Search

Biao Hou,1– 3,* Bo Li,4,* Wanjun Deng,3,* Bo Li,1,2 Bibo Ren,5 Chao Hu,3 Guowei Zhang,1,2 Fen Yang,6 Meimei Xiao,3 Songlin Xie,3 Denghui Xie1,2 1Department of Joint Surgery and Sports Medicine, Center for Orthopedic Surgery, Orthopedic Hospital of Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Academy of Orthopedics, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Hand and Foot Microsurgery, The affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, People’s Republic of China; 4Department of Radiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5College of Biomass Science and Engineering, Sichuan University, Chengdu, People’s Republic of China; 6Department of Infectious Diseases, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Denghui Xie; Songlin Xie, Email smuspine@163.com; xiesonglin0929@163.comPurpose: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation.Methods: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme’s size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA).Results: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes’ potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections.Conclusion: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.Keywords: copper nanozyme, aggregate induced emission, photodynamic antibacterial therapy, antimicrobial resistance, diabetic wound healing

Ya-Ping Chen,1,2 Heng Wang,1,3 Lei Wang,4 Dan Xie,4 Min Guo,4 Jiang-Fen Wu,5 Bang-Quan An,6 Sheng-Wen Huang1,5 1School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Clinical Laboratory, the Second People’s Hospital of Guiyang, Guiyang, Guizhou, People’s Republic of China; 3Guiyang Public Health Clinical Center, Guiyang, Guizhou, People’s Republic of China; 4Medical College of Guizhou University, Guiyang, Guizhou, People’s Republic of China; 5Medical Genetics Department, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 6Department of Blood Transfusion, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of ChinaCorrespondence: Sheng-Wen Huang, Medical Genetics Department, Guizhou Provincial People’s Hospital, No. 83, East Zhongshan Road, Nanming District, Guiyang, Guizhou, 550002, People’s Republic of China, Tel +86-851-85935128, Fax +86-851-85937194, Email hsw713@sina.comPurpose: To analyze the composition of abnormal hemoglobin and the relationship between genotype and phenotype by screening abnormal hemoglobin in a subpopulation of Guizhou, China.Patients and Methods: Routine blood evaluation, capillary electrophoresis of hemoglobin, and mutation of α - and β - thalassemia genes were evaluated in 19,976 individuals for thalassemia screening in Guizhou. Sanger sequencing of HBA1, HBA2 and HBB genes was performed in samples with abnormal bands or unexplained increases of normal bands. The types of abnormal hemoglobin were obtained by sequence analysis.Results: Abnormal hemoglobin was detected in 84 individuals (detection rate, 0.42%). Ten types each of α and β globin chain variants were detected, including most commonly Hb E, Hb New York and Hb Port Phillip. In this study, the abnormal Hb Mizuho was identified for the first time in a Chinese population, and a novel abnormal hemoglobin Hb Guiyang (HBA2: c.151C > A) was detected for the first time. Except for Hb Mizuho, other abnormal hemoglobin heterozygotes without thalassemia or iron deficiency had no significant hematological changes.Conclusion: This study enriched the molecular epidemiological data of abnormal hemoglobin in Guizhou, China and provided reference data for genetic counseling and prenatal diagnosis of abnormal hemoglobin.Keywords: abnormal hemoglobin, routine blood examination, capillary electrophoresis, DNA sequencing, Hb Mizuho, HBA2

Yueda Jihu,1,2,* Ruobing Leng,1,* Mengchang Liu,1,2 Hongjing Ren,1,2 Defu Xie,1,2 Chong Yao,1,2 Hong Yan1,2 1Clinical College of Medicine, Southwest Medical University, Lu zhou, People’s Republic of China; 2Department of Plastic and Burn Surgery, the Affiliated Hospital of Southwest Medical University, Lu zhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Yan, Email zxsswk@163.comIntroduction: Angiotensin (1– 7) (Ang-(1-7)) is an emerging component of the renin-angiotensin system (RAS) with effective anti-fibrosis properties and has been shown to interfere with epithelial-mesenchymal transition (EMT) by numerous studies. In recent years, EMT has been proposed as a new therapeutic target for skin fibrotic diseases such as keloids. However, the effect of Ang-(1-7) on EMT in skin is still unclear. Hence, the purpose of this study was to explore the effect of Ang-(1-7) on Transforming growth factor-β 1(TGF-β 1)–induced EMT of human immortalized keratinocytes HaCaT in vitro.Methods: The study involved the use of the human immortalized keratinocyte cell line (HaCaT). The cells were cultured in high-glucose DMEM medium with 10% fetal bovine serum and 1% penicillin-streptomycin. Four groups were created for experimentation: control group (Group C), TGF-β 1-treated group (Group T), Ang-(1-7)-treated group (Group A), and a group treated with both TGF-β 1 and Ang-(1-7) (Group A + T). Various assays were conducted, including a cell proliferation assay using CCK-8 solution, a scratch wound healing assay to evaluate cell migration, and Western blotting to detect protein expressions related to cell characteristics. Additionally, quantitative real-time polymerase chain reaction (PCR) was performed to analyze epithelial-mesenchymal transition (EMT) related gene expression levels. The study aimed to investigate the effects of TGF-β 1 and Ang-(1-7) on HaCaT cells.Results: We found that Ang-(1-7) not only reduced the migration of HaCaT cells induced by TGF-β 1 in vitro but also reduced the expression of α-SMA and vimentin, and restored the protein expression of E-cadherin and claudin-1. Mechanistically, Ang-(1-7) inhibits the phosphorylation levels of Smad2 and Smad3 in the TGF-β 1 canonical pathway, and suppresses the expression of EMT-related transcription factors (EMT-TFs) such as SNAI2, TWIST1, and ZEB1.Discussion: Taken together, our findings suggest that Ang-(1-7) inhibits TGF-β 1–induced EMT in HaCaT cells in vitro by disrupting the TGF-β 1-Smad canonical signaling pathway. These results may be helpful in the treatment of EMT in skin fibrotic diseases such as keloids.Keywords: angiotensin (1-7), epithelial-mesenchymal transition, transforming growth factor-β, keratinocytes

Lujia Tang,* Di Xie,* Shangyuan Wang, Chengjin Gao, Shuming Pan Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuming Pan; Chengjin Gao, Email panshuming@xinhuamed.com.cn; gaochengjin@xinhuamed.com.cnBackground: Cerebral infarction often results in post-stroke cognitive impairment, which impairs the quality of life and causes long-term disability. Astrocytes, the most abundant glial cells in the central nervous system, have a crucial role in cerebral ischemia and neuroinflammation. We explored the possible advantages of interleukin-6 (IL-6), a powerful pro-inflammatory cytokine produced by astrocytes, for post-stroke cognitive function.Methods: Mendelian randomization was applied to analyze the GWAS database of stroke patients, obtaining a causal relationship between IL-6 and stroke. Further validation of this relationship and its mechanisms was conducted. Using a mouse model of cerebral infarction, we demonstrated a significant increase in IL-6 expression in astrocytes surrounding the ischemic lesion. This protective effect of Piezo1 knockout was attributed to the downregulation of matrix metalloproteinases and upregulation of tight junction proteins, such as occludin and zonula occludens-1 (ZO-1).Results: Two-step Mendelian randomization revealed that IL-6 exposure is a risk factor for stroke. Moreover, we conducted behavioral assessments and observed that Piezo1 knockout mice that received intranasal administration of astrocyte-derived IL-6 showed notable improvement in cognitive function compared to control mice. This enhancement was associated with reduced neuronal cell death and suppressed astrocyte activation, preserving ZO-1.Conclusion: Our study shows that astrocyte-derived IL-6 causes cognitive decline after stroke by protecting the blood-brain barrier. This suggests that piezo1 knockout may reduce cognitive impairment after brain ischemia. Further research on the mechanisms and IL-6 delivery methods may lead to new therapies for post-stroke cognition.Keywords: cerebral infarction, neuroinflammation, astrocytes, blood-brain barrier, tight junctions

Diyang Xie, Zhongchen Li, Jia Yuan, Xin Yin, Rongxin Chen, Lan Zhang, Zhenggang Ren Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Ministry of Education, Fudan University, Shanghai, 200032, People’s Republic of ChinaCorrespondence: Zhenggang Ren, Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Ministry of Education, Fudan University, Shanghai, 200032, People’s Republic of China, Tel/Fax +86-21-64037181, Email ren.zhenggang@zs-hospital.sh.cnPurpose: This study aims to establish a prognostic nomogram for patients who underwent transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (HCC) after hepatectomy.Patients and Methods: Patients who underwent TACE for recurrent early- and middle-stage HCC after hepatectomy between 2009.01 and 2015.12 were included. Enrolled patients were randomly divided into training (n=345) and validation (n=173) cohorts according to a computer-generated randomized number. Independent factors for overall survival (OS) were determined and included in the nomogram based on the univariate and multivariate analyses of the training group. The nomogram was validated and compared to other prognostic models. Discriminative ability and predictive accuracy were determined using the Harrell C index (C-index), area under the receiver operating characteristic curve (AUROC), and calibration curve.Results: The final nomogram was established based on four parameters including resection-to-TACE time interval, recurrent tumor diameter, recurrent tumor number, and AFP level. The C-indexes of the nomogram for predicting OS were 0.67 (95% CI 0.63– 0.70) and 0.71 (95% CI 0.68– 0.74) in the training and validation cohort respectively. The AUROCs for predicting the 1-year, 2-year and 3-year OS based on the nomogram were also superior to those of the other models. The calibration curve for 3-year survival showed a high congruence between the predicted and actual survival probabilities. According to the scores calculated by the nomogram, patients were stratified into three subgroups: high-risk (scoring ≥ 53 points), middle-risk (scoring ≥ 26 and < 53 points), and low-risk (scoring < 26 points) subgroups with a median OS of 10.1 (95% CI 0.63– 0.70), 20.3 (95% CI 17.5– 22.5) and 47.0 (95% CI 34.2– 59.8) months, respectively.Conclusion: The proposed nomogram served as a new tool to predict individual survival in patients who underwent TACE for recurrent HCC after hepatectomy, with favorable performance and discrimination. For high-risk patients, treatment should be optimized beyond TACE alone based on the nomogram.Keywords: hepatocellular carcinoma, transarterial chemoembolization, nomogram

Xusheng Gao, Caihong Ding, Dan Xie, Qing Wang, Peipei Jiang, Yuyu Wang, Yu Xiong Department of Tuberculosis, Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Yu Xiong, Department of Tuberculosis, Shandong Public Health Clinical Center, Shandong University, No. 11, Lieshishan East Road, Licheng District, Jinan, Shandong, People’s Republic of China, Tel +8615589995880, Email yiyiruguo1@163.comBackground: In recent decades, there has been a substantial surge in the incidence of non-tuberculous Mycobacteria (NTM) infections. However, the diagnosis and management of NTM globally present significant challenges, particularly in cases involving Mycobacterium abscessus complex (MABC) infection where effective therapeutic options are limited.Case Presentation: We reported a 38-year-old female patient who was infected with MABC of skin due to “beauty needle” at a beauty salon, with mass on both cheeks, accompanied by redness, and pain, and some of them was ulcered and effused. Puncture pumping pus from bilateral cheek mass for many times, rinsed with “metronidazole”, and oral “cephalosporin” treatment did not work. Therefore, she came to our hospital. MABC was detected in abscess paracentesis pus by nucleic acid mass spectrometry, and was proved by the cultured result of the pus. Thus, the patient was diagnosed as skin MABC infection, and anti-NTM treatment was taken. However, adverse reactions such as tinnitus, hepatotoxicity and neurovirulence occurred during the initial treatment. After adjusting to the contezolid-containing regimen, these adverse reactions improved. After nearly 6 months of treatment, the cheek mass was gradually reduced and the skin ruptures were gradually healed. Follow-up for 10 months showed that the patient’s facial symptoms were significantly improved, and no drug-related adverse reactions happened.Conclusion: This was the first successful case of multiple drug resistance MABC infection of skin treated with contezolid-containing antibiotic management strategies, which exhibited remarkable efficacy and good safety in this intractable disease.Keywords: Mycobacterium abscessus complex, antibiotic therapy, contezolid, Case report

Yunbo Yan,1 Linqian Yu,1 Binyang Chen,1 Chang’an Cao,1 Hairong Zhao,1,2 Qiang Wang,1 De Xie,1 Yuemei Xi,1 Chenggui Zhang,2 Jidong Cheng1,3 1Department of Internal Medicine, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, People’s Republic of China; 3Xiamen Key Laboratory of Translational Medicine for Nucleic Acid Metabolism and Regulation, Xiamen, People’s Republic of ChinaCorrespondence: Jidong Cheng; Chenggui Zhang, Email jidongcheng36@hotmail.com; chenggui_zcg@hotmail.comBackground: Gouty arthritis is characterized by the accumulation of monosodium urate crystals (MSU) in the synovial joints and surrounding tissues. Mastoparan M (Mast-M) is a biologically active peptide composed of 14 amino acids, extracted from wasp venom. This study aims to assess the impact of Mast-M on in vitro and in vivo gouty arthritis induced by lipolyaccharide (LPS) plus MSU crystal stimulation.Methods: PMA-differentiated THP-1 macrophages were pre-treated with Mast-M or left untreated, followed by stimulation with LPS and MSU crystals. Cell lysates were collected to assess the expression of the NLRP3 inflammasome, inflammatory signaling pathways, and oxidative stress. Furthermore, to evaluate the in vivo anti-inflammatory effect of Mast-M, an experimental acute gouty arthritis mouse model was established through intra-articular injection of MSU crystals.Results: Mast-M treatment demonstrated significant inhibition of the phosphorylation of MAPKs/NF-κB signaling pathways and reduction in oxidative stress expression in LPS and MSU-induced THP-1 macrophages. This resulted in the suppression of downstream NLRP3 inflammasome activation and IL-1β release. In vivo, Mast-M effectively attenuated the inflammation induced by MSU in mice with gouty arthritis. Specifically, Mast-M reduced swelling in the paws, inhibited the infiltration of neutrophils and macrophages into periarticular tissue, and decreased the activation of the NLRP3 inflammasome and IL-1β production.Conclusion: Mast-M significantly improves gouty arthritis, and its potential mechanism may be achieved by inhibiting the MAPK/NF-κB pathway and alleviating oxidative stress, thus suppressing the activation of NLRP3 inflammasomes.Keywords: Mastoparan M, NLRP3, MAPKs, NF-κB, oxidative stress, gout

Ting Pan,1 Xuefeng Li,2 Xiaole Guo,3 Haili Wang,2 Xue Zhou,2 Rui Shang,4 Donge Xie,5 Xin Qian,6 Mengyao Dai,2 Enshuo Fan,2 Xinhua Chen,1 Chunhai Chen5 1College of Traditional Chinese Medicine, ChangChun University of Chinese Medicine, Changchun, Jilin, People’s Republic of China; 2School of Acupuncture-Moxibustion and Tuina, Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of China; 3Prevention and Treatment Center, The Third Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin, People’s Republic of China; 4Traditional Chinese Medicine Rehabilitation Center, Jilin Cancer Hospital, Changchun, Jilin, People’s Republic of China; 5Acupuncture and moxibustion Clinical Center, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of China; 6Tuina Department, Shenzhen Traditional Chinese Medicine Hospital, ShenZhen, Guangdong, People’s Republic of ChinaCorrespondence: Xinhua Chen, ChangChun University of Chinese Medicine, No. 1035 Boshuo Road, Changchun, Jilin Province, 130117, People’s Republic of China, Tel +86 13596104290, Email 187098190@qq.com Chunhai Chen, Affiliated Hospital of Changchun University of Chinese Medicine, No. 1478 Gongnong Dalu, Changchun, Jilin Province, 130021, People’s Republic of China, Tel +86 13604404239, Email 5010841@qq.comIntroduction: Adjusting internal organs and dredging channel electroacupuncture has a definite effect on type 2 diabetes, but the specific mechanism still needs to be further clarified. This study aims to investigate the effects of electroacupuncture on the gut microbiota and bile acids in db/db mice after the intervention of “adjusting internal organs and dredging channel” and further explore its mechanism of action in treating T2DM.Methods: We used db/db mice as the animal model and db/m mice from the same litter as the blank control group, a total of 4 weeks of intervention were conducted. We evaluated the effectiveness of the “adjusting internal organs and dredging channel” treatment by detecting indicators related to glucose and lipid- metabolism. Detect changes in the gut microbiota of mice in each group using 16SrDNA sequencing technology. The content of bile acids in mouse feces was determined using liquid chromatography mass spectrometry, and the correlation analysis between different bile acids and differential bacterial communities was performed. The expression levels of TGR5 and GLP-1 proteins were measured using the Western blot method.Results: Adjusting internal organs and dredging channel electroacupuncture can improve blood glucose levels in db/db mice, increase the abundance of Firmicutes and Actinobacteria, and increase the content of fecal bile acid pool heavy CA and UDCA. At the same time, it also increased the content of TGR5/GLP1 in the small intestine.Conclusion: Adjusting internal organs and dredging channel electroacupuncture can improve the disorder of glucose and lipid metabolism in db/db mice, regulate the abundance and colony composition of intestinal microbiota in mice, and regulate bile acid metabolism in mice. The interaction between bile acid and intestinal microbiota can also be observed; Mutual influence may play a role in regulating blood sugar together.Keywords: type 2 diabetes mellitus, electroacupuncture, intestinal flora, bile acid

Xie Wang,1,&ast; Nan Shao,1,&ast; Xiaoyan Zhang,1,&ast; Hong Chen,1,&ast; Ze Chang,2,&ast; Daojun Xie,3 Juan Zhang3 1The First Clinical Medical College of Anhui University of Chinese Medicine, Hefei, 230038, People’s Republic of China; 2Xiyuan Hospital of China Academy of Traditional Chinese Medicine, Beijing, 100091, People’s Republic of China; 3Department of Neurology, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daojun Xie, Department of Neurology, the First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Hefei, Anhui, People’s Republic of China, Email 482159505@qq.comBackground: Wilson’s disease (WD), an autosomal recessive genetic disease, is characterized by copper metabolism disorder. WD patients may have a series of cognitive deficits in terms of neurological symptoms. Ferroptosis (FPT), a type of programmed cell death, is involved in the pathological progression of various cognitive disorders, and silent information regulator 1 (SIRT1) is considered to be a key factor in FPT. Ferulic acid (FA) is a traditional Chinese medicine monomer, with a remarkable effect in the clinical treatment of cognitive impairment-related disease. However, its intrinsic effect on FPT is still unclear. This study aims to investigate the protective effect of FA on cognitive impairment in animal and cell models of WD, and whether the pharmacological mechanism is related to the SIRT1-mediated FPT signaling pathway.Methods: Copper-loaded WD rats and PC12 cells WD were used as models of cognitive dysfunction in vivo and in vitro, respectively. Morris Water Maze (MWM) was used to evaluate the spatial exploration and memory abilities of rats. HE staining was used to observe neuronal damage in the CA1 region of the rat hippocampus. Immunofluorescence (IF) was used to detect the expression of GPX4 protein. Transmission electron microscopy (TEM) was used to observe the ultrastructure of neurons. The levels of Fe2+, MDA, SOD, GSH, 4HNE, and ROS were detected. Western blot and qRT-PCR were used to detect the protein and mRNA levels of SIRT1, Nrf2, SCL7A11, and GPX4.Results: In the WD copper-loaded model rats, MWM, TEM, and IF results showed that FA could promote the repair of learning and memory function, improve the morphological damage to hippocampal neurons, and maintain mitochondria integrity. In the PC12 cell experiment, the MTT method showed that FA increased the viability of copper-overloaded cell models. Western blot and qRT-PCR results confirmed that FA significantly increased the expression of proteins and mRNA in SIRT1, Nrf2, SCL7A11, and GPX4. In addition, FA reversed the expression of oxidative stress-related indicators, including MDA, SOD, GSH, 4HNE, and ROS.Conclusion: FA alleviates hippocampal neuronal injury by activating SIRT1-mediated FPT, providing a valuable candidate for traditional Chinese medicine monomer for the clinical therapeutics of WD cognitive impairment.Keywords: ferulic acid, Wilson’s disease cognitive impairment, ferroptosis, SIRT1, PC12 cells

Superconducting electron cyclotron resonance ion sources (ECRISs) using NbTi coils and optimized for 28 GHz resonant heating have been successfully operated for almost two decades. Moving to higher heating frequencies requires increased magnetic fields, but traditional racetrack-and-solenoid ECRIS structures are at their limit using NbTi. Rather than moving to a superconductor untested in this field, the Mixed Axial and Radial field System (MARS) being developed at Lawrence Berkeley National Laboratory employs a novel closed-loop-coil design that more efficiently utilizes conductor fields and will allow the use of NbTi in a next-generation, 45 GHz ECRIS. This article presents the design of the shell-based support structure central to the MARS-D magnet design, as well as structural analysis of its components and optimization of pre-load parameters that will guarantee its successful operation.

Jiangfen Wu,1 Lingyan Ren,2 Xinyi Huang,3 Li Hu,2 Liangliang Zhang,2 Dan Xie,1 Zhimin Li,4 Naijian Han,4 Shengwen Huang1,2,5 1GuiZhou University Medical College, Guiyang, Guizhou, People’s Republic of China; 2Prenatal Diagnosis Center, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of China; 3School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 4Annoroad Gene Technology (Beijing) Co., Ltd, Beijing, People’s Republic of China; 5NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial, People’s Hospital, Guiyang, People’s Republic of ChinaCorrespondence: Shengwen Huang, Guizhou Provincial People’s Hospital, Nanming District, Guiyang, People’s Republic of China, Tel +8615185134701, Fax +86-851-85937194, Email hsw713@sina.comBackground: Duchenne muscular dystrophy (DMD), an X-linked recessive neuromuscular disorder, is caused by pathogenic variants in the DMD gene encoding a large structural protein in muscle cells.Methods: Two probands, a 6-year old boy and a 1-month old infant, respectively, were clinically diagnosed with DMD based on elevated levels of creatine kinase and creatine kinase isoenzyme. CNVplex and whole exome sequencing (WES) were performed for causal variants, and Sanger sequencing was used for verification.Results: CNVplex found no large deletions or duplications in the DMD gene in both patients, but WES discovered a single-nucleotide deletion in exon 48 (NM_004006.2:c.6963del, p.Asp2322ThrfsTer16) in the proband of pedigree 1, and a nonsense mutation in exon 27 (NM_004006.2:c.3637A>T, p.K1213Ter) in the proband of pedigree 2.Conclusion: The results of our study expand the mutation spectrum of DMD and enrich our understanding of the clinical characteristics of DMD. Genetic counseling was provided for the two families involved in this study.Keywords: DMD gene, exon 48, exon 27, whole exome sequencing, Duchenne muscular dystrophy

Dandan Xie,1– 3,&ast; Kai Li,1,&ast; Ruxue Feng,4,&ast; Man Xiao,5 Zhifeng Sheng,2 Yiqiang Xie1 1College of Traditional Chinese Medicine, Hainan Medical University, Haikou, Hainan, People’s Republic of China; 2National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Metabolism and Endocrinology, Health Management Center, the Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Clinical Nutrition, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, People’s Republic of China; 4Department of Stomatology, Geriatric Hospital of Hainan, Haikou, Hainan, People’s Republic of China; 5Department of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiqiang Xie, College of Traditional Chinese Medicine, Hainan Medical University, No. 3, Xueyuan Road, Haikou, Hainan, 571199, People’s Republic of China, Tel +86 13036001921, Email xieyiqiang@hainmc.edu.cn Zhifeng Sheng, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Metabolism and Endocrinology, Health Management Center, the Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China, Tel +86 13574806523, Email shengzhifeng@csu.edu.cnAbstract: Ferroptosis, an emerging form of regulated programmed cell death, has garnered significant attention in the past decade. It is characterized by the accumulation of lipid peroxides and subsequent damage to cellular membranes, which is dependent on iron. Ferroptosis has been implicated in the pathogenesis of various diseases, including tumors and diabetes mellitus. Traditional Chinese medicine (TCM) has unique advantages in preventing and treating type 2 diabetes mellitus (T2DM) due to its anti-inflammatory, antioxidant, immunomodulatory, and intestinal flora-regulating functions. Recent studies have determined that TCM may exert therapeutic effects on T2DM and its complications by modulating the ferroptosis-related pathways. Therefore, a comprehensive and systematic understanding of the role of ferroptosis in the pathogenesis and TCM treatment of T2DM is of great significance for developing therapeutic drugs for T2DM and enriching the spectrum of effective T2DM treatment with TCM. In this review, we review the concept, mechanism, and regulatory pathways of ferroptosis and the ferroptosis mechanism of action involved in the development of T2DM. Also, we develop a search strategy, establish strict inclusion and exclusion criteria, and summarize and analyze the application of the ferroptosis mechanism in TCM studies related to T2DM and its complications. Finally, we discuss the shortcomings of current studies and propose a future research focus.Keywords: ferroptosis, traditional Chinese medicine, type 2 diabetes mellitus, complications

Xiaogang Luo,1 Dongli Xie,1 Jing Su,2 Jianchen Hu1 1College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, People’s Republic of China; 2Shanghai Institute of Spacecraft Equipment, Shanghai, 200240, People’s Republic of ChinaCorrespondence: Xiaogang Luo; Jianchen Hu, Tel +86-0512-67162531, Email xgluo@suda.edu.cn; hujianchen@suda.edu.cnBackground: The wide application of multi-walled carbon nanotubes (MWCNTs) in various fields has raised enormous concerns regarding their safety for humans. However, studies on the toxicity of MWCNTs to the eye are rare and potential molecular mechanisms are completely lacking. This study was to evaluate the adverse effects and toxic mechanisms of MWCNTs on human ocular cells.Methods: Human retinal pigment epithelial cells (ARPE-19) were treated with pristine MWCNTs (7– 11 nm) (0, 25, 50, 100 or 200 μg/mL) for 24 hours. MWCNTs uptake into ARPE-19 cells was examined using transmission electron microscopy (TEM). The cytotoxicity was evaluated by CCK-8 assay. The death cells were detected by Annexin V-FITC/PI assay. RNA profiles in MWCNT-exposed and non-exposed cells (n = 3) were analyzed using RNA-sequencing. The differentially expressed genes (DEGs) were identified through the DESeq2 method and hub of which were filtered by weighted gene co-expression, protein–protein interaction (PPI) and lncRNA-mRNA co-expression network analyses. The mRNA and protein expression levels of crucial genes were verified using quantitative polymerase chain reaction (qPCR), colorimetric analysis, ELISA and Western blotting. The toxicity and mechanisms of MWCNTs were also validated in human corneal epithelial cells (HCE-T).Results: TEM analysis indicated the internalization of MWCNTs into ARPE-19 cells to cause cell damage. Compared with untreated ARPE-19 cells, those exposed to MWCNTs exhibited significantly decreased cell viabilities in a dose-dependent manner. The percentages of apoptotic (early, Annexin V positive; late, Annexin V and PI positive) and necrotic (PI positive) cells were significantly increased after exposure to IC50 concentration (100 μg/mL). A total of 703 genes were identified as DEGs; 254 and 56 of them were, respectively, included in darkorange2 and brown1 modules that were significantly associated with MWCNT exposure. Inflammation-related genes (including CXCL8, MMP1, CASP3, FOS, CXCL2 and IL11) were screened as hub genes by calculating the topological characteristics of genes in the PPI network. Two dysregulated long non-coding RNAs (LUCAT1 and SCAT8) were shown to regulate these inflammation-related genes in the co-expression network. The mRNA levels of all eight genes were confirmed to be upregulated, while caspase-3 activity and the release of CXCL8, MMP1, CXCL2, IL11 and FOS proteins were demonstrated to be increased in MWCNT-treated ARPE-19 cells. MWCNTs exposure also can induce cytotoxicity and increase the caspase-3 activity and the expression of LUCAT1, MMP1, CXCL2, and IL11 mRNA and protein in HCE-T cells.Conclusion: Our study provides promising biomarkers for monitoring MWCNT-induced eye disorders and targets for developing preventive and therapeutic strategies.Keywords: multi-walled carbon nanotubes, ocular toxicity, transcriptome, inflammation, apoptosis, long non-coding RNAs

Taichun Qiu, Chunxiao Liang, Bing Ming, Gaoyuan Liu, Furong Zhang, Ruxue Zeng, Dongmei Xie, Qing Zou Department of Radiology, Deyang People’s Hospital, Deyang, Sichuan, People’s Republic of ChinaCorrespondence: Qing Zou, Department of Radiology, Deyang People’s Hospital, 173&num; Section 3 Tai Shan Road, Deyang, Sichuan, People’s Republic of China, Tel +86 15283804266, Email zuomengren1@163.comObjective: How well cardiovascular risk models perform in selected atherosclerosis patients for predicting outcomes is unknown. We sought to compare the performance of cardiovascular risk models (Framingham, Globorisk, SCORE2 & SCORE2-OP, and an updated new model) in predicting the 4-year outcome of patients with obstructive coronary artery disease (CAD).Methods: Patients with suspected CAD who underwent coronary computed tomography angiography (CCTA) were recruited. Obstructive CAD was defined from CCTA as ≥ 50% stenosis. Computed tomography images, the scores of the cardiovascular risk models, and 4-year composite endpoints were assessed. Whether the patients underwent revascularization within 60 days after CCTA was also recorded. Multivariate regression analysis and receiver operating characteristics (ROC) curve analysis were performed.Results: A total of 95 patients (mean age: 69.5 ± 10.33 years; 69 males) with obstructive CAD were included in this study. After the ROC analysis, the Framingham, Globorisk, SCORE2 & SCORE2-OP risk score showed prediction values with AUC 0.628 (95% CI: 0.532– 0.725), 0.647 (95% CI: 0.542– 0.742), 0.684 (95% CI: 0.581– 0.776), respectively. Multivariate regression analysis showed that, among the three risk models, only SCORE2 & SCORE2-OP risk score was associated with composite endpoints (hazard ratio: 1.050; 95% CI: 1.021– 1.079; p = 0.001) after adjusting for confounding factors. The AUC of the new risk model by combing SCORE2 & SCORE2-OP risk score with revascularization and the number of obstructive vessels in predicting composite endpoints reached 0.898 (95% CI: 0.819– 0.951).Conclusion: The SCORE2 & SCORE2-OP risk score combined with the number of obstructive vessels and revascularization is predictive for adverse outcomes in patients with obstructive CAD.Graphical Abstract: Keywords: coronary computed tomography, obstructive coronary artery disease, cardiovascular risk factors, prediction model

Meng Zhang,1,&ast; Wenyi Lu,2,&ast; Danni Xie,1 Jiaxi Wang,1 Xia Xiao,2 Yedi Pu,2 Juanxia Meng,2 Hairong Lyu,2 Mingfeng Zhao2 1First Center Clinic College of Tianjin Medical University, Tianjin, 300192, People’s Republic of China; 2Department of Hematology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingfeng Zhao; Hairong Lyu, Department of Hematology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China, Email mingfengzhao@sina.com; 18802235939@163.comBackground: Metagenomic next-generation sequencing (mNGS) is a fast, sensitive and accurate diagnostic method for pathogens detection. However, reports on the application of mNGS in mucormycosis remain scarce.Methods: From January 2019 to December 2021, we recruited 13 patients with hematological malignancies who were suspected of mucormycosis and completed mNGS in D20. Then we retrospectively analyze the clinical data, diagnosis, therapeutic process, and outcomes. In order to evaluate the diagnostic value of mNGS in hematological malignancies patients with suspected mucormycosis.Results: All patients had high risk factors of Invasive Fungal Disease, including hematopoietic stem cell transplantation, immunosuppression, glucocorticoids, etc. The clinical presentations were pulmonary (n=9), rhino-orbito-cerebral (n=4). But the manifestations were nonspecific. All enrolled patients completed mNGS. And most (8/13, 61.54%) of the samples were from blood. Fungi can be detected in all specimens, including Rhizopus (n=7), Rhizomucor (n=4) and Mucor (n=2). In addition, 7/13 (53.85%) specimens were detected bacteria at the same time and virus were detected in 5/13 (38.46%). Histopathological examination was completed in 5 patients, 3 of which were completely consistent with the results of mNGS. After treatment, 6 patients were cured, while the other 7 patients died.Conclusion: mNGS may be a complementary method for early diagnosis, especially for patients who are not suitable for histopathology examination or unable to obtain culture specimen. mNGS can also help detect bacteria and viruses simultaneously, allowing for appropriate and timely antibiotic administration and thus improving patient outcomes.Keywords: metagenomic next-generation sequencing, mucormycosis, retrospectively, hematological malignancies, invasive fungal disease

Murong Xu, Yutong Li, Ying Tang, Xiaotong Zhao, Dandan Xie, Mingwei Chen Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of ChinaCorrespondence: Mingwei Chen, Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, 230032, People’s Republic of China, Tel +86-551-2923631, Fax +86-551-2922160, Email chmw1@163.comPurpose: To investigate the correlations of miR-155 expression in the peripheral blood and wound margin tissue of patients with diabetic foot ulcer (DFU) and explore the clinical value of miR-155 as a potential biomarker for the diagnosis and treatment outcomes of DFU.Methods: Sixty newly diagnosed T2DM patients without DFU (T2DM group), 112 T2DM patients with DFU (DFU group), and 60 healthy controls (NC group) were included. MiR-155 levels in the peripheral blood and wound margin tissue were determined by quantitative real-time PCR, while clinical features and risk factors of DFU were explored. Multiple stepwise logistic regression analysis was used to determine whether miR-155 expression was an independent risk factor for DFU. The diagnostic effectiveness of miR-155 level on DFU was evaluated using ROC curve analysis.Results: A significant decrease in the expression level of miR-155 was observed in T2DM group compared with NC group (P < 0.05), while a markedly increased miR-155 expression level was noted in DFU group compared with T2DM group (P < 0.01). Moreover, there was a negative correlation between the expression levels of miR-155 with healing rate of DFU. Kaplan-Meier survival curve analysis showed that the cumulative rate of unhealed DFU in miR-155 high expression group is higher than that in miR-155 low expression group, both in peripheral blood and wound margin tissue (log rank, P = 0.004, P < 0.001, respectively). The multivariate logistic regression analysis confirmed that a high expression of miR-155 was an independent risk factor for DFU. The ROC curve analysis indicated that the AUC of miR-155 for the diagnosis of DFU was 0.794, with the optimum sensitivity being 96.82% and the optimum specificity of 95.93%.Conclusion: The increased expression of miR-155 in peripheral blood of T2DM patients is closely related to the occurrence of DFU. MiR-155 is a potentially valuable biomarker for diagnosis and prognosis of DFU.Keywords: miR-155, diabetic foot ulcer, type 2 diabetes mellitus, microRNAs, biomarker

Yanli Zhao, Qunfang Ding, Taiping Lin, Xiaoyu Shu, Dongmei Xie, Langli Gao, Jirong Yue Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Qunfang Ding, Department of Geriatrics and National Clinical Research Center for Geriatrics West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Tel +86 18980601353, Email dingqf2013@126.comObjective: Hearing and vision loss have been independently associated with frailty in older adults, but the relationship between concurrent hearing and visual impairment (dual sensory impairment) and frailty is not well understood. Therefore, we aimed to examine whether dual sensory impairment is associated with frailty in older adults.Methods: This cross-sectional study was based on the data from the West China Health and Aging Trend (WCHAT) study of community-dwelling individuals aged 60 years and older. Frailty status was evaluated by the FRAIL scale and categorized as robust, prefrail and frail. Hearing and vision functions were based on self-report. We used multinomial regression models to explore the association between dual sensory impairment and frailty.Results: Of 3985 participants, 1655 (41.5%) were male and the median age was 66 years (interquartile range: 61– 68). Overall, 7.6% of participants reported hearing impairment only, 32.7% reported vision impairment only, and 28.6% reported dual sensory impairment. The prevalence of prefrailty and frailty was 60.7% and 6.1%, respectively. After adjustment for confounding variables, results from the multinomial regression analysis showed that dual sensory impairment was significantly associated with greater odds of becoming frail (OR = 2.17, 95% CI = 1.40– 3.38) compared with no impairment. When stratified by gender, dual sensory impairment was significantly associated with frailty in women (OR = 2.42, 95% CI = 1.40– 4.20) but not in men (OR = 1.30, 95% CI = 0.58– 2.91).Conclusion: Older adults with dual sensory impairment are more likely to be frail than those with no impairment, suggesting that interventions to improve sensory function may potentially help reduce the risk of frailty in older adults.Keywords: frailty, sensory impairment, vision impairment, hearing impairment

Hongxuan Wu,&ast; Pingxiu He,&ast; Dong Xie, Jianqiao Wang, Chuan Wan Department of Dermatology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuan Wan, Department of Dermatology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China, Tel +86-791-88692799, Email chuanwan@ncu.edu.cnPurpose: The long non-coding RNA (lncRNA) anti-differentiation noncoding RNA (ANCR) is closely related to the occurrence and development of various malignancies. However, its expression and potential role in basal cell carcinoma (BCC) have not been established. In this study, we characterized the effects of ANCR in BCC and its underlying mechanism.Methods: The expression of ANCR in BCC tissues and cells was detected by qRT-PCR. Proliferation, invasion, migration and apoptosis of ANCR overexpressed or knock down TE354.T and A431 cells were examined by CCK8, transwell assay, wound healing assay and flow cytometry analysis, respectively. Western blot was performed to measure the expression of apoptosis-related proteins (BAX, BCL2 and Cleaved-caspase3), epithelial-mesenchymal transformation-related proteins (E-cadherin, N-cadherin, vimentin and β-catenin), and Hedgehog-pathway-related proteins (PTCH, GLI1 and SMO). RNA pull-down assay was used to analyze the relationship between ANCR and PTCH. The effect of ANCR on BCC growth in vivo was analyzed using xenograft model. TUNEL assay was used to determine the cell apoptosis.Results: ANCR and Hedgehog pathway were more highly expressed in BCC tissues than in adjacent normal tissues. ANCR overexpression substantially promoted BCC cell proliferation, invasion, and migration, inhibited apoptosis, and up-regulated BCL2 and decreased the expression of BAX and Cleaved-caspase3 proteins. Additionally, the upregulation of N-cadherin, vimentin, β-catenin, PTCH, GLI1, and SMO expression, and downregulation of E-cadherin expression were observed after ANCR overexpression. Moreover, ANCR knockdown had the opposite effects. An RNA pull-down assay further revealed that ANCR is specifically bound to PTCH. In vivo experiments also showed that ANCR overexpression significantly increased tumor growth and decreased apoptosis, which was reversed by cyclopamine, a specific inhibitor of the Hedgehog signaling pathway.Conclusion: ANCR activates the Hedgehog signaling pathway by binding to PTCH, thereby promoting BCC progression; accordingly, ANCR could be a candidate therapeutic target in BCC.Keywords: anti-differentiation noncoding RNA, basal cell carcinoma, Hedgehog signaling pathway, PTCH, epithelial–mesenchymal transition

Zhibo Chen,1 Dewei Xie,1 Yun Li,1 Zebin Dai,2 Saina Xiang,2 Zhiyuan Chen,2 Weiqian Zhu1 1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2College of the First Clinical Medical Sciences of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Weiqian ZhuDepartment of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, People’s Republic of ChinaTel +86 577 55579372Fax +86 577 55579318Email zhuwqfyxy@aliyun.comObjective: The novel biomarker, neutrophil percentage-to-albumin ratio (NPAR), as a prognostic tool for inflammation in relation to all-cause mortality for patients afflicted by strokes has yet to be explored.Methods: Data sets associated with patient files stored within the MIMIC-III V1.4 database were obtained. Data files from 940-patients were obtained for this retrospective analysis. Clinical endpoints were determined to represent a month (30-), three months (90-) and year (365-) all-cause mortality in stroke patients were determined. In order to determine NPAR and clinical endpoint relationships, Cox proportional hazards models were utilized.Results: For all-cause mortality within a 30-day period, in an unadjusted model, the HR (95% CIs) in group B (NPAR 20.5– 25.0) and C (NPAR > 25.0) was 1.17 (0.85, 1.63) and 1.55 (1.13, 2.11) compared with group A (NPAR < 20.5). Proceeding adjustment for more confounding factors, higher NPAR still obtained significant predictive power for 30-day all-cause mortality (HR= 1.45, 95% CI: 1.05, 2.00). Statistical significance (P = 0.0196) was also observed for the other time-based subgroupings for all-cause mortality.Conclusion: A strong correlation was present between increased levels of the novel biomarker NPAR and increased risk of mortality in stroke patients.Keywords: neutrophil-albumin ratio, mortality, stroke, biomarker

Sun H, Zhang Z, Zhang T, et al. Onco Targets Ther. 2019;12:10227–10237 The Editor and Publisher of OncoTargets and Therapy are retracting the published article. Concerns were raised regarding duplicated images in Figures 1 and 3. An investigation found, specifically, The image for Figure 1D, CSE(%) 0, has been duplicated with the same image for Figure 3C, CSE(%) 0; Stattic(µM) 0.5. The image for Figure 3A, CSE(%) 0; Stattic(µM) 0 has been duplicated with the same image for Figure 3A CSE(%) 0.5; Stattic(µM) 0.5. The authors cooperated with the investigation and provided data associated with the reported study. However, despite the authors’ assistance, an adequate explanation for how the images came to be duplicated could not be provided, and the validity of the published work could not be verified. The decision was made to retract the article and the authors wish to apologize for any confusion resulting from the errors that were made. 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”.

OBJECTIVE: The non-invasive detection of Helicobacter pylori (H. pylori) and its resistance to clarithromycin and levofloxacin significantly improves the management of infected patients by enabling tailored eradication treatments without the need for endoscopic procedures. This study aimed to assess the effectiveness of real-time PCR (RT-PCR) assays in identifying H. pylori infection and antibiotic resistance in stool and gastric biopsy specimens. PATIENTS AND METHODS: Stool and gastric biopsy samples were collected from patients within three days of post-hospitalization. A total of 115 samples were analyzed for H. pylori infection, and an additional 115 samples were evaluated for resistance to clarithromycin and levofloxacin using an RT-PCR-based molecular test. Statistical analyses were performed using (SPSS 26.0 IBM Corp., Armonk, NY, USA). RESULTS: Among 115 patients (53 males, average age 50.8±13.2 years), H. pylori was detected in 93.1% of stool samples and 93.9% of gastric biopsies. The RT-PCR assay demonstrated a sensitivity of 99.1% and a specificity of 100%, with an overall diagnostic accuracy of 99.1%. Clarithromycin resistance was found in 37.3% of stool and 46.9% of gastric biopsy specimens, with the assay showing 79.6% sensitivity and 98.4% specificity. Levofloxacin resistance was identified in 32.1% of stool samples and 31.3% of gastric biopsies, with 86.3% sensitivity and 91.1% specificity of the molecular test. CONCLUSIONS: The RT-PCR-based detection of H. pylori and its resistance to clarithromycin and levofloxacin in stool samples represents a promising approach to enhance eradication therapy outcomes, potentially improving treatment efficacy. [ABSTRACT FROM AUTHOR]

Lawrence Berkeley National Laboratory in collaboration with the Institute of Modern Physics has developed a Nb3Sn-based superconducting magnet system for a fourth-generation electron cyclotron resonance source, with a goal of achieving the magnetic field required for operating at the microwave frequency of 45 GHz. The magnet system is composed of one sextupole magnet inside three solenoids of different sizes manufactured from Nb3Sn Sn round wire. Given the high stored energy density and relatively low wire copper fraction, the coils are not self-protected in the case of a quench. The study of the transient following a quench is carried out by means of the lumped-element dynamic electro-thermal program, which includes a detailed simulation of the interfilament coupling losses developing in the wire. Nonlinear effects occurring in the magnet, such as coupling loss and differential inductance reduction, have a significant impact on protecting these magnets. The resulting baseline quench protection strategy based on four independent energy extraction systems protecting the four magnets meets the quench protection requirements. Furthermore, in order to enhance the redundancy of the quench protection system and reduce the peak voltages to ground, the implementation of a coupling-loss induced quench (CLIQ) system is considered.

Yi Yang, Dan Xie, Yongbo Zhang Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Yongbo ZhangDepartment of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaEmail yongbozhang@ccmu.edu.cnBackground: The platelet-to-lymphocyte ratio (PLR) is an inflammation marker of acute ischemic stroke, but its significance in patients with hemorrhage transformation (HT) after acute ischemic stroke with large-artery atherosclerosis (AIS-LAA) is unclear, and we also identified the relationship between PLR and in-hospital mortality of HT after AIS-LAA.Methods: This was a retrospective analysis of patients with AIS-LAA. The PLR was calculated according to platelet and lymphocyte counts on admission. HT was defined on follow-up magnetic resonance imaging or computed tomography when neurologic deterioration worsened during hospitalization. The univariate analysis and multivariate logistic regression were performed to assess the association of PLR, HT and in-hospital mortality of HT after AIS-LAA.Results: We included 328 Chinese AIS-LAA patients (mean age 67.2± 11.1 years; 70.4% male). HT occurred in 38 patients (11.6%). After multivariate regression analyses, NRL (odds ratio [OR] 1.354, 95% confidence interval [CI] 1.176– 1.559, P< 0.001) and PLR (odds ratio [OR] 3.869, 95% confidence interval [CI] 2.233– 5.702, P< 0.001) were independently associated with HT after AIS-LAA. The area under the ROC curve (AUC) value of PLR (0.72, 95% CI (0.64– 0.80), P< 0.001) tested a greater discriminatory ability compared with neutrophil-lymphocyte ratio (NLR) (0.67, 95% CI (0.58– 0.76), P< 0.001). Meanwhile, PLR was found to be significantly related to HT after AIS-LAA, including in subtypes of artery-to-artery embolization (aOR 1.699, 95% CI 1.298– 3.215, P< 0.001), in-situ thrombosis (aOR4.499, 95% CI 1.344– 9.054, P< 0.001) and branch atheromatous disease (aOR3.239, 95% CI 1.098– 8.354, P< 0.001). Increased PLR predicts high in-hospital mortality of HT after AIS-LAA (OR 1.041, 95% CI (1.006– 1.077), P=0.020; aOR 1.053, 95% CI (1.004– 1.104), P=0.034).Conclusion: High PLR is associated with greater risk of HT in AIS-LAA patients, including in artery-to-artery embolization, in-situ thrombosis and branch atheromatous disease. Meanwhile, increased PLR predicts high in-hospital mortality of HT after AIS-LAA.Keywords: acute ischemic stroke, large-artery atherosclerosis, hemorrhagic transformation, platelet-to-lymphocyte ratio, in-hospital mortality

Jingbin Huang,&ast; Wenjing Lai,&ast; Qing Wang, Qin Tang, Changpeng Hu, Min Zhou, Fengling Wang, Dandan Xie, Qian Zhang, Wuyi Liu, Zhe Zhang, Rong Zhang Department of Pharmacy, The Second Affiliated Hospital of Army Medical University, ChongQing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong Zhang; Zhe Zhang Email xqpharmacylab@126.com; 15086988023@163.comIntroduction: Triple-negative breast cancer (TNBC) has the high degree of malignancy and aggressiveness. There is no targeted therapy drug. Many studies have shown that RBC membrane-coated nanoparticles achieve biological camouflage. In addition, the RGD module in the iRGD mediates the penetration of the vector across the tumor blood vessels to the tumor tissue space. Therefore, we developed iRGD-RM-(DOX/MSNs) by preparing MSNs loaded with doxorubicin as the core, and coating the surface of the MSNs with iRGD-modified RBC membranes.Methods: iRGD-RM-(DOX/MSNs) were fabricated using physical extrusion. In addition, their physical and chemical characterization, hemolytic properties, in vivo acute toxicity and inflammatory response, in vitro and in vivo safety, and qualitative and quantitative cellular uptake by RAW 264.7 cells and MDA-MB-231 cells were evaluated and compared. Furthermore, we examined the antitumor efficacy of iRGD-RM-(DOX/MSN) nanoparticles in vitro and in vivo.Results: iRGD-RM-(DOX/MSNs) have reasonable physical and chemical properties. iRGD-RM-(DOX/MSNs) escaped the phagocytosis of immune cells and achieved efficient targeting of nanoparticles at the tumor site. The nanoparticles showed excellent antitumor effects in vivo and in vitro.Conclusion: In this study, we successfully developed biomimetic iRGD-RM-(DOX/MSNs) that could effectively target tumors and provide a promising strategy for the effective treatment of TNBC.Keywords: RBC membrane, iRGD peptide, biological camouflage, targeted treatment, Triple-negative breast cancer

Ting Ye,1,&ast; Jia Feng,1,&ast; Meng Cui,2 Jia Yang,2 Xue Wan,1 Dan Xie,1 Jinbo Liu1 1Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Department of Laboratory Medicine, The Leshan People’s Hospital, Luzhou, Sichuan, 614000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ting Ye; Jinbo LiuDepartment of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Jiangyang District, Luzhou, Sichuan, 646000, People’s Republic of ChinaTel +86-830-3165730Email yeting1103@163.com; liulab2019@163.comBackground: Myocardial infarction associated transcript (MIAT) is identified as a long chain non-coding RNA (lncRNA), which was associated with myocardial infarction susceptibility. While intense efforts have been made to elucidate the relationship between MIAT and carcinogenesis, the tumor immunoreaction of MIAT remains elusive. Thus, this study aimed to investigate the role of MIAT in the immunoregulation of breast cancer (BC) and further explore the better clinical significance.Methods: The differential expression of MIAT between BC and normal/adjacent tissues was compared using Wilcoxon rank sum test. The diagnostic and prognostic values of elevated MIAT expression in BC tissues were unveiled via receiver operating characteristic (ROC) analysis and KM-plotter analysis. Limma and edgeR package were used to identify differentially expressed genes (DEGs) and microRNAs (DEMs) from TCGA database respectively. A co-expression dataset was constructed to comprehensively understand the relationship between MIAT and DEGs based on the Pearson correlation coefficient. Furthermore, GO and KEGG analyses were conducted to predict the potential functions of MIAT. We next intersected immune-related genes (IRGs) from ImmPort database with MIAT-co-expressed genes to obtain MIAT-co-expressed IRGs, in order to construct MIAT-microRNA (miRNA)-mRNA network. And the correlation between MIAT and tumor-infiltrating immune cells (TICs) and immunophenoscore (IPS) analysis was analyzed by TIMER and CIBERSORT. Finally, the reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression profiles of MIAT in serum samples.Results: The expression levels of MIAT were notably higher in BC than in normal or adjacent tissues. And MIAT expression could be used as a prognostic indicator of mortality risk in patients with BC in different aspects. Moreover, the enrichment analyses suggested that MIAT was strongly involved in BC immune response. In addition, TIMER database and CIBERSORT analyses indicated that MIAT was significantly correlated with 13 types of TICs (B cells, dendritic cells, neutrophils, CD8 T cells, CD4 memory resting T cells, CD4 memory activated T cells, gamma delta T cells, M1 macrophages, plasma cells, activated NK cells, monocytes, M2 macrophages, activated mast cells). Simultaneously, the IPS analysis implied that the higher the MIAT expression, the better the immunotherapy effect. The ROC curve analysis showed that the area under the curve (AUC) value of MIAT was 0.86 (sensitivity = 87.80%, specificity = 75.61%). And the high MIAT expression in serum was positive related to TNM stage (P = 0.032) and lymph node metastasis (P = 0.028).Conclusion: MIAT may be a valuable noninvasive diagnostic biomarker for BC and is associated with tumor-infiltrating immune cells in tumor microenvironment, suggesting MIAT as a potential target for future treatment of BC.Keywords: lncRNA MIAT, BC, biomarker, immune regulation, tumor-infiltrating, immune cells

Tingting Wu,&ast; Dandan Xie,&ast; Xiaotong Zhao, Murong Xu, Li Luo, Datong Deng, Mingwei Chen Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingwei ChenDepartment of Endocrinology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, 230032, People’s Republic of ChinaEmail chmw1@163.comObjective: To explore the correlation between the expression of miR-34c in peripheral blood of patients with type 2 diabetes mellitus (T2DM) and the onset of diabetic foot ulcer (DFU) and diabetic foot osteomyelitis (DFO).Methods: Sixty newly diagnosed patients with T2DM without DFU (T2DM group), 112 T2DM patients with DFU (DFU group) and 60 controls with normal glucose tolerance (NC group). The DFU group patients were subdivided into DFO (n=64) and NDFO (n=48) groups. Quantitative real-time PCR (qRT-PCR) method was used to determine miR-34c expression levels in the peripheral blood of subjects to analyze the clinical characteristics of DFU and DFO risk factors.Results: MiR-34c expression level in the T2DM group was marked higher than the NC group [2.99 (1.45– 6.22) vs 1.01 (0.89– 1.52)] (P < 0.05). However, the expression level of miR-34c in the DFU group was significantly higher than the T2DM group [9.65 (6.15– 18.63) vs 2.99 (1.45– 6.22)] (P < 0.01). Compared with the NDFO group, the expression level of miR-34c in the DFO group was also obviously increased [13.46 (8.89– 19.11) vs 6.02 (5.93– 14.72)] (P < 0.01). The expression level of miR-34c in DFU patients was positively correlated with the amputation rate of foot ulcers (P=0.030) and was negatively correlated with the healing rate of foot ulcers after eight weeks (P=0.025). Multifactorial logistic regression analysis showed that increased expression of miR-34c was an independent risk factor for DFU and DFO (ORDFU=3.47, ORDFO=4.25, P < 0.01). Meanwhile, the ROC curve analysis indicated that the AUC of miR-34c for the diagnosis of DFU and DFO was 0.803 and 0.904, the optimum sensitivity being was 100% and 98.7%, the optimum specificity was 98.4% and 98.4%, respectively.Conclusion: The increased expression of miR-34c in peripheral blood of T2DM patients is closely related to the occurrence, development and prognosis of DFU and DFO.Keywords: type 2 diabetes, diabetic foot, diabetic foot osteomyelitis, miRNAs

Dongli Xie,1,&ast; Jianchen Hu,1,&ast; Tong Wu,2 Kangli Cao,3 Xiaogang Luo1 1College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, People’s Republic of China; 2Shanghai LEVSON Nanotechnology Co., Ltd, Shanghai, 200444, People’s Republic of China; 3Shanghai Institute of Spacecraft Equipment, Shanghai, 200240, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaogang Luo Tel +86 512-67162531Email xgluo@suda.edu.cnBackground: Malignant pleural mesothelioma (MPM), a highly aggressive cancer, was mainly attributed to asbestos exposure. Carbon nanotubes (CNTs) share similar negative features to asbestos, provoking concerns about their contribution to MPM. This study was used to identify genes associated with CNT-induced MPM.Methods: Microarray datasets were available in the Gene Expression Omnibus database. The limma method was used to identify differentially expressed genes (DEGs) in CNT-exposed MeT5A cells (GSE48855) or mice (GSE51636). Weighted correlation network analysis (WGCNA) and protein–protein interaction (PPI) network construction were conducted to screen hub DEGs. The mRNA expression levels of hub DEGs were validated on MPM samples of GSE51024, GSE2549 and GSE42977 datasets, and their diagnostic efficacy was determined by receiver operating characteristic curve analysis. The prognostic values of hub DEGs were assessed using online tools based on The Cancer Genome Atlas data. Their functions were annotated by Database for Annotation, Visualization and Integrated Discovery (DAVID) enrichment and correlation with immune cells and markers.Results: WGCNA identified that two modules were associated with disease status. Thirty-one common DEGs in the GSE48855 and GSE51636 datasets were overlapped with the genes in these two modules. Twenty of them had a high degree centrality (≥ 4) in the PPI network. Four DEGs (FN1, fibronectin 1; UGCG, UDP-glucose ceramide glucosyltransferase; CHPF2, chondroitin polymerizing factor 2; and THBS2, thrombospondin 2) could predict the overall survival, and they were confirmed to be upregulated in MPM samples compared with controls. Also, they could effectively predict the MPM risk, with an overall accuracy of > 0.9. DAVID analysis revealed FN1, CHPF2 and THBS2 functioned in cell-ECM interactions; UGCG influenced glycosphingolipid metabolism. All genes were positively associated with infiltrating levels of immune cells (macrophages or dendritic cells) and the expression of the dendritic cell marker (NRP1, neuropilin 1).Conclusion: These four immune-related genes represent potential biomarkers for monitoring CNT-induced MPM and predicting the prognosis.Keywords: carbon nanotubes, malignant transformation, malignant pleural mesothelioma, tumor-infiltrating immune cells, prognosis, diagnosis

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

Dadi Xie,1,&ast; Fengfeng Li,1,&ast; Deshui Pang,1 Shiyuan Zhao,2 Meihua Zhang,1 Zhongfa Ren,1 Chunmei Geng,2 Changshui Wang,3 Ning Wei,4 Pei Jiang2 1Tengzhou Central People’s Hospital, Tengzhou, 277500, People’s Republic of China; 2Jining First People’s Hospital, Jining Medical University, Jining, 272000, People’s Republic of China; 3Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272000, People’s Republic of China; 4Shanting District People’s Hospital, Zaozhuang, 277200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meihua ZhangTengzhou Central People’s Hospital, Xingtan Road, Tenzhou, 277500, People’s Republic of ChinaTel/Fax +86 0632-5512227Email meihua_zhang@126.comPei JiangJining First People’s Hospital, Jning Medical University, Jiankang Road, Jining, 272000, People’s Republic of ChinaTel/Fax + 86 0537-2106208Email jiangpeicsu@sina.comPurpose: Inflammatory bowel diseases (IBD) are a chronic inflammatory disease, which affects almost all tissues in the body. Previous studies mainly focused on breathing, fecal, and urine samples of patients with IBD. However, there is no comprehensive metabolomic analysis of the serum, colon, heart, liver, kidney, cortex, hippocampus, and brown fat tissues. Therefore, the aim of our study is to evaluate the utility metabolomic analysis of target tissues in the pathogenesis of IBD in exploring new biomarkers for early diagnosis and treatment.Methods: Male Sprague–Dawley rats were randomly allocated to control and DSS-treated groups (n = 7). Dextran sulfate sodium (DSS) was orally administered for 6 weeks. Gas chromatography-mass spectrometry (GC-MS) was used for metabolite determination, multivariate statistical analysis was used to identify metabolites that were differentially expressed in two groups.Results: Our results showed that 3, 11, 12, 6, 5, 13, 13, and 11 metabolites were differentially expressed between the DSS treatment group and the control group in the serum, colon, heart, liver, kidney, cortex, hippocampus, and brown fat tissues, respectively. The most significant change of metabolites in the study was amino acid (L-alanine, L-glutamic acid, L-phenylalanine, L-proline, L-lysine, L-isoleucine, L-tryptophan, L-norleucine, L-valine, glycine, serine, L-threonine), organic acid (citric acid, 3-hydroxybutyric acid, propanoic acid), glucide (D-arabinose, D-fructose) and purine (9H-purin-6-ol, D-ribose) profiles. Several pathways were affected according to the integrated pathway analysis. These pathways ranged from amino acid metabolism (such as alanine, aspartate, and glutamate metabolism, glutathione metabolism) to purine metabolism (aminoacyl-tRNA biosynthesis).Conclusion: Using GC-MS-based profiling of metabolite changes, these results may provide a more comprehensive view for IBD and IBD-related diseases and improve the understanding of IBD pathogenesis.Keywords: inflammatory bowel disease, metabolite, GC-MS, dextran sodium sulfate, biomarker

Jin-Ling Duan,1,* Run-Cong Nie,1,2,* Zhi-Cheng Xiang,1,3,* Jie-Wei Chen,3 Min-Hua Deng,1,2 Hu Liang,1,4 Feng-Wei Wang,1 Rong-Zhen Luo,3 Dan Xie,1,3 Mu-Yan Cai1,3 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 4Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mu-Yan Cai; Dan XieState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of ChinaTel +86-20-87343193Fax +86-20-87343170Email caimy@sysucc.org.cn; xiedan@sysucc.org.cnBackground and Aim: To assess the profile of global histone modifications in small hepatocellular carcinoma (small HCC) and identify its prognostic value in predicting recurrence.Methods: The expression profiles of global histone modifications, including H2AK5AC, H2BK20AC, H3K4me2, H3K9AC, H3K18AC, H4K12AC, and H4R3me2, were evaluated with immunohistochemistry in 335 HBV related small HCC patients. Two histone signature classifiers were then developed using least absolute shrinkage and selection operator Cox regression. A nomogram was built using the classifier and independent risk factors. The performances of the classifier and nomogram were assessed by receiver operating characteristic curves.Results: Histone modifications were more pronounced in tumor tissues than in adjacent liver tissues. In tumor tissues, the risk score built based on the seven-histone signature exhibited satisfactory prediction efficiency, with an AUC = 0.71 (0.63– 0.79) for 2-year survival in the training cohort. Patients with a high risk score had shorter recurrence-free survival than those with a low risk score (HR: 1.96, 95% CI: 1.24– 3.08, p = 0.004; HR: 1.95, 95% CI: 1.12– 3.42, p = 0.019; and HR: 1.97, 95% CI: 1.39– 2.80, p < 0.001 for the training, validation and total cohorts, respectively). Furthermore, the statistical nomogram built using the histone classifier for early recurrence had a C-index = 0.68. In non-neoplastic liver tissues, the hepatic signature based on H3K4me2 and H4R3me2 was related to late recurrence (HR: 2.00, 95% CI: 1.15– 3.48, p = 0.01).Conclusion: Global histone modifications in tumor and adjacent liver tissues are novel predictors of early and late recurrence, respectively, in HBV-related small HCC patients.Keywords: small hepatocellular carcinoma, histone modifications, recurrence, LASSO, prognosis

Dong Xie,1,2,* Chenhui Xu,1,* Cheng Ye,1,* Shiqi Mei,3 Longqing Wang,1 Qi Zhu,1 Qing Chen,1 Qi Zhao,1 Zhiyan Xu,3 Jie Wei,3 Lili Yang1 1Spine Center, Department of Orthopaedics, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China; 2Department of Orthopaedics, PLA Navy No.905 Hospital, Shanghai, 200052, People’s Republic of China; 3Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lili Yang Tel +86-021-81885793Email yangll@smmu.edu.cnPurpose: Polyetheretherketone (PEEK) exhibits high mechanical strengths and outstanding biocompatibility but biological inertness that does not excite the cell responses and stimulate bone formation. The objective of this study was to construct submicro-nano structures on PEEK by femtosecond laser (FSL) for exciting the responses of MC3T3-E1 cells and gingival epithelial (GE) cells, which induce regeneration of bone/gingival tissues for long-term stability of dental implants.Materials and Methods: In this study, submicro-nano structures were created on PEEK surface by FSL with power of 80 mW (80FPK) and 160 mW (160FPK).Results: Compared with PEEK, both 80FPK and 160FPK with submicro-nano structures exhibited elevated surface performances (hydrophilicity, surface energy, roughness and protein absorption). Furthermore, in comparison with 80FPK, 160FPK further enhanced the surface performances. In addition, compared with PEEK, both 80FPK and 160FPK significantly excited not only the responses (adhesion, proliferation, alkaline phosphatase [ALP] activity and osteogenic gene expression) of MC3T3-E1 cells but also responses (adhesion as well as proliferation) of GE cells of human in vitro. Moreover, in comparison with 80FPK, 160FPK further enhanced the responses of MC3T3-E1 cells/GE cells.Conclusion: FSL created submicro-nano structures on PEEK with elevated surface performances, which played crucial roles in exciting the responses of MC3T3-E1 cells/GE cells. Consequently, 160FPK with elevated surface performances and outstanding cytocompatibility would have enormous potential as an implant for dental replacement.Keywords: polyetheretherketone; PEEK, surface modification, submicro-nano structures, functional group, cell responses

Guo Y, Zhang H, Xie D, Hu X, Song R, Zhu L. Cancer Manag Res. 2018;10:4371-4380. The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised regarding the alleged duplication of western blot bands in Figure 2 with those from another unrelated article. Specifically, Figure 2F, bands P-gp, appear to have been duplicated with the same bands from Figure 5F, p-AKT in Yang et al, 2018 (https://doi.org/10.3389/fnmol.2017.00437). In addition, western blots bands from Figure 5 also appear to have been duplicated. Specifically, Figure 5B, bands J82/DOX, GAPDH, appear to have been duplicated with the same bands from Figure 5B, T24/DOX, GAPDH. There were also unexpected similarities found between the flow cytometry images shown in Figures 4E and 4F. The authors responded to our queries but were unable to provide an adequate explanation for the duplicated images, nor were they able to provide the original data for their study. The Editor determined the findings of the study were unreliable and requested to retract the article. The authors agreed with this decision. 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”.