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Zhengyi Han,1,2 Yangyang Zhang,1,2 Chenxi Xue,3 Shiyun Jin,1,2 Qi Chen,1,2 Ye Zhang1,2 1Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China; 2Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, 230601, People’s Republic of China; 3Department of Orthopedics, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of ChinaCorrespondence: Ye Zhang, Department of Anesthesiology, The Second Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, People’s Republic of China, Tel +86-055163869480, Email zhangye_hassan@sina.comPurpose: Total Knee Arthroplasty (TKA) is a highly invasive procedure causing severe postoperative pain, which hampers early mobility. Effective pain management is crucial for optimal recovery. This study aimed to evaluate how adductor canal block (ACB) and femoral nerve block (FNB) affect opioid use and inflammation factor levels in elderly TKA patients.Methods: This prospective observational study included 120 patients who received TKA, and divided them into three groups, based on the different nerve block technique: ACB, FNB, and no intervention before general anesthesia (CON). Postoperative opioid consumption, pain assessment, inflammation factor, knee function recovery and other clinical indicators were recorded.Results: The CON group had significantly higher cumulative sufentanil consumption compared to the ACB and FNB groups at both 12 h and 48h postoperative (P< 0.001). Compared with the CON group, the ACB and FNB groups persistently had lower pain scores until 12 h at rest and 24 h during motion after surgery. The ACB group showed significantly lower serum concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) compared to the CON group at 24 h postoperative (P=0.017, P=0.009), and IL-6 levels remained significantly lower at 72 h postoperative (P=0.005). Both ACB and FNB groups achieved earlier ambulation compared to the CON group (P=0.002). On the first day postoperative, both the ACB and FNB groups showed significantly better knee motion (P< 0.001), quadriceps strength (P< 0.001), and daily mobilization (P< 0.001) compared to the CON group. Additionally, the ACB group exhibited superior quadriceps strength (P< 0.001) and daily mobilization (P< 0.001) compared to the FNB group.Conclusion: The ACB and FNB groups exhibited comparable clinical efficacy outcomes in terms of pain scores and opioid consumption. However, the ACB group experienced reduced postoperative inflammation and improved knee recovery, especially in quadriceps strength.Keywords: adductor canal block, femoral nerve block, opioid, analgesia, inflammation, TKA

Wenjie Xie,1,2,&ast; Yixun Zhang,1,2,&ast; Qianfeng Xu,1,2,&ast; Guowei Zhong,1,2 Jundong Lin,2,3 Huichan He,3 Qiuling Du,2 Huijing Tan,1,2 Muqi Chen,1,2 Zhenjie Wu,1– 3 Yulin Deng,1,2 Zhaodong Han,1– 3 Jianming Lu,1,2,4 Jianheng Ye,1,2,4 Fen Zou,1,2 Yangjia Zhuo,1,2 Weide Zhong1– 4 1Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 2Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 3Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, People’s Republic of China; 4State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, 999078, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangjia Zhuo; WeideZhong, Email eyyangjiazhuo@scut.edu.cn; zhongwd2009@live.cnPurpose: Current treatment approaches for Prostate cancer (PCa) often come with debilitating side effects and limited therapeutic outcomes. There is urgent need for an alternative effective and safe treatment for PCa.Methods: We developed a nanoplatform to target prostate cancer cells based on graphdiyne (GDY) and a copper-based metal-organic framework (GDY-CuMOF), that carries the chemotherapy drug doxorubicin (DOX) for cancer treatment. Moreover, to provide GDY-CuMOF@DOX with homotypic targeting capability, we coated the PCa cell membrane (DU145 cell membrane, DCM) onto the surface of GDY-CuMOF@DOX, thus obtaining a biomimetic nanoplatform (DCM@GDY-CuMOF@DOX). The nanoplatform was characterized by using transmission electron microscope, atomic force microscope, X-ray diffraction, etc. Drug release behavior, antitumor effects in vivo and in vitro, and biosafety of the nanoplatform were evaluated.Results: We found that GDY-CuMOF exhibited a remarkable capability to load DOX mainly through π-conjugation and pore adsorption, and it responsively released DOX and generated Cu+ in the presence of glutathione (GSH). In vivo experiments demonstrated that this nanoplatform exhibits remarkable cell-killing efficiency by generating lethal reactive oxygen species (ROS) and mediating cuproptosis. In addition, DCM@GDY-CuMOF@DOX effectively suppresses tumor growth in vivo without causing any apparent side effects.Conclusion: The constructed DCM@GDY-CuMOF@DOX nanoplatform integrates tumor targeting, drug-responsive release and combination with cuproptosis and chemodynamic therapy, offering insights for further biomedical research on efficient PCa treatment. Keywords: graphdiyne, biomimetic nanoplatform, cuproptosis, chemotherapy, prostate cancer

Zhouzhou Feng,1 Zhengcai Han,1 Yaqin Wang,1 Hong Guo,1 Jian Liu1,2 1The First Clinical Medical College of Lanzhou University, Lanzhou City, People’s Republic of China; 2Gansu Maternal and Child Health Hospital/Gansu Central Hospital, Lanzhou City, People’s Republic of ChinaCorrespondence: Jian Liu, Department of Clinical Medicine, the First Clinical Medical College of Lanzhou University, No. 1, Donggang West Road, Chengguan District, Lanzhou City, Gansu Province, People’s Republic of China, Tel +86 136 0935 4197, Email medecinliu@sina.comObjective: To comparison of the application of Vibrating Mesh Nebulizer and Jet Nebulizer in chronic obstructive pulmonary disease (COPD).Research Methods: This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements. The primary outcome measures analyzed included: The amount of inhaler in the urine sample at 30 minutes after inhalation therapy (USAL0.5), The total amount of inhaler in urine sample within 24 hours (USAL24), Aerosol emitted, Forced expiratory volume in 1 second (FEV1), Forced vital capacity (FVC).Results: Ten studies were included with a total of 314 study participants, including 157 subjects in the VMN group and 157 subjects in the JN group. The data analysis results of USAL0.5, MD (1.88 [95% CI, 0.95 to 2.81], P = 0.000), showed a statistically significant difference. USAL24, MD (1.61 [95% CI, 1.14 to 2.09], P = 0.000), showed a statistically significant difference. The results of aerosol emitted showed a statistically significant difference in MD (3.44 [95% CI, 2.84 to 4.04], P = 0.000). The results of FEV1 showed MD (0.05 [95% CI, − 0.24 to 0.35], P=0.716), the results were not statistically significant. The results of FVC showed MD (0.11 [95% CI, − 0.18 to 0.41], P=0.459), the results were not statistically significant. It suggests that VMN is better than JN and provides higher aerosols, but there is no difference in improving lung function between them.Conclusion: VMN is significantly better than JN in terms of drug delivery and utilization in the treatment of patients with COPD. However, in the future use of nebulizers, it is important to select a matching nebulizer based on a combination of factors such as mechanism of action of the nebulizer, disease type and comorbidities, ventilation strategies and modes, drug formulations, as well as cost-effectiveness, in order to achieve the ideal treatment of COPD.Keywords: chronic obstructive pulmonary disease, aerosol, vibrating mesh nebulizers, jet nebulizers, meta-analysis

Nonadherence to physicians’ recommendations can have a detrimental impact on patient health, to say nothing of the financial cost to the already unsustainable Canadian healthcare system. This comparative study aimed at gaining a deeper understanding of the factors influencing adherence to prescribed medications and lifestyle change recommendations among First Nations patients and patients of European ancestry. In-depth, face-to-face interviews were conducted with 40 participants in Northern British Columbia, Canada. Interviews were transcribed and qualitatively analyzed. Results show that medical adherence derives from an interaction between personal factors and situational or external factors. A comparative analysis revealed that a disproportionate number of First Nations patients faced situational barriers that impeded with medical adherence. These factors include geographical isolation, lack of access to a regular doctor, negative healthcare experiences, and financial constraints. Analyzed through a postcolonial interpretive lens, the research findings highlight the need to reduce systemic barriers within the healthcare system and the wider social context, especially among First Nations patients living in remote communities.

Jiaqi Tian,1,&ast; Zhengpu Han,1,2,&ast; Dandan Song,1 Yanjie Peng,1 Min Xiong,3 Zhen Chen,2 Shuyin Duan,4 Lin Zhang1,5 1Clinical Medical Research Center for Women and Children Diseases, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, People’s Republic of China; 2School of Public Health, Weifang Medical University, Weifang, People’s Republic of China; 3School of Public Health, North China University of Science and Technology, Tangshan, People’s Republic of China; 4School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 5Key Laboratory of Birth Defect Prevention and Genetic Medicine of Shandong Health Commission, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Zhang, Clinical Medical Research Center for Women and Children Diseases, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250001, People’s Republic of China, Tel +86-531-68795046, Email zhanglin8901@163.com Shuyin Duan, School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250001, People’s Republic of China, Tel +86-13419581411, Email shuyinduan@126.comAbstract: Exosomes are nano-sized membrane vesicles that transfer bioactive molecules between cells and modulate various biological processes under physiological and pathological conditions. By applying bioengineering technologies, exosomes can be modified to express specific markers or carry therapeutic cargo and emerge as novel platforms for the treatment of cancer, neurological, cardiovascular, immune, and infectious diseases. However, there are many challenges and uncertainties in the clinical translation of exosomes. This review aims to provide an overview of the recent advances and challenges in the translation of engineered exosomes, with a special focus on the methods and strategies for loading drugs into exosomes, the pros and cons of different loading methods, and the optimization of exosome production based on the drugs to be encapsulated. Moreover, we also summarize the current clinical applications and prospects of engineered exosomes, as well as the potential risks and limitations that need to be addressed in exosome engineering, including the standardization of exosome preparation and engineering protocols, the quality and quantity of exosomes, the control of drug release, and the immunogenicity and cytotoxicity of exosomes. Overall, engineered exosomes represent an exciting frontier in nanomedicine, but they still face challenges in large-scale production, the maintenance of storage stability, and clinical translation. With continuous advances in this field, exosome-based drug formulation could offer great promise for the targeted treatment of human diseases.Keywords: engineered exosomes, drug delivery, clinical application, preparation strategy

Hanyu Fang,1,2 Tairan Dong,1 Shanlin Li,1 Yihan Zhang,1 Zhuojun Han,1 Mingfei Liu,1,2 Wenjun Dong,1,2 Zheng Hong,1,2 Min Fu,3 Hongchun Zhang1,2 1Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, 100029; 2Department of Traditional Chinese Medicine for Pulmonary Diseases, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 3Department of Infectious Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100029, People’s Republic of ChinaCorrespondence: Hongchun Zhang, Department of Traditional Chinese Medicine for Pulmonary Diseases, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China, Tel +86 13701226664, Email 13701226664@139.com Min Fu, Department of Infectious Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100029, People’s Republic of China, Tel +86 13366093706, Email bdfumin@126.comObjective: Although studies on the association between COPD and lung cancer are of great significance, no bibliometric analysis has been conducted in the field of their comorbidity. This bibliometric analysis explores the current situation and frontier trends in the field of COPD and lung cancer comorbidity, and to lay a new direction for subsequent research.Methods: Articles in the field of COPD and cancer comorbidity were retrieved from Web of Science Core Collections (WoSCC) from 2004 to 2023, and analyzed by VOSviewer, CiteSpace, Biblimatrix and WPS Office.Results: In total, 3330 publications were included. The USA was the leading country with the most publications and great influence. The University of Groningen was the most productive institution. Edwin Kepner Silverman was the most influential scholar in this field. PLOS One was found to be the most prolific journal. Mechanisms and risk factors were of vital importance in this research field. Environmental pollution and pulmonary fibrosis may be future research prospects.Conclusion: This bibliometric analysis provided new guidance for the development of the field of COPD and lung cancer comorbidity by visualizing current research hotspots, and predicting possible hot research directions in the future.Keywords: COPD, lung cancer, bibliometric analysis, VOSviewer, CiteSpace

Zhiyong Han, Dan Wang, Chuanyun Jiang, Yuliang Zhang School of Business Administration, Anhui University of Finance and Economics, Bengbu, People’s Republic of ChinaCorrespondence: Yuliang Zhang, School of Business Administration, Anhui University of Finance and Economics, 962, Caoshan Road, Bengbu, 233030, People’s Republic of China, Email zyl_1203@163.comPurpose: The COVID-19 pandemic has dramatically affected all aspects of people’s lives and work, negatively impacting personal well-being and job satisfaction. Based on the conservation of resources theory, this study examines the relationship of organizational adaptive practices (OAP) responding to COVID-19 and psychological resilience (PR) with employee job satisfaction (JS) while incorporating the mediating role of emotional exhaustion (EE).Methods: We surveyed 340 employees from China through an online questionnaire, which was used under convenience sampling and finally recovered a valid sample size of 314. We used SPSS and AMOS to analyze the correlation and hypothesis testing of the collected data through structural equation modelling (SEM) and bootstrapping.Results: Both OAP and PR facilitate JS and inhibit employee EE. EE negatively predicted employee JS. EE mediated both the relationship between OAP and subordinate JS and the relationship between PR and subordinate JS.Conclusion: The study provides a new perspective on increasing JS during the COVID-19 pandemic, thereby expanding the scope of the antecedents of employee JS in crisis situations. It also reveals the mediating role of EE and deepens the research on the mechanism by which OAP and PR affect individuals, providing practical guidance for organizations to improve employee satisfaction in sudden public crisis situations.Keywords: COVID-19, organizational adaptive practices, psychological resilience, job satisfaction, emotional exhaustion

Haoran Chen,1,2,&ast; Zhongyu Han,2,&ast; Yi Wang,1,&ast; Junyan Su,3 Yumeng Lin,4 Xuhua Cheng,1 Wen Liu,1 Jingyu He,5 Yiyue Fan,6 Liuyan Chen,2 Houdong Zuo1 1Department of Orthopaedics, Chengdu Xinhua Hospital, Chengdu, 610000, People’s Republic of China; 2School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, People’s Republic of China; 3Department of Orthopaedics, The First People’s Hospital of Longquanyi District, Chengdu, 610000, People’s Republic of China; 4School of Ophthalmology, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, People’s Republic of China; 5Sichuan Judicial and Police Officers Professional College, Deyang, 618000, People’s Republic of China; 6Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houdong Zuo, Department of Orthopaedics, Chengdu Xinhua Hospital, Chengdu, 610000, People’s Republic of China, Email xhyyzhd@163.com Liuyan Chen, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, People’s Republic of China, Email Lycheecly@163.comAbstract: Ferroptosis is a new cell fate decision discovered in recent years. Unlike apoptosis, autophagy or pyroptosis, ferroptosis is characterized by iron-dependent lipid peroxidation and mitochondrial morphological changes. Ferroptosis is involved in a variety of physiological and pathological processes. Since its discovery, ferroptosis has been increasingly studied concerning bone-related diseases. In this review, we focus on the latest research progress and prospects, summarize the regulatory mechanisms of ferroptosis, and discuss the role of ferroptosis in the pathogenesis of bone-related diseases, such as osteoporosis (OP), osteoarthritis (OA), rheumatoid arthritis (RA), and osteosarcoma (OS), as well as its therapeutic potential.Keywords: ferroptosis, cell death, iron accumulation, lipid peroxidation, bone-related diseases

Hanyu Fang,1,2,&ast; Tairan Dong,1,&ast; Zhuojun Han,1 Shanlin Li,1 Mingfei Liu,1 Ying Liu,3 Qiwen Yang,1 Min Fu,4 Hongchun Zhang1,2 1Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2Department of Traditional Chinese Medicine for Pulmonary Diseases, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 3The Second Health and Medical Department, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 4Department of Infectious Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongchun Zhang, Department of Traditional Chinese Medicine for Pulmonary Diseases, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China, Tel +86 13701226664, Email 13701226664@139.com Min Fu, Department of Infectious Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100029, People’s Republic of China, Tel +86 13366093706, Email bdfumin@126.comObjective: The comorbidity of pulmonary fibrosis and COPD/emphysema has garnered increasing attention. However, no bibliometric analysis of this comorbidity has been conducted thus far. This study aims to perform a bibliometric analysis to explore the current status and cutting-edge trends in the field, and to establish new directions for future research.Methods: Statistical computing, graphics, and data visualization tools such as VOSviewer, CiteSpace, Biblimatrix, and WPS Office were employed.Results: We identified a total of 1827 original articles and reviews on the comorbidity of pulmonary fibrosis and COPD/emphysema published between 2004 and 2023. There was an observed increasing trend in publications related to this comorbidity. The United States, Japan, and the United Kingdom were the countries with the highest contributions. Professor Athol Wells and the University of Groningen had the highest h-index and the most articles, respectively. Through cluster analysis of co-cited documents, we identified the top 17 major clusters. Keyword analysis predicted that NF-κB, oxidative stress, physical activity, and air pollution might be hot spots in this field in the future.Conclusion: This bibliometric analysis demonstrates a continuous increasing trend in literature related to the comorbidity of pulmonary fibrosis and COPD/emphysema. The research hotspots and trends identified in this study provide a reference for in-depth research in this field, aiming to promote the development of the comorbidity of pulmonary fibrosis and COPD/emphysema.Keywords: COPD, pulmonary fibrosis, bibliometric analysis, VOSviewer, CiteSpace

Batudeligen, Zhiqiang Han, Hongmei Chen, Narisu, Yanhua Xu, Anda, Gegentaoli Han Institute of Clinical Pharmacology of Traditional Mongolian Medicine, Affiliated Hospital of Inner Mongolia Minzu University, Tongliao City, Inner Mongolia, People’s Republic of ChinaCorrespondence: Batudeligen, Institute of Clinical Pharmacology of Traditional Mongolian Medicine, Affiliated Hospital of Inner Mongolia Minzu University, 1742 East Huolinhe Dajie, Tongliao City, Inner Mongolia, 028007, People’s Republic of China, Tel +86- 475- 8215505, Email Batudeligen123@163.comBackground: Traditional Chinese medicine (TCM) with single or compound materials is an effective cure for liver fibrosis. Hepatic stellate cells (HSCs) play a key role in liver fibrosis pathology and have become a novel drug target for this condition.Methods: CCK-8 assay was used to determine the cytotoxicity of four components, SYPA, HSYPA, Apigenin, and Luteolin, from Deduhonghua-7 powder on HSC-T6 cells. Transforming Growth Factor β 1 (TGFβ 1)-induced fibrotic cell model and CCI4-induced fibrotic rat model were constructed, the expression of fibrosis-related genes, the pathological changes and serum biochemical markers were evaluated. Proteomic analysis was performed to determine the mechanism by which luteolin attenuated liver fibrosis, which were further confirmed by Western blot.Results: Luteolin attenuates liver fibrosis in HSC-T6 cells and luteolin decreases the liver fibrosis index level in vivo. A total of 5000 differentially expressed proteins (DEPs) were obtained using proteomic analysis. KEGG analysis found that DEPs were concentrated in various metabolic pathways, including DNA replication and repair and lysosomal signaling. GO analysis showed that molecular functions included the activity and binding of various enzymes, related cellular components included the extracellular space, lysosomal lumen, mitochondrial matrix, and nucleus, and biological processes included collagen organization and biosynthesis and the positive regulation of cell migration. Western blot results showed that CCR1, CD59, and NAGA were downregulated in TGFβ 1 treatment, while upregulated both in Lut2 and Lut10 treatment. Meanwhile, eight proteins, ITIH3, MKI67, KIF23, DNMT1, P4HA3, CCDC80, APOB, FBLN2, that were upregulated in TGFβ 1 treatment, while downregulated both in Lut2 and Lut10 treatment.Conclusion: Luteolin was shown to have a strong protective effect on liver fibrosis. CCR1, CD59, and NAGA may promote liver fibrosis while ITIH3, MKI67, KIF23, DNMT1, P4HA3, CCDC80, APOB, and FBLN2 may facilitate protection against fibrosis.Keywords: luteolin, deduhonghua-7 powder, liver fibrosis, proteomic analysis, TGFβ 1

Xiaoyan Li,1 Bin Zhang,1 Wen Ding,2 Xianfen Jia,1 Zhen Han,1 Lin Zhang,2 Yifeng Hu,2 Bing Shen,2 Huiqin Wang1 1Department of Pediatrics, Anhui Province Maternity and Child Health Hospital, Hefei, Anhui, 230001, People’s Republic of China; 2School of Basic Medicine, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of ChinaCorrespondence: Bing Shen, Department of Physiology, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, People’s Republic of China, Tel +86-551-65161132, Fax +86-551-65161126, Email shenbing@ahmu.edu.cn Huiqin Wang, Department of Pediatrics, Anhui Province Maternity and Child Health Hospital, 15 Yimin Road, Hefei, Anhui, 230001, People’s Republic of China, Tel +86-13955130296, Email 1871024765@qq.comBackground: Women who develop diabetes during pregnancy are at higher risk of preterm birth. Here, we identified differentially expressed proteins (DEPs) in the serum of umbilical cord blood samples obtained from preterm neonates delivered by women with gestational diabetes to provide therapeutic targets for clinical drug development.Materials and Methods: Umbilical cord blood was collected after delivery of preterm neonates by women with gestational diabetes and after delivery of healthy neonates by women without diabetes. DEPs in the serum samples were identified using liquid chromatography–tandem mass spectrometry. Gene Ontology (GO), cluster analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to determine the biological functions associated with these DEPs. Enzyme linked immunosorbent assay was used to confirm the key DEPs.Results: We found that 21 proteins were significantly upregulated, and 51 proteins were significantly downregulated in 72 DEPs in serum samples. GO analyses showed that the DEPs were mainly associated with the GO terms cellular process, biological regulation, cellular anatomical entity, and binding. KEGG signaling pathway analysis indicated that most of the upregulated DEPs were associated with the complement and coagulation cascades, Staphylococcus aureus infection, pertussis, HIF-1 signaling pathway and PPAR signaling pathway and that most of the downregulated DEPs were associated with the complement and coagulation cascades, dilated cardiomyopathy, pathways in cancer, Chagas disease, and hypertrophic cardiomyopathy. The results of KEGG pathway annotation and enrichment analyses indicated that changes in the complement and coagulation cascades may be importantly associated with preterm delivery of neonates by women with gestational diabetes. The key DEPs were confirmed by enzyme linked immunosorbent assay.Conclusion: Our proteomics and bioinformatics analyses identified several key proteins and the complement and coagulation cascades pathway that warrant further investigation as potential novel therapeutic targets in preterm delivery among women with gestational diabetes.Keywords: label-free LC-MS/MS, proteomics, gestational diabetes, preterm birth, complement and coagulation cascades

Jiao Ma,1,&ast; Zhuoxiao Han,1,&ast; Rui Jiao,1 Guanli Yuan,1 Cuiqing Ma,2 Xixin Yan,1 Aihong Meng1 1Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei, 050000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aihong Meng, Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, No. 215, Heping West Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email mengaihong_med@126.comBackground: PM2.5 exposure is one of the major inducements of various respiratory diseases and related mortality. Meanwhile, irisin, a metabolism and thermogenesis-related hormone, is found to be protective against acute lung injury induced by LPS, which indicates its therapeutic function in lung injury. However, the function and underlying mechanism of irisin in PM2.5-induced acute lung injury (ALI) are still unclear. This study is aimed to discover the potential mechanisms of irisin in PM2.5-induced acute lung injury.Methods: Atg5 deficient mice and cells were established to clarify the relationship between irisin and autophagy in PM2.5-induced ALI. We also used Ad-mCherry-GFP-LC3B as a monitor of autophagy flux to claim the effects of irisin on autophagy. Western blotting and qPCR were used to reveal the molecular mechanism.Results: As a result, PM2.5 exposure induced lung injury whereas mitigated by irisin. Moreover, PM2.5 hampered autophagy flux, characterized by accumulation of p62, and autophagosomes, as well as blocked autolysosomes. Irisin improved the disturbed autophagy flux, which was abrogated by deficiency of Atg5. Additionally, we demonstrated that irisin activated AMPK and inhibited mTOR, which indicated the enhanced autophagy. Moreover, blockage of AMPK by compound C terminated irisin’s induction of autophagy in cultured MH-S cells.Conclusion: Our findings reveal that irisin performs protective effects against PM2.5-induced ALI by activating autophagy through AMPK/mTOR signaling pathway.Keywords: irisin, PM2.5, acute lung injury, autophagy

Yu Huang,1,2 Yilian Xie,1,3 Lei Huang,1 Zhen Han1,2 1Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Guangdong, 518036, People’s Republic of China; 2Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of ChinaCorrespondence: Zhen Han, Email 2498159698@qq.comPurpose: No consensus has been established on the safety and effectiveness of out-of-hospital management of Vitamin K antagonists (VKA) therapy combining portable coagulometers and telemedicine. The present meta-analysis investigated the safety and effectiveness of this hybrid anticoagulants management model.Methods: The PubMed, Embase, Cochrane, and Web of Science databases were searched for papers published before May 1, 2022. To reduce bias, only randomized controlled trials were included. RevMan 5.3 (Cochrane) software was used to evaluate and analyze clinical outcomes, including the effectiveness and safety of patient management approaches, determined by the time in the therapeutic range (TTR) and occurrence of thrombotic and bleeding events.Results: Eight studies, comprising 3853 patients, were selected. The meta-analysis showed that anticoagulant management combining portable coagulometers and telemedicine significantly improved frequency of testing (mean difference [MD]= 12.95 days; 95% CI, 8.77– 17.12; I2= 92%; P< 0.01) and TTR (MD= 9.50%; 95% CI, 3.16– 15.85; I2= 87%; P< 0.01). Thromboembolism events were reduced (RR= 0.72; 95% CI, 0.51– 1.01; I2= 0%; P= 0.05), but the results were not statistically significant. And no significant differences in major bleeding events, rehospitalization rate, mortality, or overall treatment cost existed between the two groups.Conclusion: Although the safety of remote cardiovascular disease management is not superior to that of conventional outpatient anticoagulant management, it provides a more stable monitoring of coagulation status.Keywords: VKA therapy, warfarin, telemedicine, self-testing, randomized controlled studies, meta-analysis

Chao Liu,1 Dong Yang,2 Zhiyong Han2 1School of Public Administration, Hohai University, Nanjing, People’s Republic of China; 2School of Business Administration, Anhui University of Finance and Economics, Bengbu, People’s Republic of ChinaCorrespondence: Zhiyong Han, School of Business Administration, Anhui University of Finance and Economics, Bengbu, People’s Republic of China, Email hzyong@aufe.edu.cnPurpose: Although social networking services (SNSs) have attracted billions of people to maintain and extend their social relationships online, more and more passive usage behaviors have been found during the daily SNS usage. The aim of this paper is to investigate how SNS users’ continuance intention is affected by passive SNS use, subjective well-being, as well as perceived concern regarding privacy and impression management.Methods: A research model was developed according to the proposed hypotheses, and then partial least square (PLS) SEM was adopted to empirically assess the valid data collected from 389 WeChat users.Results: The findings show that passive SNS use cannot significantly undermine continuance intention, but it has a negative moderating effect on the relationship between subjective well-being and continuance intention. Besides, the results of empirical research also reveal the antecedents of passive SNS use and subjective well-being from the perspectives of privacy concern and impression management concern, and thereby present the mechanism underlying users’ continuance intention.Conclusion: This study enriches the SNS literature by indicating the moderating role of passive SNS use in the process of SNS usage, which facilitates the understanding regarding how users’ continuance intention can be influenced when they use SNSs passively. This study can help SNS providers to better understand the factors affecting users’ continuance intention in the case of passive SNS use, and then formulating effective strategies for retaining users and avoiding passive usage behaviors.Keywords: social networking services, passive SNS use, continuance intention, social well-being, WeChat

Lan Ma,1,2 Zhengpu Han,1,2 Haoyu Yin,1,2 Jiaqi Tian,1,2 Jing Zhang,3 Ning Li,3 Chunjie Ding,4 Lin Zhang2 1School of Public Health, Weifang Medical University, Weifang, 261053, People’s Republic of China; 2Clinical Medical Research Center for Women and Children Diseases, Maternal and Child Health Care Hospital of Shandong Province, Shandong University, Jinan, 250001, People’s Republic of China; 3School of Public Health, North China University of Science and Technology, Tangshan, 063210, People’s Republic of China; 4School of Public Health, Xinxiang Medical University, Xinxiang, 453000, People’s Republic of ChinaCorrespondence: Lin Zhang, Clinical Medical Research Center for Women and Children Diseases, Maternal and Child Health Care Hospital of Shandong Province, Shandong University, Jinan, 250001, People’s Republic of China, Tel +86-531-68795046, Email zhanglin8901@163.comIntroduction: Silica nanoparticles (SiNPs) are one of the most widely used inorganic nanomaterials, and exposure to SiNP has been demonstrated to induce pulmonary inflammation, primarily promoted by the NLRP3-mediated macrophage pyroptosis. However, mechanisms underlying the activation of NLRP3 signaling are complex, and whether cathepsin B (CTSB), an enzyme released by the ruptured lysosome, could trigger NLRP3 assembly is controversial.Methods: To further characterize the role of CTSB in silica-induced pyroptosis, we conducted this study by establishing SiNP exposure models in vitro. The morphological features of SiNPs were exhibited by the SEM and TEM, and the effects of SiNPs’ internalization on macrophages were examined by the TEM and immunofluorescent staining. Moreover, Western blot was performed to detect the expression of proteins related to pyroptosis and CTSB after blocking the expression of NLRP3 and CTSB.Results: We found that SiNPs internalization caused the rupture of macrophage membrane and promoted the aging of cells with increased intracellular vacuoles. Also, the expression of NLRP3, ASC, Caspase-1, GSDMD, Pro-IL-1β, IL-1β, and CTSB increased under the stimulation of SiNP, which could be suppressed by additional treatment with MCC950, an NLRP3-specific inhibitor. Besides, we found SiNP joint treatment with leupeptin, a CTSB inhibitor, could inhibit the expression of CTSB, but it had no effect on the expression of NLRP3, ASC, and Caspase-1, and the process of macrophage pyroptosis was also not affected.Conclusion: SiNP exposure induces rupture of macrophages and the release of lysosomal CTSB, but CTSB fails to specifically act on the NLRP3 inflammasome to induce pyroptosis which is causally linked to lung inflammation and fibrosis.Keywords: silica nanoparticles, NLRP3 inflammasome, cathepsin B, pyroptosis, macrophage

Chao An,1,&ast; Hongcai Yang,1,2,&ast; Xiaoling Yu,1 Zhi-Yu Han,1 Zhigang Cheng,1 Fangyi Liu,1 Jianping Dou,1 Bing Li,3 Yansheng Li,4 Yichao Li,4 Jie Yu,1 Ping Liang1 1Department of Ultrasound, PLA Medical College & 5th Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2School of Medicine, Nankai University, Tianjin, People’s Republic of China; 3National Laboratory of Pattern Recognition (NLPR), Institute of Automation, Chinese Academy of Sciences, Beijing, People’s Republic of China; 4DHC Mediway Technology CO, Ltd, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Liang; Jie Yu, Department of Ultrasound, PLA Medical College & 5th Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China, Tel +86-10-66939530, Fax +86-10-68161218, Email liangping301@126.com; yu-jie301@hotmail.comBackground and Aim: Early recurrence (ER) presents a challenge for the survival prognosis of patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate machine learning (ML) models using clinical data for predicting ER after microwave ablation (MWA).Methods: Between August 2005 and December 2019, 1574 patients with early-stage HCC underwent MWA at four hospitals were reviewed. Then, 36 clinical data points per patient were collected, and the patients were assigned to the training, internal, and external validation set. Apart from traditional logistic regression (LR), three ML models—random forest, support vector machine, and eXtreme Gradient Boosting (XGBoost)—were built and validated for their predictive ability with the area under ROC curve (AUC). Algorithms such as SHapley Additive exPlanations (SHAP) and local interpretable model-agnostic explanations (LIME) were used to realize their interpretability.Results: The three ML models all outperformed LR (P < 0.001 for all) in predictive ability. When nine variables (tumor number, platelet, α-fetoprotein, comorbidity score, white blood cell, cholinesterase, prothrombin time, neutrophils, and etiology) were extracted simultaneously using recursive feature elimination with cross-validation, the XGBoost model achieved the best discrimination among all models, with an AUC value 0.75 (95% CI [confidence interval]: 0.72– 0.78) in the training set, 0.74 (95% CI: 0.69– 0.80) in the internal validation set, and 0.76 (95% CI: 0.70– 0.82) in the external validation set, and it was interpreted depending on the visualization of risk factors by the SHAP and LIME algorithms. The predictive system of post-ablation recurrence risk stratification was provided on online (http://114.251.235.51:8001/) based on XGboost analysis.Conclusion: The XGBoost model based on clinical data can effectively predict ER risk after MWA, which can contribute to surveillance, prevention, and treatment strategies for HCC.Keywords: microwave ablation, hepatocellular carcinoma, recurrence, machine learning, risk stratification

Shuangqing Chen,1,2 Shicheng Liu,1 Siwei Xu,3 Shumin Cao,4,5 Zhaohui Han,1,2 Lingxin Kong,1,5 Dahu Ren,1,5 Guochen Duan6 1Department of Thoracic Surgery, Hebei General Hospital, Shijiazhuang, 050057, People’s Republic of China; 2Graduate School, Hebei North University, Zhangjiakou, 075000, People’s Republic of China; 3Department of Thoracic Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, 050057, People’s Republic of China; 4Department of Oncology, Hebei General Hospital, Shijiazhuang, 050057, People’s Republic of China; 5Graduate School, Hebei Medical University, Shijiazhuang, 050011, People’s Republic of China; 6Department of Thoracic Surgery, Children’s Hospital of Hebei Province, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Guochen Duan, Children’s Hospital of Hebei Province, No. 133 Jianhua South Street, Yuhua District, Shijiazhuang, 050000, People’s Republic of China, Tel +8613513380703, Email duanguoc@126.com Shicheng Liu, Hebei General Hospital, No. 348, Heping West Road, Xinhua District, Shijiazhuang, 050000, People’s Republic of China, Tel +861309388955, Email 1309388955@qq.comBackground: The routine clinical nutritional and inflammatory indicators such as serum albumin, total cholesterol and lymphocytes have been widely investigated in the prognosis of small cell lung cancer (SCLC). The Naples prognostic score (NPS), based on nutritional and inflammatory status, has been identified as a prognostic impactor in several malignancies. However, the prognostic role of NPS in SCLC has not been elucidated. This study aims to evaluate the prognostic effect of NPS in SCLC patients.Patients and Methods: Patients with SCLC were recruited at Hebei General Hospital between April 2015 and August 2021. Pretreatment clinical and laboratory data were obtained. Participants were assigned into three groups according to NPS (group 0: NPS=0, group 1: NPS=1 or 2, group 2: NPS=3 or 4). Kaplan-Meier and Cox regression analysis were performed to assess the prognostic significance of NPS. The RMS package in R software was used to draw the nomogram predictive model.Results: A total of 128 patients were enrolled. The median progression-free survival (PFS) and overall survival (OS) was 7.2 and 12.3 months, respectively. The median PFS and OS was 12.3 vs 19.8 months, 7.6 vs 14.1 months and 6.0 vs 8.45 months for the three groups respectively. There were significant differences in both OS and FPS among the three groups. Survival analysis showed that NPS was significantly correlated with both OS and PFS (P< 0.05). Lower NPS is associated with longer OS and PFS. Multivariate analysis showed that NPS has an independent prognostic impact on OS (P< 0.05). The nomogram predictive model showed that NPS has good predictive power for survival rates.Conclusion: NPS is an independent prognostic factor for OS in SCLC patients. Low NPS may predict longer OS. Therefore NPS plays a vital role in the nomogram predictive model of survival rates in SCLC patients.Keywords: small cell lung cancer, Naples prognostic score, prognostic factor, nomogram predictive model

Dongjiu Li,1,&ast; Jiayin You,2,&ast; Chengyu Mao,1,&ast; En Zhou,1,&ast; Zhihua Han,1 Junfeng Zhang,1 Tiantian Zhang,1 Changqian Wang1 1Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China; 2Department of Emergency, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tiantian Zhang; Changqian Wang, Email ZhangTT2022Dr@163.com; wangcqdr17@163.comObjective: Cardiomyocyte apoptosis critically contributes to ischemia reperfusion injury (IRI), which lacks effective therapeutic strategies. Circular RNAs (circRNAs) serve as novel diagnostic and therapeutic targets in various cardiovascular diseases. CircRNA Fbxl5 is one of the abundantly expressed circRNAs in the heart and its role in myocardial IRI remains elusive.Materials and Methods: Wild-type (WT) mice and neonatal mice ventricular myocytes (NMVMs) were used and subjected to myocardial IRI and anoxia reoxygenation (AR), respectively. Molecular and histological analyses and echocardiography were used to determine the extent of apoptosis, infarct size, and cardiac function.Results: We found that circRNA Fbxl5 was significantly upregulated in the myocardium, as well as in NMVMs subjected to AR. Knockdown of circRNA Fbxl5 ameliorated cardiomyocyte apoptosis, thereby decreasing infarct size and preserving cardiac function. Additionally, in vitro knockdown of circRNA Fbxl5 in NMVMs subjected to AR recapitulated the in vivo findings. Mechanistically, we identified that circRNA Fbxl5 directly sponged and suppressed the endogenous microRNA-146a (miR-146a), thereby weakening its inhibitory effect on MED1, which could further promote the apoptosis of cardiomyocytes.Conclusion: Our findings revealed a novel and critical role for circRNA Fbxl5 in regulating cardiomyocyte apoptosis, and added additional insight into circRNAs mediated during myocardial IRI. The underlying miR-146a-MED1 signaling serves as an important cascade in regulating the apoptosis of cardiomyocytes.Keywords: myocardial ischemia reperfusion injury, circular RNA, microRNA-146a, cardiomyocyte apoptosis

Qingen Da,1,2,&ast; Mingming Ren,2,&ast; Lei Huang,2 Jianhua Qu,1 Qiuhua Yang,3 Jiean Xu,4 Qian Ma,4 Xiaoxiao Mao,4 Yongfeng Cai,4 Dingwei Zhao,4 Junhua Luo,5 Zilong Yan,1 Lu Sun,2 Kunfu Ouyang,2 Xiaowei Zhang,6 Zhen Han,2 Jikui Liu,1 Tao Wang2 1Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China; 2Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China; 3Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, USA; 4Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of China; 5Department of Urological Surgery, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 6School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jikui Liu, Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China, Email liu8929@126.com Tao Wang, Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China, Email szwangtao@126.comObjective: We aimed to explore the prognostic patterns of ferroptosis-related genes in papillary renal cell carcinoma (PRCC) and investigate the relationship between ferroptosis-related genes and PRCC tumor immune microenvironment.Methods: We obtained the mRNA expression and corresponding clinical data of PRCC from the public tumor cancer genome atlas database (TCGA). The PRCC patients were randomly divided into two cohort, training cohort and verification cohort, respectively. Univariate Cox regression, LASSO Cox regression, multivariate Cox regression analysis were utilized to construct ferroptosis signature for PRCC patients. And then, risk prognostic model was established and verified. The correlation of ferroptosis-related signature with survival and immune microenvironment was systematically analyzed.Results: A 4-genes ferroptosis signature (CDKN1A, MIOX, PSAT1, and RRM2) was constructed. Multivariate Cox regression assay indicates that the risk score of ferroptosis signature was an independent prognostic indicator (HR=1.391, p< 0.001). The survival curve shows that the high-risk group has a poorer prognosis than the low-risk group (p< 0.001). The risk prognostic model was established based on prognostic factors of clinical-stage, hemoglobin, and risk score. The time-dependent receiver operating characteristic curve (ROC) analysis proves the predictive capacity of the ferroptosis signature, the 3 years area under the curve (AUC) is 0.890, and the 5 years AUC is 0.733. Further analysis suggested that cell cycle, pentose phosphate pathway, P53 signaling pathway were significantly enriched in the high-risk group. The significantly different fractions of dendritic cells resting, macrophage cells, and T cells follicular helper were observed in risk groups.Conclusion: This study implicates a ferroptosis signature which has a good predict capacity of the prognosis in PRCC patients. Ferroptosis-related genes may have a key role in the process of anti-tumor and serve as therapeutic targets for PRCC.Keywords: papillary renal cell carcinoma, ferroptosis, gene signature, prognosis model, tumor immune microenvironment

Yulan Huang,&ast; Shitong He,&ast; Yitian Chen, Junli Sheng, Yuling Fu, Xialin Du, Yalong Yang, Honglin Liu, Zhenyu Han, Yingqi Huang, Qian Wen, Chaoying Zhou, Xinying Zhou, Shengfeng Hu, Li Ma Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Ma; Shengfeng HuInstitute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email mali_61648322@smu.edu.cn; hushengfeng@smu.edu.cnBackground: As deubiquitinases (DUBs), ubiquitin C-terminal hydrolase (UCH)-L1 has been shown to play a crucial role in regulating diverse biological processes. However, its function in macrophage polarization remains unclear.Methods: We performed in vivo and in vitro experiments to investigate the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a kind of DUBs, in macrophage differentiation by using UCHL1-deficiency mice.Results: We demonstrated that LPS stimulation induced UCHL1 expression in macrophages. The deficiency of UCHL1 expression decreased the expression of CD80 and CD86 but increased the expression of CD206. The expression of TNF-α, IL-6, iNOS, and IL-10 was downregulated, while that of Arg1, Ym1, and Fizz1 was upregulated in UCHL1 deficient macrophages. Moreover, we observed that UCHL1 promoted the degradation of p110α through autophagy, but paradoxically increased the activity of AKT, thereby promoting polarization of macrophages into pro-inflammatory states.Conclusion: In this study, we identified UCHL1 as a positive regulator of M1 macrophage polarization. Our findings may help in developing therapeutic interventions for the treatment of inflammatory diseases and pathogenic infections.Keywords: UCHL1, macrophages, AKT, p110α, autophagy

Peiying Wei,1,2,&ast; Chang Shao,3,&ast; Min Tian,4 Mengwei Wu,5 Haibin Wang,2 Zhijiang Han,2 Hongjie Hu1 1Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Radiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Pathology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4The Fourth Clinical Medical College, Zhejiang Traditional Chinese Medicine University, Hangzhou, People’s Republic of China; 5Department of Radiology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijiang HanDepartment of Radiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, No. 261, Huansha Road, Hangzhou, 310006, People’s Republic of ChinaEmail hzjsyy@126.comHongjie HuDepartment of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of ChinaEmail hongjiehu@zju.edu.cnObjective: To investigate the value of the signal intensity on T2-weighted magnetic resonance (MR) imaging using quantitative analysis in the differentiation of parotid tumors.Materials and Methods: MR data of 80 pleomorphic adenomas (PAs), 68 Warthin tumors (WTs), and 34 malignant tumors (MTs) confirmed by surgery and histology were retrospectively analyzed. The signal intensities of tumor, normal parotid gland, spinal cord, and buccal subcutaneous fat were measured, and the signal intensity ratios (SIRs) between the tumor and the three references were calculated. Receiver operating characteristic curve was used to determine the optimal threshold and diagnostic efficiency of SIR for differentiating PAs, WTs, and MTs.Results: The area under the curve (AUC) of tumor to parotid gland SIR (SIRP), tumor to spinal cord SIR (SIRC), and tumor to buccal subcutaneous fat SIR (SIRF) for differentiating PAs and WTs was 0.922, 0.918, and 0.934, respectively. The sensitivity and specificity at an optimal SIR threshold were 86.3% and 91.2%, 80.0% and 97.1%, and 85.0% and 94.1%, respectively. The AUC of SIRP, SIRC, and SIRF for distinguishing PAs from MTs was 0.793, 0.802, and 0.774, respectively. The sensitivity and specificity at an optimal SIR threshold was 86.3% and 61.8%, 80.0% and 73.5%, and 82.5% and 73.5%, respectively. The AUC of SIRP, SIRC, and SIRF for distinguishing WTs from MTs was 0.716, 0.709, and 0.759, respectively. The sensitivity and specificity at an optimal SIR threshold were 61.8% and 82.4%, 55.9% and 82.4%, and 64.7% and 86.8%, respectively.Conclusion: SIRP, SIRC, and SIRF on T2-weighted MR images had high diagnostic efficiency for differentiating between PAs and WTs, while SIRP and SIRC for differentiating between PAs and MTs, and SIRF for differentiating between WTs and MTs had relatively high diagnostic efficiency.Keywords: parotid tumor, signal intensity ratio, pathology, magnetic resonance imaging, T2-weighted imaging

Zhongbo Han, Chunxia Yang, Qingfeng Wang, Meng Wang, Xi Li, Chao Zhang Department of Gastrointestinal Surgery, Zibo Central Hospital, Shandong University, Zibo, Shandong, People’s Republic of ChinaCorrespondence: Chao ZhangDepartment of Gastrointestinal Surgery, Zibo Central Hospital, Shandong University, 54 West Gongqingtuan Road, Zibo, Shandong, 255000, People’s Republic of ChinaTel +86 05333570671Fax +86 05333570672Email zhangchao20202021@163.comPurpose: High rate of perineal surgical site infection (SSI) is the most common complication following abdominoperineal resection (APR), especially for extralevator abdominoperineal excision (ELAPE). The purpose of this study was to investigate the effect of continuous negative pressure drainage combined with intermittent irrigation (CNPDCII) in the presacral space on the perineal SSI following laparoscopic ELAPE for low rectal cancer.Patients and Methods: The clinical data of 99 patients with low rectal cancer who underwent laparoscopic ELAPE surgery were retrospectively analyzed. Among the 99 patients, 46 patients received CNPDCII and 53 patients received conventional drainage in the presacral space after ELAPE. Self-made irrigation drainage tube: took a silicone drainage tube, cut 3 side holes at every 2cm intervals at the front end, and fixed a flexible tube of an intravenous needle at the front end of the silicone drainage tube. The conventional drainage tube or self-made irrigation drainage tube was placed in the presacral space and poked out from the inside of the ischial tuberosity. The incidence of SSI and other perioperative indicators between the two groups was compared within 30 days after surgery.Results: There was no statistical difference in clinicopathological features between the two groups of patients (p> 0.05). A statistically lower rate of SSI was found in CNPDCII group (17.4%, 8/46) than the conventional drainage group (35.8%, 19/53). The drainage tube retention time (7.8± 1.2 d VS 9.4± 1.6 d) and the postoperative hospital stay (9.7± 1.4 d VS 11.9± 2.3 d) in CNPDCII group were significantly shortened than the conventional drainage group. There was no statistical difference in operating theatre time and intraoperative blood loss between the two groups. Multivariate analysis confirmed that CNPDCII was an independent protective factor for SSI after ELAPE.Conclusion: CNPDCII can effectively reduce the incidence of SSI following laparoscopic ELAPE, which is simple, safe and effective.Keywords: low rectal cancer, extralevator abdominoperineal excision, negative pressure drainage, surgical site infection

Zhongbo Han,1,* Dawei Chen,2,* Yan Li,3 Guangshuai Zhou,3 Meng Wang,1 Chao Zhang1 1Department of Gastrointestinal Surgery, Zibo Central Hospital, Shandong University, Zibo, Shandong, People’s Republic of China; 2Department of General Surgery, Jiangyin People′s Hospital, School of Medicine, Southeast University, Jiangyin, Jiangsu, People’s Republic of China; 3Department of Quality and Safety Management, Zibo Central Hospital, Shandong University, Zibo, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao ZhangDepartment of Gastrointestinal Surgery, Zibo Central Hospital, Shandong University, 54 West Gongqingtuan Road, Zibo, 255000, Shandong, People’s Republic of ChinaTel +86 05333570671Fax +86 05333570672Email zhangchao20202021@163.comPurpose: To develop a risk scoring system that can predict the incidence of anastomotic leakage after laparoscopic rectal cancer surgery.Patients and Methods: The clinical data of 387 patients with rectal cancer who underwent laparoscopic low anterior resection were retrospectively collected. Univariable and multivariable logistic regression analyses were used to evaluate independent risk factors for postoperative anastomotic leakage. A simplified points system was then developed based on the corresponding regression coefficient β of each risk factor. Receiver operating characteristic (ROC) analysis was used to evaluate the performance and the optimal cut-off value in predicting anastomotic leakage. The performance of the points system was then externally validated in an independent cohort of 192 patients based in another institution.Results: Anastomotic leakage occurred in 36 of 387 patients with rectal cancer (9.30%). Logistic multivariable regression analysis showed that males, maximum tumor diameter (≥ 5cm), operation time (≥ 180min), preoperative chemoradiation, intraoperative blood transfusion and the anastomosis level from the anal verge (≤ 5cm) were independent risk factors for the incidence of anastomotic leakage. According to the scoring standard, the risk points of each patient were calculated. ROC analysis based on the risk points showed that the area under the curve (AUC) was 0.795 (95% CI:0.752– 0.834) and the optimal cut-off value was 6, yielding a sensitivity of 88.89% and a specificity of 62.96%. Using this risk points system, the AUC of another cohort of 192 patients from another institution who underwent laparoscopic low anterior resection for rectal cancer was 0.853 (95% CI:0.794– 0.900, p< 0.001) and patients with risk points ≥ 6 had a 21.05% chance of developing anastomotic leakage.Conclusion: This risk points system for predicting anastomotic leakage following laparoscopic rectal cancer surgery may be useful for surgeons in their decisions to perform intraoperative diversion stoma, which can reduce the incidence of postoperative anastomotic leakage.Keywords: anastomotic leakage, rectal cancer, laparoscopic surgery, risk score

Lili Bai,* Wangjie Sun,* Zhe Han, Hua Tang Tianjin Life Science Research Center, Tianjin Key Laboratory of Inflammation Biology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua TangTianjin Life Science Research Center, Tianjin Key Laboratory of Inflammation Biology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Tianjin 300070, People’s Republic of ChinaTel/Fax +86 22 23542503Email tangh@tmu.edu.cnAim: To explore the role and potential mechanism of circSND1 in cervical cancer (CC).Main Methods: qRT-PCR was used to determine the expression of circSND1 in tumor necrosis factor-α (TNF-α)-treated HeLa cells. CircSND1 overexpression and knockdown were performed to indicate the functional role of circSND1 in vitro and in vivo. Luciferase assay was used to analyze promoter activity. The expression and regulation of circSND1, miR-125a-3p and FUT6 were evaluated using EGFP fluorescent reporter assay and rescue experiments. Immunofluorescence and Western blot assays were used to analyze the activation of nuclear factor-κB (NF-κB).Results: In HeLa cells, TNF-α up-regulated the expression of circSND1 by activating the NF-κB signaling pathway. Overexpression of circSND1 significantly increased the migration and invasion and the epithelial–mesenchymal transition (EMT) process of CC cells, and promoted tumor metastasis in xenograft nude mouse model, whereas down-regulation of circSND1 exerted opposite effects. Furthermore, circSND1 enhanced the expression of FUT6 via sponging miR-125a-3p, and FUT6 activated NF-κB signaling pathway.Conclusion: We found that circSND1 promoted the expression of FUT6 and the malignant behavior of cervical cancer through the ceRNA mechanism, and there was a TNF-α/NF-κB/circSND1/miR-125a-3p/FUT6/NF-κB positive feedback pathway between them, which suggests that circSND1 can be a promising prognostic marker and therapeutical target for cervical cancer.Keywords: circSND1, miR-125a-3p, FUT6, NF-κB, ceRNA, cervical cancer

Zhan T, Zhu Q, Han Z, et al. Cancer Manag Res. 2020;12:1483–1492. The authors have advised Figure 4C on page 1490 is incorrect. Due to an error at the time of figure assembly Figure 4D and Figure 4C were inadvertently duplicated. The correct Figure 4 is shown below. Figure 4 miR-455-3p restrains Wnt/β-catenin signaling via TAZ. (A and B) Expression of β-catenin, Cyclin D and C-myc in pancreatic cancer cells transfected with miR-455-3p mimic or miR-455-3p mimic plus TAZ expression vector was detected by qPCR. (C and D) Western blot analysis of β-catenin, Cyclin D and C-myc in PANC1 and MIAPaCa2 cells transfected with miR-455-3p mimic or miR-455-3p mimic plus TAZ expression vector β-actin is used as loading control vs miR-455-3p mimics/mimic control group, miR-455-3p mimics/miR-455-3p mimics+TAZ group. *p

PurposeAggressive angiomyxoma (AAM) was identified as a distinct clinicopathological entity in 1983. Since then, a few cases of its occurrence in the scrotum have been reported. This case series was performed to increase clinicians' understanding of the clinical features and treatment of AAM in the scrotum.MethodsWe evaluated the clinical presentations, treatments, and follow-up of two patients with AAM in the scrotum in our hospital and 34 cases reported in the literature.ResultsAmong the 36 patients, the average age was 48.3 ± 20.6 years old (range from 1 to 81); the average maximum diameter of the tumor was 8.36 cm (1.6–25 cm); the site of one (2.78%) patient was located in the epididymis, two (5.56%) in the testes, five (13.89%) in the spermatic cord, and 28 (77.77%) in the scrotum. The clinical symptoms were generally non-specific and 20 patients inadvertently discovered their slow-growing painless masses. The treatments for all these patients were surgical excision once the tumor had been found and one case underwent excision followed by radiotherapy. The median follow-up time for the remaining 32 cases was 24.5 months (1 to 84 months). Recurrence occurred in three cases (9.09%) at the primary sites and no cases of distant metastasis.ConclusionAAM of the scrotum can occur in middle-aged and elderly men. The clinical manifestation generally involves a long history of asymptomatic masses or swelling in the scrotum. Ultrasound is the most commonly used diagnostic technique but magnetic resonance imaging may be more effective. The mainly treatment is surgical excision and postoperative histopathological examination is still the gold standard for its diagnosis. Although it is locally aggressive, metastasis is extremely rare in males.

Dongjiu Li,1,* Chengyu Mao,1,* En Zhou,1,* Jiayin You,2,* Erhe Gao,3 Zhihua Han,1 Yuqi Fan,1 Qing He,1 Changqian Wang1 1Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China; 2Department of Emergency, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China; 3Center for Translational Medicine, Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA*These authors contributed equally to this workCorrespondence: Changqian Wang Email wangcqdr17@163.comObjective: Post myocardial infarction (MI) fibrosis has been identified as an important factor in the progression of heart failure. Previous studies have revealed that microRNA-21 (miR-21) plays an important role in the pathogenesis of fibrosis. The purpose of this study was to explore the role of miR-21 in post-MI cardiac fibrosis.Material and Methods: MI was established in wild-type (WT) and miR-21 knockout (KO) mice. Primary mice cardiac fibroblasts (CFs) were isolated from WT and miR-21 KO mice and were treated with angiotensin II (Ang II) or Sprouty1 (Spry1) siRNA. Histological analysis and echocardiography were used to determine the extent of fibrosis and cardiac function.Results: Compared with WT mice, miR-21 KO mice displayed smaller fibrotic areas and decreased expression of fibrotic markers and inflammatory cytokines. In parallel, Ang II-induced myofibroblasts transformation was partially inhibited upon miR-21 KO in primary CFs. Mechanistically, we found that the expression of Spry1, a previously reported target of miR-21, was markedly increased in miR-21 KO mice post MI, further inhibiting ERK1/2 activation. In vitro studies showed that Ang II activated ERK1/2/TGF-β/Smad2/3 pathway. Phosphorylated Smad2/3 further enhanced the expression of α-SMA and FAP and may promote the maturation of miR-21, thereby downregulating Spry1. Additionally, these effects of miR-21 KO on fibrosis were reversed by siRNA-mediated knockdown of Spry1.Conclusion: Our findings suggest that miR-21 promotes post-MI fibrosis by targeting Spry1. Furthermore, it mediates a positive feedback on Ang II, thereby inducing the ERK/TGF-β/Smad pathway. Therefore, targeting the miR-21–Spry1 axis may be a promising therapeutic option for ameliorating post-MI cardiac fibrosis.Keywords: cardiac fibrosis, myocardial infarction, microRNA-21, Sprouty1, ERK/TGF-β/Smad signaling pathway

Yizhou Peng,1 Li Meng,1 Xuemei Hu,2 Zhiqiang Han,3 Zhenya Hong1 1Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s People’s Republic of China; 3Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Zhenya HongDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie-Fang Avenue, Wuhan 430030, Hubei, People’s Republic of ChinaTel/Fax +86 027-83665046Email hongzhenya@126.comZhiqiang HanCancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie-Fang Avenue, Wuhan 430030, Hubei, People’s Republic of ChinaEmail hanzq2003@126.comBackground: The selective Janus-activated kinase inhibitor ruxolitinib (rux) is now widely used to treat myelofibrosis and polycythemia vera due to its remarkable effect of reducing splenomegaly and improving constitutional symptoms. With opportunistic infections secondary to rux constantly reported; however, an increasing number of studies have begun to investigate the mechanism and underlying immunosuppressive effect of rux.Case Presentation: We report two cases of tuberculosis (TB) in primary myelofibrosis patients during rux therapy. The first patient received rux soon after diagnosis, and tracheobronchial TB (TBTB) and bronchoesophageal fistula were found after 4 months. After discontinuation of rux, antituberculosis therapy (ATT) was introduced. The second patient initiated rux due to progressive splenomegaly after 7.5 years of interferon therapy and was diagnosed with disseminated TB after 2 months. He received ATT as well. His rux was maintained due to the high burden of systematic symptoms and splenomegaly. Both myelofibrosis and TB were well controlled in these patients.Conclusion: This is the first case report that describes rux-related TBTB accompanied by a bronchoesophageal fistula. Through a review of the literature, we provide supporting evidence to the finding that intrinsic disorders of myeloproliferative neoplasms and rux-induced immunologic deregulation together lead to TB. We highlight the importance of screening for latent TB infection and timely chemoprophylaxis before rux therapy. Once TB is diagnosed during treatment, rux is recommended to be stopped and active ATT should begin quickly.Keywords: myelofibrosis, ruxolitinib, tuberculosis, infection

Zhiduan Cai,1,* Yulin Deng,1,* Jianheng Ye,2 Yangjia Zhuo,3 Zezhen Liu,2 Yingke Liang,3 Hui Zhang,3 Xuejin Zhu,2 Yong Luo,3 Yuanfa Feng,4 Ren Liu,2 Guo Chen,5 Yongding Wu,3 Zhaodong Han,3 Yuxiang Liang,3 Funeng Jiang,3 Weide Zhong1– 4,6 1Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou 510180, People’s Republic of China; 3Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, People’s Republic of China; 4Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510230, People’s Republic of China; 5Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, People’s Republic of China; 6School of Medicine, Jinan University, Guangzhou, Guangdong 510632, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weide ZhongGuangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of ChinaEmail zhongwd2009@live.cnPurpose: Citrate synthase (CS) is a rate-limiting enzyme in the citrate cycle and is capable of catalyzing oxaloacetate and acetyl-CoA to citrate. CS has been uncovered to be upregulated in a variety of cancers, and its expression and clinical significance in prostate cancer (PCa) remain unknown.Methods: In this study, we examined the association between CS expression level and clinicopathological features of prostate cancer patients in a TMA cohort and the public cancer database (The Cancer Genome Atlas-Prostate Adenocarcinoma, TCGA-PRAD). The CS knockdown cell lines were constructed to study the effects of CS downregulation on proliferation, colony formation, migration, invasion, and cell cycle of prostate cancer cells in vitro. And the effect of CS downregulation on tumor growth in mice was studied in vivo. In addition, the metabolomics and mitochondrial function were detected in the CS knockdown cell lines.Results: CS expression level in PCa tissues was higher than that in normal tissues (P < 0.05). CS upregulation was significantly associated with high Gleason score (P < 0.05), advanced pathological stage (P < 0.001), and biochemical recurrence (P < 0.001). Functionally, decreased expression of CS inhibited PCa cell proliferation, colony formation, migration, invasion and cell cycle in vitro, and inhibited tumor growth in vivo. In addition, CS downregulation exerted potential inhibitory effects on the lipid metabolism and mitochondrial function of PCa cells.Conclusion: In conclusion, these findings suggested that CS upregulation may contribute to the aggressive progression and poor prognosis of PCa patients, which might be partially associated with its influences on the cell lipid metabolism and mitochondrial function.Keywords: prostate cancer, citrate synthase, prognosis, lipid metabolism

Hui Shi,1,2,* Shuo Sun,1,* Haoyue Xu,3,* Zongren Zhao,3 Zhengzhong Han,3 Jun Jia,3 Dongmei Wu,4 Jun Lu,4 Hongmei Liu,3,5 Rutong Yu1,3,5 1Clinical Medical College, Nanjing Medical University, Nanjing, People’s Republic of China; 2The Second People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 3Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, People’s Republic of China; 5Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rutong Yu; Hongmei Liu Tel +86 13182310079; +86 17716228111Email yu.rutong@163.com; liuhongmei816@sina.comIntroduction: Temozolomide (TMZ) is the first-line chemotherapeutic option to treat glioma; however, its efficacy and clinical application are limited by its drug resistance properties. Polo-like kinase 1 (PLK1)-targeted therapy causes G2/M arrest and increases the sensitivity of glioma to TMZ. Therefore, to limit TMZ resistance in glioma, an angiopep-2 (A2)-modified polymeric micelle (A2PEC) embedded with TMZ and a small interfering RNA (siRNA) targeting PLK1 (siPLK1) was developed (TMZ-A2PEC/siPLK).Materials and Methods: TMZ was encapsulated by A2-PEG-PEI-PCL (A2PEC) through the hydrophobic interaction, and siPLK1 was complexed with the TMZ-A2PEC through electrostatic interaction. Then, an angiopep-2 (A2) modified polymeric micelle (A2PEC) embedding TMZ and siRNA targeting polo-like kinase 1 (siPLK1) was developed (TMZ-A2PEC/siPLK).Results: In vitro experiments indicated that TMZ-A2PEC/siPLK effectively enhanced the cellular uptake of TMZ and siPLK1 and resulted in significant cell apoptosis and cytotoxicity of glioma cells. In vivo experiments showed that glioma growth was inhibited, and the survival time of the animals was prolonged remarkably after TMZ-A2PEC/siPLK1 was injected via their tail vein.Discussion: The results demonstrate that the combination of TMZ and siPLK1 in A2PEC could enhance the efficacy of TMZ in treating glioma.Keywords: co-delivery, polymeric micelle, siPLK1, TMZ, drug resistance, glioma

Luo Zhao, Yingzhi Qin, Dongjie Ma, Li Li, Zhijun Han, Shanqing Li, Hongsheng Liu Department of Thoracic Surgery, Peking Union Medical College Hospital, CAMS & PUMC, Beijing 100730, People’s Republic of ChinaCorrespondence: Hongsheng LiuDepartment of Thoracic Surgery, Peking Union Medical College Hospital, Beijing 100730, People’s Republic of ChinaTel +86 18519667758Fax +86 10 69152630Email pumchlhsnj@163.comPurpose: To assess the use of video-assisted thoracoscopic surgery to treat lung metastases from refractory choriocarcinoma.Patients and Methods: We reviewed patients diagnosed with refractory choriocarcinoma who underwent lung resection by video-assisted thoracoscopic surgery combined with chemotherapy between October 2013 and August 2019 at the Peking Union Medical College Hospital. The surgical records, pathologic findings and survival rates were analyzed.Results: The study included 73 patients who underwent 78 thoracoscopic surgeries. Most patients underwent lobectomy (48.7%), and 17 patients (21.8%) underwent resection of more than one lobe. The median operation time and bleeding volume were 95 minutes and 50 mL, respectively. The median duration of chest tube use and hospital stay were 3 days and 4 days, respectively. Postoperative complications were documented in 6 patients (7.7%). The thoracic lymph nodes were harvested in 51 patients (65.4%), but none of these patients had positive nodes. A total of 69.2% of the patients had positive pathologic findings. The mean follow-up time was 30 months. During follow-up, 11 patients experienced disease relapse, and 2 of them died because of brain metastasis. The overall disease-free rate was 83.6%, and the survival rate was 97.0% after excluding those lost to follow-up. Patients with decreased postoperative β-hCG showed a higher disease-free rate during follow up (P< 0.05).Conclusion: The minimally invasive video-assisted thoracoscopic approach is a valuable and safe treatment for refractory choriocarcinoma patients with lung metastases. Lymphadenectomy is not suggested for these patients. Patients with decreased postoperative β-hCG levels may achieve a much better prognostic result.Keywords: video-assisted thoracoscopic surgery, lung metastases, choriocarcinoma

Ting Zhan, 1,* Qingxi Zhu, 1,* Zheng Han, 1 Jie Tan, 1 Meng Liu, 1 Weijie Liu, 1 Wei Chen, 1 Xiaoli Chen, 1 Xueting Chen, 2 Junsheng Deng, 2 Xia Tian, 1 Xiaodong Huang 1 1Department of Gastroenterology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan 430060, People’s Republic of China; 2Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodong Huang; Xia Tian Tel +86 1388619054; +86 13871480868Email 13297056720@163.com; hcwy100@163.comBackground: Pancreatic cancer (PC) is a highly invasive tumor with a poor prognosis, short overall survival rate and few chemotherapeutic choices. Despite the importance of finding ways to treat pancreatic cancer, the mechanisms of tumor progression have not been fully elucidated. microRNA-455-3p (miR-455-3p) has been reported to play an important role in several cancers, but its function in pancreatic cancer remains unclear.Methods: To investigate the biological functions, miRNAs mimics or inhibitors were transfected into pancreatic cancer cells. Flow cytometry was used to detect cell apoptosis. Wound healing and Transwell assays were employed to observe cell invasion and migration abilities. The expression of Bcl-2, Bax, caspase-3, E-cadherin, N-cadherin, Snail, β-Catenin, c-Myc and Cyclin D1 were evaluated by qPCR and Western blot.Results: We confirmed that inhibition of miR-455-3p decreases cell apoptosis and increases cell migration, invasion and EMT of pancreatic cancer, whereas forced overexpression of miR-455-3p has the opposite effect. Furthermore, we demonstrated that the tumor suppression effects of miR-455-3p were partially reversed by TAZ overexpression. In addition, miR-455-3p led to inactivation of Wnt/β-catenin signaling in pancreatic cancer cells, and TAZ overexpression restored the inhibition of Wnt/β-catenin signaling.Conclusion: Taken together, our data demonstrated that miR-455-3p functions as an important tumor suppressor that suppresses the Wnt/β-catenin signaling pathway via TAZ to inhibit tumor progression in pancreatic cancer. We conclude that the miR-455-3p/TAZ/Wnt axis may be a potential therapeutic target for pancreatic cancer.Keywords: miR-455-3p, Wnt, apoptosis, metastasis, EMT

Yuxiu Shen, Zaigang Han, Shuang Liu, Yang Jiao, Ying Li, Hongyan Yuan Department of Pharmacology, Affiliated Hospital of Beihua University, Jilin City, Jilin Province 132000, People’s Republic of ChinaCorrespondence: Yuxiu ShenDepartment of Pharmacology, Affiliated Hospital of Beihua University, No. 12, Jiefang Middle Road, Jilin City, Jilin Province 132000, Tel +86- 13384401555Email shenyuxiu1680@163.comPurpose: This study was aimed to explore the anti-tumor effect of curcumin on breast cancer (BC) and the underlying mechanism involving Tafazzin (TAZ)/Yes-associated protein (YAP) axis.Methods: Different concentrations of curcumin (0, 10, 20 and 30 μM) were used to treat BC cells (MCF-7 and MDA-MB-231 cells). The viability, colony formation, apoptosis, migration, and invasion of BC cells were detected by MTT, colony formation, flow cytometry, wound-healing and transwell assay, respectively. The protein expression of TAZ and YAP (effectors of Hippo signaling pathway) was detected by Western blot. MDA-MB-231 cells were injected into mice to verify the anti-tumor effect of curcumin in vivo.Results: Curcumin (20 and 30 μM) inhibited the proliferation, migration and invasion, and promoted the apoptosis of MCF-7 and MDA-MB-231 cells. Curcumin decreased the protein expression of TAZ and YAP in MCF-7 and MDA-MB-231 cells. Overexpression of YAP reversed the anti-tumor effect of curcumin on MDA-MB-231 cells. In addition, curcumin (100, 200 and 300 mg/kg/d) inhibited the growth of tumor xenografts in mice, and down-regulated the protein expression of TAZ and YAP in tumor xenografts. However, curcumin at a concentration of 300 mg/kg/d slowed the increasing of body weight in mice.Conclusion: Curcumin inhibited the tumorigenesis of BC by blocking TAZ/YAP axis.Keywords: curcumin, breast cancer, Hippo signaling pathway, proliferation, metastasis

Jia He, 1, 2 Xiaoyun Zhou, 1, 2 Li Li, 1, 2 Zhijun Han 1, 2 1Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing 100730, People’s Republic of China; 2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of ChinaCorrespondence: Zhijun HanDepartment of Thoracic Surgery, Peking Union Medical College Hospital, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, People’s Republic of ChinaEmail handi473984@163.comBackground: Lung squamous cell carcinoma (LUSC) accounts for approximately 30% of all lung cancers that possesses the highest occurrence and mortality in all cancer types. Long noncoding RNAs have been reported to modulate tumor development for several decades.Aim of the Study: This research aims to investigate the role of MAGI2-AS3 in LUSC.Methods: RT-qPCR tested genes (including MAGI2-AS3, miR-374a/b-5p and CADM2) expression. Cell proliferation was detected by colony formation and EdU assays. Cell migration and invasion were evaluated by transwell assay. Flow cytometry analysis of apoptotic cells and Western blot analysis on apoptosis-related genes were applied to measure cell apoptosis. Nuclear-cytoplasmic fractionation and FISH assay positioned MAGI2-AS3. The combination between miR-374a/b-5p and MAGI2-AS3 (or CADM2) was determined by luciferase reporter assay and RIP assay.Results: MAGI2-AS3 inhibited the proliferative, migratory and invasive capability of LUSC cells with upregulated expression. Additionally, MAGI2-AS3 overexpression promoted cell apoptosis. We discovered that MAGI2-AS3 was located in the cytoplasm. Hereafter, we found out that MAGI2-AS3 targeted miR-374a/b-5p. CADM2 was targeted by miR-374a/b-5p. Finally, rescue assays indicated that the promoting effects of miR-374a/b-5p amplification on biological activities were restored by CADM2 addition.Conclusion: In conclusion, lncRNA MAGI2-AS3 suppressed LUSC by regulating miR-374a/b-5p/CADM2 axis, which might potentially serve as a therapeutic marker for LUSC patients.Keywords: lung squamous cell carcinoma, LUSC, MAGI2-AS3, miR-374a/b-5p, CADM2

Rui Cui,1,2 Xiao-hui Wang,3 Chao Ma,4 Tong Liu,5 Zhi-gang Cheng,1 Zhi-yu Han,1 Fang-yi Liu,1 Xiao-ling Yu,1 Jie Yu,1,* Ping Liang1,* 1Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China; 2Department of Ultrasonography, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, People’s Republic of China; 3Department of Ultrasonography, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, People’s Republic of China; 4Department of Ultrasonography, Qiqihaer Hospital of Chinese Medicine, Qiqihaer 161000, People’s Republic of China; 5Department of Ultrasonography, Hebei Chest Hospital, Shijiazhuang 050000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ping Liang; Jie YuDepartment of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, People’s Republic of ChinaTel +86-10-66939530Fax +86-10-68161218Email liangping301@hotmail.com; yu-jie301@hotmail.comPurpose: To compare overall survival (OS) and progression-free survival (PFS) between microwave ablation (MWA) and transarterial chemoembolization (TACE) for solitary hepatocellular carcinoma (HCC) smaller than 5 cm.Methods: Patients with solitary HCC smaller than 5cm who initially underwent MWA or TACE were identified in Chinese PLA General Hospital from June 2010 to October 2015. Propensity score matching (PSM) was performed with a 1:1 matching protocol. OS and PFS were compared by using the log-rank test. After matching, subgroup analysis based on tumor size (≤3cm/3.1–5cm) was also conducted. Prognostic factors for OS and PFS were assessed with Cox proportional hazard regression model.Results: A total of 202 patients (MWA, n=120; TACE, n=82) were identified. After matching, 116 patients were included (58 patients for each treatment group). MWA provided significantly better OS and PFS than TACE for both the entire cohort (OS, P

Xiaoqing Tian,1 YinFeng He,2 Zhe Han,3 HongMin Su,4 Chao Chu4 1Department of Orthopeadic Surgery, Heze Mudan People’s Hospital, Heze City, Shandong 274000, People’s Republic of China; 2Department of Joint Surgery, Heze Municipal Hospital, Heze City, Shandong 274000, People’s Republic of China; 3Department of Traumatic Surgery, Heze Municipal Hospital, Heze City, Shandong 274000, People’s Republic of China; 4Department of Spinal Surgery, Heze Municipal Hospital, Heze City, Shandong 274000, People’s Republic of ChinaCorrespondence: Chao ChuDepartment of Spinal Surgery, Heze Municipal Hospital, 2888 Caozhou West Road, Heze City, Shandong 274000 People’s Republic of ChinaEmail chaochuaaa@126.comBackground: To date, the impact and potential molecular mechanisms of CLDN12 and its association with malignancy in osteosarcoma have not been determined.Materials and methods: In the present study, the expression profiles of CLDN12 in osteosarcoma cell lines and tissues were explored by immunohistochemistry. A fetal osteoblast cell line was transfected with a eukaryotic expression plasmid, and endogenous CLDN12 in osteosarcoma cells were silenced through an RNA interference (RNAi) method. These transfections were verified, and the activation state of Thr308 site in protein kinase B (Akt) was explored by Western blotting. Moreover, the malignant phenotype of osteosarcoma cells was evaluated by cell counting kit-8 (CCK-8), colony formation, Transwell, and wound-healing assays. Furthermore, osteoblast cells were treated with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 to determine the impact of the PI3K/Akt signaling pathway on cell migration ability.Results: The results revealed that CLDN12 was overexpressed and localized in the cytoplasm of osteosarcoma cells, and its overexpression was associated with an unfavorable prognosis, irrespective of tumor node metastasis stage. In addition, the knockdown of CLDN12 in cultured osteosarcoma cells markedly attenuated cell proliferation and migration, as indicated by the Cell Counting Kit-8 assay, colony formation assay, scratch wound healing assay and Transwell migration assay. The results also demonstrated that the overexpression of CLDN12 increased the activation of Thr308 site in Akt in fetal osteoblast cells, and the PI3K inhibitor LY294002 partially decreased CLDN12-promoted proliferation and metastasis.Conclusion: In conclusion, the results of the present study indicated that CLDN12 promoted cell proliferation and migration through the PI3K/Akt signaling pathway in osteosarcoma cells, suggesting that CLDN12 may be a potential agent in the treatment of patients with osteosarcoma.Keywords: tight junction, claudin-12, osteosarcoma, metastasis, protein kinase B

Abstract In multiple tumor types, prediction of response to immune therapies relates to the presence, distribution and activation state of tumor infiltrating lymphocytes (TILs). Although such therapies are, to date, unsuccessful in gliomas, little is known on the immune contexture of TILs in these tumors. We assessed whether low and high-grade glioma (LGG and HGG, grade II and IV respectively) differ with respect to number, location and tumor reactivity of TILs; as well as expression of molecules involved in the trafficking and activation of T cells. Intra-tumoral CD8 T cells were quantified by flow cytometry (LGG: n = 12; HGG: n = 8) and immunofluorescence (LGG: n = 28; HGG: n = 28). Neoantigen load and expression of Cancer Germline Antigens (CGAs) were assessed using whole exome sequencing and RNA-seq. TIL-derived DNA was sequenced and the variable domain of the TCRβ chain was classified according to IMGT nomenclature. QPCR was used to determine expression of T cell-related genes. CD8 T cell numbers were significantly lower in LGG and, in contrast to HGG, mainly remained in close vicinity to blood vessels. This was accompanied by lower expression of chemo-attractants CXCL9, CXCL10 and adhesion molecule ICAM1. We did not observe a difference in the number of expressed neoantigens or CGAs, nor in diversity of TCR-Vβ gene usage. In summary, LGG have lower numbers of intra-tumoral CD8 T cells compared to HGG, potentially linked to decreased T cell trafficking. We have found no evidence for distinct tumor reactivity of T cells in either tumor type. The near absence of TILs in LGG suggest that, at present, checkpoint inhibitors are unlikely to have clinical efficacy in this tumor type.

Zhaofei Wan,1 Yan Fan,2 Xiaojun Liu,1 Jiahong Xue,1 Zhenhua Han,1 Canzhan Zhu,1 Xinhong Wang1 1Department of Cardiovascular Medicine, Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Cardiovascular Medicine, Gansu Provincial Hospital, Lanzhou, People’s Republic of ChinaCorrespondence: Xinhong WangDepartment of Cardiovascular Medicine, Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi 710004, People’s Republic of ChinaTel +86 298 632 0430Email wangxinhongshx@163.comBackground: NLRP3 inflammasome can be activated by high glucose and links inflammation and metabolic disease. This study aimed to investigate the role of NLRP3 inflammasome in hyperglycemia-induced endothelial inflammation and diabetic atherosclerosis.Methods: NLRP3 levels in peripheral blood mononuclear cell (PBMC) and plasma IL-1β level were measured in diabetes patients. The activation of NLPR3 was detected in diabetic ApoE−/− mice and human umbilical vein endothelial cells (HUVECs).Results: Compared with healthy controls, NLRP3 expression levels in PBMC and plasma IL-1β level were significantly higher in diabetes patients but considerably decreased after lifestyle interventions and medicine. Moreover, carotid atherosclerosis was significantly related to plasma IL-1β level in diabetes patients. In diabetic atherosclerosis mouse model, NLRP3 knockdown suppressed NLRP3 inflammasome activation, inhibited the expression of adhesion molecules ICAM-1 and VCAM-1 in intima, reduced atherosclerosis and stabilized atherosclerotic plaque. In vitro, the expression of NLRP3 inflammasome components and the secretion of IL-1β were augmented by high glucose in HUVECs. Moreover, either high glucose or IL-1β promoted the expression of adhesion molecules, which were suppressed by NLRP3 knockdown or IL-1β receptor antagonist.Conclusion: These findings provide novel insights into pathological mechanisms of diabetic atherosclerosis and have potential therapeutic implications for cardiovascular complications in diabetes.Keywords: NLRP3 inflammasome, diabetes, atherosclerosis, inflammation

Chao An,* Xin Li,* Ping Liang, Jie Yu, Zhigang Cheng, Zhiyu Han, Fangyi Liu, Linan Dong Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, 100853, China *These authors contributed equally to this work Purpose: This study aimed to investigate the clinical value of a tumor map for assessing the ablative effect after ultrasound-guided percutaneous microwave ablation (US-PMWA) for hepatocellular carcinoma (HCC). Methods: The medical records of 68 patients (49 male and 19 female, 59.9±12.7 years) with HCC who underwent US-PMWA from May 2013 to May 2017 were reviewed. A tumor map was generated from the fusion of three-dimensional (3D) visualization images based on the preoperative target tumor and postoperative ablation area, to evaluate whether the ablation area covering the tumor has reached a 5 mm ablative margin (AM). The lesions were divided into two groups according to the tumor maps: group A (failed to achieve AM) and group B (achieved AM). The cumulative local tumor progression (LTP) rates of both groups were statistically analyzed using the log-rank test. Results: Success rate of tumor map generation was 100% (68/68), and no residual tumors were found. MWA-related 3D images, which included target tumor volume, ablation area volume, and residual liver ratio, were compared between groups A and B (P=0.295, P=0.772, and P=0.527, respectively). Technique effectiveness rate (91.7% vs 100%) was achieved in the two groups, showing no significant statistical differences (P=0.672). The 3-, 6-, 9-, and 12-month LTP rate was 8.3%, 16.7%, 20.8%, and 34%, respectively, for group A and 0%, 2.8%, 2.8%, and 2.8%, respectively, for group B, showing significant statistical differences (P

Teming Zhang,1,* Zheng Han,1,* Arvine Chandoo,1,* Xincheng Huang,1 Xiangwei Sun,1 Lele Ye,2 Changyuan Hu,3 Xiangyang Xue,2 Yingpeng Huang,1 Xian Shen,1 Wenjun Chang,4 Xiaoming Lin5 1Department of General Surgery, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Department of Environmental Hygiene, Second Military Medical University, Shanghai People’s Republic of China; 5Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou, People’s Republic of China *These authors contributed equally to this work Background and aim: Periostin is a protein from the Fascilin family. It is commonly present in normal tissues and is responsible for cell adhesion. Evidence has emerged showing that changes in periostin expression play an important role in tumor initiation, development, and progression. This study aims to investigate the effect of periostin in gastric cancer (GC) patients who underwent gastrectomy. Seven hundred and forty-seven GC patients who underwent gastrectomy between December 2006 and July 2011 were included in this study. Methods: Seven hundred and forty-seven cancer tissues and 70 paired adjacent normal tissues were collected. Periostin expression was evaluated by immunohistochemistry. The Gene Expression Omnibus database was used to study the association between the mRNA level and patient’s overall survival. The tumor microenvironment was also studied. Results: Periostin expression in stroma was downregulated in tumor tissues but it was upregulated in the epithelial cells. After dividing the tissues according to the Lauren Classification, we found that periostin expression in stroma and epithelial cells was higher in intestinal type than in diffuse type (P

Xiufang Su,1 Xingbing Huang,2 Yu Jin,3 Shouwen Wan,4 Zili Han5 1Department of Psychiatry, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, People’s Republic of China; 3Faculty of Maternal and Child Health, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Guangzhou Dr Su Health Industry (Group) Co., Ltd, Guangzhou, People’s Republic of China; 5Department of Psychiatry, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China Background: The prevention of cognitive impairment is a crucial public health issue, and leisure activities have been studied as the strategy of the cognitive preservation. The aim of the study was to explore the possible relationship between social activity and cognitive function among community-dwelling Chinese elderly in two big cities of Southern China. Participants and methods: Altogether, 557 nondemented older adults aged 60 years and older (73.4±6.5 years) were recruited in the social centers in Hong Kong and Guangzhou. A leisure activity questionnaire was used to measure the social activity participation. Cognitive function was examined using a neuropsychological battery. The association between social activity and cognitive function was analyzed using the multiple linear regression analysis. Results: Social activities had a weak relationship with cognitive performance when measured in terms of overall participation. Attending an interest class had significant association with the Cantonese version of Mini Mental State Examination, the word list learning test, the delayed recall test, and the trail making test. Religious activity showed significant association with the word list learning test and the digit vigilance test. Singing had significant association with the Category Verbal Fluency Test (CVFT) and the trail making test. Conclusion: Some individual social activity items may be associated with better cognitive function among the community Chinese elderly independently of other factors. Keywords: social activity, cognitive function, Chinese elderly

Nan Li,1–3,* Zhenzhen Han,1,2,4,* Lin Li,1,2 Bing Zhang,1–3 Zhidong Liu,1–3 Jiawei Li1,2 1Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2Institute of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 4Baokang Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China *These authors contributed equally to this work Purpose: The objective of this study was to investigate the effects of the solid lipid nanoparticles of baicalin (BA-SLNs) on an experimental cataract model and explore the molecular mechanism combined with bioinformatics analysis.Materials and methods: The transparency of lens was observed daily by slit-lamp and photography. Lenticular opacity was graded. Two-dimensional gel electrophoresis (2-DE) was employed to analyze the differential protein expression modes in each group. Proteins of interest were subjected to protein identification by nano-liquid chromatography tandem mass spectrometry (LC–MS/MS). Bioinformatics analysis was performed using the Ingenuity Pathway Analysis (IPA) online software to comprehend the biological implications of the proteins identified by proteomics.Results: At the end of the sodium selenite-induced cataract progression, almost all lenses from the model group developed partial nuclear opacity; however, all lenses were clear and normal in the blank group. There was no significant difference between the BA-SLNs group and the blank group. Many protein spots were differently expressed in 2-DE patterns of total proteins of lenses from each group, and 65 highly different protein spots were selected to be identified between the BA-SLNs group and the model group. A total of 23 proteins were identified, and 12 of which were crystalline proteins.Conclusion: We considered crystalline proteins to play important roles in preserving the normal expression levels of proteins and the transparency of lenses. The general trend in the BA-SLN-treated lenses’ data showed that BA-SLNs regulated the protein expression mode of cataract lenses to normal lenses. Our findings suggest that BA-SLNs may be a potential therapeutic agent in treating cataract by regulating protein expression and may also be a strong candidate for future clinical research. Keywords: BA-SLNs, 2-DE patterns, nano-LC–MS/MS, IPA, SDS-PAGE

Ryan A Kelley,1 Shannon M Conley,1 Rasha Makkia,1 Jamie N Watson,1 Zongchao Han,1 Mark J Cooper,2 Muna I Naash3 1Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; 2Copernicus Therapeutics, Inc., Cleveland, OH, USA; 3Department of Biomedical Engineering, University of Houston, Houston, TX, USA Introduction: DNA nanoparticles (NPs) comprising polylysine conjugated to polyethylene glycol efficiently target murine photoreceptors and the retinal pigment epithelium (RPE) and lead to long-term phenotypic improvement in models of retinal degeneration. Advancing this technology requires testing in a large animal model, particularly with regard to safety. So, herein we evaluate NPs in non-human primates (baboon). Methods and results: NPs with plasmids carrying GFP and a ubiquitous, RPE-specific, or photoreceptor-specific promoter were delivered by either subretinal or intravitreal injection. We detected GFP message and protein in the retina/RPE from eyes dosed with NPs carrying ubiquitously expressed and RPE-specific vectors, and GFP message in eyes injected with NPs carrying photoreceptor-specific vectors. Importantly, we observed NP DNA in the retina/RPE following intravitreal injection, indicating the inner limiting membrane does not prevent NP diffusion into the outer retina. We did not observe any adverse events in any baboon, and there were no NP-associated changes in retinal function. Furthermore, no systemic or local inflammatory reaction to the vectors/injections was observed, and no NP DNA was found outside the eye. Conclusion: Taken together with the well-established rodent safety and efficacy data, these findings suggest that DNA NPs may be a safe and potentially clinically viable nonviral ocular therapy platform for retinal diseases. Keywords: DNA nanoparticles, non-human primate, nonviral gene transfer, baboon, gene therapy, safety, ocular gene transfer

Abstract Background Treatment with the combination of ureteroscopy and thulium laser ablation may provide an alternative to radical nephroureterectomy (RNU) for patients with upper tract urothelial carcinoma (UTUC). The purpose of this study was to investigate the efficacy and safety of this technique. Methods We performed a retrospective review of the data for patients who were treated surgically for upper tract urothelial carcinoma in a single center. It included 32 patients treated by endoscopic thulium laser resection and 107 patients treated by radical nephroureterectomy (RNU). We compared the data of patient sex, age at diagnosis, location of carcinoma, length of hospitalization, tumor site, size, grade, recurrence, preoperative creatinine and postoperative creatinine in two groups. Patients were examined by ureteroscopy every 3 months during the first year after surgery, then every 6 months each year. Results All 32 patients were treated successfully, among which 6 were operated by a flexible ureteroscope. The average tumor size was 13 ± 7 mm in diameter. The tumor was rated as low grade in 27 patients and high grade in 5 patients. Ureteral stricture developed in 4 patients 3 months later after surgery, but the stricture was succesfully treated through endoscopic dilation. Seven patients had tumor recurrence, 3 of which underwent nephroureterectomy during the follow-up. Postoperative creatinine levels (umol/L) were respectively 89 ± 7.5 in laser group and 123 ± 15.4 in RNU group (p

Hongbo Tang,1 Hongli Chen,2 Yajing Jia,2 Xiaoyan Liu,1 Zhaohong Han,1 Aihua Wang,1 Qi Liu,1 Xinlei Li,1 Xin Feng1 1Department of Pharmacy, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 2School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China Abstract: The regular accumulation of nanoparticles in the liver makes them hepatotoxic and decreases the circulation time, thus reducing their therapeutic effect. Resolving this problem will be significant in improving bioavailability and reducing side effects. In this study, we reduced the phagocytosis of epirubicin (EPI)-loaded folic acid-conjugated pullulan acetate (FPA/EPI) nanoparticles by Kupffer cells (KCs) through internalization and nuclear factor kappa B (NF-kB) signal pathway inhibitors, thus allowing development of FPA/EPI nanoparticles as a nanodrug delivery system (NDDS) based on our previous study. FPA/EPI nanoparticles were prepared by the dialysis method. Rat KCs were preincubated with the following individual or compound inhibitors: chlorpromazine (CPZ), nystatin (NY), colchicine (Col), amiloride (AMR), and pyrrolidine dithiocarbamate (PDTC). Dose- and time-dependent cellular uptake effects of inhibitors on FPA/EPI nanoparticles were determined through fluorometry. The cytokine levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 were tested in culture supernatants by bead-based multiplex flow cytometry. The uptake study demonstrated that inhibitors had an obvious inhibitory effect (P