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Xiu-Jie Zhao,1 Chun-Yu Bai,2 Xiao-Yan Li,1 Lei Wang,2 Ren-Ping Wang,2 Yue Xia,1,2 Gang Liu,1 Hong-Liang Zhao,1,* Hong-Zun Xu2,* 1Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People’s Republic of China; 2Department of Cardiology, Shijiazhuang Great Wall Cardiovascular Hospital, Shijiazhuang, 050035, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong-Liang Zhao; Hong-Zun Xu, Email Doc_zhl@163.com; 116281970@qq.comAbstract: Carvajal syndrome is a rare hereditary cardiocutaneous syndrome caused by the variants of the desmoplakin (DSP) gene. In this study, we report a patient of Carvajal syndrome with a novel homozygous missense variant of DSP gene. We diagnosed a 7-year-old female patient with Carvajal syndrome characterized by dilated cardiomyopathy, palmoplantar keratoderma, woolly hair, and dental dysplasia, who disclosed a novel homozygous missense variant c.4597C > T (p.Q1533X) in exon 6 of the DSP gene found for the first time. Both her parents were heterozygous for the identified nonsense variant c.4597C > T (p.Q1533X) in DSP gene but neither showed evidence of Carvajal syndrome, indicating that this novel variant causes the disease in an autosomal recessive manner. Genotypes of Carvajal syndrome are even broader than so far anticipated. When patients with dilated cardiomyopathy, palmoplantar keratoderma, woolly hair, and dental dysplasia are found in clinical practice, Carvajal syndrome should be highly suspected, and family gene sequencing should be actively carried out.Keywords: Carvajal syndrome, desmoplakin, genotype, variant, novel

Shu-Jie Pang,1,&ast; Zhe Sun,1,&ast; Wen-Feng Lu,1,&ast; Hui Si-Ma,1 Zhi-Peng Lin,2 Yang Shi,1 Ying-Cheng Yang,1 Xi-Jun Zhao,1 Guang-Shun Yang,1 Guang-Zhi Jin,3 Ning Yang1 1Department V of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People’s Republic of China; 2Department of Hepatobiliary Surgery, The 940th Hospital of CPLA Joint Logistics Support Force, Lanzhou, 730050, People’s Republic of China; 3Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Yang, Department V of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People’s Republic of China, Tel +86 21 81877591, Fax +86 21 6556 6851, Email lancet00@163.com Guang-Zhi Jin, Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, People’s Republic of China, Email jgzhi@hotmail.comBackground: RBM10ʹs function in hepatocellular carcinoma (HCC) has rarely been addressed. We intend to explore the prognostic significance and therapeutic meaning of RBM10 in HCC in this study.Methods: Multiple common databases were integrated to analyze the expression status and prognostic meaning of RBM10 in HCC. The relationship between RBM10 mRNA level and clinical features was also assessed. Multiple enrichment analyses of the differentially expressed genes between RBM10 high- and low- transcription groups were constructed by using R software (version 4.0.2). A Search Tool for Retrieval of Interacting Genes database was used to construct the protein–protein interaction network between RBM10 and other proteins. A tumor immune estimation resource database was employed to identify the relationship between RBM10 expression and immune cell infiltrates. The prognostic value of RBM10 expression was validated in our HCC cohort by immunohistochemistry test.Results: The transcription of RBM10 mRNA was positively correlated with tumor histologic grade (p < 0.001), T classification (p < 0.001), and tumor stage (p < 0.001). High transcription of RBM10 in HCC predicted a dismal overall survival (p = 0.0037) and recurrence-free survival (p < 0.001). Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Gene Set Enrichment Analysis all revealed that RBM10 was involved in the regulation of cell cycle, DNA replication, and immune-related pathways. Tumor immune estimation analysis revealed that RBM10 transcription was positively related to multiple immune cell infiltrates and the expressions of PD-1 and PD-L1.Conclusion: RBM10 was demonstrated to be a dismal prognostic factor and a potential biomarker for immune therapy in HCC in that it may be involved in the immune-related signaling pathways.Keywords: RBM10, hepatocellular carcinoma, prognosis, differentially expressed gene, integrated bioinformatics analysis

Bin Ren,1,2,&ast; Zhong-Chao Cai,1,&ast; Xue-Jie Zhao,1 Lin-Song Li,1 Mei-Xia Zhao1 1Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Jinming Campus, Kaifeng, Henan, 475004, People’s Republic of China; 2School of Mathematics and Statistics, Henan University, Jinming Campus, Kaifeng, 475004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei-Xia ZhaoKey Laboratory of Natural Medicine and Immune Engineering of Henan Province, Henan University, Jinming Campus, Kaifeng, Henan, 475004, People’s Republic of ChinaEmail zhaomeixia2011@henu.edu.cnPurpose: Gold nanoparticles (AuNPs) with good physical and biological properties are often used in medicine, diagnostics, food, and similar industries. This paper explored an AuNPs drug delivery system that had good target selectivity for folate-receptor overexpressing cells to induce apoptosis.Methods: A novel drug delivery system, Au@MPA-PEG-FA-PTX, was developed carrying paclitaxel (PTX) on folic acid (FA) and polyethylene glycol (PEG)-modified AuNPs. The nanomaterial was characterized by transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and ultraviolet-visible spectroscopy (UV-Vis). Also, the biological activity of the AuNPs drug delivery system was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HL-7702, Hela, SMMC-7721, and HCT-116 cells. Furthermore, apoptotic activity using annexin V-FITC, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) levels was estimated by flow cytometry and fluorescence microscopy.Results: Au@MPA-PEG-FA-PTX exhibited a distinct core-shell structure with a controllable size of 28± 1 nm. Also, the AuNPs maintained good dispersion and spherical shape uniformity before and after modification. The MTT assay revealed good antitumor activity of the Au@MPA-PEG-FA-PTX against the Hela, SMMC-7721, and HCT-116 cells, while Au@MPA-PEG-FA-PTX produced better pharmacological effects than PTX in isolation. Further mechanistic investigation revealed that effective internalization of AuNPs by folate-receptor overexpressing cancer cells induced cell apoptosis through excessive production of intracellular ROS.Conclusion: The AuNPs drug delivery system showed good target selectivity for folate-receptor overexpressing cancer cells to induce target cell-specific apoptosis. These AuNPs may have great potential as theranostic agents such as in cancer.Keywords: gold nanoparticles, folic acid, paclitaxel, drug delivery system, apoptosis

Shu Li,1 Fu-Zheng Guo,2 Xiu-Juan Zhao,1 Qi Wang,3 Hui Wang,3 You-Zhong An,1 Feng-Xue Zhu1,21Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Trauma Centre, Peking University People’s Hospital, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaPurpose: Active surveillance of carbapenem-resistant Enterobacteriaceae (CRE) may contribute to the decline of the infection rate. Individualized active surveillance of CRE could cost less than screening all patients. However, the impact of individualized active surveillance on the CRE infection rate in intensive care units (ICUs) has not been well described.Patients and methods: We retrospectively studied the clinical data of all patients admitted in the ICUs of a tertiary-care hospital in China from 2015 to 2017 during two periods, before and after the implementation of individualized active surveillance. During period 1 (January 2015–April 2016), no screening protocol was used. During period 2 (May 2016–December 2017), we implemented active CRE screening for selected patients according to their clinical characteristics. The trend of CRE rate infection was analyzed by a joinpoint regression model, and multivariate analysis was performed to analyze the association of active surveillance, Acute Physiology and Chronic Health Evaluation (APACHE) II score, prior antimicrobial use, length of mechanical ventilation (MV) before infection, and other risk factors with CRE infection rate.Results: A total of 5,372 patients were included. After assessing the patients’ clinical characteristics, 72.3% (3,882/5,372) were considered to be at high risk of CRE infection. During period 1, the infection percent of CRE increased by 13.04% every month (95% CI: 5.2–21.5). During period 2, the infection rate decreased (monthly percent change, −3.57%; 95% CI −6.9 to −0.1, P

Xinjun Zhao,1,2,* Yue Hua,1,2,* Hongmei Chen,1,2,* Haiyu Yang,3,* Tao Zhang,1,2,* Guiqiong Huang,4,* Huijie Fan,1,2 Zhangbin Tan,1,2 Xiaofang Huang,1,2 Bin Liu,5 Yingchun Zhou1,21The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangdong, Guangzhou, People’s Republic of China; 2Nanfang Hospital, Southern Medical University, Guangdong, Guangzhou, People’s Republic of China; 3Jiangmen Wuyi Traditional Chinese Medicine Hospital, Guangdong, Jiangmen, People’s Republic of China; 4Huizhou Hospital of Traditional Chinese Medicine, Huizhou, People’s Republic of China; 5The Second Affiliated Hospital of Guangzhou Medical University, Guangdong, Guangzhou, People’s Republic of China*These authors contributed equally to this workBackground: Aldehyde dehydrogenase-2 (ALDH2) has a protective effect on ischemic heart disease. Here, we examined the protective effects of ALDH2 on cardiac fibrosis through modulation of the Wnt/ß-catenin signaling pathway in a rat model of myocardial infarction (MI).Methods: Wistar rats were divided into the sham (control), MI (model), and ALDH2 activator (Alda-1) groups. After 10 days of treatment, the left ventricular (LV) remodeling parameters of each animal were evaluated by echocardiography. Myocardial fibrosis was evaluated by Masson’s trichrome staining and Sirius Red staining. Expression levels of collagen types I and III and β-smooth muscle actin (α-SMA) were examined. Finally, the expression and activity of ALDH2 and the levels of several Wnt-related proteins and genes, such as phospho-glycogen synthase kinase (GSK)-3β, GSK-3β, β-catenin, Wnt-1, WNT1-inducible signaling-pathway protein 1, and tumor necrosis factor (TNF)-α, were also analyzed.Results: After MI, the heart weight/body weight ratio, LV dimension at end diastole, and LV dimension at end systole were decreased, while the LV ejection fraction and LV fractional shortening were increased in the Alda-1 group. Myocardial fibrosis was also reduced in the Alda-1 group, accompanied by decreased expression collagen types I and III and α-SMA. β-Catenin, phosphorylated GSK-3β, and Wnt-1 levels were significantly increased in the model group. Interestingly, this alteration was partly reversed by Alda-1 treatment. Immunohistochemical staining showed that numerous WNT1-inducible signaling-pathway protein 1 (WISP-1)- and TNF-α-positive cells were found in the model group. However, few WISP-1- and TNF-α-positive cells were detected in the Alda-1 group.Conclusion: The reduction of cardiac fibrosis and the down-regulation of β-catenin, phosphorylated GSK-3β, Wnt-1, and WISP-1 may be mediated by increased ALDH2 activity, leading to reduction of MI-related cardiac fibrosis.Keywords: myocardial infarction, aldehyde dehydrogenase, cardiac fibrosis, Wnt signaling

Jingping Liu,1 Shuyun Liu,1 Younan Chen,1 Xiaojun Zhao,2 Yanrong Lu,1 Jingqiu Cheng1 1Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, 2Laboratory of Nanomedicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: Islet transplantation is considered to be a curative treatment for type 1 diabetes mellitus. However, disruption of the extracellular matrix (ECM) leads to β-cell destruction and graft dysfunction. In this study, we developed a functionalized self-assembling peptide, KLD-F, with ECM mimic motifs derived from fibronectin and collagen IV, and evaluated its effect on β-cell function and proliferation. Atomic force microscopy and rheological results showed that KLD-F could self-assemble into a nanofibrous scaffold and change into a hydrogel in physiological saline condition. In a three-dimensional cell culture model, KLD-F improved ECM remodeling and cell-cell adhesion of INS-1 β-cells by upregulation of E-cadherin, fibronectin, and collagen IV. KLD-F also enhanced glucose-stimulated insulin secretion and expression of β-cell function genes, including Glut2, Ins1, MafA, and Pdx-1 in INS-1 cells. Moreover, KLD-F promoted proliferation of INS-1 β-cells and upregulated Ki67 expression by mediating cell cycle progression. In addition, KLD-F improved β-cell function and proliferation via an integrin/focal adhesion kinase/extracellular signal-regulated kinase/cyclin D pathway. This study highlights the fact that the β-cell-ECM interaction reestablished with this functionalized self-assembling peptide is a promising method to improve the therapeutic efficacy of islet transplantation. Keywords: extracellular matrix, self-assembling peptide, islet transplantation, β-cell proliferation, insulin secretion

Xiaojing Zhao,1,2,* Qi Chen,3,* Wei Liu,1,2 Yusang Li,3 Hebin Tang,3 Xuhan Liu,1,2 Xiangliang Yang1,2 1College of Life Science and Technology, 2National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, 3Department of Pharmacology, College of Pharmacy, South-Central University for Nationalities, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Liver cancer is a leading cause of cancer deaths worldwide. The combination therapy of cytotoxic and chemosensitizing agents loaded in nanoparticles has been highlighted as an effective treatment for different cancers. However, such studies in liver cancer remain very limited. In our study, we aim to develop a novel lipid nanoparticles loaded with doxorubicin (DOX) (an effective drug for liver cancer) and curcumin (Cur) (a chemosensitizer) simultaneously, and we examined the efficacy of chemotherapy in liver cancer. DOX and Cur codelivery lipid nanoparticles (DOX/Cur-NPs) were successfully prepared using a high-pressure microfluidics technique, showing a mean particle size of around 90 nm, a polydispersity index 90% for both DOX and Cur. The blank lipid nanoparticles were nontoxic, as determined by a cell cytotoxicity study in human normal liver cells L02 and liver cancer cells HepG2. In vitro DOX release studies revealed a sustained-release pattern until 48 hours in DOX/Cur-NPs. We found enhanced cytotoxicity and decreased inhibitory concentration (IC)50 in HepG2 cells and reduced cytotoxicity in L02 cells treated with DOX/Cur-NPs, suggesting the synergistic effects of DOX/Cur-NPs compared with free DOX and DOX nanoparticles (NPs). The optimal weight ratio of DOX and Cur was 1:1. Annexin-V-fluorescein isothiocyanate/propidium iodide double staining showed enhanced apoptosis in HepG2 cells treated with DOX/Cur-NPs compared with free DOX and DOX-NPs. An in vivo experiment showed the synergistic effect of DOX/Cur-NPs compared with DOX-NPs on liver tumor growth inhibition. Taken together, the simultaneous delivery of DOX and Cur by DOX/Cur-NPs might be a promising treatment for liver cancer. Keywords: doxorubicin, curcumin, codelivery, liver cancer, cytotoxicity, tumor growth inhibition

Dongxi Xiang,1 Yang Zheng,2 Wei Duan,1 Xiujing Li,3 Jianjian Yin,3 Sarah Shigdar,1 Michael Liam O’Connor,1 Manju Marappan,1 Xiaojuan Zhao,4 Yingqiu Miao,3 Bin Xiang,5 Conglong Zheng31School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia; 2Department of Pharmacology, Osaka University, Osaka, Japan; 3Department of Biology, Medical College, Dalian University, Liaoning, People’s Republic of China; 4Department of Gynaecology and Obstetrics, Qingdao Central Hospital, Shandong, People’s Republic of China; 5Department of Oral Medicine and Medical Research Center, Medical College, Dalian University, Liaoning, People’s Republic of ChinaAbstract: Silver nanoparticles (AgNPs) have attracted much attention as antimicrobial agents and have demonstrated efficient inhibitory activity against various viruses, including human immunodeficiency virus, hepatitis B virus, and Tacaribe virus. In this study, we investigated if AgNPs could have antiviral and preventive effects in A/Human/Hubei/3/2005 (H3N2) influenza virus infection. Madin-Darby canine kidney cells infected with AgNP-treated H3N2 influenza virus showed better viability (P

Xiang DX, Zheng Y, Duan W, et al. Int J Nanomedicine. 2013;8:4103–4114.On page 4103, the author affiliations were incorrectly listed. The correct affiliations are listed below.Dongxi Xiang1,2Yang Zheng3Wei Duan2Xiujing Li1Jianjian Yin1Sarah Shigdar2Michael Liam O’Connor2Manju Marappan2Xiaojuan Zhao4Yingqiu Miao1Bin Xiang5Conglong Zheng1 1Department of Biology, Medical College, Dalian University, Liaoning, People’s Republic of China; 2School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia; 3Department of Pharmacology, Osaka University, Osaka, Japan; 4Department of Gynaecology and Obstetrics, Qingdao Central Hospital, Shandong, People’s Republic of China; 5Department of Oral Medicine and Medical Research Center, Medical College, Dalian University, Liaoning, People’s Republic of ChinaView original paper by Xiang et al.