDA) to enhance the immobilization of bovine serum albumin (BSA).Results: Surface characterization revealed that the PDA-BSA coating was successfully constructed on the surface of PLLA materials, significantly improving their hydrophilicity. Furthermore, in vivo and in vitro studies demonstrated that this PDA-BSA coating enhanced the anticoagulant properties and pro-endothelialization effects of the PLLA material surface while inhibiting the inflammatory response and neointimal hyperplasia at the implantation site.Conclusion: These findings suggest that the PDA-BSA coating provides a multifunctional biointerface for PLLA stent materials, markedly improving their biocompatibility. Further research into the diverse applications of this coating in vascular implants is warranted. Keywords: vascular stent, Poly-L-lactic acid, albumin, biomimetic coating, stealth effect

Xiaochun Zhou,1– 3,&ast; Kaiying He,1,3,&ast; Jing Zhao,1,3 Guohua Wei,3 Qicai You,1,3 Hongxuan Du,1,3 Wenjiao Gu,1,2 Haiyu Niu,1,4 Qiaoying Jin,1,5 Jianqin Wang,3 Futian Tang1,2 1The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 2Department of Cardiovascular Disease, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 3Department of Nephrology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 4Department of Tumor, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 5Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Futian Tang, Department of Cardiovascular Disease, The Second Hospital & Clinical Medical School, Lanzhou University, No. 82, Cuiyingmen, Lanzhou, Gansu, People’s Republic of China, Tel +8613321330515, Email Tangfutian2023@126.comPurpose: To investigate the therapeutic effect and underlying mechanism of a traditional Chinese medicine (TCM) mixture consisting of Astragalus, rhubarb, and saffron in a mouse model of diabetic kidney disease (DKD).Methods: Forty-eight db/db mice received no TCM (DKD model), low-dose TCM, medium-dose TCM, or high-dose TCM, and an additional 12 db/m mice received no TCM (normal control). Intragastric TCM or saline (controls) was administered daily for 24 weeks. Blood glucose, body weight, serum creatinine (SCr), blood urea nitrogen (BUN), blood lipids, and urinary microalbumin were measured every four weeks, and the urinary albumin excretion rate (UAER) was calculated. After 24 weeks, kidney tissues were collected for transcriptome sequencing, and the main functions of these genes were determined via functional enrichment analysis.Results: Compared with the DKD model group, the medium-dose and high-dose TCM groups had significantly decreased levels of SCr, BUN, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and UAER (all p< 0.05). We identified 42 genes that potentially functioned in this therapeutic response, and the greatest effect on gene expression was in the high-dose TCM group. We also performed functional enrichment analysis to explore the potential mechanisms of action of these different genes.Conclusion: A high-dose of the Astragalus-rhubarb-saffron TCM provided the best prevention of DKD. Analysis of the kidney transcriptome suggested that this TCM mixture may prevent DKD by altering immune responses and oxygen delivery by hemoglobin.Keywords: diabetic kidney disease (DKD), mixture of astragalus, rhubarb, saffron, transcriptome sequencing, db/db mice

Xiaolan Zhang, Hongyang Du, Xiaoxiao Liu, Luyao Liu, Tingwei Zhang Department of Dermatology, The First Affiliated Hospital of JinZhou Medical University, Jinzhou, 121001, People’s Republic of ChinaCorrespondence: Xiaolan Zhang, Department of Dermatology, The First Affiliated Hospital of JinZhou Medical University, Jinzhou, 121001, People’s Republic of China, Tel +86-13840698157, Email xiaolanzhang_84@163.comPurpose: KAP studies serve to enhance health consciousness and furnish foundational data for appraising, strategizing, and enacting disease management and prejudice eradication initiatives. There remains a dearth of published studies elucidating the dimensions of knowledge, attitudes, and practices among psoriasis patients in China. To investigate the knowledge, attitudes and practices (KAP) towards psoriasis among patients and their family members in Northern China.Methods: This web-based, cross-sectional study was conducted among psoriasis patients and their family members through a self-administered questionnaire.Results: Among patients (n=260), their mean KAP scores were 9.76± 5.69 (range: 0– 19), 35.64± 11.48 (range: 14– 70), and 56.73± 10.98 (range: 16– 80), respectively. Among family members (n=237), their mean KAP scores were 11.93± 5.34 (range: 0– 19), 35.80± 4.34 (range: 8– 40), and 37.04± 4.38 (range: 8– 40), respectively. Structural equation modeling (SEM) analysis for patients indicated significant and negative path relations between knowledge and attitudes (β=− 2.271, P< 0.001), and between knowledge and practice (β=− 0.398, P< 0.001). Extended SEM analysis, which divides knowledge into K1, K2, and K3 parts, showed negative path relations between K3 and attitude (β=− 1.300, P=0.002), between attitude and practice (β=− 0.634, P< 0.001). Moreover, SEM for family members showed positive path relations between knowledge and attitude (β=1.536, P< 0.001), between attitude and practice (β=0.682, P< 0.001).Conclusion: Patients in Northern China demonstrated insufficient knowledge, negative attitude, and proactive practice, while their family members had insufficient knowledge, positive attitude, and proactive practice toward psoriasis. It is recommended to implement educational interventions addressing knowledge gaps among patients and families.Keywords: knowledge, attitude, practice, psoriasis, patients and family members, questionnaire, cross-sectional study

Huimin Du,1 Kexin Wang2 1First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang People’s Republic of China; 2Gynecology Department, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumchi, People’s Republic of ChinaCorrespondence: Huimin Du, First Affiliated Hospital of Huzhou University, 158, Square Back Road, Huzhou, Zhejiang Province, 313000, People’s Republic of China, Email huimindu@naver.com

Huimin Du,1 Tong Wu2 1Department of Otolaryngology, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang People’s Republic of China; 2Department of Otolaryngology, Xinjiang Medical University Affiliated First Hospital, Urumqi, People’s Republic of ChinaCorrespondence: Huimin Du, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, 313000, People’s Republic of China, Email huimindu@naver.com

Huimin Du,1 Tong Wu2 1Department of Otolaryngology, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang People’s Republic of China; 2Department of Otolaryngology, Xinjiang Medical University Affiliated First Hospital, Urumqi, People’s Republic of ChinaCorrespondence: Huimin Du, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, 313000, People’s Republic of China, Email huimindu@naver.com

Mengqi Wang,1,&ast; Shuting Lan,1,&ast; Wenqi Zhang,1,&ast; Qin Jin,2 Hua Du,3 Xiaomei Sun,1 Lijun He,1 Xiangyun Meng,1 Liya Su,1 Gang Liu1 1Key Laboratory of Medical Cell Biology, Department of Achievement Transformation, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gang Liu, Email 20190043@immu.edu.cnIntroduction: The anti-cancer potency of copper-doped carbon quantum dots (Cu-CDs) against breast cancer progression needs more detailed investigations.Methods: With urea and ethylene glycol applied as carbon sources and copper sulfate used as a reactive dopant, Cu-CDs were synthesized in the current study by a one-step hydrothermal synthesis method, followed by the characterization and biocompatibility evaluations of Cu-CDs. Subsequently, the anti-cancer potency of Cu-CDs against breast cancer progression was confirmed by these biochemical, molecular, and transcriptomic assessments, including viability, proliferation, migration, invasion, adhesion, clonogenicity, cell cycle distribution, apoptosis, redox homeostasis, and transcriptomic assays of MDA-MB-231 cells.Results: The biocompatibility of Cu-CDs was confirmed based on the non-significant changes in the pathological and physiological parameters in the Cu-CDs treated mice, as well as the noncytotoxic effect of Cu-CDs on normal cells. Moreover, the Cu-CDs treatments not only decreased the viability, proliferation, migration, invasion, adhesion, and clonogenicity of MDA-MB-231 cells but also induced the redox imbalance, cell cycle arrest, and apoptosis of MDA-MB-231 cells via ameliorating the mitochondrial dysfunctions and regulating the MAPK signaling pathway.Conclusion: Our findings confirmed the biosafety and excellent anti-cancer potency of Cu-CDs against breast cancer progression by tapping into mechanisms that disrupt malignant behaviors and oxidative homeostasis of breast cancer cells.Keywords: copper, carbon quantum dots, breast cancer, oxidative stress, MAPK signaling pathway

Yan Chen,1,&ast; Han Du,1,&ast; Xin Wang,1,&ast; Baixing Li,1 Xuzhuo Chen,2 Xiao Yang,1 Changqing Zhao,1 Jie Zhao1 1Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China; 2Department of Oral Surgery, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changqing Zhao; Xiao Yang, Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China, Email zhaocq9hospital@163.com; walkingweapon@outlook.comIntroduction: The crosstalk between intervertebral disc degeneration (IVDD) and type 2 diabetes mellitus (T2DM) has been investigated. However, the common mechanism underlying this phenomenon has not been clearly elucidated. This study aimed to explore the shared gene signatures of IVDD and T2DM.Methods: The expression profiles of IVDD (GSE27494) and T2DM (GSE20966) were acquired from the Gene Expression Omnibus database. Five hub genes including ANGPTL4, CCL2, CCN3, THBS2, and INHBA were preliminarily screened. GO (Gene Ontology) enrichment analysis, functional correlation analysis, immune filtration, Transcription factors (TFs)-mRNA-miRNA coregulatory network, and potential drugs prediction were performed following the identification of hub genes. RNA sequencing, in vivo and in vitro experiments on rats were further performed to validate the expression and function of the target gene.Results: Five hub genes (ANGPTL4, CCL2, CCN3, THBS2, and INHBA) were identified. GO analysis demonstrated the regulation of the immune system, extracellular matrix (ECM), and SMAD protein signal transduction. There was a strong correlation between hub genes and different functions, including lipid metabolism, mitochondrial function, and ECM degradation. The immune filtration pattern grouped by disease and the expression of hub genes showed significant changes in the immune cell composition. TFs-mRNA-miRNA co-expression networks were constructed. In addition, pepstatin showed great drug-targeting relevance based on potential drugs prediction of hub genes. ANGPTL4, a gene that mediates the inhibition of lipoprotein lipase activity, was eventually determined after hub gene screening, validation by different datasets, RNA sequencing, and experiments.Discussion: This study screened five hub genes and ANGPTL4 was eventually determined as a potential target for the regulation of the crosstalk in patients with IVDD and T2DM.Keywords: ANGPTL4, biomarker, functional analysis, intervertebral disc degeneration, type 2 diabetes mellitus

Cheng Qin, Zhiping Qi, Su Pan, Peng Xia, Weijian Kong, Bin Sun, Haorui Du, Renfeng Zhang, Longchuan Zhu, Dinghai Zhou, Xiaoyu Yang Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Xiaoyu Yang, Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, TX, 130041, People’s Republic of China, Email yangxiaoy@jlu.edu.cnAbstract: Spinal cord injury (SCI) treatment represents a major challenge in clinical practice. In recent years, the rapid development of neural tissue engineering technology has provided a new therapeutic approach for spinal cord injury repair. Implanting functionalized electroconductive hydrogels (ECH) in the injury area has been shown to promote axonal regeneration and facilitate the generation of neuronal circuits by reshaping the microenvironment of SCI. ECH not only facilitate intercellular electrical signaling but, when combined with electrical stimulation, enable the transmission of electrical signals to electroactive tissue and activate bioelectric signaling pathways, thereby promoting neural tissue repair. Therefore, the implantation of ECH into damaged tissues can effectively restore physiological functions related to electrical conduction. This article focuses on the dynamic pathophysiological changes in the SCI microenvironment and discusses the mechanisms of electrical stimulation/signal in the process of SCI repair. By examining electrical activity during nerve repair, we provide insights into the mechanisms behind electrical stimulation and signaling during SCI repair. We classify conductive biomaterials, and offer an overview of the current applications and research progress of conductive hydrogels in spinal cord repair and regeneration, aiming to provide a reference for future explorations and developments in spinal cord regeneration strategies. Keywords: neural tissue engineering, electrical stimulation, electrical signal, conductive biomaterials, spinal cord injury microenvironment

Chuqian Chen,1,&ast; Qinglu Wu,2,&ast; Junfeng Zhao,3 Guoxiang Zhao,4 Xiaoming Li,5 Hongfei Du,2 Peilian Chi6,7 1Department of Medical Humanities, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Institute of Advanced Studies in Humanities and Social Sciences, Beijing Normal University, Zhuhai, Guangdong, People’s Republic of China; 3Institute of Psychology and Behavior, Henan University, Kaifeng, Henan, People’s Republic of China; 4Department of Psychology, Henan Normal University, Xinxiang, Henan, People’s Republic of China; 5Department of Health Promotion, Education, and Behavior, University of South Carolina, Columbia, SC, USA; 6Department of Psychology, Faculty of Social Sciences, University of Macau, Macau, People’s Republic of China; 7Centre for Cognitive and Brain Sciences, University of Macau, Macau, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peilian Chi, Department of Psychology, Faculty of Social Sciences, University of Macau, Mailing: E21-3049, Macau, 999078, People’s Republic of China, Tel +853 8822-4025, Email peilianchi@um.edu.moPurpose: The study aims to understand how enacted stigma influences bereavement coping at the style (scale) level and the specific pathways at the strategy (item) level.Methods: The longitudinal data of 755 children orphaned by parental Acquired Immune Deficiency Syndrome (AIDS) in rural China were used. Grief processing and deliberate grief avoidance were measured at wave 1 (baseline) and wave 2 (one-year follow-up) to reflect bereavement coping in the contexts of being with family members, being with friends, being with community members, and being alone. Enacted stigma that measured at wave 1 was used to assess the experienced stigma of these AIDS-orphaned children. Network analyses were run following regressions.Results: Controlling for demographics and baseline-level bereavement coping, multivariate regressions revealed that enacted stigma at wave 1 significantly predicted grief processing and deliberate grief avoidance at wave 2. Network analyses showed that, for grief processing, stigma increased searching for meaning alone and with friends and expressing feelings to community members, which then provoked the same strategy across contexts. Meanwhile, stigma triggered the deliberate grief avoidance network by initially suppressing the expression of feelings to community members.Conclusion: Enacted stigma contributes to bereavement coping. Stigma stirs up complex feelings but forces AIDS-orphaned children to suppress expressions, and it increases needs to process grief through meaning making but cuts supporting forces by promoting avoidance. Interventions are imperative to reduce stigma, improve emotion regulation, and facilitate meaning making for people bereaved by stigmatized deaths.Keywords: enacted stigma, bereavement coping, AIDS, orphans, network analysis, parental loss

Lili Kang,1 Changle Li,1 Huifeng Du2 1School of Health Management, Fujian Medical University, Fuzhou, People’s Republic of China; 2School of Health Management, Inner Mongolia Medical University, Hohhot, People’s Republic of ChinaCorrespondence: Huifeng Du, School of Health Management, Inner Mongolia Medical University, Chilechuan Dairy Development Zone, Hohhot, 010110, People’s Republic of China, Email dhfeng2009_9@163.comPurpose: Medical care delay or avoidance increases morbidity and mortality risk and is costly for the national healthcare system. The objective of this study was to identify factors associated with medical care delay or avoidance among Chinese adults during the COVID-19 pandemic.Materials and Methods: A cross-sectional analysis was conducted using data from the 2020 China Family Panel Study (CFPS). The CFPS was conducted from July to December 2020 during the COVID-19 pandemic. The final sample included 4369 adults. A logistic regression model was employed to identify the factors associated with medical care delay or avoidance.Results: The empirical results indicate that regardless of rural-urban residence, older adults and adults with chronic conditions were less likely to delay or avoid medical care during the pandemic. However, individuals who had completed more than three years of college showed a higher likelihood of delaying or avoiding medical care. In urban areas, larger family sizes, greater general trust in physicians, and higher provider structural quality were associated with a decreased probability of delaying or avoiding medical care during the pandemic. In contrast, employed adults were more likely to delay or avoid medical care. In rural areas, current smokers were more likely to delay or avoid medical care during the pandemic.Conclusion: This study has identified several factors affecting medical care delay or avoidance, some of which are amenable to policy changes. Policymakers can help improve the utilization of health facilities and patient health outcomes by implementing a series of reforms.Keywords: delay or avoidance behavior, medical care, COVID-19 pandemic, China

Xinxin Yu,1 Haixin Du,1 Dongyan Li,1 Peizhen Sun,2 Shiyi Pi1 1Department of Psychology, Guangxi Normal University, Guilin, 541004, People’s Republic of China; 2Department of Psychology, Jiangsu Normal University, Xuzhou, 221116, People’s Republic of ChinaCorrespondence: Dongyan Li; Peizhen Sun, Email 15919691798@163.com; peizheng311@163.comPurpose: High school students face various pressures such as academic and interpersonal relationships, which can easily lead to depression. Social exclusion is one of the important influencing factors for adolescent depression, but there is still limited research on the mechanisms of the impact that social exclusion has on depression. Therefore, this study aimed to explore the effect of social exclusion on depression among high school students, as well as the mediating role of thwarted belongingness and the moderating role of cognitive reappraisal.Methods: Researchers assessed 1041 high school students using the Center for Epidemiologic Studies Depression Scale (CES-D), Adolescent Social Exclusion Scale, Interpersonal Needs Scale, and Emotion Regulation Scale.Results: (1) Social exclusion was negatively associated with cognitive reappraisal (r = − 0.224, p < 0.001), and positively associated with thwarted belongingness and depression (r = 0.657, 0.490, p < 0.001). Thwarted belongingness was positively associated with depression (r = 0.617, p < 0.001), and negatively associated with cognitive reappraisal (r = − 0.325, p < 0.001). Cognitive reappraisal was negatively associated with depression (r = − 0.280, p < 0.01). (2) Social exclusion could directly predict depression, 95% CI [0.08, 0.21]. Thwarted belongingness played a partial mediating role between social exclusion and depression, 95% CI [0.30, 0.40]. (3) Cognitive reappraisal moderated the predictive effect of thwarted belongingness on depression.Conclusion: Social exclusion can influence depression through thwarted belongingness and cognitive reappraisal, and educators can reduce depression by decreasing thwarted belongingness and promoting the use of cognitive reappraisal strategies by high school students.Keywords: high school students, social exclusion, thwarted belongingness, cognitive reappraisal, depression

Qinglu Wu,1 Hongjian Cao,2– 4 Hongfei Du1 1Institute of Advanced Studies in Humanities and Social Sciences, Beijing Normal University, Zhuhai, People’s Republic of China; 2Applied Psychology Program, School of Humanities and Social Science, The Chinese University of Hong Kong (Shenzhen), Shenzhen, People’s Republic of China; 3Department of Psychology, The University of Hong Kong, Hong Kong, People’s Republic of China; 4Department of Human Development & Family Science, Florida State University, Tallahassee, FL, USACorrespondence: Qinglu Wu, Email qinglu-wu@hotmail.comPurpose: The association between work stress and depressive symptoms has been well documented. More research is still needed to further investigate the underlying explanatory process mechanism and the potential protective function of personal resource in attenuating the negative effect of work stress on mental health. To address this gap and informed by the stress process model and emotion regulation theory,the present study examined the indirect role of work-related rumination and the buffering effect of self-compassion in university teachers, a population with increased vulnerabilities for both work stress and mental health issues.Methods: This study collected data from 727 university teachers (Mage = 37.65 ± 7.77 years, 61.5% women) through an online survey. Indirect effect analysis and moderation effect analysis were implemented using structural equation modeling via Mplus.Results: Work stress was directly and indirectly associated with depressive symptoms through work-related rumination, and self-compassion moderated the associations between (a) work stress and depressive symptoms and (b) work-related rumination and depressive symptoms. The direct and indirect effects of work stress on depressive symptoms were weaker in university teachers with high levels of self-compassion than in those with low levels of self-compassion.Conclusion: Work stress was associated with depressive symptoms through a cognitive pathway. The findings deepen our understanding of the link between work stress and mental health outcomes by revealing the indirect role of cognitive processes, the protective function of emotion regulation strategies, and their interplay. Reducing work-related rumination and strengthening self-compassion may constitute effective interventions to alleviate the negative effects of work stress on mental health.Keywords: work stress, work-related rumination, self-compassion, depressive symptoms, university teachers

Jing Ren,1,&ast; Qinhui Wang,1,&ast; Linna Liu,1 Yunfeng Xiao,1 Peigang Ji,2 Hui Du,3 Shan Wang,4 Yao Zheng,1 Qi Yang1 1Department of Pharmacy, the Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Neurosurgery, the Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 3Xi’an Institute for Food and Drug Control, Xi’an, Shaanxi, People’s Republic of China; 4Department of Pharmacy, NYU Langone Hospital – Long Island, Mineola, NY, USA&ast;These authors contributed equally to this workCorrespondence: Qi Yang, Tel +86 15829673096, Fax +86-029-84777154, Email 376230719@qq.comAbstract: Post-neurosurgical infections caused by multidrug-resistant Enterobacterales are difficult to treat due to limited therapeutic options. Ceftazidime-avibactam (CAZ-AVI), a combination of cephalosporin and a novel β-lactamase inhibitor, has exhibited potential activity against multi/extensive drug-resistant (MDR/XDR) gram-negative bacilli. Several reports have described the successful treatment of central infections caused by MDR/XDR Pseudomonas aeruginosa or Enterobacterales. However, data on the efficacy and effective drug distribution of CAZ-AVI in the central nervous system (CNS), particularly in children, are lacking. We report a case of a 4-year-old girl with post-neurosurgical meningitis and abscess caused by extended-spectrum β-lactamase-producing Escherichia coli successfully treated with CAZ-AVI. CAZ-AVI therapeutic drug monitoring was performed to evaluate its efficacy and effective drug distribution in the CNS. We measured CAZ (15.6, 7.1, and 3.5 μg/mL) and AVI (4.0, 2.1, and 1.2 μg/mL) in cerebrospinal fluid (CSF) samples obtained 3, 5, and 7 h after the administration of the 15th CAZ-AVI dose (2.5 g, q8h, iv), respectively. We also measured CAZ (57.0 and 25.8 μg/mL) and AVI (11.3 and 4.5 μg/mL) in serum samples obtained 3 and 5 h after the administration, respectively. CAZ-AVI achieved an adequate CSF concentration throughout the drug interval. Our case provides evidence for using CAZ-AVI to treat CNS infections.Keywords: therapeutic drug monitoring, cerebrospinal fluid, central nervous system, infection

Yicheng Wen,1,&ast; Xiaofang Xie,1,&ast; Ping Xu,2,&ast; Chengcheng Yang,1 Zhichen Zhu,1 Jie Zhu,1 Jingnan Lv,1 Haifang Zhang,1 Liang Chen,3,4 Hong Du1 1Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Clinical Laboratory, The Fifth People’s Hospital of Suzhou, Suzhou, Jiangsu, People’s Republic of China; 3Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ, USA; 4Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ, USA&ast;These authors contributed equally to this workCorrespondence: Hong Du, Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, People’s Republic of China, Email hong_du@126.comBackground: Shewanella genus, as an important carrier of resistance genes, has the potential to transmit resistance to many antimicrobials in many circumstances, especially in aquatic environment. The aim of the study was to describe the risk of Shewanella xiamenensis in hospital environment through analysis of genomic comparison and resistance status.Methods: Seven S. xiamenensis strains were isolated from hospital wastewater. PCR and Sanger sequencing were carried out for detection of common carbapenemase genes. Antimicrobial susceptibility testing was performed to determine the antimicrobial profile. Whole genome sequencing was applied, and sequences were further used for genomic analysis.Results: Seven Shewanella xiamenensis were all positive for blaNDM and blaOXA-48. Antimicrobial susceptibility testing showed all Shewanella xiamenensis were resistant to cefotaxime, ceftazidime, imipenem, meropenem, gentamycin and trimethoprim-sulfamethoxazole. Whole genome sequencing and phylogenetic analysis demonstrated the diversity of Shewanella xiamenensis despite isolating from one wastewater pool.Conclusion: To the best of our knowledge, this is the first report of detection of three types blaOXA-48-like genes in one hospital in China. And we have detected multi-drug resistant S. xiamenensis from hospital wastewater. This emphasizes that the presence of naturally existing carbapenemases in the environment may be significantly overlooked and that the blaOXA-48-like genes in China may originate through the horizontal gene transfer from S. xiamenensis to Enterobacterales rather than import from other countries.Keywords: OXA-48, NDM, Shewanella xiamenensis, hospital wastewater, reservoir, horizontal transmission, surveillance, New Delhi metallo-β-Lactamase

Zhuoyin Qiu,1,2,&ast; Tingting Guo,1,2,&ast; Xihua Sheng,1,2 Ying Tang,1,2 Huaping Du1,2 1Department of Neurology, Suzhou Ninth People’s Hospital, Suzhou, People’s Republic of China; 2Department of Neurology, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaping Du, Department of Neurology, Suzhou Ninth People’s Hospital, No. 2666, Ludang Road, Wujiang District, Suzhou, Jiangsu, 215000, People’s Republic of China, Tel +86 512-82885052, Email duhuaping226@126.comPurpose: This study aims to investigate the prognostic value of the peripheral neutrophil-to-lymphocyte ratio (NLR) in patients with chronic internal carotid artery occlusion (CICAO) complicated by cerebral infarction.Patients and Methods: The clinical data of 99 CICAO patients complicated by cerebral infarction were retrospectively analyzed. The modified Rankin Scale (mRS) was used to assess their 3-month prognosis, and a multivariate logistic regression model was established to explore risk factors for poor prognosis.Results: Multivariate logistic regression analysis demonstrated that NLR (OR=2.114; 95% CI: 1.129– 3.959) and baseline National Institute of Health Stroke Scale (NIHSS; OR=1.288, 95% CI: 1.053– 1.574) score were risk factors of poor prognosis. The area under the receiver operator characteristic (ROC) curve of NLR in predicting the 3-month outcome after onset was 0.717 (95% CI: 0.606– 0.828, P< 0.000). The optimal cut-off value was 3.22, with a sensitivity of 0.743 and a specificity of 0.791.Conclusion: NLR is an independent risk factor for the poor prognosis of CICAO patients complicated by cerebral infarction and can serve as an indicator for clinical prognosis.Keywords: chronic internal carotid artery occlusion, cerebral infarction, neutrophil-to-lymphocyte ratio, prognosis, predictive factors

Ruijia Liu,1,2,&ast; Xu Cao,1,2,&ast; Yijun Liang,1,2 Xiaobin Li,1 Qian Jin,1 Ying Li,3 Hongbo Du,1,2 Xiaobin Zao,1,4 Yong’an Ye1,2 1Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Institute of Liver Diseases, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong’an Ye; Xiaobin Zao, Email yeyongan@vip.163.com; A3417@bucm.edu.cnBackground: Hepatocellular carcinoma (HCC) is one of the most malignant tumors worldwide. The ST6 β-galactoside α-2, 6-sialyltransferase 1 (ST6GAL1) has been found aberrantly expressed in a variety of cancers including HCC, but its function and mechanism in regulating liver inflammation remain to be investigated. This study aimed to explore the role of ST6GAL1 in HCC. The data of ST6GAL1 expression, prognosis, and clinical parameters were collected and further analyzed from the public databases including The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), and Gene Expression Omnibus (GEO). The HCC rat model was constructed by intraperitoneal injection of diethylnitrosamine. The mRNA and protein expression levels of ST6GAL1 in rat liver tissues were detected by real-time quantitative polymerase chain reaction, capillary electrophoresis, and Western blot.Results: The ST6GAL1 mRNA and protein expression levels were both lower in HCC tissues compared with normal liver tissues in the public databases and HCC rat model. The survival analysis showed that upregulation of ST6GAL1 was an independent prognostic factor for good prognosis in HCC patients. The ST6GAL1 mRNA expression showed a negative correlation with ST6GAL1 methylation levels. Enrichment analysis showed that ST6GAL1 expression was most associated with metabolic, cancer, estrogen, axon guidance, cAMP, and PI3K-AKT signaling pathways. The ST6GAL1 mRNA expression negatively correlated with liver inflammation status and proportion of NK CD56bright, NK CD56dim, pDC, and CD8+ T cells in liver.Conclusion: Compared with normal tissues, ST6GAL1 was lower expressed in HCC tumor tissues, and the downregulation of ST6GAL1 was associated with a poor prognosis in HCC patients. ST6GAL1 could further affect the infiltration of immune cells to exert anti-inflammation function in liver. Our study indicated that ST6GAL1 could be a potential biomarker and therapeutic target to assess the prognosis and regulate the immune cells infiltration level of HCC.Keywords: hepatocellular carcinoma, ST6GAL1, prognosis, immune infiltration, biomarker

Feng Gu,1,2,&ast; Shan Hu,3,&ast; Yunjian Wu,4,&ast; Changyu Wu,4 Ying Yang,5 Bing Gu,6 Hong Du1 1Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People’s Republic of China; 2Department of Laboratory Medicine, Xuzhou Central Hospital, Xuzhou, 221000, People’s Republic of China; 3Department of Laboratory Medicine, Xuzhou Tumor Hospital, Xuzhou, 221005, People’s Republic of China; 4School of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 5Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing, 100850, People’s Republic of China; 6Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Du; Ying Yang, Email hong_du@126.com; y_ying_77@163.comPurpose: Candida infection has a high mortality rate, and the increasing prevalence of non-Candida albicans drug resistance in recent years poses a potential threat to human health. Non-Candida albicans has long culture cycles, and its firm cell walls making it difficult to isolate DNA for sequencing.Materials and Methods: Fe3O4@PEI (PEI, polyvinyl imine) was mixed with clinical samples to form Fe3O4@PEI@non-Candida albicans and enriched them with magnets. Triangular silver nanoplates enhanced the surface-enhanced Raman scattering (SERS) signal. SERS was used to detect the fingerprint spectrum of non-Candida albicans. Then, orthogonal partial least squares discriminant analysis (OPLS-DA) was used to analyze the drug resistance of non-Candida albicans.Results: SERS combined with OPLS-DA could well analyze the drug resistance of non-Candida albicans. Through 10-fold-cross validation, the accuracy of training and test data is greater than 99%, indicating that the model has good classification ability. We used SERS for the first time to detect the drug resistance of non-Candida albicans directly.Conclusion: This approach can be utilized without causing damage to the cell wall and can be accomplished in as little as 90 minutes. It can provide timely guidance for the treatment of patients with good clinical application potential.Keywords: non-Candida albicans, SERS, drug resistance, OPLS-DA

Keli Wen, Hu Du, Binfei Tang, Bin Xiong, An Zhang,&ast; Pengfei Wang&ast; Department of Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: An Zhang; Pengfei Wang, Department of Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Road, Yuzhong District, Chongqing, 400010, People’s Republic of China, Tel +86 23-63693452, Email zhangan@Hospital.cqmu.edu.cn; 13436027816@163.comPurpose: The purpose of our study was to explore the prognostic value of complete blood count and myocardial markers combination with Sequential Organ Failure Assessment (SOFA) score in predicting the 28-day mortality among sepsis patients.Patients and methods: A retrospective observational cohort study was performed. Three hundred and nineteen sepsis patients who were hospitalized at the Second Affiliated Hospital of Chongqing Medical University, China, from January 2019 to September 2021 were included. The clinical and laboratory data, the Acute Physiological and Chronic Health Evaluation II (APACHE II) score and SOFA score at the time of the initial sepsis diagnosis were collected, and the predictive values of the single and combination variables for 28-day mortality were compared.Results: The derivation cohort consisted of 221 patients and included 59 (26.7%) died. The area under the curve (AUC) [95% confidence interval (CI)] of RDW and cTnT were 0.735 (0.663– 0.807) and 0.753 (0.678– 0.827) for mortality, and the cut-off value were 14.05% and 0.039 ng/mL, respectively. The combination of RDW, cTnT and the SOFA score showed a better performance for the prediction of mortality, and the AUC was significantly higher than that of the SOFA score (0.791 vs 0.726, DeLong test: P=0.032). Multivariate Cox analysis identified that the combination of RDW, cTnT and the SOFA score (HR=6.133, P=0.004) and APACHE II score (HR=1.093, P< 0.001) were independent detrimental factors for 28-day mortality. The validation cohort consisted of 98 patients and included 23 (23.5%) died. Similarly, the AUC of the RDW, cTnT and the SOFA score combination is significantly higher than that of the SOFA score (0.821 vs 0.739, DeLong test: P=0.035).Conclusion: RDW and cTnT showed good performance in predicting 28-day mortality rates among patients with sepsis. Combined RDW and cTnT with the SOFA score can significantly improve the predictive value of SOFA score for the prognosis of sepsis.Keywords: sepsis, septic shock, Sequential Organ Failure Assessment score, red blood cell distribution width, cardiac troponin T, marker

Meiyue Dong,1,* Haitao Du,2,* Xueling Li,2 Ling Zhang,2 Xiaoming Wang,3,4 Zhenguo Wang,4 Haiqiang Jiang1,4,5 1Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, People’s Republic of China; 2School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People’s Republic of China; 3Experimental Centre, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People’s Republic of China; 4Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic research, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People’s Republic of China; 5Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenguo Wang; Haiqiang Jiang, Email zhenguow@126.com; jhq12723@163.comBackground: Agarwood, as a traditional Chinese medicine, has great potential value for the treatment of tranquilization. However, its potential mechanisms and biomarkers are still unclear.Methods: In this study, ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS)-based metabonomics was adopted to discover the potential biomarkers in mice after agarwood incense smoke (AIS) intervention. Furthermore, the chemical components in agarwood were identified based on UHPLC-Q-Exactive Orbitrap-MS. The global view of potential compound-target-pathway (C-T-B) network was constructed through network pharmacology to understand the potentially material basis of biomarkers.Results: Metabolic profiling indicated that the metabolic changed significantly in mice serum after AIS intervention. A total of 18 potential biomarkers closely related to insomnia and emotional disease were identified, mainly involving in tryptophan metabolism, arginine and proline metabolism, cysteine and methionine metabolism and steroid hormone biosynthesis pathways. A total of 138 components in agarwood were identified based on UHPLC-Q-Exactive Orbitrap-MS. The results showed that mainly compounds such as flidersia type 2-(2-phenylethyl) chromones (FTPECs) and sesquiterpenes exerted good docking abilities with key target proteins, which were involved in multiple diseases including depression and hypnosis.Conclusion: In conclusion, this study enhanced current understanding of the change of metabolic markers after AIS intervention. Meanwhile, it also confirmed the feasibility of combining metabolomics and network pharmacology to identify active components and elucidate the material basis of biomarkers and mechanisms.Keywords: agarwood, biomarkers, metabolomics, chemical constituents, network pharmacology

Chao Jiang,1,2,&ast; Si Yin,1,&ast; Jianmin Wei,3,&ast; Weigong Zhao,1 Xiaohui Wang,1,2 Yongyuan Zhang,1,2 Dingjun Hao,2 Heng Du1 1Department of Orthopaedics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Spine Surgery, Baoji City Hospital of Traditional Chinese Medicine, Baoji, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Heng DuDepartment of Orthopaedics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaEmail drdu18@126.comObjective: The purpose of this study was to introduce and evaluate the early clinical outcomes of the full-endoscopic posterior lumbar interbody fusion (Endo-PLIF) technique with epidural anesthesia (EA) for single-segment lumbar degenerative diseases.Methods: In this retrospective case series study, we explored the feasibility and effectiveness of the Endo-PLIF with EA for single-segment lumbar degenerative diseases. Between March 2018 and January 2019, a series of 24 patients with single-segment lumbar degenerative diseases underwent Endo-PLIF surgery and were followed up for a minimum of 12 months (15.21± 2.27 months). Clinical outcomes including visual analog scale (VAS) scores for back and leg pain, Oswestry Disability Index (ODI) scores, and the Short Form-36 health survey questionnaire (SF-36) were evaluated preoperatively, and postoperatively at 3 days and at 3, 6, and 12-months.Results: All patients underwent successful single-segment Endo-PLIF surgery. The mean operation time was 209.17± 39.49 min, and average amount of bleeding was 43.33± 14.87 mL. The VAS for lower extremity pain and back pain significantly improved at 3 days, and at 3, 6, 12 months compared with preoperative, respectively. The ODI scores decreased from 42.04± 3.96 to 12.75± 2.71 (P< 0.001) at preoperative and 12 months postoperatively, respectively. The SF-36 Physical Component Scores (PCS) improved from 34.96± 4.63 preoperatively to 52.08± 6.05 (P< 0.001) at 12 months postoperatively. Additionally, the SF-36 Mental Component Scores (MCS) improved from 39.38± 5.70 at preoperative to 53.13± 5.97 (P< 0.001) at 12 months postoperatively. Two patients experienced dysesthesia, and one patient had a wound infection.Conclusion: Endo-PLIF with EA is a feasible and valuable technique for the treatment of single-segment lumbar degenerative diseases in selected patients.Keywords: full-endoscopic posterior lumbar interbody fusion, lumbar degenerative disease, lumbar fusion, clinical outcome

Huahua Du,1 Li Liang,1 Jiahui Li,1 Qingqing Xiong,1 Xin Yu,2 Hong Yu3 1MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Science, Zhejiang University, Zhejiang, 310058, People’s Republic of China; 2Department of Anesthesia, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Zhejiang, 310016, People’s Republic of China; 3Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Zhejiang, 310016, People’s Republic of ChinaCorrespondence: Hong YuDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Zhejiang, 310016, People’s Republic of ChinaTel +86-571-86044817Fax +86-571-86090063Email blueyu000@zju.edu.cnPurpose: Lipocalin-2 (Lcn2) is an acute-phase protein and elevated in several inflammatory diseases. This study aimed to determine whether Lcn2 alleviates inflammation and explore the underlying cellular mechanisms.Methods: C57BL/6 Lcn2-deficient (Lcn2−/-) male mice were intraperitoneally injected with lipopolysaccharide (LPS) to build systemic inflammation model. The inflammatory processes were investigated. The morphology of villi was measured by scanning electron microscopy (SEM). The levels of inflammatory factors were detected by ELISA and qPCR analysis. The production of Lcn2 was determined with immunofluorescence staining by confocal microscope. The molecular mechanism of Lcn2 in bone marrow-derived macrophages (BMDMs) was analyzed by mass spectrometry (MS)-based quantitative proteomic analysis.Results: Compared to wild-type (WT) mice injected with LPS, Lcn2−/- mice injected with LPS showed increased inflammatory damage in jejunum and ileum, and significantly elevated the levels of multiple pro-inflammatory cytokines. After determining that Lcn2 was mainly located in the cytoplasm of macrophages, we isolated BMDMs from Lcn2−/- mice to evaluate their function. During LPS challenge, transcripts of pro-inflammatory cytokines were all significantly increased in BMDMs from Lcn2−/- mice, while those of anti-inflammatory cytokines were significantly decreased when compared with the cytokines in BMDMs from WT mice. A label-free relative quantitation proteomics analysis showed that LPS-treated BMDMs from Lcn2−/- mice had elevated levels of pro-inflammatory pathways, but reduced phagocytosis and autophagy when compared with LPS-treated BMDMs from WT mice.Conclusion: These findings demonstrated that Lcn2 was a potent protective factor in response to systemic inflammation and might be an indispensable factor for macrophage functions.Keywords: Lcn2, systemic inflammation, macrophages, BMDMs

Di Niu,1,2,* Liang Li,3,* Hexi Du,1,2 Haoqiang Shi,1,2 Jun Zhou,1,2 Sheng Tai,1,2 Hanjiang Xu,1,2 Wei Chen,1,2 Cheng Yang,1,2 Chaozhao Liang1,2 1Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Institute of Urology and Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cheng Yang; Chaozhao LiangDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, ChinaTel +86-18010865815; +86-13505604595Email chengyang_md@163.com; liang_chaozhao@ahmu.edu.cnPurpose: To investigate feasibility, repeatability and usefulness of contrast-enhanced ultrasonography (CEUS) in the assessment of kidney wound recovery after laparoscopic nephron-sparing surgery (LNSS) or robot-assisted nephron-sparing surgery (RANSS) and preliminarily research the clinical factors associated with the length of extravasation (LOE).Patients and Methods: From April 2019 to January 2020, 130 patients that underwent LNSS or RANSS in our hospital were included, and 90 patients (90/130) received CEUS examinations each one day from the postoperative day 1. The discovery of the cessation of contrast medium extravasation from the renal wound was the primary endpoint named “ultrasonic healing”, and LOE ranged from the day of surgery to “ultrasonic healing”. Patient, tumor, perioperative factors and LOE were collected. Univariate analysis and multivariate linear regression analysis were applied for the determination of factors associated with LOE.Results: The average postoperative LOE was 1.76 days (standard deviation, 1.115; 95% confidence interval: 1.52– 1.99). Ultrasonic healing within three days was observed in 95.6% patients (86/90). Univariable and multivariable analyses showed that R and A components in R.E.N.A.L. nephrometry score were associated with LOE. Anterior location and R component score of 2 (tumor size> 4cm) were related to longer LOE than posterior location and R score of 1 (tumor size< 4cm). The incidence of complications in patients with LOE over one day was higher than those with LOE of one day.Conclusion: CEUS was feasible, repeatable and useful in the assessment of kidney wound recovery. Tumor size and location were related to LOE after minimally invasive nephron-sparing surgery (MINSS). Length of stay after MINSS within three days might be relatively safe.Keywords: nephron-sparing surgery, minimally invasive, CEUS, wound healing

Xiangtian Ling,1 Xinqi Ma,1 Xielan Kuang,1 Yuxiu Zou,1 Han Zhang,1 Han Tang,1 Han Du,1 Binbin Zhu,1 Hao Huang,1 Qing Xia,1 Minghao Chen,1 Danyi Mao,1 Dongli Chen,1 Huangxuan Shen,1,2 Jianhua Yan1 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, People’s Republic of China; 2Biobank of Eye, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, People’s Republic of ChinaCorrespondence: Huangxuan Shen; Jianhua YanZhongshan Ophthalmic Center, Sun Yat-Sen University, 54 Xianlie Road, Guangzhou, 510060, People’s Republic of ChinaTel +8620-8733-5261; +8620-8733-0484Fax +8620-8733-3271Email shenhx@mail.sysu.edu.cn; yanjh2011@126.comPurpose: To assess the cellular and molecular effects of lidocaine on muscles/myoblasts.Methods: Cultured myogenic precursor (C2C12) cells were treated with varying concentrations of lidocaine.Results: Cell viability of C2C12 cells was inhibited by lidocaine in a concentration-dependent manner, with concentrations ≥ 0.08%, producing a dramatic reduction in cell viability. These ≥ 0.08% concentrations of lidocaine arrested cell cycles of C2C12 cells in the G0/G1 phase. Moreover, lidocaine inhibited cell migration and myogenic processes in C2C12 cells at low concentrations. Results from QRT-PCR assays revealed that following treatment with lidocaine, Notch1, Notch2, Hes1, Csl and Dll4 all showed higher levels of expression, while no changes were observed in Mmal1, Hey1, Dll1 and Jag1.Conclusion: This work provides the first description of the effects of lidocaine upon the regeneration of muscles and maintenance of satellite cells at the cellular and molecular levels. In specific, we found that the Dll4-Notch-Csl-Hes1 axis was up-regulated suggesting that the Notch signaling pathway was involved in producing these effects of lidocaine. These findings provide a new and important foundation for future investigations into the effects of drug therapies in muscle diseases.Keywords: local anesthetics, C2C12 cells, myogenic differentiation, strabismus, Notch signaling pathway

Wang W, Nie W, Liu D, et al. Int J Nanomedicine. 2018;13:7003–7018. The authors have advised the representative image of the migratory HVSMCs for the TCP (Figure 13A) and PLLA/PLGA/PCL scaffold (Figure 13B) on Page 7017 were overlapped. Following a review of the original images, the authors found different sets of images were mixed when processing the data which resulted in the incorrect image to be used for PLLA/PLGA/PCL (Figure 13B). The correct Figure 13 is shown below. Figure 13 (A–D) The representative image of the migratory HVSMCs located on the lower site of Transwell membrane for the TCP, PLLA/PLGA/PCL, PLLA/PLGA/PCL-Heparin, and PLLA/PLGA/PCL-PDGF-BB scaffolds, respectively. (E) The quantification of HVSMCs migration. Abbreviations: HVSMCs, human vascular smooth muscle cells; PCL, poly(ε-caprolactone); PDGF-BB, platelet-derived growth factor-BB; PLGA, poly(lactic-co-glycolic acid); PLLA, poly(L-lactic acid); TCP, tissue culture plate. Notes: *PP

Zhonglun Chen, Mouxiao Su, Zhaokun Li, Hongcai Du, Shanshan Zhang, Mingjun Pu, Yun Zhang Department of Neurology, MianYang Central Hospital, Mianyang, Sichuan 621000, People’s Republic of ChinaCorrespondence: Yun ZhangDepartment of Neurology, Mianyang Central Hospital, 12 Changjia Alley, Mianyang, Sichuan Province 621000, People’s Republic of ChinaTel/ Fax +86 816-2246359Email zhangyun_neuro@126.comBackground and Aims: The metabolic syndrome (MetS) is believed to contribute to a higher probability of developing cardiovascular diseases. This study aimed to investigate whether MetS could predict the prognosis in ischemic stroke patients after endovascular thrombectomy (EVT).Methods: Between January 2016 and September 2019, patients treated with EVT due to large vessel occlusions in anterior circulation were prospectively recruited. MetS was defined using the International Diabetes Federation criteria after admission. The primary outcome was a 3-month poor outcome (modified Rankin scale score of 3– 6). Secondary outcomes included symptomatic intracranial hemorrhage (sICH) and mortality at 3 months. Multivariable logistic regression models were used to assess the relationship between MetS and clinical outcomes.Results: A total of 248 patients were enrolled (mean age, 66.7 years; 37.5% female) and 114 (46.0%) met with the MetS criteria. The median National Institutes of Health Stroke Scale score was 15.0. There were 131 (52.8%) patients achieving the poor outcome at 3 months, among which 26 (10.5%) patients developed sICH. The mortality at 3 months was 19.0% (47/248). In multivariable analysis, MetS was significantly correlated to poor outcome (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.29– 4.78, P = 0.014). The risk for poor outcome was positively associated with the increased number of MetS components (OR 1.78; 95% CI 1.39– 2.35, P = 0.001). No significant findings were found in the association of MetS with sICH and mortality.Conclusion: Our data demonstrated that MetS was associated with poor prognosis in acute ischemic patients treated with EVT.Keywords: metabolic syndrome, ischemic stroke, endovascular thrombectomy, prognosis

Bin Yan,1 Hanzhi Du,2 Juan Zhao,2 Di Wu,2 Jie Wang,2 Guang Yang,3 Mengchang Wang2 1Department of Clinical Research Centre, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Hematology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of ChinaCorrespondence: Mengchang Wang Department of HematologyThe First Affiliated Hospital of Xi’an Jiaotong University, No. 277, Yanta West Road, Xi’an 710061, People’s Republic of ChinaTel +86 13772196075Email swallow3956@sina.comBackground: Previous studies have found that neck circumference (NC) is associated with cardiovascular disease risk factors. This study investigated the relationship between NC and the incidence of angina pectoris (AP).Methods: Altogether 4821 participants (2212 males and 2609 females) from the Sleep Heart Health Study (SHHS) with a mean age of 63.4± 11.0 years were selected in this study. Anthropometric measurements, including NC, waist circumference (WC), hip circumference (HC), and body mass index (BMI), were collected at baseline. AP was defined as the first occurrence between baseline and 2011. Linear and logistic regression analysis was used to explore the association between NC and incidences of AP.Results: There was a significant difference in NC between AP and controls in both male (41.1± 3.1 cm vs 40.3± 3.2 cm; p< 0.001) and female (35.2± 3.1 cm vs 34.9± 2.9 cm; p=0.006). Multivariable linear regression analysis showed that NC (every cm increase) was independently associated with the incidence of AP in both male (odds ratio [OR] 1.067; 95% confidence interval [CI] 1.035– 1.100; p< 0.001) and female (OR 1.067; 95% CI 1.035– 1.101; p< 0.001).Conclusion: NC was significantly associated with the incidence of AP in both male and female. The role of NC in the incidence of AP is worthy of further investigation.Keywords: angina pectoris, neck circumference, SHHS, obesity, community-based population

Fangbin Song,1,2 Hui Du,1,2 Aimin Xiao,1,2 Chun Wang,1,2 Xia Huang,1,2 Peisha Yan,1,2 Zhihong Liu,1,2 Xinfeng Qu,3 Jerome L Belinson,4,5 Ruifang Wu1,2 1Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Shenzhen Key Laboratory on Technology for Early Diagnosis of Major Gynecological Diseases, Shenzhen, People’s Republic of China; 3Sanming Project of Medicine in Shenzhen, Peking University Shenzhen Hospital, Shenzen, People’s Republic of China; 4Preventive Oncology International, Inc., Cleveland Heights, OH, USA; 5Gynecologic Oncology Division, Women’s Health Institute, Cleveland Clinic, Cleveland, OH,USACorrespondence: Ruifang Wu; Hui DuDepartment of Obstetrics and Gynecology, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Shenzhen, Guangdong 518036, People’s Republic of ChinaEmail wurfpush@126.com; duhui_107108@163.comPurpose: When used for cervical cancer primary screening, liquid-based cytology (LBC) has a high specificity but a low sensitivity. For histological diagnosis of high-grade lesions, p16INK4a immunostaining has proven to be useful. Therefore, our objective was to evaluate the use of p16INK4a immuno-cytology as a primary screen and a secondary screen after primary high-risk human papillomavirus (hrHPV) screening or LBC screening.Methods: A total of 1197 cytology slides were immuno-stained using automatic p16INK4a staining system (PathCIN®p16INK4a) in two studies from cervical screening programs. In the primary screening study, 875 slides were randomly selected and analyzed for p16INK4a. In the secondary screening study, 322 of the remaining slides were chosen by virtue of being HPV 16/18+, other hrHPV+/LBC≥ASC-US, or HPV-negative/LBC ≥LSIL. The sensitivity and specificity for detection of cervical intraepithelial neoplasia 2/3 or worse (CIN2+/CIN3+) were compared based on p16INK4a, LBC and HPV test results.Results: In combining two studies, there were 431 cases with biopsy pathology. They included 83 cases with CIN2+ and 41 cases with CIN3+. The p16 positivity rate increased with pathologic and cytologic severity (P< 0.0001). For primary screening: p16 immuno-cytology was more specific than HPV testing and was similar in sensitivity. Also, p16 immuno-cytology compared favorably with routine LBC (≥ASC-US or ≥LSIL) in sensitivity and specificity. For secondary screening: after LBC screening, “Triaging ASC-US with p16” gave a higher specificity and a similar sensitivity as compared to the “Triaging ASC-US with hrHPV” algorithm. After HPV primary screening, p16 immuno-cytology was more specific than LBC (≥ASC-US); the calculated colposcopy referral rate was also decreased by using p16 immuno-cytology as triage. Triage of “HPV16/18 and p16” had higher specificity and similar sensitivity as compared to triage of “HPV16/18 and LBC ≥ASC-US”.Conclusion: For primary screening, p16INK4a immuno-cytology compares favorably to routine LBC and HPV testing. p16INK4a immunostaining could be an efficient triage to reduce the colposcopy referral rate after primary hrHPV screening or LBC screening. Therefore, p16INK4a immuno-cytology may be applicable as a favorable technology for cervical cancer screening.Keywords: cervical intraepithelial neoplasia, human papillomavirus, p16, immunochemical staining, cervical cancer screening

Mengshi Xu,1,* Liang Xu,2,* Huaping Du,1 Wanying Shan,1 Jie Feng,1 Guojie Zhai,1 Xiuyan Yang1 1Department of Neurology, Suzhou Ninth People’s Hospital, Suzhou, Jiangsu 215200, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiuyan Yang; Guojie Zhai Email yangxiuyan335@163.com; 125461985@qq.comBackground and Aims: Decreased serum retinoic acid (RA) levels have been shown to be linked with increased mortality in cardiovascular diseases. This study aimed to investigate the relationship between serum RA and 3-month functional outcome after ischemic stroke.Methods: Between January 2019 and September 2019, we prospectively recruited ischemic stroke patients within 24 hrs of symptom onset. Serum RA levels were measured for all patients at admission. The primary outcome was defined as poor functional outcome (modified Rankin Scale 3– 6) at 90 days. The secondary outcome was defined as early neurological deterioration (END), which is considered as an increase of ≥ 1 point in motor power or total National Institutes of Health Stroke Scale score of ≥ 2 points within 7 days.Results: A total of 217 patients were included in the analysis. The median RA levels were 2.9 ng/mL. Ninety-four (43.3%) and 65 (30.0%) patients experienced 3-month poor outcome and END, respectively. After adjusted for potential confounders, decreased levels of serum RA were associated with a higher risk of poor outcome (P for trend = 0.001) and END (P for trend = 0.002). Adding RA quartile to the existing risk factors improved risk prediction for poor outcome [net reclassification improvement (NRI) = 42.6%, P = 0.001; integrated discrimination improvement (IDI) = 5.7%, P = 0.001] and END (NRI index = 45.4%, P = 0.001; IDI = 4.3%; P = 0.005).Conclusion: Low serum RA levels at baseline were associated with poor prognosis at 90 days after ischemic stroke, suggesting that RA may be a potential prognostic biomarker for ischemic stroke.Keywords: acute ischemic stroke, retinoic acid, early neurological deterioration, functional outcome

Mei-ling Wu, Yi-ping Lin, Yan-li Wei, Hong-jian Du, Xiao-qian Ying, Wen-zhuang Tan, Bi-e Tang Faculty of Medicine, Jinhua Polytechnic, Zhejiang, People’s Republic of ChinaCorrespondence: Bi-e TangFaculty of Medicine, Jinhua Polytechnic, No. 1188 Wuzhou Street, Jinhua City, Zhejiang Provinc, People’s Republic of ChinaEmail tangbiejh@163.comBackground: Calycosin (CAL), a type of O-methylated isoflavone extracted from the herb Astralagusmembranaceus (AM), is a bioactive chemical with antioxidative, antiphlogistic and antineoplastic activities commonly used in traditional alternative Chinese medicine. AM has been shown to confer health benefits as an adjuvant in the treatment of a variety of diseases.Aim: The main objective of this study was to determine whether CAL influences the cytochrome P450 (CYP450) system involved in drug metabolism.Methods: Midazolam, tolbutamide, omeprazole, metoprolol and phenacetin were selected as probe drugs. Rats were randomly divided into three groups, specifically, 5% Carboxymethyl cellulose (CMC) for 8 days (Control), 5% CMC for 7 days + CAL for 1 day (single CAL) and CAL for 8 days (conc CAL), and metabolism of the five probe drugs evaluated using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).Results: No significant differences were observed for omeprazole and midazolam, compared to the control group. Tmax and t1/2 values of only one probe drug, phenacetin, in the conc CAL group were significantly different from those of the control group (Tmax h: 0.50± 0.00 vs 0.23± 0.15; control vs conc CAL). Cmax of tolbutamide was decreased about two-fold in the conc CAL treatment group (conc vs control: 219.48 vs 429.56, P< 0.001).Conclusion: Calycosin inhibits the catalytic activities of CYP1A2, CYP2D6 and CYP2C9. Accordingly, we recommend caution, particularly when combining CAL as a modality therapy with drugs metabolized by CYP1A2, CYP2D6 and CYP2C9, to reduce the potential risks of drug accumulation or ineffective treatment.Keywords: calycosin, herb-drug interactions, UPLC-MS/MS, cocktail, CYP450

Lin Wang,1,2 Xianzi Wen,1 Fengming Luan,1 Tao Fu,2 Chao Gao,2 Hong Du,1 Ting Guo,1 Jing Han,1 Longtao Huangfu,1 Xiaojing Cheng,1 Jiafu Ji1,21Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 2Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of ChinaCorrespondence: Xiaojing ChengKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of ChinaTel +86 108 819 6760Email chengli@bjmu.edu.cnJiafu JiKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of ChinaTel +86 108 819 6048Email jijiafu@hsc.pku.edu.cnPurpose: Eukaryotic translation initiation factor (EIF) plays a vital role in protein synthesis. EIF3B is a core subunit of the EIF3 family, and is overexpressed in many tumors. EIF3B is associated with an unfavorable prognosis, as well as the genesis and development of tumors. However, the potential role of EIF3B in gastric cancer (GC) remains unknown. In the current study, we explored the clinical significance and the possible mechanism of EIF3B in the progression of GC.Methods: EIF3B expression was analyzed in 78 GC tissue samples through quantitative PCR and in 94 GC tissue samples through immunohistochemistry (IHC) staining. The correlation between EIF3B and clinicopathological features was analyzed in GC tissues. The role of EIF3B in GC progression was investigated through in vitro and in vivo assays.Results: EIF3B expression was upregulated in GC tissues (73.4%, IHC). High expression of EIF3B was significantly correlated with the depth of tumor invasion, lymph node metastasis and TNM stage (P=0.000, 0.000 and 0.000, respectively). Multivariate analysis indicated that GC patients with high EIF3B expression suffered a poorer 5-year survival. EIF3B promoted GC cell proliferation and was strongly associated with proliferating cell nuclear antigen (PCNA) expression in GC samples (P=0.009). It also enhanced tumor cell migration and invasion, which were affected through epithelial-mesenchymal transition (EMT) and the Stat3 signaling pathway. Knockdown of EIF3B in GC cells suppressed the growth of xenograft tumors and lung metastatic colonization in vivo. Furthermore, gene set enrichment analysis (GSEA) and Western blot results demonstrated that EIF3B activated the PI3K/AKT/mTOR signaling pathway.Conclusion: Our results suggest that EIF3B plays an oncogenic role in GC progression and serves as an independent prognostic factor for GC patients.Keywords: EIF3B, gastric cancer, prognosis, PI3K/AKT/mTOR pathway

Meng-Lin Nie,1 Jing Han,1 Han-Chen Huang,2,3 Ting Guo,1 Long-Tao Huangfu,1 Xiao-Jing Cheng,1 Xiao-Mei Li,1 Hong Du,1 Qing-Da Li,1 Xian-Zi Wen,1 Jia-Fu Ji1,41Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 2Key Laboratory of RNA Biology, Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People’s Republic of China; 3Centre for Cognitive Machines and Computational Health (CMaCH), The School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Gastrointestinal Surgery, Peking University Cancer Hospital, Beijing, People’s Republic of ChinaPurpose: Emerging evidence has shown that long noncoding RNAs (lncRNAs) participate in oncogenesis and tumor progression. We previously found a novel lncRNA p4516 which was closely associated with prognosis by preliminary study of lncRNA expression profile from paired tumors and nontumor tissues in 198 gastric cancer (GC) patients. However, the exact biological functions and the underlying molecular mechanisms of p4516 in gastric tumorigenesis still remain unclear.Materials and methods: The RNA fluorescence in situ hybridization (RNA-FISH) analysis, cytoplasmic and nuclear RNA isolation and qRT-PCR were applied to determine the subcellular localization of p4516. Expression levels of p4516 were assessed using qRT-PCR in both GC cell lines and in 142 primary GC tissues. Correlations between p4516 expression and GC patients’ clinicopathological parameters were analyzed. Gain- and loss-of-function experiments were employed to investigate the role of p4516 in proliferation, migration and invasion both in vitro and in vivo. In addition, Western blotting and immunohistochemical staining were used to examine the protein expression levels.Results: LncRNA p4516 was mainly localized in the nucleus of GC cells and p4516 tended to have higher expression levels in GC cells compared to the normal gastric mucosa-derived cells GES-1. Furthermore, higher expression levels of p4516 correlated with worse clinical outcomes in GC patients and acted as an independent prognostic biomarker. Functional analysis revealed that p4516 participated in the regulation of GC cell proliferation, invasion and migration both in vivo and in vitro. Moreover, p4516 was involved in epithelial–mesenchymal transition (EMT) in GC cells.Conclusion: Our study demonstrated the oncogenic role of novel lncRNA p4516 in the gastric carcinogenesis for the first time. High expression of p4516 may act as prognostic marker in patient with gastric cancer.Keywords: LncRNA, p4516, Gastric cancer, EMT

Weizhong Wang,1 Wei Nie,1 Dinghua Liu,1 Haibo Du,1 Xiaojun Zhou,1 Liang Chen,1 Hongsheng Wang,1 Xiumei Mo,1 Lei Li,2 Chuanglong He1 1Key Laboratory of Science & Technology of Eco-Textiles, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China; 2Department of Gastroenterology, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China Introduction: The fast degradation of vascular graft and the infiltration of smooth muscle cells (SMCs) into the vascular graft are considered to be critical for the regeneration of functional neo-vessels. In our previous study, a novel dual phase separation technique was developed to one-pot prepare macroporous nanofibrous poly(l-lactic acid) (PLLA)/poly(ε-caprolactone) (PCL) vascular scaffold by phase separating the immiscible polymer blend. However, the slow degradation of PLLA/PCL limited cell infiltration. Herein, we hypothesized that poly(lactic-co-glycolic acid) (PLGA) would be miscible with PLLA but immiscible with PCL. Then, PLGA can be introduced into the PLLA/PCL blend to fabricate macroporous nanofibrous scaffold with improved biodegradability by using dual phase separation technique. Materials and methods: The miscibility of PLGA with PLLA and PCL was evaluated. Then, the PLLA/PLGA/PCL scaffold was prepared by dual phase separation technique. The prepared scaffolds were characterized in terms of the morphology, in vitro degradation, mechanical properties, and cells’ infiltration and viability for human vascular SMCs (HVSMCs). Finally, platelet-derived growth factor-BB (PDGF-BB) was immobilized on the scaffold and its effect on the bioactivity of HVSMCs was studied. Results: PLGA is miscible with PLLA but immiscible with PCL as hypothesized. The addition of PLGA enlarged the pore size and improved the biodegradability of composite scaffold. Notably, PLLA/PLGA/PCL scaffold with the blend ratio of 30:40:30 possessed improved pore interconnectivity for cells’ infiltration and enough mechanical properties. Moreover, HVSMCs could grow and infiltrate into this scaffold, and surface modification with PDGF-BB on the nanofibrous scaffold enhanced HVSMCs migration and proliferation. Conclusion: This study provides a strategy to expand dual phase separation technique into utilizing ternary even multinary polymer blend to fabricate macroporous nanofibrous scaffold with improved physicochemical properties. The prepared PLLA/PLGA/PCL scaffold would be promising for the regeneration of functional tunica media in vascular tissue engineering. Keywords: immiscible polymer blend, porous, nanofibrous, vascular scaffold, PDGF-BB

Yu-Teng Ma,1,2 Xiao-Fang Xing,1 Bin Dong,3 Xiao-Jing Cheng,1 Ting Guo,1 Hong Du,1 Xian-Zi Wen,1 Jia-Fu Ji1,2 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China; 2Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China; 3Department of Pathology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China Background: Glucose-6-phosphate isomerase (GPI) is a glycolytic-related enzyme that interconverts glucose-6-phosphate and fructose-6-phosphate in the cytoplasm. This protein is also secreted into the extracellular matrix by cancer cells and is, therefore, also called autocrine motility factor (AMF). Methods: To clarify the roles of AMF/GPI in gastric cancer (GC), we collected 335 GC tissues and the corresponding adjacent noncancerous tissues, performed immunohistochemical studies, and analyzed the relationship between AMF/GPI expression and the patients’ clinicopathologic features. Results: AMF/GPI expression was found to be significantly higher in the GC group than in the corresponding noncancerous tissue group (P

Meng Huang,1,2 Hexi Du,3 Li Zhang,3 Hong Che,4 Chaozhao Liang3 1Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; 2Department of Ultrasound, The East District of First Affiliated Hospital of Anhui Medical University, The People’s Hospital of Feidong, Hefei, Anhui, China; 3Department of Urology, The First Affiliated Hospital of Anhui Medical University and Institute of Urology, Anhui Medical University, Hefei, Anhui, China; 4Department of Cardiology, The First Affiliated Hospital of Anhui Medical University and Institute of Urology, Anhui Medical University, Hefei, Anhui, China Background: Hypoxia-inducible factor-1α (HIF-1α) plays an important role in tumor growth, invasion, and metastasis. The aim of this study was to perform a meta-analysis to explore the association of HIF-1α expression with clinicopathological significance in patients with prostate cancer (PCa). Methods: A detailed literature search was made in PubMed, Embase, Cochrane Library, China Biology Medicine disc (CBM), and China National Knowledge Infrastructure (CNKI) up to August 21, 2017. Odds ratios (ORs) with 95% CIs were calculated to evaluate the strength of the correlations. Analysis of pooled data was performed using Review Manager 5.3 software. Results: Eventually, 14 studies were identified and involved in this meta-analysis. The rate of HIF-1α protein expression was significantly higher in PCa than in nonmalignant prostate tissues (OR=12.01, 95% CI: 8.22–17.55, P

Yamin Yang,1 Yue Hu,2 Henry Du,3 Lei Ren,4 Hongjun Wang5 1Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, China; 2Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, USA; 3Department of Chemical Engineering and Materials Sciences, Stevens Institute of Technology, Hoboken, NJ, USA; 4Department of Biomaterials, College of Materials, Xiamen University, Xiamen, Fujian, China; 5Department of Biomedical Engineering, Chemistry and Biological Sciences, Stevens Institute of Technology, Hoboken, NJ, USA Introduction: In recognition of the potentials of gold nanoparticles (Au NPs) in enhanced photodynamic therapy (PDT) for cancer, it is desirable to further understand the shape-dependent surface plasmonic resonance (SPR) properties of various gold nanostructures and evaluate their performances in PDT. Materials and methods: Monodispersed colloidal spherical solid Au NPs were synthesized by UV-assisted reduction using chloroauric acid and sodium citrate, and hollow gold nanorings (Au NRs) with similar outer diameter were synthesized based on sacrificial galvanic replacement method. The enhanced electromagnetic (EM) field distribution and their corresponding efficiency in enhancing singlet oxygen (1O2) generation of both gold nanostructures were investigated based on theoretical simulation and experimental measurements. Their shape-dependent SPR response and resulted cell destruction during cellular PDT in combination with 5-aminolevulinic acid (5-ALA) were further studied under different irradiation conditions. Results: With comparable cellular uptake, more elevated formation of 1O2 in 5-ALA-enabled PDT was detected with the presence of Au NRs than that with Au NPs under broadband light irradiation in both cell-free and intracellular conditions. As a result of the unique morphological attributes, exhibiting plasmonic effect of Au NRs was still achievable in the near infrared (NIR) region, which led to an enhanced therapeutic efficacy of PDT under NIR light irradiation. Conclusion: Shape-dependent SPR response of colloidal Au NPs and Au NRs and their respective effects in promoting PDT efficiency were demonstrated in present study. Our innovative colloidal Au NRs with interior region accessible to surrounding photosensitizers would serve as efficient enhancers of PDT potentially for deep tumor treatment. Keywords: gold nanoparticles, colloidal gold nanorings, surface plasmonic resonance, photodynamic therapy

Yanling Wang,1 Jihong Liu,1 Xuemei Wang,1 Zongjian Liu,2 Fengwu Li,1 Fenghua Chen,3 Xiaokun Geng,1 Zhili Ji,2 Huishan Du,1 Xiaoming Hu1,3 1Department of Neurology, China-America Institute of Neuroscience, 2Central Laboratory, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Neurology, Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Background: Stroke has high mortality and morbidity. Biomarkers are required for to predict stroke outcomes, which could help clinicians to provide rationale approaches for patient management. The dynamic changes in circulating immune cells have been reported in stroke patients and animal models of stroke.Aim: The aim of this study was to explore biomarkers to predict stroke outcomes by investigating the relationship between the frequencies of circulating immune cells and stroke outcomes.Methods: In all, 50 acute ischemic stroke (AIS) patients were enrolled. Their blood samples were collected upon hospital admission and on day 1 and day 7 after stroke, and the leukocyte subsets were analyzed by flow cytometry. The dynamic changes in some types of immune cells in the AIS course and their correlation with clinical parameters were analyzed. Blood samples from 123 age- and gender-matched healthy subjects were used as controls.Results: The proportions of T-lymphocytes and NK cells in stroke patients were significantly lower than in healthy controls. The frequencies of B- and T-lymphocytes were negatively correlated with stroke severity at onset, including neurological deficits as assessed by National Institutes of Health Stroke Scale (NIHSS), and infarct volume as measured by the diffusion-weighted images (DWIs) of magnetic resonance (MR). Logistic regression analysis showed that modified Rankin scale (mRs) scores, a score system for the long-term neurological dysfunctions, were negatively correlated with the percentage of B-lymphocytes at stroke onset.Conclusion: The proportions of B- and T-lymphocytes are associated with neurological outcomes of stroke patients and might be used as an indicator for severity and prognosis of ischemic stroke. Keywords: lymphocytes, stroke, neurological deficits, infarct

Wen Wang,1–3,* Yang Li,1–3,* Xiaomei Liu,3 Minghua Jin,3 Haiying Du,3 Ying Liu,3 Peili Huang,1,2 Xianqing Zhou,1,2 Lan Yuan,4 Zhiwei Sun1–3 1School of Public Health, Capital Medical University, Beijing, 2Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 3School of Public Health, Jilin University, Changchun, Jilin, 4Medical and Healthy Analysis Centre, Peking University, Beijing, People's Republic of China *These authors contributed equally to this work Abstract: Silica nanoparticles (SNPs) are one of the most important nanomaterials, and have been widely used in a variety of fields. Therefore, their effects on human health and the environment have been addressed in a number of studies. In this work, the effects of amorphous SNPs were investigated with regard to multinucleation in L-02 human hepatic cells. Our results show that L-02 cells had an abnormally high incidence of multinucleation upon exposure to silica, that increased in a dose-dependent manner. Propidium iodide staining showed that multinucleated cells were arrested in G2/M phase of the cell cycle. Increased multinucleation in L-02 cells was associated with increased generation of cellular reactive oxygen species and mitochondrial damage on flow cytometry and confocal microscopy, which might have led to failure of cytokinesis in these cells. Further, SNPs inhibited cell growth and induced apoptosis in exposed cells. Taken together, our findings demonstrate that multinucleation in L-02 human hepatic cells might be a failure to undergo cytokinesis or cell fusion in response to SNPs, and the increase in cellular reactive oxygen species could be responsible for the apoptosis seen in both mononuclear cells and multinucleated cells. Keywords: silica nanoparticles, human hepatic cell L-02, multinucleation, cell cycle, cell dysfunction, apoptosis

Sarwat Salim, Haiming Du, Sumalee Boonyaleephan, Jim WanUniversity of Tennessee Health Science Center, Memphis, TN, USAPurpose: To compare the surgical outcomes of the Ex-PRESS glaucoma filtration device in African American and white glaucoma patients.Design: Retrospective comparative case series.Methods: This was a comparative case series of 36 eyes of 36 African Americans and 43 eyes of 43 whites that underwent placement of the Ex-PRESS glaucoma filtration device under a partial-thickness scleral flap for uncontrolled glaucoma. All eyes received intraoperative mitomycin C. The primary outcome measures were intraocular pressure (IOP), number of postoperative glaucoma medications, and surgical success. Surgical success was defined as IOP between 5 and 18 mm Hg, with or without glaucoma medications, without further glaucoma surgery, or loss of light perception vision. Results: Average follow-up was 31.9 ± 9.8 (range, 14.6–47) months for African Americans and 30.7 ± 8.6 (range, 14.3–47) months for whites. At 33 months, surgical success was 80.0% in the African American group and 83.3% in the white group (P = 1.00). Reasons for surgical failure included increased IOP (3 eyes, 3.8%), persistent hypotony with maculopathy (1 eye, 1.3%), and further surgery (4 eyes, 5.06%). Compared with preoperative values, the mean postoperative IOP and number of glaucoma medications were significantly reduced in both groups, and no statistical difference was observed between the two groups at 33 months. Postoperative complications were similar in the two groups.Conclusions: Similar surgical outcomes were observed in African American and white glaucoma patients after implantation of the Ex-PRESS glaucoma filtration device. This latest modification of glaucoma filtration surgery may be a better surgical option for African Americans given its potential advantages of no tissue removal, predictable outcomes related to consistent lumen size and controlled flow, fewer postoperative complications, and overall reduced inflammation. Keywords: glaucoma, trabeculectomy, Ex-PRESS glaucoma filtration device, antimetabolites, African American, White