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Xiang Li,1,2 Jun Zhang,3 Zhongxue Fu1 1Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of General Surgery, Chongqing University FuLing Hospital, Chongqing, People’s Republic of China; 3Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Zhongxue Fu, Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, No. 1 Shuanghu Branch Road, Huixing Street, Yubei District, Chongqing, People’s Republic of China, Email fzx19990521@126.comPurpose: This study aims to investigate the correlation between a novel integrated inflammatory marker: The inflammation-combined prognostic index (ICPI), combining NLR, PLR, and MLR, with the clinicopathological characteristics and overall survival (OS) of gastric cancer (GC).Patients and Methods: Data from 876 patients with GC were retrospectively analyzed from January 1, 2017, to April 30, 2023. PSM was employed to mitigate confounding factors between groups. Receiver operating characteristic (ROC) curves were utilized to determine the optimal cutoff value. Univariate, LASSO, and multivariate regression analyses were executed. Subsequently, a nomogram for predicting OS was developed and validated.Results: The cohort with a poor prognosis exhibited significantly elevated levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and ICPI (P< 0.001). Similarly, higher levels of NLR, PLR, MLR, and ICPI were associated with a poorer prognosis (P< 0.001). Following regression analysis, ICPI, T-stage, lymph node ratio (LNR), and primary site were identified as independent risk factors affecting OS. A nomogram was constructed based on these factors to predict 1-, 3-, and 5-year OS, yielding C-indexes of 0.8 and 0.743 for the training and validation sets, respectively. The calibration curves demonstrated close alignment between predicted and actual results, indicating high predictive accuracy. Moreover, the decision curve underscored the practical utility of the model.Conclusion: The new inflammatory parameter ICPI integrates NLR, PLR and MLR. The ICPI-based nomogram and web calculator accurately predict OS in patients with GC.Keywords: gastric cancer, ICPI, PSM, nomogram, OS

Xinyao Shui,1,&ast; Jingsong Chen,2– 4,&ast; Ziyue Fu,1 Haoyue Zhu,1 Hualin Tao,2– 4 Zhaoyinqian Li2– 4 1Clinical Medical College, Southwest Medical University, Luzhou, People’s Republic of China; 2Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Luzhou, People’s Republic of China; 4Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaoyinqian Li, Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Jiangyang District, Luzhou, Sichuan, 646000, People’s Republic of China, Email lizhaoyinqian@swmu.edu.cnAbstract: Ischemic stroke is the most common type of stroke, which is the main cause of death and disability on a global scale. As the primary immune cells in the brain that are crucial for preserving homeostasis of the central nervous system microenvironment, microglia have been found to exhibit dual or even multiple effects at different stages of ischemic stroke. The anti-inflammatory polarization of microglia and release of neurotrophic factors may provide benefits by promoting neurological recovery at the lesion in the early phase after ischemic stroke. However, the pro-inflammatory polarization of microglia and secretion of inflammatory factors in the later phase of injury may exacerbate the ischemic lesion, suggesting the therapeutic potential of modulating the balance of microglial polarization to predispose them to anti-inflammatory transformation in ischemic stroke. Microglia-mediated signaling crosstalk with other cells may also be key to improving functional outcomes following ischemic stroke. Thus, this review provides an overview of microglial functions and responses under physiological and ischemic stroke conditions, including microglial activation, polarization, and interactions with other cells. We focus on approaches that promote anti-inflammatory polarization of microglia, inhibit microglial activation, and enhance beneficial cell-to-cell interactions. These targets may hold promise for the creation of innovative therapeutic strategies.Keywords: microglia, ischemic stroke, phagocytosis, polarization, crosstalk, anti-inflammatory, therapeutic targets

Nan Jiang,1,&ast; Wei Jin,2,&ast; Zhenghui Fu,3,&ast; He Cao,1 Hong Zheng,3 Quqing Wang,1 Qiongting Zhang,3 Kang Ju,3 Jiwei Wang1 1Key Laboratory of Health Technology Assessment of Ministry of Health, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2Department of Patriotic Public Health and Health Promotion instruction, Shanghai Municipal Center for Health Promotion, Shanghai, People’s Republic of China; 3Shanghai Changning Mental Health Center (Affiliated to East China Normal University), Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiwei Wang, Key Laboratory of Health Technology Assessment of Ministry of Health, School of Public Health, Fudan University, Shanghai, People’s Republic of China, Email jiweiwang@fudan.edu.cn Kang Ju, Shanghai Changning Mental Health Center (Affiliated to East China Normal University), Shanghai, People’s Republic of China, Email jukang2009@163.comPurpose: This study aims to explore the serial mediating effect of stigma and depression on the association between social support and medication adherence.Patients and Methods: A cross-sectional survey was undertaken in the Changning District of Shanghai using a five-part questionnaire from August to December 2023. A convenient sampling method was employed, and 35 patients with schizophrenia were invited from each of the 9 streets in Changning District to participate in the survey, resulting in a total of 305 valid questionnaires collected. The questionnaire measured social support, stigma, depression, medication adherence, and demographic characteristics. Data analysis involved descriptive statistics, independent samples t-tests, ANOVA, Pearson correlation analysis, and the bootstrap method.Results: There was a direct and significantly positive association between social support and medication adherence (β = 0.69, p < 0.001). Moreover, increased levels of stigma (β = - 0.45, p = 0.013) and depression (β = - 0.09, p = 0.017) were both associated with a decline in medication adherence. Bootstrapping analysis revealed that the association between social support and medication adherence operated indirectly through stigma (β = 0.11, 95% CI: 0.03, 0.18). Additionally, social support was indirectly associated with medication adherence through depression (β = 0.15, 95% CI: 0.04, 0.30). Further analysis indicated that social support had an indirect association with medication adherence through both stigma and depression (β = 0.04, 95% CI: 0.01, 0.07).Conclusion: Stigma and depression serially mediate the association between social support and medication adherence among patients with schizophrenia. This serial multiple mediation model underscores the importance of integrating social support interventions with psychological interventions aimed at reducing stigma and depression, thereby effectively enhancing medication adherence in patients with schizophrenia.Keywords: social support, stigma, depression, medication adherence, schizophrenia

Zhen-Zhen Wang,1– 3,&ast; Hang Li,4,&ast; Anish R Maskey,2,&ast; Kamal Srivastava,2,5,&ast; Changda Liu,6,&ast; Nan Yang,2,5 Taoyun Xie,7 Ziyi Fu,8 Junxiong Li,9 Xiaohong Liu,10 Hugh A Sampson,6 Xiu-Min Li2,11 1Academy of Chinese Medical Science, Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 2Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY, USA; 3Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan, People’s Republic of China; 4Central Lab, Shenzhen Bao’an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, People’s Republic of China; 5General Nutraceutical Technology, Elmsford, NY, USA; 6Department of Pediatrics, Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 7The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 8The First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 9Guangdong Province Hospital of Integrated Chinese and Western Medicine, Foshan, Guangdong, People’s Republic of China; 10Department of Respiratory Medicine, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 11Department of Otolaryngology, Westchester Medical Center New York Medical College, Valhalla, NY, USA&ast;These authors contributed equally to this workCorrespondence: Xiu-Min Li, Tel +1 914-594-4197, Email XiuMin_Li@NYMC.eduIntroduction: Neutrophil predominant airway inflammation is associated with severe and steroid-resistant asthma clusters. Previously, we reported efficacy of ASHMI, a three-herb TCM asthma formula in a steroid-resistant neutrophil-dominant murine asthma model and further identified Ganoderic Acid C1 (GAC1) as a key ASHMI active compound in vitro. The objective of this study is to investigate GAC1 effect on neutrophil-dominant, steroid-resistant asthma in a murine model.Methods: In this study, Balb/c mice were systematically sensitized with ragweed (RW) and alum and intranasally challenged with ragweed. Unsensitized/PBS challenged mice served as normal controls. Post sensitization, mice were given 4 weeks of oral treatment with GAC1 or acute dexamethasone (Dex) treatment at 48 hours prior to challenge. Pulmonary cytokines were measured by ELISA, and lung sections were processed for histology by H&E staining. Furthermore, GAC1 effect on MUC5AC expression and on reactive oxygen species (ROS) production in human lung epithelial cell line (NCI-H292) was determined by qRT-PCR and ROS assay kit, respectively. Computational analysis was applied to select potential targets of GAC1 in steroid-resistant neutrophil-dominant asthma. Molecular docking was performed to predict binding modes between GAC1 and Dex with TNF-α.Results: The result of the study showed that chronic GAC1 treatment, significantly reduced pulmonary inflammation (P < 0.01– 0.001 vs Sham) and airway neutrophilia (P < 0.01 vs Sham), inhibited TNF-α, IL-4 and IL-5 levels (P < 0.05– 0.001 vs Sham). Acute Dex treatment reduced eosinophilic inflammation and IL-4, IL-5 levels, but had no effect on neutrophilia and TNF-α production. GAC1 treated H292 cells showed decreased MUC5AC gene expression and production of ROS (P < 0.001 vs stimulated/untreated cells). Molecular docking results showed binding energy of complex GAC1-TNF was − 10.8 kcal/mol.Discussion: GAC1 may be a promising anti-asthma botanical drug for treatment of steroid-resistant asthma.Keywords: asthma, mouse model, neutrophilic inflammation, Ganoderma, ganoderic acid

Qingsong Liu,1,2,&ast; Lunyu Li,2,&ast; Dan Zheng,1 Songlin Jin,2 Xiaotian Guan,2 Zeting Fu,2 Zhigang Xiong,1 Haili Ding3 1Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2School of Sports Medicine and Health, Chengdu Sport University, Chengdu, People’s Republic of China; 3Insititute of Sports Medicine and Health, Chengdu Sport University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haili Ding, No. 2, Gymnasium Road, Chengdu, Sichuan, People’s Republic of China, Tel +86 13688467479, Email dingdingtang111@163.comPurpose: This study examined the underlying mechanisms of SJD’s anti-inflammatory and analgesic effects on acute GA flares.Methods: This study used pharmacology network and molecular docking methods. The active ingredients of ShuiJingDan (SJD) were obtained from the Traditional Chinese Medicine Systems Pharmacology Analysis Platform (TCMSP), and the relevant targets of GA were obtained from the Online Mendelian Inheritance in Man (OMIM) database and Therapeutic Target Database (TTD). The core drug group–target–disease Venn diagram was formed by crossing the active ingredients of SJD and the relevant targets. Gene Ontology (GO) analysis was conducted for functional annotation, DAVID was used for Kyoto Encyclopedia of Genes, and Genomes pathway enrichment analysis, and R was used to find the core targets. The accuracy of SJD network pharmacology analysis in GA treatment was verified by molecular docking simulations. Finally, a rat GA model was used to further verify the anti-inflammatory mechanism of SJD in the treatment of GA.Results: SJD mainly acted on target genes including IL1B, PTGS2, CXCL8, EGF, and JUN, as well as signal pathways including NF-κB, Toll-like receptor (TLR), IL-17, and MAPK. The rat experiments showed that SJD could significantly relieve ankle swelling, reduce the local skin temperature, and increased the paw withdrawal threshold. SJD could also reduce synovial inflammation, reduced the concentrations of interleukin-1β (IL-1β), IL-8, and COX-2 in the synovial fluid, and suppressed the expression of IL1B, CXCL8, and PTGS2 mRNA in the synovial tissue.Conclusion: SJD has a good anti-inflammatory effect to treat GA attacks, by acting on target genes such as IL-1β, PTGS2, and CXCL8.Keywords: ShuiJingDan, gouty arthritis, network pharmacology, molecular docking, IL-1β, COX-2

Yicheng Guo,1 Huiqun Gan,1 Shigui Xu,1 Guosheng Zeng,2 Lili Xiao,2 Zhijun Ding,2 Jie Zhu,3 Xinglong Xiong,3 Zhiyuan Fu1 1Department of Pharmacy, Dermatology Hospital of Jiangxi Province, Nanchang, People’s Republic of China; 2Jiangxi Provincial Clinical Research Center for Skin Diseases, Nanchang, People’s Republic of China; 3Candidate Branch of National Clinical Research Center for Skin Diseases, Nanchang, People’s Republic of ChinaCorrespondence: Zhiyuan Fu, Department of Pharmacy, Dermatology Hospital of Jiangxi Province, 388, Yinbing Road, Nanchang, Jiangxi, People’s Republic of China, Tel +86 13970827820, Email fuzhiyuan0774@yeah.netPurpose: This study aims to confirm the efficacy of Xijiao Dihuang decoction (XJDHT), a classic prescription, in treating psoriasis and to explore the potential therapeutic mechanism.Methods: For pharmacodynamic analysis, a mouse model of imiquimod cream (IMQ)-induced psoriasis was constructed. Active ingredients and genes of XJDHT, as well as psoriasis-related targets, were obtained from public databases. Intersecting genes (IGEs) of XJDHT and psoriasis were collected by Venn Diagram. A protein–protein interaction (PPI) network of IGEs is constructed through the STRING database. The Molecular Complex Detection (MCODE) and Cytohubba plug-ins of Cytoscape software were used to identified hub genes. In addition, we conducted enrichment analysis of IGEs using the R package clusterProfiler. Hub genes were validated via external GEO databases. The influence of XJDHT on Hub gene expression was examined by qPCR and ELISA, and molecular docking was used to evaluate the binding efficacy between active ingredients and hub genes.Results: The results revealed that XJDHT possesses 92 potential genes for psoriasis, and 8 Hub genes were screened. Enrichment analysis suggested that XJDHT ameliorate psoriasis through multiple pathways, including AGE-RAGE, HIF-1, IL-17 and TNF signaling pathway. Validation data confirmed the differential expression of IL6, VEGFA, TNF, MMP9, STAT3, and TLR4. Molecular docking revealed a strong affinity between active ingredients and Hub genes. The efficacy of XJDHT in improving psoriatic lesions in model mice was demonstrated by PASI score and HE staining, potentially attributed to the down-regulation of VEGFA, MMP9, STAT3, TNF, and IL-17A, as evidenced by ELISA and qPCR.Conclusion: This study employed network pharmacology and in vitro experiments to identify the potential mechanisms underlying the therapeutic effects of XJDHT on psoriasis, providing a new theoretical basis for its clinical application in the treatment of psoriasis.Keywords: psoriasis, Xijiao Dihuang decoction, network pharmacology, molecular docking, angiogenesis

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

Chenrui Zhang,1 Jinping Li,2 Rong Lu,2 Song Wang,2 Zheng Fu,2 Zhi Yao1 1Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People’s Republic of China; 2Kangzhe Pharmaceutical Technology Development Company, Ltd., Tianjin, People’s Republic of ChinaCorrespondence: Zhi Yao, Tianjin Medical University, Tianjin, 300070, People’s Republic of China, Tel/Fax +8622-83336817, Email yaozhi@tmu.edu.cn Zheng Fu, Kangzhe Pharmaceutical Technology Development Company, Tianjin, 300110, People’s Republic of China, Tel/Fax +86 13821232027, Email fuzhengcn@vip.sina.comBackground: The number of incidences of antimicrobial resistance is rising continually, necessitating new and effective antibacterial drugs. The present study aimed to assess the in vitro and in vivo activity of XF-73 against antibiotic-resistant Staphylococcus aureus (S. aureus) isolates and to investigate the potential mechanism of action of XF-73.Methods: The in vitro antibacterial activity of XF-73 and comparator antibacterial drugs, (mupirocin, fusidine, retapamulin, vancomycin, erythromycin, linezolid and daptomycin), against S. aureus (both antibiotic sensitive and resistant strains) was assessed using a broth microdilution method. Two different superficial Staphylococcal skin infection murine models were established to study the in vivo efficacy of XF-73 against antibiotic-resistant strains. The effect of XF-73 on the ultrastructure and cellular morphology of S. aureus was studied using transmission electron microscopy (TEM) and scanning electron microscopy (SEM).Results: The MICs (minimum inhibitory concentration) determined by the broth microdilution method for XF-73 demonstrated that the compound had a high potency against S. aureus isolates with varying susceptibility to the study drugs. Also, the antibacterial activity of XF-73 was superior or similar to most of the tested antibacterial drugs. We also found that the XF-73 dermal formulation significantly inhibited S. aureus survival in both the murine skin tape-stripping and suture superficial skin infection models, maintained a consistently high inhibitory capacity against the antibiotic-resistant strains tested and was significantly more effective than mupirocin ointment, a commonly used antibiotic for the treatment of skin infections. The morphological studies using TEM suggest that XF-73 had a rapid (2 minute) bacterial cell wall disruption activity, with longer incubation (10 minute) subsequently causing membrane damage. SEM analysis demonstrated that this cell wall and cell membrane disruption did not lead to disintegration of the plasma membrane, and did not cause bacterial cell lysis.Conclusion: Therefore, XF-73 may be an effective drug alternative to combat multi-drug-resistant skin infections in the clinical setting.Keywords: antibiotic resistance, mupirocin-resistant strains, skin infections, bacterial cell membrane, in vivo, S. aureus

Jian Gong,1,2,&ast; Weiwei Wu,3,&ast; Liguo Qiu,1,2 Xi Wang,1,2 Jianwei Bao,1,2 Jinjing Wang,4 Lifang Cheng,1,2 Zhiyuan Fu,1,5 Fengming Hu1,2 1Department of Integrated Traditional Chinese and Western Medicine of Dermatology, Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China; 2Jiangxi Provincial Clinical Research Center for Skin Diseases, Nanchang, Jiangxi, People’s Republic of China; 3Department of Plastic and Dermatological Surgery, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 4Clinical School of Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 5Department of Pharmacy, Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyuan Fu, Department of Pharmacy, Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China, Tel +86 13970827820, Fax +86-0791-85207512, Email 1074586168@qq.com Fengming Hu, Department of Integrated Traditional Chinese and Western Medicine of Dermatology, Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China, Tel +86 13970935828, Fax +86-0791-85207512, Email 18970802429@163.comAbstract: Psoriasis is an immune-mediated chronic inflammatory dermatosis influenced by hereditary and environmental factors. Human immunodeficiency virus (HIV) infection affects the immune system and exacerbates psoriatic lesions. We report the case of a 33-year-old male patient diagnosed with psoriasis vulgaris, psoriatic arthritis and HIV infection. Acitretin capsules, etanercept and high-active antiretroviral therapy (HAART) were effective. Two months after etanercept was discontinued, his condition worsened. After switching to secukinumab combined with HAART, the symptoms of psoriatic arthritis resolved rapidly after four weeks, with a Disease Activity Index for Psoriatic Arthritis score of 0. The time to achieve psoriasis area and severity index 40, 75, 90, and 100 were 2, 4, 8, and 29 weeks. The treatment was maintained for 1 year with no adverse reactions. Regarding the stable CD4+ T lymphocyte count and the viral load, administering anti-IL-17 monoclonal antibodies is an effective treatment option for psoriasis patients.Keywords: psoriasis, HIV, etanercept, secukinumab, biologics

Chen Tian,1,&ast; XiaoLei Xue,2,&ast; Ye Chen,3,&ast; Ruiyuan Liu,4 Yutong Wang,5 Sheng Ye,4 Zeyu Fu,5 Yingrui Luo,5 Shengmiao Wang,5 Xiaofeng He,1 Huajin Pang1 1Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 2Department Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 3Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Department of Radiology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, 510260, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Medical Image Processing, School of BioMedical Engineering, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 5Cancer Research Institute, Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaofeng He; Huajin Pang, Tel +86 13760661610, Email ozonetherapy@126.com; nfyyphj@163.comIntroduction: Second near-infrared photothermal therapy (NIR-II PTT) has become a promising strategy for treating cancer in terms of safety and potency. However, the application of NIR-II PTT was limited in the treatment of deep-buried solid tumors due to the low dose of NIR-II absorption nanomaterials and the inadequate laser energy in the deep tumor.Methods: Herein, the authors report the engineering of NIR-II absorbing polyaniline nanorods, termed HPW@PANI Nanorods, for in situ NIR-II PTT based on optical fibers transmission of laser power and transarterial infusion for the treatment of orthotopic hepatocellular carcinoma in the rabbit. HPW@PANI Nanorods were prepared via chemical oxidant polymerization of aniline under phosphotungstic acid, which exhibited effective NIR-II absorption for hyperthermia ablation cells.Results: HPW@PANI Nanorods were fast and efficiently deposited into primary orthotopic transplantation VX2 tumor in rabbits via transarterial infusion. Furthermore, an optical fiber was interventionally inserted into the primary VX2 tumor to transmit 1064nm laser energy for in situ NIR-II PTT, which could ablate primary tumor, inhibit distant tumor, and suppress peritoneal metastasis.Conclusion: This study provides new insights into the application of in situ NIR-II PTT based on optical fibers transmission of laser power and transarterial injection of NIR-II absorption nanomaterials to treat deep-buried tumors.Graphical Abstract: Keywords: NIR-II absorption nanomaterials, orthotopic animal model, transarterial infusion, optical fiber transmission of laser power, deep-buried tumors

Qi Zhou, Kezhu Hou, Zhiqiang Fu Department of Thoracic Surgery, Shanghai Shidong Hospital, Shanghai, 200438, People’s Republic of ChinaCorrespondence: Kezhu Hou; Zhiqiang Fu, Department of Thoracic Surgery, Shanghai Shidong Hospital, Yangpu District, Shanghai, 200438, People’s Republic of China, Email phuang718@163.com; fuzhiqiang1311@163.comIntroduction: Mangiferin is a plant antitumor compound with poor water solubility and low bioavailability. In this study, transferrin-modified mangiferin-loaded solid lipid nanoparticles (Tf-modified MGF-SLNs) were prepared to overcome the above defects.Methods: Tf-modified MGF-SLNs were prepared by the emulsification-solvent evaporation method. The physicochemical properties of Tf-MGF-SLNs such as particle size, zeta potential and in vitro drug release were investigated. We also demonstrated the effect of Tf-MGF-SLNs in lung cancer.Results: The mean hydrodynamic diameter of the Tf-MGF-SLNs was 121.8± 2.9 nm with a polydispersity index of 0.134± 0.03. According to TEM micrographs, Tf-MGF-SLNs are spherical and uniform, and the EE% was found to be 72.5± 2.4%. In vitro release, we identified an initial burst effect release, followed by controlled release, in SLNs at both pHs and the Tf-MGF-SLNs drug accumulation release percentages reached over 68% at pH 4.0 and 72% at pH 7.4 in 6 hours, respectively. In vivo studies showed that depending on surface modification, Tf-MGF-SLNs, which suggested that cell internalization was changed and more drugs entered the cells successfully.Discussion: Tf-MGF-SLNs were highly efficient in suppressing the tumor growth in xenograft tumor model. Sustained release of the drug delivery system and Tf-modified MGF-SLNs played a major role. Tf-MGF-SLNs would be a promising formulation for the treatment of lung cancer.Keywords: transferrin, mangiferin, SLNs, A549 lung cancer cell

ScN in the rock salt structure is a well-investigated material due to its desirable properties like the high hardness or large thermal conductivity. Recent computations by Adamski et al. [Appl. Phys. Lett. 115, 232103 (2019)] showed that ScN/GaN heterostructures exhibit an outstanding polarization gradient which would be beneficial for polarization induced electron gases. The pseudobinary semiconductor Sc x Al 1 − x N, when maintaining the cubic rock salt structure, could be beneficial for tailoring the polarization gradient using the Sc dependency of material properties. The structural properties of rs-Sc x Al 1 − x N are not fully discovered yet, thus in this work, DC-magnetron sputtered cubic rock salt Sc x Al 1 − x N thin films with 0.55 < x < 1.00 were grown and analyzed on ScN(111)/Si(111). The epitaxial relation of ScN(111) thin films on the Si(111) substrate is determined to be ScN[110] ∥ Si[100]. Furthermore, concentration dependent properties like the lattice parameter of Sc x Al 1 − x N were measured [a(ScN) = 4.50 Å, a(Sc0.55Al0.45N) = 4.30 Å] and the stress σ within the layers was determined. The crystal quality was evaluated using ω -scans, revealing FWHM = 1.14 ° for Sc0.95Al0.05N. The diameters of the columns were determined by atomic force microscopy and scanning electron microscopy and they are range from 34 to 59 nm for 0.55 < x < 1.00. At x = 0.55 , Sc x Al 1 − x N columns in the hexagonal wurtzite as well as cubic rock salt structure were detected. This information about the structural specifications of Sc x Al 1 − x N in the rock salt structure forms the basis for further investigations and experimental confirmation of the electric properties of ScN/GaN heterostructures or even a Sc x Al 1 − x N/GaN based approach for improved structures for high-electron-mobility transistors. [ABSTRACT FROM AUTHOR]

Bingwei Hu,1,2 Liang Li,2 Hongwei Wang,2 Tingting Ma,2 Zhimei Fu,2 Xianhui Kang,3 Zhiying Feng1 1Department of Pain, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Anesthesiology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Zhiying Feng; Xianhui KangThe First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, Zhejiang, People’s Republic of China, Email fzy1972@zju.edu.cn; kxhui66@zju.edu.cnPurpose: Epidural anesthesia (EA) is the main anesthesia method for transforaminal percutaneous endoscopic lumbar discectomy (PELD). Reducing the concentration of ropivacaine can help preserve tactile sensation, allowing patients to provide timely feedback to the surgeons when a nerve root is contacted to avoid nerve injury. Therefore, a 90% effective concentration (EC90) that allows for mild pain [visual analog scale (VAS) score ≤ 3] while maximizing tactile sensation must be identified.Methods: The concentration of ropivacaine for EA was varied for consecutive patients in this study using a two-stage biased-coin design (BCD) according to the response of the previous patient; the concentration used for the first patient was 0.2%. When the previous patient had a negative response (VAS score > 3), the concentration used for the next one was increased by 0.015%. When the previous patient had a positive response (VAS score ≤ 3), the concentration used for the next one had an 89% probability of remaining the same and an 11% probability of being reduced by 0.015%. The EC90 of ropivacaine was estimated using isotonic regression, and the 95% confidence interval (CI) was estimated using the bootstrapping method in R.Results: A total of 58 patients were included in the study. The calculated EC90 was 0.294% [95% CI (0.271%, 0.303%)]. Among 13 patients who reported unintended nerve root contact during the operation, none were found to have irreversible nerve injury after the operation.Conclusion: To preserve maximum tactile sensation, the EC90 of ropivacaine was 0.294% for patients with allowed mild pain. This concentration could allow for timely feedback when the nerve root is contacted, to avoid nerve injury.Keywords: minimum effective concentration, epidural anesthesia, ropivacaine, transforaminal percutaneous endoscopic lumbar discectomy, biased-coin design, isotonic regression

Wen Hu,1,2,&ast; Panpan Yang,3,&ast; Zhenzhen Fu,1 Yongqing Wang,4 Ying Zhou,1 Zhengqin Ye,1 Yingyun Gong,1 Aijie Huang,1 Luning Sun,4 Yang Zhao,5 Tao Yang,1 Zhong Li,6,7 Xian-Cheng Jiang,8 Weinan Yu,2 Hongwen Zhou1,6 1Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Affiliated Huai’an Hospital of Xuzhou Medical College, Huai’an, Jiangsu, People’s Republic of China; 3Department of Respiratory Diseases, The Affiliated Huai’an Hospital of Xuzhou Medical College, Huai’an, Jiangsu, People’s Republic of China; 4Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5School of Public Health Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 6Key Laboratory of Rare Metabolic Diseases, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 7Jiangsu Province Key Laboratory of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 8Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, Brooklyn, NY, USA&ast;These authors contributed equally to this workCorrespondence: Hongwen Zhou, Department of endocrinology, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +862583718836-6893, Fax +862583781781, Email drhongwenzhou@njmu.edu.cn Weinan Yu, Department of Endocrinology and Metabolism, Huai’an Hospital Affiliated to Xuzhou Medical University and Huai’an Second People’s Hospital, Huai’an, 223001, People’s Republic of China, Email hayuweinan@163.comObjective: Branched-chain amino acids (BCAAs) are essential AAs which are widely used as antioxidants in patients with liver and kidney dysfunction. However, BCAAs are strongly correlated with insulin resistance (IR) and diabetes. This study aimed to evaluate the relationship among BCAAs, oxidative stress, and type 2 diabetes mellitus (T2DM) in a Chinese population.Methods: Anthropometric and biochemical examinations were performed in 816 individuals who participated in the Huai’an Diabetes Prevention Program. Serum BCAAs concentrations were measured by hydrophilic interaction chromatography-tandem mass spectrometric method. Oxidative stress was evaluated by malondialdehyde (MDA) as an index of lipid peroxidation and the superoxide dismutase (SOD) activity.Results: A total of 816 participants were divided into three groups: normal glucose metabolism (NGM), prediabetes, and newly-diagnosed diabetes mellitus (NDM). Subjects in NDM group show higher MDA and lower SOD levels than subjects in other groups. L-Val levels positively correlated with MDA levels and negatively with SOD in NDM groups. After adjusting for T2DM risk factors, high L-Val levels were significantly associated with higher BMI, WC, FPG, increased LnTG and decreased HDL-C. L-Val was also independently associated with NDM (OR 1.06, 95% CI 1.02– 1.10; P = 0.005). Furthermore, the odds ratios for NDM among participants with high L-Val (≥ 35.25μg/mL) levels showed a 2.25-fold (95% CI 1.11– 4.57; P = 0.024) increase compared to participants with low L-Val (< 27.26 μg/mL) levels after adjusting for MDA and confounding factors.Conclusion: High serum L-Val levels are independently associated with oxidative stress, thus promoting IR and NDM. Further study should be done to clarify the mechanism.Keywords: branched chain amino acids, oxidative stress, new diagnosed type 2 diabetes mellitus, hydrophilic interaction chromatography-tandem mass spectrometric method

Li He,1,&ast; Zhi Fu,2,&ast; Menglong Wang,2 Xin Wang,1 Lu Wang,1 Guangming Li,2 Dongdong Lin2 1Department of Intensive Care Unit, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Department of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangming Li; Dongdong LinDepartment of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of ChinaTel +86 10 83997733; Tel/Fax +86 10 83997733Email gm_drli@163.com; dongdlin01@163.comObjective: To evaluate and explore the effectiveness of the new prevention and control measures for the donor-derived infection (DDI) associated with CRO after liver transplantation.Methods: The data of 120 organ donors and recipients from January 2018 to May 2020 were retrospectively analyzed at The Liver Transplantation Center of Beijing Youan Hospital, Capital Medical University, to investigate the epidemiological status of CRO in donors. The cases were divided into two groups. The implemented group was treated according to the execution of a clustered CRO prevention and control measure based on active screening combined with early initiation of prophylactic/therapeutic administration of antibiotics. The effectiveness of the prevention and control measures was evaluated by comparing the length of postoperative ICU stay, total postoperative length of hospital stay, duration of ventilator use, duration of restricted antibiotics use, the incidence of DDI, incidence and composition distribution of DDI-related CRO, and incidence of severe DDI-relevant adverse events between the two groups.Results: There was a high detection rate of 39.32% (105 strains) of drug-resistant bacteria in the donors. Fifty-six strains of CRO were detected. Participants in group B, which implemented the new prevention and control measures, were transferred out of the ICU sooner (P = 0.023), used fewer restrictive antibiotics (P = 0.003), and were discharged more quickly (P = 0.013) than those in group A. Postoperative DDI incidences (P = 0.113) and severe DDI-related adverse events were not statistically different between the two groups (P = 0.062). CR-Kp-related DDI was less common in group B (P = 0.021).Conclusion: The situation of donor-derived drug-resistant bacterial infections remains critical. The clustered prevention and control measures for CRO based on active screening combined with early initiation of prophylactic/therapeutic application of antibiotics would be beneficial.Keywords: organ donation, liver transplantation, drug-resistant bacteria, epidemiology, carbapenem-resistant Enterobacteriaceae, active screening, novel β-lactamase inhibitors

Xujie Xi,&ast; Zhaoli Fu,&ast; Tianwen Liu,&ast; Yanfeng Lin, Wenbin Wu, Jianmin Li, Ming Luo, Beiping Zhang Department of Spleen and Stomach Diseases, The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Beiping ZhangDepartment of Spleen and Stomach Diseases, The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, 510120, Guangdong Province, People’s Republic of ChinaTel +86-13602762766Email beipingzhang@21cn.comObjective: The purpose of this study was to establish and verify a risk-scoring system for colorectal adenoma recurrence.Methods: A total of 359 patients with colorectal adenoma who underwent polypectomy from October 2017 to December 2018 were included in this retrospective study. Information including taking traditional Chinese medicine, demographic characteristics, adenoma characteristics were collected. The patients will review the colonoscopy one year after surgery. The patients were divided into a modeling cohort (216 cases) and a model validation cohort (143 cases) according to the ratio of 6:4. Modeling and model verification were performed by logistic regression, ROC curve, nomogram (calibration chart) and other methods.Results: After adjusting for confounding factors by logistic regression, it was found that taking Chinese medicine, the number, size, site, pathological type and morphology of adenoma were independent influencing factors for the recurrence of colorectal adenoma. The area under the ROC curve (AUC) in the model validation cohort of established risk scoring system was 0.771 (95% CI: 0.694– 0.847), indicating that there was good consistency.Conclusion: The established risk prediction model of colorectal adenoma recurrence and its risk scoring system performed well and had high predictive value.Keywords: colorectal adenoma, recurrence, prediction model, risk scoring system

Che X, Lu R, Fu Z, et al. Drug Des Devel Ther. 2018;12:3357–3368. At the authors request, the Editor and Publisher of Drug Design, Development and Therapy wish to retract the published article. The authors became aware of concerns relating to the alleged duplication of images in Figure 7. Specifically, Figure 7B, Medium (100x), appears to have been duplicated with the same image for Figure 7E, YSL 0.4 mg/ml (100x), which has been flipped. While some original data was still available, the authors were unable to retrieve all of it in a satisfactory manner. In addition, some to the key cellular extraction material had not been well preserved. While the authors were still confident in the overall findings described in the article, to maintain the integrity of the scientific publication record, they decided it appropriate to request a retraction rather than pursue a corrigendum. The editor agreed with decision and approved the authors retraction request. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Po-En Chiu,1,2,&ast; Zhonghua Fu,3,&ast; Guan-Wei Jian,4,5 Ching-Hsuan Huang,2,6 Te-Mao Li,2 Li-Wei Chou7– 9 1Department of Chinese Medicine, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan; 2School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 3Institute of Fu’s Subcutaneous Needling, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan; 5Department of Chinese Medicine, Sinying Hospital, Ministry of Health and Welfare, Tainan, Taiwan; 6Department of Chinese Traumatology Medicine, China Medical University Hospital, Taichung, Taiwan; 7Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; 8Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan; 9Department of Physical Medicine and Rehabilitation, Asia University Hospital, Asia University, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Li-Wei ChouDepartment of Physical Medicine and Rehabilitation, China Medical University Hospital, No. 2 Yuh-Der Road, Taichung, 40447, TaiwanTel +886-4-22052121-2381Fax +886-4-22026041Email chouliwe@gmail.comBackground: Knee osteoarthritis (OA) is a common clinical disease. Knee pain is the major symptom of knee OA and the primary reason why patients seek treatment. Fu’s subcutaneous needling (FSN) has been used to treat knee OA for more than 20 years. However, the establishment of treatment methods and rigorous evaluation of FSN’s efficacy are still lacking. A randomized single-blind clinical trial will be conducted to evaluate whether FSN treatment can immediately alleviate pain due to knee OA surrounding the patella and the curative effective of 1-week and 2-week treatments. In addition, the feasibility and initial effect of FSN treatment for patients with knee OA will be discussed.Materials and Methods: Patients with confirmed knee OA, as diagnosed by doctors using X-ray films or from clinical symptoms, who are over 50 years old will be participants recruited. They will be randomly assigned either FSN treatment or transcutaneous electrical nerve stimulation treatment. In addition, their pressure pain threshold, muscle tone of lower leg muscle, and physical ability will be measured. Participants will be asked to complete the questionnaires of Western Ontario and McMaster Universities Osteoarthritis Index and Lequesne’ index as the measurements for quality of life.Results: The findings of this study will reveal whether FSN or transcutaneous electrical nerve stimulation is clinically efficacious for treating pain due to knee OA, with respect to muscle stiffness, gait, dynamic balance, the pressure pain threshold, and quality of life before and after treatment.Study Registration: This study is approved by the Research Ethics Committee of China Medical University & Hospital, Taichung, Taiwan (CMUH107-REC3-027) and registered at the ClinicalTrials.gov Protocol Registration and Results System (registration number NCT04356651).Keywords: dry needling, Fu’s subcutaneous needling, knee osteoarthritis, myofascial trigger point, tightened muscle

Zuli Fu,1,2 Qian Xu,1 Chiyuan Zhang,1,3 Hui Bai,1 Xuliang Chen,1 Yanfeng Zhang,1 Wanjun Luo,1 Guoqiang Lin1 1Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Cardiovascular Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Guoqiang LinDepartment of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of ChinaTel/Fax +86-731-84327097Email lgq186snoopy@126.comPurpose: Post-operative delirium (POD) is a common complication after aortic surgery with poor outcomes. Blood pressure may play a role in the occurrence of POD. The study aimed to identify whether admission systolic blood pressure (SBP) level in the intensive care unit (ICU) is correlated with POD in acute Stanford type A aortic dissection (AAAD) patients undergoing aortic surgery.Patients and Methods: We conducted a single-center retrospective cohort study enrolling consecutive 205 patients with acute type A aortic dissection undergoing aortic surgery. Patients were divided into 3 groups: low, normal, and high SBP level group. Outcomes of interest were POD, 30-day mortality and other complications including acute kidney injury, cardiac complications, spinal cord ischemia, stroke, and pneumonia. Confusion Assessment Method for Intensive Care Unit (CAM-ICU) method was used to assess POD. Univariate and multivariate logistic regression, Cox regression, and subgroup analysis were performed to uncover the association between SBP and POD.Results: The mean age of these patients was 51± 16 years old. Thirty-six patients (17.6%) developed POD. Patients with high admission SBP were more likely to develop POD (P < 0.01). Univariate analysis showed that high admission SBP was associated with a higher risk of POD among AAAD patients (OR, 3.514; 95% CI, 1.478– 8.537, P < 0.01). Multivariate logistic regression model confirmed that high SBP was an independent predictor of POD. Subgroup analysis indicated that patients with anemia and high admission SBP were at higher risk of POD.Conclusion: High admission SBP was positively associated with the incidence of POD in AAAD patients who underwent surgical repair in ICU.Keywords: acute Stanford type A aortic dissection, intensive care unit, major surgery, post-operative delirium, systolic blood pressure

Xiulei Zhang,1 Zhihao Fu,2 Xiao Zhang2 1Department of Microbiome Laboratory, Henan Provincial People’s Hospital, Zhengzhou University, Zhengzhou, 450003, People’s Republic of China; 2Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, Zhengzhou University, Zhengzhou, 450003, People’s Republic of ChinaCorrespondence: Xiulei Zhang; Xiao Zhang Email zxiulei@mail.ustc.edu.cn; hnsyzhangxiao@163.comPurpose: TP53 mutation is the most common genetic variation type in Hepatocellular carcinoma (HCC). We aim to illustrate the landscape of genomic alterations and TP53 mutation related and directly regulated lncRNA prognosis markers.Materials and Methods: Utilizing the clinical and transcriptome data from The Cancer Genome Atlas (TCGA) website, we present the landscape of genomic alterations and RNA differential expression profiles. By analyzing the ENCODE TP53 ChIP-seq data, we get the TP53 chromatin binding profiles. By Kaplan–Meier (KM) survival analysis and ROC analysis, we identify lncRNA prognosis markers.Results: TP53 ranks the highest mutation frequency gene and the maximum mutation type of TP53 is Missense Mutation (> 2.5× 104). TP53 mutation showed poor clinical outcome among the pathological Stage II and Stage III HCC patients. By differential expression analysis of the TP53 wild type and mutation HCC, we find thousands of misregulated genes, including 699 differential expression lncRNAs (p < 0.05, |log2FC| ≥ 1). Functional enrichment analysis of the misregulated genes shows that TP53 mutation events mainly alter DNA replication, cell cycle and immune response signaling pathways. By estimation of tumor-infiltrating immune cells through CIBERSORT, we find that the TP53 mutation events are significantly correlated with the different proportions of nine immune cells. We then integratively analyze the differential expression lncRNAs in TP53 wild type and mutation groups and the TP53 ChIP-seq binding lncRNAs, and get 112 overlap lncRNAs. By Kaplan–Meier survival analysis and ROC analysis, we identify two lncRNAs (RP4-736L20.3 and SNRK-AS1) that show significant prognosis value. Using the collected HCC samples, we validate the misregulated expression of RP4-736L20.3 and SNRK-AS1.Conclusion: The work presents the landscape of genomic variations and two TP53 mutation related and directly regulated lncRNA prognosis markers of HCC.Keywords: hepatocellular carcinoma, genomic variations, TP53 mutation, lncRNA, prognosis marker, HCC

Yao-Fang Liu,1 Zheng Fu,1 Shao-Wei Chen,1 Xiao-Ping He,2 Ling-Ye Fan1 1Department of Reproductive Technology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Prosthodontics, The Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of ChinaCorrespondence: Ling-Ye FanDepartment of Reproductive Technology, The Affiliated Hospital of Southwest Medical University, No. 25 of Taiping Street, Jiangyang District, Luzhou, 646000, People’s Republic of ChinaTel/Fax +86 0830 3165649Email lingyefan_cnsd@163.comBackground: This study aimed to examine the differences in anxiety and depression between infertile Chinese couples in diverse stages of in vitro fertilization-embryo transfer (IVF-ET) and their relationship with the IVF-ET outcomes.Methods: From February 2016 to December 2018, a total of 247 couples that were undergoing IVF-ET were randomly selected for this study. On the day they started their treatment (T1), the day human chorionic gonadotropin was administered (T2), and 4 days after the embryo transfer (T3), self-designed questionnaires, the Self-Rating Anxiety Scale, and the Self-Rating Depression Scale were completed to investigate anxiety and depression in different stages.Results: Age had an effect on the anxiety and depression in women. Male infertility type and the cause of infertility had an effect on the anxiety and depression in men. The incidence of anxiety in women in the T1, T2, and T3 stages was 29.96%, 44.94%, and 17.81%, respectively. The anxiety scores of women were 46.14 ± 8.37, 50.83 ± 8.50, and 44.09 ± 8.17, respectively, which were significantly higher than those of men (p < 0.05). The anxiety score in stage T2 was the highest in women, and the depression score of women in stage T1 was the highest. The incidence of anxiety in men in the T1, T2, and T3 stages was 20.65%, 8.50%, and 6.07%, respectively. The incidence of anxiety was not significantly different in diverse stages (p > 0.05), and the same result was obtained for the incidence of depression. The anxiety and depression scores of the infertile couples in different stages were not related to the outcome of IVF-ET.Conclusion: The incidence of anxiety and depression in infertile couples in diverse stages of IVF-ET is different, especially in women, and the anxiety and depression of infertile couples in the process of IVF-ET may not be related to the outcome of assisted pregnancy.Keywords: anxiety, couple, depression, in vitro fertilization-embryo transfer, outcome

This paper was attempted to investigate the microstructure degradation and low cycle fatigue (LCF) performance of a serviced K465 Ni‐based superalloy turbine blade. LCF tests were carried out with small‐scale plate specimens sampled from the blades. Relationship between residual LCF life and microstructure state was estimated. The results indicate that the coarsening of γ/γ′ phases was the most significant microstructure degradation mode for the serviced blades. Both the γ matrix width and the γ′ precipitate diameter increased with the increase of service duration, while the γ′ precipitate volume fraction slightly decreased. The most severe microstructure degradation occurred at the leading edge along the chord direction, particularly at 50–70 % airfoil spans. The residual LCF life exhibited an accelerated decrease characteristic as increases of microstructure degradation degree. The coarsened microstructure diminished shear resistance of the superalloy, which resulted in additional accumulated inelastic deformation and a corresponding reduction in LCF life. Highlights: Service induced microstructure evolution and LCF life decay of a blade were investigated.Coarsening was identified as the main degradation form of γ/γ' phases in serviced blade.Accelerated decrease of residual LCF life was identified as increases of coarsening.Reduced plastic deformation resistance owing to coarsening is crucial to decay LCF life. [ABSTRACT FROM AUTHOR]

Qi Zhou, Zhiqiang Fu Department of Thoracic Surgery, Shanghai Shidong Hospital, Yangpu District, Shanghai 200438, People’s Republic of ChinaCorrespondence: Zhiqiang Fu Tel +86 21-25066666Email Fuzhiqiang1311@163.comBackground: To establish the co-delivery liposomes of gefitinib (GFT) and curcumin (CUR) via oral administration with the goals of improving the synergistic effect and reducing acquired drug resistance.Methods: We prepared liposomes (LPs) which can embed the anticancer compound GFT and CUR and investigated whether they could enhance the antitumor effects of anticancer drugs against MDR. The LPs system was characterized by transmission electron microscopy (TEM), particle size, encapsulation efficiency, cellular uptake and cell viability. In addition, the release characteristics and pharmacodynamics of the LPs were also studied in detail.Results: The results showed that GFT/CUR LPs were characterized by small particle size of about 130 nm and negative zeta potential of about − 22.2 mV, and the drug controlled to release slowly on a biphasic pattern. Compared with control groups, GFT/CUR LPs showed a higher cellular uptake and cell inhibition rates. Through pharmacodynamics analysis, we found that two compounds (GFT and CUR) were incorporated into one LPs carrier, which played a good role in synergistic effect.Conclusion: Co-delivery of GFT and CUR has the potential to improve cancer treatment efficacy and overcome acquired resistance, especially towards GFT-resistant cells.Keywords: gefitinib, curcumin, co-delivery, cellular uptake, cell viability, pharmacodynamics

Xiuting Huang,1,* Xiuying Zhang,1,* Xianghai Zhou,1 Xueyao Han,1 Zuodi Fu,2 Yufeng Li,2 Linong Ji1 1Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing 100044, People’s Republic of China; 2Department of Endocrinology and Metabolism, Capital Medical University Pinggu Teaching Hospital, Beijing 101200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yufeng LiDepartment of Endocrinology and Metabolism, Capital Medical University Pinggu Teaching Hospital, No. 59, Xinping North Street, Pinggu District, Beijing 101200, People’s Republic of ChinaTel/Fax +86 10 89978790Email doctorlyf@126.comLinong JiDepartment of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, No. 11, Xizhimen South Street, Xicheng District, Beijing 100044, People’s Republic of ChinaTel +86 10 88324108Fax +86 10 88325534Email jilinong@gmail.comAim: Impaired glucose metabolism and thyroid dysfunction (TD) are the two most common chronic metabolic disorders. This study aimed to investigate the epidemiological characteristics of TD in different status of glucose tolerance in a community-based Chinese population and to understand the association between TD and glucose metabolism.Methods: A community-based population study of metabolic disease was conducted from June 2013 to September 2014 in Beijing, China. Residents aged 26– 76 years were selected according to gender and age composition using multi-stage stratified random sampling process. All participants underwent serum thyroid function and thyroid-associated antibody tests. The status of glucose tolerance was determined using 75g-oral glucose tolerance test. Chi-square test was used to compare the differences in prevalence. Multivariate logistic regression analysis was used to determine the impact of insulin resistance (IR) on thyroid function.Results: By analyzing 3986 participants who were included in the survey, the prevalence of type 2 diabetes (T2DM) and pre-diabetes (pre-DM) was 18.59% and 26.79%, respectively. The prevalence of TD was 8.81%, with overt hyperthyroidism accounting for 0.38%; subclinical hyperthyroidism, 1.86%; overt hypothyroidism, 0.70%; and subclinical hypothyroidism, 5.87%. The prevalence of TD increased with gradually deteriorated glucose tolerance (7.63% in those with normal glucose tolerance, 9.27% in pre-DM, and 11.61% in T2DM) in both men and women. Each unit of higher HOMA-IR was associated with 7% higher likelihood of having subclinical hypothyroidism.Conclusion: The coexisting of TD with T2DM and pre-DM is high in this community-based Chinese population, suggesting a close relationship between TD and glucose metabolism.Keywords: type 2 diabetes, pre-diabetes, thyroid dysfunction, epidemiology

Zhaobo Liu, Zhi Fu, Guangming Li, Dongdong Lin Department of General Surgery, Beijing Youan Hospital, Capital Medical University, Beijing 100069, People’s Republic of ChinaCorrespondence: Guangming LiDepartment of General Surgery, Beijing Youan Hospital, Capital Medical University, Beijing 100069, People’s Republic of ChinaEmail liguangming@ccmu.edu.cnDongdong LinDepartment of General Surgery, Beijing Youan Hospital, Capital Medical University, Beijing 100069, People’s Republic of ChinaTel +86-10-83997466Fax +86-10-63293371Email ldd1231@ccmu.edu.cnBackground: The majority of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage that excludes them from potentially curative surgical treatment. Lenvatinib is associated with a high objective response rate (ORR) (40.6%) in advanced HCC, indicating the potential for tumor downstaging and conversion to surgical intervention. We report the case of a patient with recurrent, advanced HCC who achieved a partial response and downstaging following third-line treatment with lenvatinib but missed the opportunity for conversion hepatectomy.Case Presentation: A male Chinese patient aged 42 years presented with an obstructive liver lesion, revealed by CT imaging to be a single tumor in segments V and VIII of the liver, without macrovascular invasion. The patient had chronic hepatitis B infection, Barcelona Clinic Liver Cancer (BCLC) Stage A, normal liver function (Child-Pugh Score 5 and Grade A) and AFP level 4.45 ng/mL. The patient underwent a successful hepatectomy but experienced recurrence 14 months later. The recurrent tumor was detected at an early stage and the patient underwent successful radiofrequency ablation and transarterial chemoembolization. After a further 11 months, the patient experienced a second relapse characterized by multiple disseminated metastases in the left and right lobes of the liver and possible macrovascular invasion, equal to BCLC Stage B/C. The patient received lenvatinib and achieved a partial response with complete disappearance of a number of lesions, recovering to BCLC Stage A and becoming eligible for liver transplantation. However, the patient refused surgery and after 4 months experienced progressive disease.Conclusion: Our case suggests that radical treatment, such as conversion hepatectomy or liver transplantation, should be undertaken quickly following downstaging and within the expected PFS time associated with lenvatinib. However, further studies are required to provide additional evidence for this treatment strategy.Keywords: hepatocellular carcinoma, lenvatinib, conversion hepatectomy, liver transplantation

Jing Zhu,1,2,* Zhiling Zhao,3,* Bin Wu,4 Zhihong Shi,5 Qingrong Nie,6 Zhen Fu,7 Zhaofu Zeng,1 Weihua Hu,1 Minglin Dong,1 Mengqing Xiong,1 Ke Hu1 1Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The People’s Hospital of China Three Gorges University, Yichang, Hubei, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 5Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xian, Shanxi, People’s Republic of China; 6Division of Respiratory Disease, Liangxiang Hospital of Yanjing Medical College, Capital Medical University, Beijing, People’s Republic of China; 7Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Hu Email huke-rmhospital@163.comObjective: The aim of this study was to explain “obesity paradox” in chronic obstructive pulmonary disease (COPD) by evaluating the effect of body mass index (BMI) on lung function in Chinese patients with COPD.Methods: A total of 1644 patients diagnosed with COPD were recruited from four Chinese tertiary hospitals and were divided into four groups including underweight, normal weight, overweight and obese according to BMI classification standard. The medical data of these patients were collected and used for the multiple linear regression analyses.Results: After adjustment for age, sex, educational level, economic status, smoking status, alcohol consumption, duration of COPD history, events of acute exacerbation in previous year, hypertension, diabetes mellitus, cardiovascular disease, cerebrovascular disease and osteoporosis, BMI had a curvilinear correlation with the forced expiratory volume in the first second (FEV1) in patients with Global Initiative for Obstructive Lung Disease (GOLD) 1– 2 grade (first-order coefficient β, 0.09; 95% CI, 0.03– 0.16; second-order coefficient β, − 0.002; 95% CI, − 0.003–-0.001; P< 0.01). However, BMI had a positive correlation with FEV1 in patients with GOLD 3– 4 grade (β, 0.01; 95% CI, 0.008– 0.017; P< 0.01) when BMI was used as a quantitative variable. When BMI was used as a qualitative variable, only FEV1 in overweight group with GOLD 1– 2 grade was significantly higher than that of normal weight group (P< 0.01). Interestingly, both overweight and obese groups had higher FEV1 in GOLD 3– 4 grade compared with normal weight group (β, 0.06; 95% CI, 0.02– 0.11; β, 0.11; 95% CI, 0.04– 0.18; P< 0.01). The effect of BMI on predicted percentage of FEV1 (FEV1%) was similar to that of FEV1 in different GOLD grades.Conclusion: Obesity only had a protective effect on lung function in COPD patients with GOLD 3– 4 grade rather than GOLD 1– 2 grade.Trial Registry: ClinicalTrials.gov, No.: NCT 03182309, URL: www.clinicaltrials.gov.Keywords: overweight, obesity

Xiaona Yuan,1 Zhenshuai Fu,2 Pengfei Ji,3 Lubo Guo,4 Ali O Al-Ghamdy,5 Ali Alkandiri,4,6 Ola A Habotta,7 Ahmed E Abdel Moneim,8 Rami B Kassab8 1Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450000, People’s Republic of China; 2Department of ICU, Sunshine Union Hospital, Weifang City, Shandong Province 261000, People’s Republic of China; 3Department of Ophthalmology, Zhengzhou Second Hospital, Zhengzhou City, Henan Province 450000, People’s Republic of China; 4Department of Pharmacy, Central Hospital Affiliated to Shandong First Medical University, Jinan City, Shandong Province 250013, People’s Republic of China; 5Biology Department, Faculty of Science and Arts, Al Baha University, Almakhwah, Saudi Arabia; 6Laboratory Technology Department, College of Technological Studies, Safat 13092, Kuwait; 7Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt; 8Department of Zoology and Entomology, Faculty of Science, Helwan University, Helwan 11795, EgyptCorrespondence: Lubo GuoDepartment of Pharmacy, Central Hospital Affiliated to Shandong First Medical University, Jinan City, Shandong Province 250013, People’s Republic of ChinaTel +86 18331125851Email guo700777@sina.comIntroduction: Epilepsy is a chronic neurological condition characterized by behavioral, molecular, and neurochemical alterations. Current antiepileptic drugs are associated with various adverse impacts. The main goal of the current study is to investigate the possible anticonvulsant effect of selenium nanoparticles (SeNPs) against pentylenetetrazole (PTZ)-mediated epileptic seizures in mice hippocampus. Sodium valproate (VPA) was used as a standard anti-epileptic drug.Methods: Mice were assigned into five groups (n=15): control, SeNPs (5 mg/kg, orally), PTZ (60 mg/kg, intraperitoneally), SeNPs+PTZ and VPA (200 mg/kg)+PTZ. All groups were treated for 10 days.Results: PTZ injection triggered a state of oxidative stress in the hippocampal tissue as represented by the elevated lipoperoxidation, heat shock protein 70 level, and nitric oxide formation while decreased glutathione level and antioxidant enzymes activity. Additionally, the blotting analysis showed downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the epileptic mice. A state of neuroinflammation was recorded following the developed seizures represented by the increased pro-inflammatory cytokines. Moreover, neuronal apoptosis was recorded following the development of epileptic convulsions. At the neurochemical level, acetylcholinesterase activity and monoamines content were decreased in the epileptic mice, accompanied by high glutamate and low GABA levels in the hippocampal tissue. However, SeNP supplementation was found to delay the onset and decreased the duration of tonic, myoclonic, and generalized seizures following PTZ injection. Moreover, SeNPs were found to provide neuroprotection through preventing the development of oxidative challenge via the upregulation of Nrf2 and HO-1, inhibiting the inflammatory response and apoptotic cascade. Additionally, SeNPs reversed the changes in the activity and levels of neuromodulators following the development of epileptic seizures.Conclusion: The obtained results suggest that SeNPs could be used as a promising anticonvulsant drug due to its potent antioxidant, anti-inflammatory, and neuromodulatory activities.Keywords: epilepsy, selenium nanoparticles, oxidative stress, neuroinflammation and apoptosis, monoamines, GABA and glutamate

Rescuing seal pups is an important conservation action for spotted seals Phoca largha. Gut microbiota are directly associated with host health and diet metabolism. Therefore, knowledge gained from gut microbiota variations of spotted seal pups held in captivity after rescue can help formulate comprehensive rescue plans for the future. In this study, we collected feces from a rescued spotted seal pup every 3 d during the rescue process. Fecal bacterial communities were measured by high-throughput sequencing based on 16S rRNA amplification. Firmicutes were the most dominant bacteria, comprising >70% of the total gut microbiota. Moreover, differences in fecal bacterial communities of the rescued spotted seal pup between rescue and release were compared. At release, the abundances of 2 potential bacteria related to gut health, Blautia producta and Cetobacterium somerae, were remarkably lower, while Clostridium perfringens, a key mammalian pathogen, was significantly higher in the feces of the released pup. Moreover, the pup experienced a bout of diarrhea during its time in captivity, which resulted in a momentary change in its gut microbiota. Fusobacterium was recognized as a potential causative pathogen for the diarrhea. This study contributes to our understanding of gut microbiota variations in spotted seal pups during the rescue period.

Kelie Chen,1,2,* Yuequn Niu,3,* Shengchao Wang,1,* Zhiqin Fu,4 Hui Lin,1,2 Jiaoying Lu,2 Xinyi Meng,2 Bowen Yang,2 Honghe Zhang,1 Yihua Wu,1,2 Dajing Xia,1,2 Weiguo Lu1 1Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, People’s Republic of China; 2Department of Toxicology, School of Public Health, School of Medicine, Zhejiang University, Hangzhou 310058, People’s Republic of China; 3Department of Thoracic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, People’s Republic of China; 4Department of Gynecological Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dajing XiaDepartment of Toxicology, School of Public Health, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, People’s Republic of ChinaTel/ Fax +86-0571-88208140Email dxia@zju.edu.cnWeiguo LuDepartment of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou, Zhejiang 310006, People’s Republic of ChinaTel +86-571-8706-1501Fax +86-571-87061878Email lbwg@zju.edu.cnBackground: Heterogeneity plays an essential role in ovarian cancer. Patients with different clinical features may manifest diverse patterns in diagnosis, treatment, and prognosis. The aim of the present study was to identify a novel ovarian cancer–classification model through cluster analysis and assess its significance in prognosis.Methods: Among patients diagnosed with ovarian cancer in the Women’s Hospital School of Medicine, Zhejiang University between January 2014 and May 2019, 328 patients were included in a K-mean cluster analysis and 176 patients followed up. Major clinical indicators, overall survival, and recurrence-free survival in different subgroups were compared.Results: Two clusters for ovarian cancer were identified and grouped as noninflammatory (n=247) and inflammatory subtypes (n=81). Compared with the noninflammatory subgroup, the inflammatory subgroup presented a statistically significantly higher level of median CRP (median (IQR) 20.4 [7.8– 47.3] vs 1.2 [0.4– 3.5], p< 0.001), neutrophil percentage (median (IQR) 76.9 [72.6– 81.3] vs 66.2 [61.0– 72.0], p< 0.001), leukocyte count (median (IQR) 8.9 [7.0– 10.0] vs 6.0 [5.1– 7.2], p< 0.001), fibrinogen (median (IQR) 5.0 [4.4– 6.0] vs 3.4 [2.9– 3.9], p< 0.001), and platelet count (median (IQR) 324 [270– 405] vs 229 [181.5– 269], p< 0.001). During a median follow-up of 52 months, 21 participants (16.3%) died in the noninflammatory group, while 14 (29.8%) died in the inflammatory group (HR 2.15, 95% CI 1.09– 4.23; p=0.024). Death/recurrence was observed in 38 (29.5%) patients from the noninflammatory group and 25 (53.2%) from the inflammatory group (HR 2.32, 95% CI 1.40– 3.85; p< 0.001).Conclusion: Our study revealed a novel classification model of ovarian cancer that features inflammation. Inflammation predicts shorter survival and poorer prognosis, suggesting the significance of inflammation in the management of ovarian cancer.Keywords: ovarian cancer, classification, heterogeneity, cluster analysis, inflammation, prognosis

Meng Li,1,* Xiuying Zhang,1,* Xianghai Zhou,1 Xueyao Han,1 Rui Zhang,1 Zuodi Fu,2 Lianying Wang,2 Ying Gao,1 Yufeng Li,2 Linong Ji1 1Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing, People’s Republic of China; 2Department of Endocrinology and Metabolism, Capital Medical University Pinggu Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linong JiDepartment of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing 100044, People’s Republic of ChinaTel/Fax +86-10-88324371Email jiln@bjmu.edu.cnYufeng LiDepartment of Endocrinology and Metabolism, Capital Medical University Pinggu Hospital, Beijing 101200, People’s Republic of ChinaTel/Fax +86-10-89978790Email doctorlyf@126.comPurpose: We aimed to ascertain the association between thyrotropin (TSH) levels in euthyroid state and the prevalence of metabolic syndrome (MetS) in a community-based Chinese population.Participants and Methods: Based on a large and well-characterized community cohort in Beijing, China, 1831 men and 1742 women with serum TSH levels within the reference range (0.50– 4.78 μIU/mL) were stratified by quartiles of TSH (Q1-4). MetS was identified according to the criteria of International Diabetes Federation guidelines. Poisson regression models were used to estimate the association between serum TSH and the prevalence of MetS and its components before and after adjustment for potential confounding factors. The reported association was measured using the prevalence ratio (PR) with its respective 95% confidence interval (95% CI).Results: The prevalence of MetS in euthyroid population across TSH quartiles (Q1-4) was 38.9%, 44.6%, 41.0%, and 47.7%, respectively, in men (P = 0.045), and 47.7%, 46.6%, 46.9%, and 54.6%, respectively, in women (P = 0.032). Compared with the reference group TSH-Q1, the prevalence of MetS was higher among TSH-Q4 group both in men (PR = 1.27; 95% CI: 1.09, 1.48, P = 0.002) and women (PR = 1.21; 95% CI: 1.07, 1.37, P = 0.003) even after adjustment for age, lifestyle factors, serum levels of free triiodothyronine (FT3), and free thyroxine (FT4). Most of the components of MetS were common in higher serum TSH levels within the normal range.Conclusion: The prevalence of MetS and most of its components increased in the higher TSH group in euthyroid Chinese population.Keywords: thyroid hormones, obesity, hypertension, hyperglycemia

Saixu Huang, 1–3,* Zhiyong Huang, 1–3,* Zhiqin Fu, 3,* Yamin Shi, 3, 4 Qi Dai, 1, 2 Shuyan Tang, 3 Yongwei Gu, 3 Youfa Xu, 3 Jianming Chen, 3, 4 Xin Wu, 3 Fuzheng Ren 1, 2 1Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Engineering Research Centre of Pharmaceutical Process Chemistry, Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China; 3Shanghai Weier Biological Medicine Science and Technology Co. Ltd., Shanghai, People’s Republic of China; 4Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fuzheng RenSchool of Pharmacy, East China University of Science and Technology, No. 130, Meilong Road, Shanghai 200237, People’s Republic of ChinaTel/Fax +86 21 6425 3255Email fzren@ecust.edu.cnXin WuShanghai Weier Biological Medicine Science and Technology Co. Ltd., No. 358, Tian Chen Road, Shanghai 201799, People’s Republic of ChinaTel/Fax +86 21 3119 8947Email xinwu007@126.comPurpose: Nimodipine (NIMO) is used clinically to treat ischemic damage resulting from subarachnoid hemorrhage. However, clinical application of NIMO is limited by poor aqueous solubility and low safety. To overcome these limitations, a novel two-vial NIMO-loaded nanoemulsion (NIMO-TNE) was designed in this study.Methods: NIMO-TNE was prepared by mixing a nimodipine-polyethylene glycol 400 (NIMO-PEG400) solution and a commercially available 20% injectable blank nanoemulsion (BNE). Drug distribution in NIMO-TNE, physical stability, and dilution stability were evaluated in vitro, and pharmacokinetics and pharmacodynamics were evaluated in vivo. Safety was assessed using the hemolysis test and the intravenous irritation test, and acute toxicity of NIMO-TNE was compared with that of commercial Nimotop injection.Results: Drug loading (DL) in NIMO-TNE was enhanced 5-fold compared with that in Nimotop injection. The mean particle size of NIMO-TNE was 241.53 ± 1.48 nm. NIMO-TNE and NIMO-TNE diluted in 5% glucose injection and 0.9% sodium chloride was stable for a sufficient duration to allow for clinical use. In addition, NIMO-TNE exhibited a similar pharmacokinetic profile and similar brain ischemia reduction in a rat middle cerebral artery occlusion (MCAO) model compared to Nimotop injection. Furthermore, NIMO-TNE did not induce hemolysis at 37°C, and NIMO-TNE induced less intravenous irritation than Nimotop injection. Moreover, NIMO-TNE could be injected at a 23-fold higher dose than the LD 50 of Nimotop injection with no obvious toxicity or side effects.Conclusion: NIMO-TNE is a promising formulation suitable for intravenous injection, is easy to prepare, and exhibits excellent safety.Keywords: nimodipine, nanoemulsion, pharmacokinetics, MCAO, LD50

Yongwei Gu,1,2,* Juanjuan Ma,2,* Zhiqin Fu,1,2,* Youfa Xu,1,2 Baoan Gao,1,2 Jianzhong Yao,3 Wei Xu,1 Kedan Chu,1 Jianming Chen1,2 1Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian 350108, People’s Republic of China; 2Shanghai Wei Er Biopharmaceutical Technology Co., Ltd., Shanghai 201707, People’s Republic of China; 3School of Pharmacy, Second Military Medical University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Xu; Jianming ChenDepartment of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian 350108, People’s Republic of ChinaTel/fax +86-591-22861693; +86-21-31198900-8949Email 2000017@fjtcm.edu.cn; chenjm0711@163.comPurpose: The objective of the present study was to develop a liposomal drug delivery system based on combretastatin A4 (CA4) prodrugs modified with varying alkyl chains and investigate the in vitro drug conversion from prodrug and in vivo antitumor effect.Methods: The prodrug of CA4 was synthesized with stearyl chloride (18-carbon chain), palmitoyl chloride (16-carbon chain), myristoyl chloride (14-carbon chain), decanoyl chloride (10-carbon chain), and hexanoyl chloride (6-carbon chain) at the 3′-position of the CA4. Subsequently, it was encapsulated with liposomes through the thin-film evaporation method. Furthermore, the characteristics of prodrug-liposome were evaluated using in vitro drug release, conversion, and cytotoxicity assays, as well as in vivo pharmacokinetic, antitumor, and biodistribution studies.Results: The liposome system with loaded CA4 derivatives was successfully developed with nano-size and electronegative particles. The rate of in vitro drug release and conversion was reduced as the fatty acid carbon chain lengthened. On the contrary, in vivo antitumor effects were improved with the enlargement of the fatty acid carbon chain. The results of the in vivo pharmacokinetic and tissue distribution studies indicated that the reduced rate of CA4 release with a long carbon chain could prolong the circulation time and increase the drug concentration in the tumor tissue.Conclusion: These results suggested that the release or hydrolysis of the parent drug from the prodrug was closely related with the in vitro and in vivo properties. The slow drug release of CA4 modified with longer acyl chain could prolong the circulation time and increase the concentration of the drug in the tumor tissue. These effects play a critical role in increasing the antitumor efficacy.Keywords: combretastatin A4, liposome, prodrug, drug release, anticancer

Zhuo Fu,1 Yan Jiao,2 Yan-Qing Li,3 Jian-Ji Ke,2 Yan-Hui Xu,4 Bao-Xing Jia,2 Bin Liu1 1Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of China; 3Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, People’s Republic of China; 4Department of Digestive, China-Japan Union Hospital Affiliated to Jilin University, Changchun, Jilin 130033, People’s Republic of ChinaCorrespondence: Bin LiuDepartment of Hand and Foot Surgery, The First Hospital of Jilin University, No. 71 Xinmin Street, Changchun, Jilin 130021, People’s Republic of ChinaEmail blwork@126.comPurpose: Liver cancer has a high incidence of mortality. DNA replication and posttranscriptional modifications play important roles in the development of liver cancer. Pescadillo (PES1) is a nuclear protein that is involved in embryonic development, ribosome synthesis, DNA replication, and cell cycle progression. Recently, abnormal PES1 expression was reported in several tumors, including neuroblastoma, colon cancer, gastric cancer, and breast cancer. Based on bio-informatic analysis, cell experiments and animal models, the aim of this study is to investigate the expression patterns and specific roles of PES1 in liver cancer.Patients and methods: PES1 expression was represented by boxplots. The correlation between PES1 expression and clinical features was assessed by the chi-squared test and Fisher’s exact tests. Kaplan–Meier curves compared overall survival between different levels of PES1 expression, and Cox analysis selected potential variables associated with overall survival. The MTT assay investigated the proliferation rate, the scratch assay assessed the migratory ability, and the Transwell assay evaluated the invasion capacity of tumor cells in vitro. Animal models were used to confirm the tumorigenic roles of PES1 in vivo. GSEA illustrated the molecular mechanisms that PES1 participated in.Results: We found that PES1 was highly expressed in liver cancer tissues, served as a diagnostic marker, and correlated with poor overall survival (OS) and relapse-free survival (RFS) in patients. In vitro studies indicated that PES1 promoted tumor cell proliferation (P=0.0034), migration (P=0.0026), and invasion (P=0.0008), and this tumorigenic role was confirmed in animal models. GSEA further illuminated molecular mechanisms that PES1 participated in liver cancer occurrence and progression.Conclusion: This study suggested that PES1 was upregulated in liver cancer and correlated with poor prognosis, by promoting tumor cell proliferation, migration, and invasion, and PES1 may be a novel diagnostic and prognostic bio-marker and a promising therapeutic target in liver cancer.Keywords: liver cancer, PES1, diagnosis, tumorigenesis, prognosis

The direct impact of structural quality on the ferroelectric properties of hexagonal Al1–xScxN with an Sc-content of x = 0.3 was investigated using dynamic hysteresis measurements, high-resolution x-ray diffraction (HRXRD), and atomic force microscopy. The films investigated were deposited on p-doped (001)-Si substrates by reactive pulsed DC magnetron sputtering under different gas mixtures to vary the structural quality and surface morphology between samples. Misoriented grains were identified as ferroelectrically inactive, as these grains resulted in an underestimation and distortion of the ferroelectric quantities. In fact, a high amount of misoriented volume was found to have a significant effect on the coercive electric field, as this is mainly determined by the crystal strain in the ferroelectric [0001]-oriented regions, independent of its origin. Furthermore, it was concluded that the crystal quality does not have a pronounced effect on the coercive field strength. Conversely, the polarization in the film is mainly determined by the crystal quality, as a difference of 1° in the HRXRD FWHM of the ω-scan resulted in a 60% loss of polarization. The amount of polarization was influenced to a lesser extent by the misoriented grains since the ferroelectric volume of the layers was only slightly overestimated. This reveals that optimizing reproducible and transferable properties, such as crystal quality and surface morphology, is more reasonable, as the film with the lowest misoriented volume and the highest degree of c-axis orientation showed the highest polarization. [ABSTRACT FROM AUTHOR]

Evaluating the ecological risks of metals and identifying their sources is useful for preventing and controlling heavy metal pollution in water bodies. Four sediment cores (S1~-S4) were collected from the Changhu Reservoir of South China to determine lead (Pb) concentrations and geochemical fractions, as well as the isotopic compositions of core S1. The results show that Pb concentrations increased from the upstream site (S1:173.2 mg kg-1) to the downstream site (S4:313.5 mg kg-1), resulting in a moderate to significant enrichment in the sediments. Sediment Pb in the geochemical fractions followed a decreasing order of residual (F4:54.7%) > reducible (F2: 23.1%) > oxidizable (F3: 16.6%) > acid-soluble fraction (F1: 5.8%). The geoaccumulation index (Igeo) and risk assessment code (RAC) showed that sediments were moderately polluted by Pb in S1 and S2 core, while sediments were moderately to heavily polluted in S3 and S4 core. The ecological risk of Pb in all sediment samples is generally at a low risk level, except for the sediments at a depth of 30-40 cm in the S4 core. Significant correlation between Pb concentration and 206Pb/207Pb ratios suggested possible binary mixing of Pb. In the present study, mining activities, which was the major anthropogenic Pb source base on its isotopic composition, contributed significantly (means: 45.3-77.5%) to sediment Pb. The anthropogenic Pb in sediments is most likely to come from Sphalerite and Galena. [ABSTRACT FROM AUTHOR]

Jingxian Duan,1 Yuling Wu,2 Jikui Liu,3 Jiajia Zhang,2 Zhichao Fu,2 Tieshan Feng,2 Ming Liu,2 Jie Han,2 Zhicheng Li,1 Shifu Chen1,2 1Department of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 2Department of Oncology, HaploX Biotechnology Co. Ltd, Shenzhen 518000, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, People’s Republic of ChinaCorrespondence: Shifu ChenDepartment of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of ChinaTel +86 135 1042 7830Email sf.chen@siat.ac.cnAbstract: Being one of the most lethal cancers that exhibit high levels of heterogeneity, hepatocellular carcinoma (HCC) is associated with diverse oncogenic pathways underpinned by varied driver genes. HCC can be induced by different etiological factors including virus infection, toxin exposure or metabolic disorders. Consequently, patients may display varied genetic profiles, and may respond differently to the treatments involving inhibition of target pathways. These DNA/RNA mutations, copy number variations, chromatin structural changes, aberrant expression of non-coding RNAs and epigenetic modifications were considered as biomarkers in the application of precision medication. To explore how genetic testing could contribute to early diagnosis, prognosis, treatment and postoperative monitoring of HCC, we conducted a systematic review of genetic markers associated with different pathologies. Moreover, we summarized on-going clinical trials for HCC treatment, including the trials for multiple kinase inhibitors and immune checkpoint blockade (ICB). The efficacy of ICB treatment in HCC is not as good as what was observed in lung cancer and melanoma, which might be due to the heterogeneity of the microenvironment of the liver.Keywords: genetic biomarkers, hepatocellular carcinoma, genomic sequencing, clinical trials

Kexin Ma,* Bing Dong,* Liming Wang, Chongyu Zhao, Zhaoyu Fu, Chi Che, Wuguang Liu, Zexuan Yang, Rui LiangDepartment of Hepatobiliary Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China*These authors contributed equally to this workPurpose: To develop and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in patients with surgically resected intrahepatic cholangiocarcinoma (ICC).Patients and methods: The nomograms were developed using a development cohort of 947 ICC patients after surgery selected from Surveillance, Epidemiology, and End Results database, and externally validated using a training cohort of 159 patients admitted at our institution. Nomograms for OS and CSS were established based on the independent prognostic factors identified by COX regression models and Fine and Grey’s models, respectively. The performance of the nomograms was validated internally and externally by using the concordance index (c-index), and calibration plot, and compared with that of AJCC 8th edition TNM staging system by using c-index and decision curve analysis.Results: Age, T stage, M stage, lymph node ratio (LNR) level and tumor grade were independent prognostic predictors for OS in ICC patients, while T stage, M stage, LNR level and tumor grade were independent prognostic predictors for CSS. Nomogram predicting OS was with a c-index of 0.751 on internal validation and 0.725 up to external validation, while nomogram for CSS was with a c-index of 0.736 on internal validation and 0.718 up to external validation. Calibration plots exhibited that the nomograms-predicted and actual OS/CSS probabilities were fitted well on both internal and external validation. Additionally, the nomograms exhibited superiority over AJCC 8th edition TNM staging system with higher c-indices and net benefit gains, in predicting OS and CSS in ICC patients after surgery.Conclusion: The constructed nomograms could predict OS and CSS with good performance, which could be served as an effective tool for prognostic evaluation and individual treatment strategies optimization in ICC patients after surgery in clinical practice.Keywords: intrahepatic cholangiocarcinoma, overall survival, cancer-specific survival, nomogram