Search

Qingbao Guo,1,2,* Manli Xie,3,* Qian-Nan Wang,4,* Jingjie Li,1,2 Simeng Liu,1,2 Xiaopeng Wang,1,2 Dan Yu,5 Zhengxing Zou,5 Gan Gao,1,2 Qian Zhang,5 Fangbin Hao,1,2 Jie Feng,5 Rimiao Yang,5 Minjie Wang,1,2 Heguan Fu,5 Xiangyang Bao,5 Lian Duan2 1Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Department of Neurosurgery, First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Occupational Diseases, Xi’an Central Hospital, Xi’an, Shanxi, People’s Republic of China; 4Department of Neurosurgery, Eighth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 5Department of Neurosurgery, Fifth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangyang Bao; Lian Duan, Email bzy123@163.com; duanlian307@sina.comBackground: Moyamoya disease (MMD) signifies a cerebrovascular disorder with obscure origin and a more rapid and severe progression in children than adults. This investigation aims to uncover age-associated distinctions through proteomic and metabolomic profiling to gain insights into the underlying mechanisms of MMD.Methods: Twelve MMD patients—six children and six adults—along with six healthy controls (HC), participated, each providing a 10 mL blood sample. Serum proteomic and metabolomic analyses were conducted using ultra-performance liquid chromatography and high-resolution mass spectrometry, complemented by bioinformatics to identify differential biomolecules and their interactions. Pathway implications were ascertained using GO and KEGG enrichment analysis.Results: Notable proteomic and metabolomic discrepancies were observed between pediatric and adult MMD subjects. A total of 235 and 216 proteins varied in adult and pediatric cases compared to HCs, with 73 proteins shared. In addition, 129 and 74 anionic, plus 96 and 104 cationic metabolites, were differentially expressed in the pediatric and adult groups, respectively, with 34 anionic and 28 cationic metabolites in common. Age-specific biomolecules further characterized these distinctions. Enrichment analysis pinpointed immunity and inflammation pathways, with vitamin digestion and absorption highlighted as pivotal in pediatric MMD.Conclusion: This study unveils distinct metabolic and proteomic patterns within pediatric and adult MMD patients. The critical role of the vitamin digestion and absorption pathway in the pathogenesis of pediatric MMD offers novel insight into disease mechanisms. Keywords: proteomics, metabolomics, pediatric patients, moyamoya disease, integration analysis

Mengjie Xie,1,* Fansu Meng,2,* Panpan Wang,3,* Alicia Marcelina Díaz-García,4 Marina Parkhats,5 Ralph Santos-Oliveira,6 Mulazim Hussain Asim,7 Nazish Bostan,8 Honghui Gu,9 Lina Yang,9 Qi Li,9 Zhenjiang Yang,9 Haibiao Lai,2 Yu Cai1 1State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China / Guangdong Key Laboratory of Traditional Chinese Medicine Informatization / International Science and Technology Cooperation Base of Guangdong Province/School of Pharmacy, Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 2Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, Guangdong, 528400, People’s Republic of China; 3The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 4Bioinorganic Laboratory, Faculty of Chemistry, University of Havana, Havana, 1400, Cuba; 5B. I. Stepanov Institute of Physics, National Academy of Sciences of Belarus, Minsk, 220072, Belarus; 6Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Laboratory of Nanoradiopharmacy and Synthesis of New Radiopharmaceuticals, Rio de Janeiro, RJ, 21941906, Brazil; 7College of Pharmacy, University of Sargodha, Punjab, 40100, Pakistan; 8Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan; 9Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, 518033, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu Cai; Haibiao Lai, Email caiyu8@sohu.com; lhb8829@163.comAbstract: Data published in 2020 by the International Agency for Research on Cancer (IARC) of the World Health Organization show that breast cancer (BC) has become the most common cancer globally, affecting more than 2 million women each year. The complex tumor microenvironment, drug resistance, metastasis, and poor prognosis constitute the primary challenges in the current diagnosis and treatment of BC. Magnetic iron oxide nanoparticles (MIONPs) have emerged as a promising nanoplatform for diagnostic tumor imaging as well as therapeutic drug-targeted delivery due to their unique physicochemical properties. The extensive surface engineering has given rise to multifunctionalized MIONPs. In this review, the latest advancements in surface modification strategies of MIONPs over the past five years are summarized and categorized as constrast agents and drug delivery platforms. Additionally, the remaining challenges and future prospects of MIONPs-based targeted delivery are discussed. Keywords: Nanopreparations, Organic Nanomaterials, Inorganic Nanomaterials, Surface Engineering, Targeted Delivery

Hao Kang,1,2,* Fansu Meng,3,* Fengjie Liu,4 Mengjie Xie,4 Haibiao Lai,3 Pengfei Li,5 Xingwang Zhang4 1Department of Medicinal Chemistry and Pharmaceutical Analysis, Anhui College of Traditional Chinese Medicine, Wuhu, People’s Republic of China; 2Wuhu Modern Technology Research and Development Center of Chinese Medicine and Functional Food, Wuhu, People’s Republic of China; 3Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, People’s Republic of China; 4Department of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China; 5Department of Oncology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haibiao Lai; Xingwang Zhang, Email lhb8829@163.com; zhangxw@jnu.edu.cnAbstract: Ferroptosis, a unique form of regulated cell death driven by iron-dependent lethal lipid peroxidation, is implicated in various stress-related diseases like neurodegeneration, vasculopathy, and metabolic disturbance. Stress-related diseases encompass widespread medical disorders that are influenced or exacerbated by stress. These stressors can manifest in various organ or tissue systems and have significant implications for human overall health. Understanding ferroptosis in these diseases offers insights for therapeutic strategies targeting relevant pathways. This review explores ferroptosis mechanisms, its role in pathophysiology, its connection to stress-related diseases, and the potential of ferroptosis-targeted nanomedicines in treating conditions. This monograph also delves into the engineering of ferroptosis-targeted nanomedicines for tackling stress-related diseases, including cancer, cardia-cerebrovascular, neurodegenerative, metabolic and inflammatory diseases. Anyhow, nanotherapy targeting ferroptosis holds promise by both promoting and suppressing ferroptosis for managing stress-related diseases.Keywords: ferroptosis, stress-related diseases, lipid peroxidation, nanoparticles, nanomedicine, targeted therapy

Jianqiang Liang,1,* Weixiong Chen,2,* Yanhui Zhou,3 Weijia Meng,3 Man Xie,3 Yunying Weng,1 Luxuan Qin,1 Jianmin Li,4 Guanyi Wu1,5,6 1College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 2School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; 3College of Pharmacology, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 4Department of Dermatology, The Third Affiliated Hospital, Guangxi Medical University, Nanning, People’s Republic of China; 5Key Laboratory for Complementary and Alternative Medicine Experimental Animal Models of Guangxi, Nanning, People’s Republic of China; 6Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guanyi Wu, School of Basic Medicine, Guangxi University of Chinese Medicine, 13 Wu He Road, Nanning, Guangxi, 530299, People’s Republic of China, Email wugy@gxtcmu.edu.cnPurpose: This study seeks to investigate the effect of evodiamine on psoriasis and psoriatic pruritus.Methods: Imiquimod-induced psoriasiform dermatitis in mice was used as a model, and evodiamine was topically applied for seven days. The mice were observed daily for skin damage on the back, clinical score and their scratching behavior was recorded. Blood samples were collected on the final day of the experiment, and the serum levels of pruritus-associated inflammatory cytokines tumor necrosis factor (TNF) -α, interleukin (IL) − 23, and IL-17A were measured using enzyme-linked immunosorbent assay. Histopathological changes were observed in Hematoxylin and Eosin-stained skin specimens. The expression levels of transient receptor potential vanilloid (TRPV) 1, TRPV3, TRPV4, and the pruritus-related mediators Substance P (SP), nerve growth factor (NGF), and calcitonin gene-related peptide (CGRP) in the skin lesions were analyzed using Western blot and qRT-PCR. The effect of evodiamine on the exploratory behavior, motor, and coordination abilities of mice was assessed using open field, suspension, and Rota-Rod experiments. Molecular docking was utilized to verify the binding of evodiamine to the residues of TRPV1, TRPV3, and TRPV4.Results: Evodiamine reduced pruritus and inhibited inflammation by decreasing the levels of inflammatory mediators TNF-α, IL-23, and IL-17A in the serum of Imiquimod-induced mice and attenuated the mRNA and protein expression levels of SP, NGF, CGRP, TRPV1, TRPV3, and TRPV4 in the skin.Conclusion: Evodiamine is an effective treatment for psoriasis and pruritus, due to its ability to inhibit immune inflammation and pruritic mediators.Keywords: evodiamine, TRP channel, psoriasis

Mengxiao Xie,1,* Jian Liu,2,* Jieyuan Zheng,1 Jingchao Wang,1 Dongsheng Han1,3,4 1Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Intensive Care Unit, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Key Laboratory of Clinical in vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, People’s Republic of China; 4Institute of Laboratory Medicine, Zhejiang University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongsheng Han, Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Email hands@zju.edu.cn; hands1103@163.comObjective: To understand the clinical features, diagnosis and treatment of Lemierre syndrome (LS), a high-risk and low-prevalence infectious disease.Methods: We present the severe LS case that was diagnosed using metagenomic next-generation sequencing (mNGS) in our hospital, and systematically summarized the diagnosis and treatment strategies of patients that reported LS from 2006 to 2022.Results: The 24-year-old patient in our hospital suffered from cranial nerve paralysis, a neurological complication rarely seen in LS cases. The causative agent (Fusobacterium necrophorum, Fn) of this patient was only detected by mNGS tests, and the reads number of Fn detected by plasma mNGS tests was decrease as the patients gradually improved, indicating plasma mNGS is valuable in monitoring treatment efficacy. Although most of the cases retrieved from the literature showed typical symptoms, such as a history of sore throat, septic emboli, and internal jugular vein thrombosis, clinical manifestations were still relatively heterogeneous (eg, diversity of predisposing factors and pathogens, differences in pulmonary imaging features).Conclusion: We summarized the clinical presentation, diagnosis, treatment, and regression of 17 symptomatic cases reported LS to provide clinicians with knowledge about this rare but fatal disease. mNGS assays should be considered as early as possible to identify the responsible pathogens for acute and critically ill patients with suspected infections in order to implement accurate and effective treatment.Keywords: lemierre syndrome, Fusobacterium necrophorum, metagenomic next-generation sequencing, thrombophlebitis, sepsis

Min Yang,1,2 Mengyao Xie,1,2 Jiajun Guo,1,2 Yuqing Zhang,1,2 Yan Qiu,1,2 Zhibiao Wang,1,2 Yonghong Du1,2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Zhibiao Wang; Yonghong Du, State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Tel/Fax +86-23-68485000 ; +86-23-68485021, Email wangzb@cqmu.edu.cn; duyonghong@cqmu.edu.cnBackground: Candida albicans (C. albicans) forms pathogenic biofilms, and the dense mucus layer secreted by the epithelium is a major barrier to the traditional antibiotic treatment of mucosa-associated C. albicans infections. Herein, we report a novel anti-biofilm strategy of mucus-permeable sonodynamic therapy (mp-SDT) based on ultrasound (US)-mediated amphotericin B-loaded PEGylated PLGA nanoparticles (AmB-NPs) to overcome mucus barrier and enable the eradication of C. albicans biofilm.Methods: AmB-NPs were fabricated using ultrasonic double emulsion method, and their physicochemical and sonodynamic properties were determined. The mucus and biofilm permeability of US-mediated AmB-NPs were further investigated. Moreover, the anti-biofilm effect of US-mediated AmB-NPs treatment was thoroughly evaluated on mucus barrier abiotic biofilm, epithelium-associated biotic biofilm, and C. albicans-induced rabbit vaginal biofilms model. In addition, the ultrastructure and secreted cytokines of epithelial cells and the polarization of macrophages were analyzed to investigate the regulation of local cellular immune function by US-mediated AmB-NPs treatment.Results: Polymeric AmB-NPs display excellent sonodynamic performance with massive singlet oxygen (1O2) generation. US-mediated AmB-NPs could rapidly transport through mucus and promote permeability in biofilms, which exhibited excellent eradicating ability to C. albicans biofilms. Furthermore, in the vaginal epithelial cells (VECs)-associated C. albicans biofilm model, the mp-SDT scheme showed the strongest biofilm eradication effect, with up to 98% biofilm re-formation inhibition rate, improved the ultrastructural damage, promoted local immune defense enhancement of VECs, and regulated the polarization of macrophages to the M1 phenotype to enhance macrophage-associated antifungal immune responses. In addition, mp-SDT treatment exhibited excellent therapeutic efficacy against C. albicans-induced rabbit vaginitis, promoted the recovery of mucosal epithelial ultrastructure, and contributed to the reshaping of a healthier vaginal microbiome.Conclusion: The synergistic anti-biofilm strategies of mp-SDT effectively eradicated C. albicans biofilm and simultaneously regulated local antifungal immunity enhancement, which may provide a new approach to treat refractory drug-resistant biofilm-associated mucosal candidiasis.Keywords: C. albicans biofilm, PEGylated nanoparticles, mucus penetration, sonodynamic therapy

Mi Lin,* Menghua Xie,* Zhi Li School of Public Policy and Administration, Chongqing University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhi Li, Email cqulzzz@126.comPurpose: Error management is an important element of organizational management research, and organizational error tolerance has gradually received attention from researchers in recent years. Most previous studies concluded that organizational error tolerance positively affects both the perceived organizational support and job performance of public sector employees, but few have examined the relationship between organizational error tolerance and change-oriented organizational citizenship behavior.Methods: This research examines how organizational error tolerance affects change-oriented organizational citizenship behavior using an experimental approach (Study 1, N = 162 and Study 2, N = 228) and a field survey approach (Study 3, N = 377).Results: The results indicate that organizational error tolerance increases psychological empowerment, which in turn increases change-oriented organizational citizenship behavior. Public service motivation plays a moderating role in this process. Specifically, the positive mediating effect of organizational error tolerance on change-oriented organizational citizenship behavior through psychological empowerment was not significant when the level of public service motivation was high, while it was significant when the level of public service motivation was low.Conclusion: This study clarifies the mechanism and boundary conditions of the effect of organizational error tolerance on change-oriented organizational citizenship behavior, provides a more comprehensive and dialectical perspective for research on organizational error tolerance, and extends research on psychological empowerment and change-oriented organizational citizenship behavior.Keywords: organizational error tolerance, psychological empowerment, change-oriented organizational citizenship behavior, public service motivation, organizational management, employee behavior

Yang M, Xie M, Guo J, et al. Int J Nanomedicine. 2023;18:7941-7963. We, the Editor and Publisher of the journal International Journal of Nanomedicine are retracting the published article. Following publication of the article, the authors raised concerns about the duplication of images from Figures 2, 6, 9, 11 and 12. Specifically, The image for Figure 2A, SEM image of AmB-NPs, has been duplicated with the image for Figure 3B, SEM image of BM2-LVFX-NPs, from Li G, Li J, Hou Y, et al. Levofloxacin-Loaded Nanosonosensitizer as a Highly Efficient Therapy for Bacillus Calmette-Guérin Infections Based on Bacteria-Specific Labeling and Sonotheranostic Strategy. Int J Nanomedicine. 2021;16:6553-6573. https://doi.org/10.2147/IJN.S321631. Images for Figure 6C, AmB-NPs and US+AmB have been duplicated but show a different colour intensity. Images for Figure 9C, Control and US, have been duplicated. Images for Figure 11C, C. albicans CD86, AmB and IL-4 CD206, AmB-NPs, have been duplicated. Images for Figure 11C, C. albicans CD86, US+AmB-NPs and IL-4 CD206, US, have been duplicated but show a different immunofluorescene staining intensity. Images for Figure 12C, AmB and US+AmB, have been duplicated but one of the images has been flipped. Images for Figure 12D, US+AmB and US+AmB-NPs, have been duplicated. The authors were cooperative and responded to our queries but were unable to provide a satisfactory explanation for the duplicated images but did provide some original data for the study. However, as verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the authors agree with this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Renke Chen,1,&ast; Mengxiao Xie,2,&ast; Shenlong Wang,1 Fei Yu,2– 4 Dan Zhang,2– 4 Lingjun Yuan,2 Jieyuan Zheng,2 Jingchao Wang,2 Jieting Zhou,2 Binxiao Li,2 Shufa Zheng,2– 4 Yongsheng Fan,1 Dongsheng Han2– 4 1The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Key Laboratory of Clinical in vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, People’s Republic of China; 4Institute of Laboratory Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongsheng Han, Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Email hands@zju.edu.cn Yongsheng Fan, School of Basic Medical Sciences, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email fyszjtcm@163.comBackground: Metagenomic next-generation sequencing (mNGS) is a promising tool for improving antimicrobial therapy and infection control decision-making in complex infections. Secondary infection surveillance using mNGS in COVID-19 patients has rarely been reported.Methods: Respiratory pathogen and antibiotic resistance prediction were evaluated by BALF mNGS for 192 hospitalized COVID-19 patients between December 2022 and February 2023.Results: Secondary infection was confirmed in 83.3% (160/192) of the COVID-19 patients, with bacterial infections (45%, 72/160) predominating, followed by mixed bacterial and fungal infections (20%, 32/160), and fungal infections (17.5%, 28/160). The incidence of bacterial or viral secondary infection was significantly higher in patients who were admitted to the ICU, received mechanical ventilation, or developed severe pneumonia (all p< 0.05). Klebsiella pneumoniae (n=30, 8.4%) was the most prevalent pathogen associated with secondary infection followed by Acinetobacter baumannii (n=29, 8.1%), Candida albicans (n=29, 8.1%), Aspergillus fumigatus (n=27, 7.6%), human herpes simplex virus type 1 (n=23, 6.4%), Staphylococcus aureus (n=20, 5.6%) and Pneumocystis jiroveci (n=14, 3.9%). The overall concordance between the resistance genes detected by mNGS and the reported phenotypic resistance in 69 samples containing five clinically important pathogens (ie, K. pneumoniae, A. baumannii, S. aureus, P. aeruginosa and E. coli) that caused secondary infection was 85.5% (59/69).Conclusion: mNGS can detect pathogens causing secondary infection and predict antimicrobial resistance for COVID19 patients. This is crucial for initiating targeted treatment and rapidly detect unsuspected spread of multidrug-resistant pathogens.Keywords: COVID-19, SARS-CoV-2, metagenomic next-generation sequencing, antibiotic resistance

Yijia Hao,1 Shaozhuang Liu,2 Teng Liu,2 Xin Huang,2 Mengshuang Xie,3 Dexiang Wang4 1Cheeloo College of Medicine, Shandong University, Jinan, 250033, People’s Republic of China; 2Division of Bariatric and Metabolic Surgery, Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of China; 3Department of Geriatrics & Key Laboratory of Cardiovascular Proteomics of Shandong Province, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of ChinaCorrespondence: Dexiang Wang, Email wangdexiang@qiluhospital.comObjective: We explore risk factors related to severe obstructive sleep apnea (OSA) in obese patients, including pulmonary ventilation function, diffusion function, and impulse oscillometry (IOS) data.Methods: The medical records of 207 obese patients who were prepared to undergo bariatric surgery in a hospital from May 2020 to September 2021 were retrospectively reviewed. Polysomnography (PSG), pulmonary ventilation function, diffusion function, and IOS parameters were collected according to the ethical standards of the institutional research committee (registration number: KYLL-202008-144). Logistic regression analysis was used to analyze the related independent risk factors.Results: There were significantly statistical difference in a number of pulmonary ventilation and diffusion function parameters among the non-OSAHS group, the mild-to-moderate OSA group, and the severe OSA group. However, only airway resistance parameters R5%, R10%, R15%, R20%, R25%, and R35% increased with increasing OSA severity and were positively correlated with apnea hypopnea index (AHI). Age (P = 0.012, 1.104 (1.022, 1.192)), body mass index (P< 0.0001, 1.12 (1.057, 1.187)), gender (P = 0.003, 4.129 (1.625, 10.49)), and R25% (P = 0.007, 1.018 (1.005, 1.031)) were independent risk factors for severe OSA. In patients aged 35 to 60, RV/TLC (P = 0.029, 1.272 (1.025, 1.577)) is an independent risk factor for severe OSA.Conclusion: R25% was an independent risk factor for severe OSA in obese individuals, while RV/TLC was also an independent risk factor in those aged 35 to 60. Pulmonary function tests (PFTs), particularly IOS levels, are recommended to assess severe OSA in obese patients.Keywords: obstructive sleep apnea syndrome, obesity, pulmonary function

Zhifeng Huang,1,&ast; Hui Gan,1,&ast; Yiyun Huang,2,&ast; Huiqing Zhu,1 Tingting Liu,1 Tong Chen,1 Runpei Lin,1 Manrong Xie,2 Baoqing Sun1 1Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Helong Street Community Health Service Center, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing Sun; Manrong Xie, Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510180, People’s Republic of China, Tel +86 18816781502, Email sunbaoqing@vip.163.com; Xmr20041103@163.comPurpose: To investigate the lifestyle and stress of mothers during pregnancy to analyze the risk factors for the disease in early childhood.Patients and Methods: A cross-sectional survey was conducted from January 2022 to June 2022 in a sub-district in Guangzhou, China. A total of 3437 valid questionnaires were eventually collected. The questionnaire consisted of 56 questions in three sections included questions on child’s birth conditions and early life environment, questions on mother’s lifestyle during pregnancy, and questions about father.Results: 49.75% of the children were likely to have allergic diseases (suspected allergy group). There were more boys in the suspected allergy group (58% vs 50%), and the percentage of children born at first birth was also higher in the suspected allergy group (61% vs 51%). 67% to 69% of children had suspicious allergies when one parent claimed an allergy, and 80.1% when both parents reported an allergy. The results of the multifactorial logistic model showed that male had 1.49 (1.28 to 1.73) times the risk of allergic diseases than female, and preterm births increased the risk of allergic diseases by 1.53 (1.13– 2.07) times compared to full-term births. Both unplanned pregnancies and pregnancy complications increased the risk of allergic diseases in children before school age [1.34 (1.15– 1.55) and 1.82 (1.46– 2.26)]. Among pregnant women who reported regular passive smoking, the risk of the disease was increased 2.43 (1.71 to 3.50) times in preschool children. Reported allergies in all family members were significant risk factors for allergic diseases in children, especially mother [2.88 (2.41~3.46)]. In the prenatal period, maternal negative emotions are more common in children with suspected allergies.Conclusion: Nearly half of the children in the region suffer from allergic diseases. Sex, birth order and full-term delivery all contributed to early childhood allergy. Family history of allergy, especially maternal, was the most important risk factor, and the number of family members with allergy was significantly associated with the allergy in children. Maternal effects are also reflected in prenatal conditions such as unplanned pregnancy, smoke exposure, pregnancy complications, and prenatal stress.Keywords: cross-sectional, heritability, risk factor, questionnaire, allergic rhinitis

Mengjie Chen,1,&ast; Kan Xu,2,&ast; Yuting He,1,&ast; Jianjun Jin,3 Ruolin Mao,1 Lei Gao,1 Yi Zhang,4 Gang Wang,5 Peng Gao,6 Min Xie,7 Chunfang Liu,8 Zhihong Chen1 1Department of Respiratory and Critical Care Medicine of Zhongshan Hospital, Shanghai Institute of Respiratory Disease, Fudan University, Shanghai, People’s Republic of China; 2Geriatric Department of Zhongshan Hospital, Shanghai Institute of Respiratory Disease, Fudan University, Shanghai, People’s Republic of China; 3Research Center of Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Air Liquide Holding Co., Ltd, Shanghai, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Department of Respiratory Medicine, The Second Affiliated Hospital of Jilin University, Changchun, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji Medical 10 College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 8Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihong Chen, Department of Respiratory and Critical Care Medicine of Zhongshan Hospital, No. 180 Fenglin Road, Shanghai, People’s Republic of China, Tel +86-21-64041990-2445, Fax +86-21-64187165, Email chen.zhihong@zs-hospital.sh.cn Chunfang Liu, Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, 12&num; Wlmq Road, Shanghai, People’s Republic of China, Email Chunfang_liu@fudan.edu.cnPurpose: The progression of an abnormal inflammatory response plays a crucial role in the lung function decline of chronic obstructive pulmonary disease (COPD) patients. Compared to serum biomarkers, inflammatory biomarkers in induced sputum would be a more reliable reflection of inflammatory processes in the airways.Patients and Methods: A total of 102 COPD participants were divided into a mild-to-moderate group (FEV1%pred≥ 50%, n=57) and a severe-to-very-severe group (FEV1%pred< 50%, n=45). We measured a series of inflammatory biomarkers in induced sputum and analyzed their association with lung function and SGRQ in COPD patients. To evaluate the relationship between inflammatory biomarkers and the inflammatory phenotype, we also analyzed the correlation between biomarkers and airway eosinophilic phenotype.Results: We found increased mRNA levels of MMP9, LTB4R, and A1AR and decreased levels of CC16 mRNA in induced sputum in the severe-to-very-severe group. After adjustment for age, sex and other biomarkers, CC16 mRNA expression was positively associated with FEV1%pred (r=0.516, p=0.004) and negatively correlated with SGRQ scores (r=− 0.3538, p=0.043). As previously known, decreased CC16 was related to the migration and aggregation of eosinophils in airway. It was also found that CC16 had a moderate negative correlation with the eosinophilic inflammation in airway (r=− 0.363, p=0.045) in our COPD patients.Conclusion: Low CC16 mRNA expression levels in induced sputum were associated with low FEV1%pred and a high SGRQ score in COPD patients. Sputum CC16 as a potential biomarker for predicting COPD severity in clinical practice might attribute to the involvement of CC16 in airway eosinophilic inflammation.Keywords: COPD, induced sputum, airway inflammation, biomarkers, lung function, CC16

Mengdi Xie,1,&ast; Kang Yuan,2,&ast; Xinyi Zhu,2,&ast; Jingjing Chen,3 Xiaohao Zhang,4 Yi Xie,2 Min Wu,1 Zhaojun Wang,2 Rui Liu,2 Xinfeng Liu1,2,5 1Department of Neurology, Jinling Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 3Department of Neurology, Changhai Hospital, Navy Medical University, Shanghai, People’s Republic of China; 4Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 5Stroke Center & Department of Neurology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinfeng Liu, Department of Neurology, Jinling Hospital, Nanjing Medical University, No. 305 East Zhongshan Road, Nanjing, Jiangsu Province, 210000, People’s Republic of China, Tel +86 2584801861, Fax +86 2584805169, Email xfliu2@vip.163.com Rui Liu, Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210000, Jiangsu Province, People’s Republic of China, Tel +86 2584801861, Fax +86 2584805169, Email liurui8616@163.comBackground: Systemic immune inflammation has been investigated as a prognostic marker of different diseases. This study is designed to assess the association of systemic immune-inflammation index (SII) with long-term mortality of stroke-associated pneumonia (SAP) patients.Methods: Patients aged ≥ 18 years with SAP were selected from the Nanjing Stroke Registry Program in China. We retrospectively evaluated systemic immune-inflammation response with SII and pneumonia severity with the pneumonia severity index and the confusion, uremia, elevated respiratory rate, hypotension, and aged 65 years or older score. To explore the correlation between SII and mortality in SAP patients, multivariable Cox regressions and competing risk regressions were conducted. Mediation analysis was also performed to assess the role of pneumonia severity.Results: Among 611 patients in the SAP population, death occurred in 164 patients (26.8%) during the median follow-up of 3.0 (1.2– 4.6) years. In multivariate analysis, higher SII scores could predict increased mortality in patients with SAP (adjusted hazard ratio 2.061; 95% confidence interval, 1.256– 3.383; P = 0.004), and the association was mediated by pneumonia severity. Moreover, adding SII to traditional models improved their predictive ability for mortality.Conclusion: Our study displayed that SII was characterized in SAP patients with different prognoses. Elevated SII scores increased the risk of mortality. Further research is required for the clinical practice of the index among SAP patients.Keywords: systemic immune-inflammation index, stroke-associated pneumonia, mortality, China

Xiao-Lin Wei,1 Qiang-Lin Zeng,2 Min Xie,3 Yong Bao1 1Department of Respirology, Taikang Sichuan Hospital, Chengdu, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengdu University School of Clinical Medicine, Chengdu University, Chengdu, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Yong Bao, Department of Respirology, Taikang Sichuan Hospital, No. 881, Xianghe 1st Street, Huayang Street, Tianfu New District, Sichuan, 610213, People’s Republic of China, Email byong65@163.comObjective: To investigate the distribution and drug resistance of pathogens among hospitalized patients in the respiratory unit during the COVID-19 pandemic, analyze the risk factors of drug resistance, construct a risk prediction model.Methods: This study isolated 791 strains from 489 patients admitted to the Affiliated Hospital of Chengdu University, who were retrospectively enrolled between December 2019 and June 2021. The patients were divided into training and validation sets based on a random number table method (8:2). The baseline information, clinical characteristics, and culture results were collected using an electronic database and WHONET 5.6 software and compared between the two groups. A risk prediction model for drug-resistant bacteria was constructed using multi-factor logistic regression.Results: K. pneumoniae (24.78%), P. aeruginosa (17.19%), A. baumannii (10.37%), and E. coli (10.37%) were the most abundant bacterial isolates. 174 isolates of drug-resistant bacteria were collected, ie, Carbapenem-resistant organism-strains, ESBL-producing strains, methicillin-resistant S. aureus, multi-drug resistance constituting 38.51%, 50.57%, 6.32%, 4.60%, respectively. The nosocomial infection prediction model of drug-resistant bacteria was developed based on the combined use of antimicrobials, pharmacological immunosuppression, PCT> 0.5 ng/mL, CKD stage 4– 5, indwelling catheter, and age > 60 years. The AUC under the ROC curve of the training and validation sets were 0.768 (95% CI: 0.624– 0.817) and 0.753 (95% CI: 0.657– 0.785), respectively. Our model revealed an acceptable prediction demonstrated by a non-significant Hosmer-Lemeshow test (training set, p=0.54; validation set, p=0.88).Conclusion: K. pneumoniae, P. aeruginosa, A. baumannii, and E. coli were the most abundant bacterial isolates. Antimicrobial resistance among the common isolates was high for most routinely used antimicrobials and carbapenems. COVID-19 did not increase the drug resistance pressure of the main strains. The risk prediction model of drug-resistant bacterial infection is expected to improve the prevention and control of antibacterial-resistant bacterial infection in hospital settings.Keywords: COVID-19, respiratory and critical care medicine, drug-resistant bacteria, risk factors, line chart

Meilian Xie,1,2 Aiping Wang,1 Zhaoxia Lin3 1Department of Public Service, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Nursing, Beijing Ditan Hospital Capital Medical University, Beijing, People’s Republic of China; 3Infection Center, Beijing Ditan Hospital Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Aiping Wang, Department of Public Service, the First affiliated Hospital of China Medical University, Shenyang, People’s Republic of China, Email jianghaoran88@hotmail.comObjective: Our study aims to completely understand the experience of gynecological related symptoms (GRS) and the association between GRS and quality of life (QOL) among HIV-infected women in China.Design: A cross-sectional, multicenter survey.Setting: The HIV/AIDS designated medical institutions of seven regions in China.Participants: One hundred and fifty-three women with HIV infection.Primary and Secondary Outcome Measures: Primary outcome measures included the score of GRS and QOL from analysis sample.Results: Among 153 participants, 60.13% were asymptomatic, and 39.87% were symptomatic according to their self-report data. In the symptomatic group, 47.54% reported only one symptom, 18.03% reported 2 symptoms, others reported more than 3 symptoms. The most common symptoms were vaginal discharge (25.49%), followed by irregular period (18.95%), bad cramps (13.07%), vaginal odor (11.11%), and vaginal itching (10.46%). The mean score of QOL was 86.82 ± 15.53. The symptomatic group had higher score than the asymptomatic group on each domain of QOL. GRS were negatively correlated with QOL after adjustment for confounding factors. Correlation matrix of GRS and six domains of QOL demonstrated significant negative correlation with each domain of QOL, especially the most strongly negative correlation with physical function of participants. But the association between GRS and environmental domain was weaker.Conclusion: These findings present the multidimensionality of common gynecologic related symptoms and highlight the clinically meaningful associations between GRS and quality of life among women with HIV infection in China. There is an urgent need to take measures to increase vaginal care and education in advance, delivered by trusted health professionals.Keywords: women living with HIV/AIDS, symptoms, gynecologic related symptoms, quality of life

Kun He,1 Mengyi Xie,1 Jingdong Li,1 Yi He,2 Yaolin Yin2 1Institute of Hepato-Biliary-Pancreatic-Intestinal disease, North Sichuan Medical College, Nanchong, People’s Republic of China; 2Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of ChinaCorrespondence: Jingdong Li, Institute of Hepato-Biliary-Pancreatic-Intestinal disease, North Sichuan Medical College, 234 Fujiang Road, Shunqing District, Nanchong, 637000, People’s Republic of China, Tel +86 18215521587, Fax +86 817-2222856, Email 362043561@qq.comPurpose: To examine the expression, clinical significance, and potential regulatory mechanism of centromere protein O (CENPO) in hepatocellular carcinoma (HCC).Methods: CENPO expression in pan-cancer was studied using the TCGA-GTEx database, in HCC and normal liver tissues using the GEO and TCGA databases, and in clinical HCC samples by RT-qPCR. The diagnostic value of CENPO was assessed using receiver operating characteristic curves. Univariate and multivariate regression analyses of factors associated with HCC prognosis were performed. CENPO function and its mechanism in HCC were explored using GO, KEGG, and GSEA analyses of differentially expressed genes (DEGs). Association of CENPO expression with immune cell infiltration and immune checkpoint-associated molecules was conducted using TCGA data and the TIMER2.0 database. Relationships between CENPO expression and DNA methylation were analyzed using the UALCAN and cBioPortal databases. CENPO expression in HCC cell lines was detected using RT-qPCR.Results: CENPO is upregulated in most cancers, including HCC and cell lines, and is a potential biomarker for HCC diagnosis (AUC = 0.936, 95% CI: 0.911– 0.960). Higher CENPO expression was associated with poorer outcomes in patients with HCC (OS, p = 0.004; DSS, p = 0.002; PFI, p < 0.001), and CENPO was an independent predictor of factors influencing overall survival in HCC. DEGs between samples with high and low CENPO levels were enriched in various biological processes, including activation of the G2M checkpoint and other signaling pathways, while CENPO expression correlated with HCC immune cell infiltration and immune checkpoint-associated molecules, as well as CENPO promoter methylation (p < 0.001).Conclusion: In HCC and cell lines, CENPO is overexpressed, a potential diagnostic marker and an indicator of poor prognosis. CENPO may regulate HCC development by influencing nuclear division and tumor immune infiltration and is regulated by methylation, making it a potential target for HCC immunotherapy.Keywords: HCC, diagnosis, prognosis, biomarker, immune checkpoints, methylation

Lichuan Zeng,1,&ast; Qu Wang,2,&ast; Haodong Liao,1,&ast; Fengchun Ren,1 Yudong Zhang,1 Jian Du,3 Huaqiang Liao,1 Mingguo Xie,1 Wenbin Wu3 1Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Ultrasound, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingguo Xie, Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, People’s Republic of China, Email 767030837@qq.com Wenbin Wu, Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, People’s Republic of China, Email wwb1201@vip.sina.comPurpose: We aimed to investigate the prevalence of fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs) and the clinical–radiological correlation in transient ischemic attack (TIA) patients.Materials and Methods: We performed a retrospective analysis of TIA patients who had undergone magnetic resonance imaging (MRI) within 24 h of symptom onset. Two independent neuroradiologists investigated the presence of FVHs, large-artery severe stenosis or occlusion (LASO) in magnetic resonance angiograms, and the nature of factors associated with FVH.Results: A total of 207 patients were enrolled in this study. FVHs were detected in 42 (20.3%) patients, in whom atrial fibrillation (AF) was confirmed in 25 (59.5%) cases and LASO was confirmed in 30 (71.4%) cases. The corresponding figures were 33 (20.0%) and 10 (6.1%), respectively, for the 165 FVH-negative patients. Logistic regression analysis showed that time from symptom onset to MRI (odds ratio [OR] = 0.82, 95% CI 0.76– 0.97, p = 0.042), previous stroke (OR = 2.95, 95% CI 1.58– 6.74, p = 0.002), AF (OR = 5.83, 95% CI 2.24– 9.46, p < 0.001), and LASO (OR = 4.28, 95% CI 2.96– 10.28, p < 0.001) were independently associated with FVH. Overall, the sensitivity and specificity of FVH for predicting LASO were 0.75 and 0.93, respectively, and the positive predictive value, negative predictive value, and accuracy were 0.71, 0.94, and 0.89, respectively. The area under the receiver operating characteristic curve was 0.839. FVH-positive TIA patients with LASO had less AF (14 [46.7%] versus 11 [91.7%], p = 0.019) and longer times from symptom onset to MRI (6.8 ± 2.8 h versus 4.8 ± 1.3 h, p = 0.004) than those without LASO.Conclusion: The presence of FVH could be an important marker in TIA patients. Many factors, including LASO, AF, and time from symptom onset to MRI, are associated with the detection of FVH.Keywords: FLAIR vascular hyperintensity, hyperintense vessel, transient ischemic attack, magnetic resonance imaging

Shuai Xia,1,&ast; Liyan Ma,2,&ast; Guoxing Wang,1 Jie Yang,1 Meiying Zhang,3 Xuechen Wang,1 Jianrong Su,2 Miaorong Xie1 1Department of Emergency and Critical Care Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 2Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 3Department of Emergency Center, Peking University First Hospital, Peking University, Beijing, 100050, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianrong Su, Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong’an Road, Xicheng District, Beijing, 100050, People’s Republic of China, Email youyilab@163.com Miaorong Xie, Department of Emergency and Critical Care Center, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong’an Road, Xicheng District, Beijing, 100050, People’s Republic of China, Email xiemiao27@126.comPurpose: To investigate the antimicrobial activity of berberine and the mechanism by which it combats methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from patients with bloodstream infections.Methods: Fifteen clinical MRSA isolates were collected, and their Multi-locus Sequence Types (MLST) were examined. The minimum inhibitory concentration (MIC) and combined antibacterial activity of berberine alone, and when combined with clindamycin and rifampicin separately, were determined. Additionally, two MRSA strains (ST239 and ST5) were selected to perform the time-killing assay and biofilm formation test. Cell wall alterations and cell membrane integrity were measured by confocal laser scanning microscopy (CLSM) and electron microscopy to assess the influence on cell morphology.Results: Our data showed berberine was effective against MRSA at MIC values varying from 256 to 64 mg&ast;L− 1 for different MLST types. Berberine alone, and when combined with clindamycin and rifampicin separately, displayed excellent antibacterial activity which reduced the bacterial counts by 2lgCFU&ast;mL within 24h and significantly weakened biofilm formation compared with control strain. Additionally, bacterial cytological profiling indicates that berberine destroyed the structure of the cell walls, membrane integrity and further changed the cell morphology with concentration increased.Conclusion: In our study, berberine has excellent anti-MRSA activities and has synergistic antibacterial property when combined with clindamycin and rifamycin separately, and the mechanism of activities involves the destruction of cell wall and membrane.Keywords: methicillin-resistant Staphylococcus aureus, berberine, multi-locus sequence types, synergistic effects, biofilm, mechanism

Yuting Luo, Rong Chen, Zhikun Ning, Nantao Fu, Minghao Xie Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Minghao XieDepartment of General Surgery, The First Affiliated Hospital of Nanchang University, 17 Yongwai Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +8613672207521, Email minghao_xie@foxmail.comPurpose: Although well-differentiated papillary thyroid carcinoma (PTC) has an indolent nature and usually an excellent prognosis, some patients experience disease recurrence or death. The aim of this study was to identify prognostic markers to stratify PTC patients.Patients and Methods: Eight gene-expression profiles (GSE3467, GSE3678, GSE5364, GSE27155, GSE33630, GSE53157, GSE60542, and GSE104005) were obtained from the Gene Expression Omnibus and used to analyze differentially expressed genes (DEGs) between PTC tissues and non-tumor tissues. Univariable Cox regression survival analysis and Lasso-penalized Cox regression analysis were performed to identify prognostic genes and establish a risk-score model based on the integrated DEGs. Kaplan–Meier (KM) and receiver operating characteristic (ROC) curves were used to validate the prognostic performance of the risk score. A nomogram was constructed based on The Cancer Genome Atlas dataset and Multivariable Cox regression analysis.Results: A total of 165 upregulated and 207 downregulated DEGs were screened. A four-gene signature including PAPSS2, PCOLCE2, PTX3, and TGFBR3 was identified. The risk-score model showed a strong diagnosis performance for identifying patients with a poor prognosis. KM analysis showed that patients with low risk scores had a significantly more favorable overall survival (OS) than those with high risk scores (p = 0.0002). ROC curves based on the four-gene signature showed better performances in predicting 1-, 3-, and 5-year survival than did the American Joint Committee on Cancer staging system (area under the curve: 0.86 vs 0.84, 0.80 vs 0.63, and 0.79 vs 0.73, respectively). Furthermore, when combined with age and tumor status from the nomogram, the four-gene signature achieved a good performance in guiding postoperative follow-up surveillance of patients with PTC.Conclusion: The four-gene signature was found to be a novel and reliable biomarker with great potential for clinical application in risk stratification and OS prediction in patients with PTC.Keywords: gene signature, overall survival, papillary thyroid cancer, prognosis

Yongli Zhang,1,2 Mengyao Xie,1,2 Ruoyan Xue,1,2 Qi Tang,1,2 Xiaohui Zhu,1,2 Jian Wang,1,2 Hua Yang,1,2 Chao Ma3– 5 1Department of Otolaryngology, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 2Translational Medicine Center, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 3Institute of Basic Medical Sciences, Department of Human Anatomy, Histology and Embryology, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, People’s Republic of China; 4Joint Laboratory of Anesthesia and Pain, Peking Union Medical College, Beijing, 100730, People’s Republic of China; 5Chinese Institute for Brain Research, Beijing, 102206, People’s Republic of ChinaCorrespondence: Jian Wang; Hua YangDepartment of Otolaryngology, Peking Union Medical College Hospital, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel +86 13673164261; +86 13701127757Fax +86-10-69156311Email wangjianent@163.com; dr_yanghua2021@163.comPurpose: Rapid and accurate diagnosis of the pathological characteristics of head and neck cancer and tumor resection margins is important. The DiveScope cell morphology analyzer (DiveScope) is a new endomicroscope that can rapidly image living tissues and cells. In this study, we preliminarily examined the accuracy of the DiveScope for determining the malignancy of head and neck cancers and the positivity/negativity of tumor resection margins and determined the consistency between diagnostic results with the DiveScope and those of frozen section pathology to provide a foundation for further clinical trials in pathological diagnosis of head and neck cancers and tumor resection margins.Methods: Head and neck cancer samples and resection margin samples were rapidly stained ex vivo before observation under the DiveScope cell morphology analyzer. Experienced pathologists distinguished the benignity and malignancy of the tumors based on images obtained by the DiveScope in a double-blind manner to validate the diagnostic performance of the analyzer.Results: We found that the cell morphology, cell nucleus morphology, karyoplasmic ratio, and even the nucleolus could be clearly distinguished. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of benign and malignant head and neck cancer according to DiveScope results were 10.55 and 0.04, respectively. The PLR and NLR of the head and neck cancer resection margins according to the DiveScope were 19.01 and 0, respectively.Conclusion: The DiveScope showed high accuracy in determining the benignity and malignancy of head and neck cancer and the positivity/negativity of resection margins, and its results were highly consistent with those of intraoperative frozen section pathology tests.Keywords: the DiveScope cell morphology analyzer, head and neck cancer, resection margins, pathological diagnosis

Yang Wang,1 Xiangyu Yin,2 Mengshuang Xie,3 Qin Wang,1 Wei Wang,4 Wenbo Yi,1 Jingui Yu1 1Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; 2Department of Joint Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, China; 3Department of Geriatric Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; 4Department of Pulmonary and Critical Care Medicine, School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, ChinaCorrespondence: Jingui YuDepartment of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 Wenhua West Road, Jinan, Shandong, 250012, ChinaTel +8618560086868Fax +8653182166458Email yujingui1109@126.comPurpose: With the use of pulmonary function tests (PFTs) as a preoperative examination, it is not rare to screen out airflow limitation (AFL) in asymptomatic patients undergoing lung surgeries. This study aims to elucidate whether there is a difference in the prevalence and prognosis of postoperative pulmonary complications (PPCs) between asymptomatic patients with newly diagnosed AFL and the normal population undergoing lung surgeries.Patients and Methods: The medical records of asymptomatic patients undergoing lung surgeries who were spirometrically diagnosed with AFL between January and October 2017 were collected in Qilu hospital. These patients were subsequently followed up until February 2021. The diagnosis of PPCs was based on a recommended consensus definition. The incidence of PPCs between the newly diagnosed AFL group and the normal group was compared and a propensity score-matched analysis (PSM) was performed. The survival analysis was performed to investigate the long-term prognosis of the two groups.Results: Overall, 535 asymptomatic subjects were recruited and 126 subjects (11.4%) were spirometrically diagnosed as AFL. The incidence of PPCs was significantly higher in the newly diagnosed AFL group than in the normal population (28.6%VS 14.4%, P < 0.001), especially in the FEV1/FVC≤ 65% group (P < 0.001), which were all confirmed by PSM analysis. Furthermore, these patients were at a higher risk of ICU admissions (P < 0.001) and 90-day hospital readmissions secondary to PPCs (P < 0.001). No significant differences were found in the overall, in-hospital and 90-day mortality between the AFL group and the normal group (P values > 0.05).Conclusion: Asymptomatic patients with AFL are at higher risk of PPCs than the general population after lung surgeries, along with an increase in ICU admissions and 90-day hospital readmissions secondary to PPCs. Although these patients tended to report worse current conditions, they were similar in the in-hospital, 90-day and overall mortality during the follow-up.Keywords: pulmonary function tests, newly diagnosed airflow limitation, propensity score-matched analysis, postoperative outcomes

Salih Samo,1,2 Falak Hamo,2 Anand S Jain,1 Rushikesh H Shah,1 Vaishali Patel,1 Lucie F Calderon,1 Mengdan Xie,1 Parit Mekaroonkamol,1 Steven A Keilin,1 Qiang Cai1 1Division of Digestive Diseases-Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; 2Division of Gastroenterology, Hepatology and Motility-Department of Medicine, The University of Kansas School of Medicine, Kansas City, KS, USACorrespondence: Qiang CaiEmory University School of Medicine, 1365 Clifton Road, B1262, Atlanta, GA, 30322, USATel +1 404-778-2714Fax +1 404-778-2578Email qcai@emory.eduPurpose: Peroral endoscopic myotomy (POEM) after prior myotomy (PM-POEM) can be technically challenging with possible increased adverse events. We aimed to assess gas leak and mucosal injury incidence during PM-POEM, compared to an index POEM (iPOEM), and post-procedure extubation time.Patients and Methods: A retrospective study comparing PM-POEM to iPOEM from March 2016 to August 2018.Results: There were 21 subjects in the PM-POEM and 56 subjects in the iPOEM. The PM-POEM group was younger (average age 44.33 vs 57.57 years, p=0.0082). Gas leak incidence did not differ between groups (28.6% in PM-POEM vs 14.3% in iPOEM, p=0.148). For cases with imaging available postoperatively, there was a trend towards higher incidence of gas leak in the PM-POEM, but it was not statistically significant (60% vs 42.1%, p=0.359). The post-procedure extubation time was not different between PM-POEM and iPOEM (11.38 vs 9.46 minutes, p=0.93), but it was longer when gas leak occurred (15.92 vs 8.67 minutes, p=0.027). The odds of mucosal injury were four-fold higher (OR, 4.31; 95% CI, 1.32– 14.08), and more clips were used to close mucosal injuries (0.62 vs 0.14 clips, p=0.0053) in the PM-POEM group. More procedures were deemed difficult or challenging in the PM-POEM (33.3% vs 7.1%, p=0.007). The number of clips used to close the mucosotomy was not different between groups (4.05 vs 3.84 clips, p=0.498). Although the myotomy was shorter in PM-POEM, it was not statistically significant (6.38 vs 7.14 cm, p=0.074). However, the procedure was longer in PM-POEM (61.28 vs 45.39 minutes, p=0.0017). There was no intervention or ICU admission required pertinent to the procedure.Conclusion: Performing PM-POEM can be more difficult with more mucosal injuries. Gas leak was associated with a slightly longer post-procedure extubation time, but clinical relevance is unclear given incidence of gas leak was unknown at time of extubation.Keywords: peroral endoscopic myotomy, Heller’s myotomy, achalasia, gas leak, mucosal injury

Xianyun Xu,1,* Qiongjun Xie,2,* Mingfeng Xie,3 Yong Zeng,3 Qian Liu1 1Key Laboratory of Prevention and treatment of cardiovascular and cerebrovascular diseases of Ministry of Education, Jiangxi Provincial Clinical Research Center for Vascular Anomalies, Basic Medical School, Gannan Medical University, Ganzhou, Jiangxi, 341000, People’s Republic of China; 2Basic Medical School, Gannan Medical University, Ganzhou, Jiangxi, 341000, People’s Republic of China; 3Department of Pediatric Surgery, Jiangxi Provincial Clinical Research Center for Vascular Anomalies, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, The First Affiliate Hospital of Gannan Medical University, Ganzhou, Jiangxi, 341000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian LiuKey Laboratory of Prevention and treatment of cardiovascular and cerebrovascular diseases of Ministry of Education, Jiangxi Provincial Clinical Research Center for Vascular Anomalies, Basic Medical School, Gannan Medical University, Ganzhou, Jiangxi, 341000, People’s Republic of ChinaEmail liuqiangmu2017@126.comBackground: Small nucleolus RNA Host Gene 8 (SNHG8) belongs to a subgroup with long non-coding RNAs. LncRNA SNHG8 presents up-regulated in miscellaneous cancers, like gastric cancer, liver cancer, and esophageal squamous cell cancer. Nevertheless, the expression pattern and the pathological function of lncRNA SNHG8 in breast cancer remain obscure.Methods: We examined the expression levels of lncRNA SNHG8 in the tissue samples and cell lines from breast cancer via RT-qPCR in the present study. The functions of lncRNA SNHG8 on the progression of breast cancer cell were examined by CCK-8, EdU, Transwell chamber assays, and flow cytometry analyses. The expression of proteins was assessed using Western blot assay.Results: We found that proliferation, migration, and invasion of breast cancer cells were significantly inhibited due to knockdown of lncRNA SNHG8, while inducing apoptosis of these cells. Mechanistically, SNHG8 functioned as an inhibitor of miR-634 in tumor tissues.Conclusion: LncRNA SNHG8 sponged the miR-634 to increase the expression level of ZBTB20, thus further aggravating the malignancy of breast cancer. Hence, the lncRNA SNHG8-miR-634-ZBTB20 axis may be a promising therapeutic target to treat breast cancers.Keywords: small nucleolus RNA host gene 8, microRNA-634, breast cancer, ZBTB20

Lichuan Zeng,1 Huaqiang Liao,1 Fengchun Ren,1 Yudong Zhang,1 Qu Wang,2 Mingguo Xie1 1Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Ultrasound, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of ChinaCorrespondence: Mingguo Xie; Qu WangHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of ChinaEmail 767030837@qq.com; 444028177@qq.comAbstract: Percutaneous computed tomography (CT)-guided transthoracic needle biopsy (TTNB) is a valuable procedure for obtaining tissue or cells for diagnosis, which is especially indispensable in thoracic oncology. Pneumothorax and hemoptysis are the most common complications of percutaneous needle biopsy of the lung. According to reports published over the past decades, pneumothorax incidence in patients who underwent TTNB greatly varies. The morbidity of pneumothorax after CT-guided TTNB depends on several factors, including size and depth of lesions, emphysema, the number of pleural surfaces and fissure crossed, etc. Attention to biopsy planning and technique and post-biopsy precautions help to prevent or minimize potential complications. Many measures can be taken to help prevent the progression of a pneumothorax, which in turn might reduce the number of pneumothoraces requiring chest tube placement. A multitude of therapeutic options is available for the treatment of pneumothorax, varying from observation and oxygen treatment, simple manual aspiration, to chest tube placement. When a pneumothorax develops during the biopsy procedure, it can be manually aspirated after the needle is retracted back into the pleural space or by inserting a separate needle into the pleural space. Biopsy side down positioning of the patient after biopsy significantly reduces the incidence of pneumothorax and the requirement of chest tube placement. Aspiration in biopsy side down position is also recommended for treating pneumothorax when simple manual aspiration is unsuccessful or delayed pneumothorax occurred. Chest tube placement is an important treatment strategy for patients with a large or symptomatic pneumothorax. Clinicians are encouraged to understand the development, prevention, and treatment of pneumothorax. Efforts should be made to reduce the incidence of pneumothorax in biopsy planning and post-biopsy precautions. When pneumothorax occurs, appropriate treatment should be adopted to reduce the risk of worsening pneumothorax.Keywords: pneumothorax, lung biopsy, aspiration, chest tube placement, computed tomography, CT

Liwei Cui,1 Haijun Li,2 Mengshuang Xie,1 Xia Xu,2 Yingmei Zhang,3 Wei Wang,1 Shuang Dou,1 Wei Xiao1 1Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Cadre Health Care, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 3Department of Pulmonary Medicine, Linyi People’s Hospital, Linyi, People’s Republic of ChinaCorrespondence: Wei XiaoDepartment of Pulmonary Medicine, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, People’s Republic of ChinaEmail xiaowei4226@163.comBackground and Objective: The link between ADAM9 and airway remodeling and emphysema severity in COPD patients has not been elucidated. Here, we investigated the relationship between ADAM9 levels in sputum and airway epithelium and the clinical characteristics of COPD patients.Methods: A sputum cohort and a lung tissue cohort were included in the study. Pulmonary function and computed tomography data were analyzed in COPD patients, non-COPD smokers, and non-smokers. Soluble ADAM9 and interleukin 8 (IL-8) levels in sputum supernatants as well as surface ADAM9 expression in airway epithelium were detected. Emphysema scores were calculated by the percentage of low attenuation area (%LAA-950), and airway remodeling was measured via airway thickening and loss of airway counts.Results: Both soluble ADAM9 levels in sputum and relative surface ADAM9 expression in airway epithelium were increased in COPD patients. Sputum ADAM9 levels were negatively correlated with forced expiratory volume in 1 s of predicted (FEV1% of predicted) and positively correlated with sputum IL-8 levels, but not with CT measured emphysema nor airway remodeling. The ADAM9 expression in airway epithelia was positively correlated with %LAA-950 and airway wall thickening parameters (wall area percentage, WA%; the square root of the wall area in a standard airway with a 10 mm internal perimeter, Pi-10), while negatively correlated with airway counts derived from the 4th to 9th bronchial generations.Conclusion: Airway ADAM9 levels in sputum and airway epithelium were both elevated in COPD patients compared to non-COPD controls. Sputum ADAM9 seemed to be associated with inflammatory responses in COPD, while epithelial ADAM9 was more correlated with emphysema and airway remodeling.Keywords: chronic obstructive pulmonary disease, proteinase with a disintegrin and a metalloproteinase domain-9, computed tomography, emphysema, airway remodeling

Xianzhe Yu,1,* Lingling Zhu,2,* Jiewei Liu,2,* Ming Xie,1 Jiang Chen,3 Jianguo Li1 1Gastrointestinal Department, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, People’s Republic of China; 2Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianguo LiGastrointestinal Department, The Affiliated Hospital of Zunyi Medical University, Huichuan Area, Dalian Road 149, Zunyi 563000, Guizhou, People’s Republic of ChinaTel +86 851-28608241Fax +86 22 6036 3013Email lijianguo826@163.comJiang ChenDepartment of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, Zhejiang Province, People’s Republic of ChinaEmail chenjiang520@zju.edu.cnAbstract: Colorectal cancer (CRC) is the third most common malignant tumor in the world and the second leading cause of cancer-related deaths, with the liver as the most common site of distant metastasis. The prognosis of CRC with liver metastasis is poor, and most patients cannot undergo surgery. In addition, conventional antitumor approaches such as chemotherapy, radiotherapy, targeted therapy, and surgery result in unsatisfactory outcomes. In recent years, immunotherapy has shown good prospects in the treatment of assorted tumors by enhancing the host’s antitumor immune function, and it may become a new effective treatment for liver metastasis of CRC. However, challenges remain in applying immunotherapy to CRC with liver metastasis. This review examines how the microenvironment and immunosuppressive landscape of the liver favor tumor progression. It also highlights the latest research advances in immunotherapy for colorectal liver metastasis and identifies immunotherapy as a treatment regimen with a promising future in clinical applications.Keywords: immunotherapy, colorectal cancer, liver metastasis, tumor immune microenvironment, immune checkpoint inhibitors, deficient DNA mismatch repair

Mingrui Xie Medway NHS Foundation Trust, Gillingham, Kent, UKCorrespondence: Mingrui Xie, Medway NHS Foundation Trust, Windmill Road, Gillingham, Kent, ME7 5NY, UK, Tel +447857121148, Email mingrui.xie@nhs.net

Mingrui Xie Medway NHS Foundation Trust, Gillingham, Kent, UKCorrespondence: Mingrui Xie, Medway NHS Foundation Trust, Windmill Road, Gillingham, Kent, ME7 5NY, UK, Tel +447747267027, Email mingrui.xie@nhs.net

Yining Wu,1,* Jia Wei,1,* Wei Zhang,1,2 Mengxiao Xie,1,2 Xueying Wang,1 Jian Xu1,2 1Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2National Key Clinical Department of Laboratory Medicine, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian XuDepartment of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, People’s Republic of ChinaTel/ Fax +86 25 68303453Email xu_jian79@163.comPurpose: Lung cancer is a leading cause of cancer-related death, with lung adenocarcinoma (LUAD) representing the most common subtype. Recently, exosome-based biomarkers have provided new diagnostic approaches for malignancies. We aimed to identify specific exosomal microRNAs (miRNAs) as noninvasive biomarkers for LUAD.Patients and Methods: A total of 110 participants were enrolled and randomly divided into two sets: the discovery set (n=20) and the validation set (n=90). Exosomes were isolated from serum, and miRNAs were subsequently extracted. Candidate miRNAs (miR-21, miR-221-3p, miR-222-3p, miR-223, miR-638 and miR-1290) were detected by quantitative real-time PCR (qRT-PCR) in the discovery set. The upregulated miR-1290 was then selected for further analysis in the validation set along with three tumor markers (CEA, CYFRA21-1 and NSE). The diagnostic and prognostic value of exosomal miR-1290 were estimated through receiver-operating characteristic (ROC) and survival analysis.Results: Serum exosomal miR-1290 was significantly upregulated in LUAD patients compared to healthy controls (P< 0.001) and decreased after resection (P=0.0029). Its expression level was associated with tumor stage, tumor size, lymph node and distant metastasis (all P < 0.05). Exosomal miR-1290 had a higher diagnostic efficacy than CEA, CYFRA21-1 and NSE, with a sensitivity of 80.0% and specificity of 96.7% (AUC: 0.937, 95% CI: 0.890– 0.985; P< 0.001). Moreover, LUAD patients with a high level of exosomal miR-1290 had significantly poorer progression-free survival (PFS) than those with a low level of exosomal miR-1290 (mean PFS: 14 months vs 37 months, P< 0.001). Cox proportional hazards model analysis demonstrated that exosomal miR-1290 could be an independent risk factor for the prognosis of LUAD (HR=7.80, P=0.017).Conclusion: Serum exosomal miR-1290 could be a potential diagnostic and prognostic biomarker for LUAD.Keywords: lung adenocarcinoma, circulating miRNA, exosome, biomarker

Wenying Yan,1 Mei Xie,2 Rong Li,3 Hongmei Hu,3 Biao Tang,3 Jie Shen4 1Department of Gynecology, Wangjiang Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Chengdu Second People’s Hospital, Chengdu, Sichuan Province, People’s Republic of China; 3Department of Gynecology, Sichuan Maternal and Child Health Hospital, Chengdu, Sichuan Province, People’s Republic of China; 4Department of Orthopaedics, The First Hospital Affiliated to AMU (Southwest Hospital), Chongqing, People’s Republic of ChinaCorrespondence: Jie ShenDepartment of Orthopaedics, The First Hospital Affiliated to AMU (Southwest Hospital), 30 Gaotan Yanzheng Street, Shapingba District, Chongqing 400038, People’s Republic of ChinaEmail drshenjie@126.comIntroduction: Hypoxia-mediated tumor metastasis, progression and drug resistance are major clinical challenges in ovarian cancer. Meanwhile, the genetic basis of these traits is still not clear. RT-qPCR, as an efficient and sensitive gene expression technique, has been widely used for gene analyses, providing a basis for in-depth understanding of molecular changes in different microenvironments. However, there is currently a lack of suitable reference genes to normalize the data associated with hypoxia in ovarian cancer cells.Methods: A systematic method is needed to select the most suitable reference gene. Here, eight candidate reference genes (GAPDH, β-actin, 18S RNA, TUBB, PPIA, TBP, RPL13A and SDHA) from humans were selected to assess their expression levels in SKOV3 cells under hypoxia. The geNorm and NormFinder programs were utilized to evaluate the expression stabilities of these selected candidate reference genes.Results: Interestingly, 18S RNA was considered to be an ideal reference gene for the normalization of target gene expression under hypoxic conditions. Furthermore, this result was confirmed in another two ovarian cancer cell line, CAOV3 and OVCAR3 cell line. Finally, these results suggest that appropriate reference genes should be selected before performing gene expression analysis during hypoxic environmental exposure.Conclusion: 18S RNA can be used as an appropriate reference gene for the study of gene expression in ovarian cancer samples under hypoxia by RT-qPCR.Keywords: reference genes, ovarian cancer, hypoxia, EMT

Menghua Xie,1 Lin Cai,1 Jingduo Li,1 Jing Zhao,1 Yingxue Guo,1 Zaiyu Hou,1 Xiupeng Zhang,1 Hua Tian,2 Ailin Li,2 Yuan Miao1 1Department of Pathology, The College of Basic Medical Sciences and The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Radiotherapy, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Yuan Miao Tel +86 248 328 2248Email cmumiaoyuan@163.comPurpose: FAM110B is a member of the FAM110 family (family with sequence similarity 110), which is a component of the centrosome associated proteins. Previous studies have shown that FAM110B may be involved in the process of cell cycle and may play a role in carcinogenesis and tumor progression. Using an online database, we found that FAM110B may predict favorable prognosis in non-small cell lung cancer (NSCLC). Therefore, the role of FAM110B playing in NSCLC needs to be further investigated.Patients and Methods: Online databases and immunohistochemistry were used to predict the expression and prognostic value of FAM110B in NSCLC samples. Immunofluorescence staining was used to investigate the subcellular distribution of FAM110B. Western blot, MTT, colony formation, and matrigel invasion assay were used to detect the expression and the effect of FAM110B on mediating proliferation and invasion in NSCLC cell lines.Results: In this study, immunohistochemistry results showed that FAM110B expression significantly correlated with early TNM staging (P=0.020) and negative regional lymph node metastasis (P=0.006). Kaplan–Meier survival analysis found that the median survival time of patients with positive FAM110B expression (56.181± 2.348 months) was significantly longer than those with negative FAM110B expression (47.701± 2.997 months, P=0.024). Moreover, overexpression of FAM110B inhibited the proliferation and invasion of A549, H1299, and LK2 cell lines. Conversely, FAM110B RNAi exerted opposite effects in the above cell lines. Furthermore, FAM110B overexpression downregulated the active β‐catenin, phosphorylation of GSK-3β (p-GSK-3β), cyclin B1, cyclin D1, MMP2, and MMP7, and upregulated the phosphorylation of β-catenin (p-β-catenin) in A549 and H1299 cells. Besides, the FAM110B-induced depressions of p-GSK-3β and active β-catenin were reversed after being treated with Wnt/β-catenin inhibitor, XAV-939.Conclusion: In summary, our results demonstrated that the overexpression of FAM110B restricts the proliferation and invasion of NSCLC cells by inhibiting Wnt/β-catenin signaling. Our study reveals the antitumor function of FAM110B in NSCLC and indicates that FAM110B is a potential therapeutic target.Keywords: FAM110B, NSCLC, Wnt/β-catenin signaling, proliferation, invasion

Mengshuang Xie, Liwei Cui, Jinhuan Liu, Wei Wang, Jun Li, Wei Xiao Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Wei XiaoDepartment of Pulmonary and Critical Care Medicine, Qilu Hospital, Shandong University, 107 Wenhua West Road, Jinan 250012, People’s Republic of ChinaTel/ Fax +86 53182166294Email xiaowei4226@163.comBackground and Objective: The reference equations and diagnostic criteria play a critical role in the interpretation of pulmonary function tests (PFTs). The aim was to investigate the impacts of different reference equations and diagnostic criteria on the frequency of airway obstruction in adult people of a large teaching hospital of North China.Methods: The spirometry data of all adult people who underwent PFTs in Qilu hospital from April 2012 to November 2015 were collected. Two spirometry reference equations, namely, Zhongshan-2011 and Global Lung Function Initiative 2012 (GLI-2012) were compared. The frequency of airway obstruction using different spirometry prediction equations and diagnostic criteria including forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 92% of predicted value and FEV1/FVC

Shuai Xia,1 Liyan Ma,2 Guoxing Wang,1 Jie Yang,1 Meiying Zhang,3 Xuechen Wang,1 Jianrong Su,2 Miaorong Xie1 1Department of Emergency and Critical Care Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 2Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 3Department of Emergency Center, Peking University First Hospital, Peking University, Beijing, 100050, People’s Republic of ChinaCorrespondence: Miaorong Xie, Department of Emergency and Critical Care, Center, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong’an Road, Xicheng District, Beijing, 100050, People’s Republic of China, Email xiemiao27@126.com View the original paper by Mr Xia and colleagues This is in response to the Letter to the Editor

Wei Wang,1,* Shuang Dou,1,* Wenyan Dong,2 Mengshuang Xie,1 Liwei Cui,1 Chunyan Zheng,1 Wei Xiao1 1Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Geriatric Medicine, The Second Hospital of Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Background: COPD is an important comorbidity of lung cancer, but the impact of COPD on the outcomes of lung cancer remains uncertain. Because both COPD and lung cancer are heterogeneous diseases, we evaluated the link between COPD phenotypes and the prognosis of different histological subtypes of lung cancer.Methods: In this retrospective study, subjects with a newly and pathologically confirmed diagnosis of lung cancer were enrolled from patients preparing for lung cancer surgery. All participants underwent pulmonary function test (PFT). The diagnosis of COPD was based on GOLD criteria. Lung cancer subtypes and COPD phenotypes were categorized by WHO classification of lung tumors and computer quantitative analysis of PFT. The HRs were estimated by Cox regression analysis.Results: Among 2,222 lung cancer patients, 32.6% coexisted with COPD. After adjustment for age, sex, body mass index (BMI), smoking status, and therapy method, COPD was significantly associated with the decreased overall survival (OS) of lung cancer (HR 1.28, 95% CI 1.05–1.57). With the increased severity of COPD, the OS of lung cancer was gradually worsened (HR 1.23, 95% CI 1.08–1.39). But surgical treatment and high BMI were independent prognostic protective factors (HR 0.46, 95% CI 0.37–0.56; HR 0.96, 95% CI 0.94–0.99). Moreover, in terms of disease heterogeneity, emphysema-predominant phenotype of COPD was an independent prognostic risk factor for squamous carcinoma (HR 2.53, 95% CI 1.49–4.30). No significant relationship between COPD phenotype and lung cancer prognosis was observed among adenocarcinoma, small cell lung cancer, large cell lung cancer, and other subtype patients.Conclusion: These findings suggest that COPD, especially emphysema-predominant phenotype, is an independent prognostic risk factor for squamous carcinoma only. Keywords: lung cancer, COPD, prognosis, histology, disease heterogeneity

Xiaoying Li,1,* Xin Hong,2,* Xianshu Gao,1 Xiaobin Gu,1 Wei Xiong,3 Jing Zhao,4 Hongliang Yu,5 Ming Cui,1 Mu Xie,1 Yun Bai,1 Shaoqian Sun6 1Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, China; 2Department of Urology, Peking University International Hospital, Peking University, Beijing, China; 3Department of Oncology, Tangshan People’s Hospital, Hebei, China; 4Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China; 5Department of Radiation Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China; 6College of Biochemical Engineering, Beijing Union University, Beijing, China *These authors contributed equally to this work Purpose: In our previous study, we found that AKR1C3 was a radioresistance gene in KY170R cells. Downregulating the expression of AKR1C3 could enhance the radiosensitivity of esophageal carcinoma cells. In this study, we investigated whether methyl jasmonate (MeJ), an inhibitor of Aldo-keto reductase family1 member C3 (AKR1C3), could overcome radiation resistance in AKR1C3 highly expressed cells.Patients and methods: We used clone formation assays to detect radiosensitivity effects. Flow cytometry assays were used to detect reactive oxygen species (ROS) accumulation and apoptosis. Enzyme linked immunosorbent assays (ELISAs) were used to detect the concentrations of prostaglandin F2 (PGF2) and prostaglandin D2 (PGD2) in the cells after incubation with MeJ. Western blotting was used to detect AKR1C3 and peroxisome proliferator-activated receptor gamma (PPARγ) expression.Results: We found that AKR1C3 was highly expressed in radioresistant esophageal carcinoma cells. MeJ inhibited the expression of AKR1C3 and enhanced the radiation sensitivity of esophageal carcinoma cells expressing high levels of AKR1C3 (P0.05).The radiation sensitivity effect of MeJ also depended upon the generation of ROS in KY170R cells; 48 h after irradiation, ROS levels in the MeJ group was twofold higher than in the untreated KY170R cells (P0.05).Conclusion: Our results indicate that MeJ can increase the radiation sensitivity of AKR1C3-overexpressing KY170R cells by inhibiting the 11-ketoprostaglandin reductase activity of AKR1C3 and increasing cellular ROS levels. Keywords: radiosensitivity, esophageal carcinoma, methyl jasmonate, AKR1C3

Jiang-yang Xue,1 Chao Huang,2 Wei Wang,1 Hai-bo Li,1 Ming Sun,3 Min Xie2 1Center for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, China; 2Central Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, China; 3Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, TX, USA Abstract: Multiple studies have demonstrated that lncRNAs extensively participate in human cancer proliferation and metastasis. Epigenetic modification, transcriptional and posttranscriptional regulatory mechanisms are involved in lncRNA-led tumorigenesis and transfer. Recently, a novel identified homeobox (HOX) A11 antisense lncRNA, HOXA11-AS, 1,628 bp in length, has been excessively highlighted to be an essential initiator and facilitator in the process of malignant tumor proliferation and metastasis. As found in many reports, HOXA11-AS can not only act as a molecular scaffold of PRC2, LSD1 and DNMT1 to epigenetically modify chromosomes in the nucleus but also occur as ceRNA competitively sponging miRNAs in the cytoplasm. Furthermore, HOXA11-AS may function as a potential biomarker for cancer diagnosis and prognosis. In this review, we summarize the evolvement and mechanisms of HOXA11-AS in proliferation and metastasis of various human cancers. Keywords: HOXA11-AS, proliferation, metastasis, EMT, ceRNA, lncRNA, molecular scaffold

Shuang Dou,1 Chunyan Zheng,1 Liwei Cui,1 Mengshuang Xie,1 Wei Wang,1 Hui Tian,1 Kang Li,1 Kaidi Liu,1 Xinyu Tian,1 Xin Wang,1 Qun Zhang,1 Xin Ai,1 Junchao Che,1 Qixiao Liu,1 Haijun Li,2 Wei Xiao1 1Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Cadre Health Care, Qilu Hospital, Shandong University, Jinan, People’s Republic of China Background: COPD has been identified as an etiology or related disease of bronchiectasis, and bronchiectasis has been classified as a comorbidity of COPD. In this study, we investigated the prevalence of bronchiectasis in different phenotypes of COPD subjects and the correlation between bronchiectasis and different phenotypes, especially emphysema. Methods: COPD patients were recruited from April 2012 to December 2015. The presence of bronchiectasis and related information were statistically analyzed. COPD subjects were separated into subgroups in two ways: COPD with and without bronchiectasis groups and emphysema-predominant (emphysema index, EI≥9.9%) and non-emphysema-predominant (EI

Xiaobin Gu,1 Xianshu Gao,1 Ming Cui,1 Mu Xie,1 Mingwei Ma,1 Shangbin Qin,1 Xiaoying Li,1 Xin Qi,1 Yun Bai,1 Dian Wang2 1Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, People’s Republic of China; 2Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, USA Objective: This study was aimed to compare survival outcomes in high-risk prostate cancer (PCa) patients receiving external beam radiotherapy (EBRT) or radical prostatectomy (RP). Materials and methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PCa patients with high-risk features who received RP alone or EBRT alone from 2004 to 2008. Propensity-score matching (PSM) was performed. Kaplan–Meier survival analysis was used to compare cancer-specific survival (CSS) and overall survival (OS). Multivariate Cox regression analysis was used to identify independent prognostic factors. Results: A total of 24,293 patients were identified, 14,460 patients receiving RP and 9833 patients receiving EBRT. Through PSM, 3828 patients were identified in each group. The mean CSS was 128.6 and 126.7 months for RP and EBRT groups, respectively (P20 ng/mL were significant risk factors for both CSS and OS. Conclusion: This study suggested that survival outcomes might be better with RP than EBRT in high-risk PCa patients aged

Yun Bai,1 Xian-shu Gao,1 Shang-bin Qin,1 Jia-yan Chen,1 Meng-meng Su,1 Qing Liu,2 Xiu-bo Qin,2 Ming-wei Ma,1 Bo Zhao,1 Xiao-bin Gu,1 Mu Xie,1 Ming Cui,1 Xin Qi,1 Xiao-ying Li1 1Department of Radiation Oncology, Peking University First Hospital, Beijing, China; 2Department of Medical Imaging, Peking University First Hospital, Beijing, China Purpose: Bulky non-small cell lung cancer (NSCLC) is difficult to achieve effective local control by conventionally fractionated radiotherapy (CRT). The present work aims to evaluate the safety and efficacy of partial stereotactic ablative boost radiotherapy (P-SABR) in bulky NSCLC. Patients and methods: From December 2012 through August 2017, 30 patients with bulky NSCLC treated with P-SABR technique were analyzed. The P-SABR plan consisted of one partial SABR plan (5–9 Gy/f, 3–6 fractions) to gross tumor boost (GTVb), followed by one CRT plan to the planning target volume (PTV). GTVb was the max volume receiving SABR to guarantee the dose of organs-at-risks (OARs) falloff to about 3 Gy/f. The total dose of PTV margin was planned to above 60 Gy. The simply CRT plans were created using the same planning parameters as the original plan, with the goal to achieve comparable OARs doses and PTV margin dose to the P-SABR plan. Dosimetric variables were acquired in both P-SABR and compared CRT plans. Toxicity, local control, and survival were also evaluated. Results: Median follow-up in survivors was 10.3 months (range=2.3–39.4 months). Eleven patients (36.7%) had partial response (PR) and ten patients (33.3%) had stable disease (SD). Two-year overall survival was 55.6%. Two-year local control rate was 85.7%. No severe acute side effects .CTCAE Grade III were observed. Compared to the simply CRT plan, P-SABR plans achieved similar doses to the OARs and Dmin, but increased dose at the isocenter, Dmean, Dmax, and biological equivalent dose (BED) significantly (P

Wei Wang,* Mengshuang Xie,* Shuang Dou, Liwei Cui, Chunyan Zheng, Wei Xiao Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China *These authors contributed equally to this work Background: COPD is considered an independent risk factor for lung cancer. COPD and lung cancer are both very heterogeneous diseases, and the study herein investigates the link between COPD phenotypes and specific histological subtypes of lung cancer.Methods: This case–control study comprised 2,283 patients with newly diagnosed pathological lung cancer and 2,323 non-lung cancer controls. All participants underwent pulmonary function tests. The diagnosis of COPD was based on Global Initiative for Chronic Obstructive Lung Disease criteria. Subtypes of the two diseases were categorized according to 2015 World Health Organization classification of lung cancer and computer quantification of airway collapse on maximum expiratory flow volume. ORs were estimated using logistic regression analysis.Results: The prevalence of COPD was higher (32.8%) in lung cancer patients compared to controls (16.0%). After adjustment for age, sex, body-mass index, and smoking status, the presence of COPD significantly increased the risk of lung cancer (OR 2.88, 95% CI 2.48–3.34) and all common histological subtypes (ORs 2.04–5.26). Both emphysema-predominant and non-emphysema-predominant phenotypes of COPD significantly increased the risk of lung cancer (OR 4.43, 95% CI 2.85–6.88; OR 2.82, 95% CI 2.40–3.31). Higher risk of squamous-cell carcinoma and small-cell lung cancer was observed in patients with the emphysema-predominant than the non-emphysema-predominant phenotype (OR 1.73, 95% CI 1.03–2.89; OR 3.74, 95% CI 1.64–8.53). Conclusion: COPD was an independent risk factor for lung cancer and all common histological subtypes. Both emphysema-predominant and non-emphysema-predominant phenotypes of COPD significantly increased the risk of lung cancer. Relative to non-emphysema-predominant phenotype of COPD, emphysema-predominant phenotype had a higher risk of squamous-cell carcinoma and small-cell lung cancer. Keywords: lung cancer, COPD, risk, phenotype, histology

Shuang Dou,1 Chunyan Zheng,1 Xiuli Ji,2 Wei Wang,1 Mengshuang Xie,1 Liwei Cui,1 Wei Xiao1 1Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Pulmonary Disease, Jinan Traditional Chinese Medicine Hospital, Jinan, People’s Republic of China Background: Pulmonary vascular disease, especially pulmonary hypertension, is an important complication of COPD. Bronchiectasis is considered not only a comorbidity of COPD, but also a risk factor for vascular diseases. The main pulmonary artery to aorta diameter ratio (PA:A ratio) has been found to be a reliable indicator of pulmonary vascular disease. It is hypothesized that the co-existence of COPD and bronchiectasis may be associated with relative pulmonary artery enlargement (PA:A ratio >1).Methods: This retrospective study enrolled COPD patients from 2012 through 2016. Demographic and clinical data were collected. Bhalla score was used to determine the severity of bronchiectasis. Patient characteristics were analyzed in two ways: the high (PA:A >1) and low (PA:A ≤1) ratio groups; and COPD with and without bronchiectasis groups. Logistic regression analysis was used to assess risk factors for high PA:A ratios.Results: In this study, 480 COPD patients were included, of whom 168 had radiographic bronchiectasis. Patients with pulmonary artery enlargement presented with poorer nutrition (albumin, 35.6±5.1 vs 38.3±4.9, P

Genxia Li,1,* Na Yang,2,* Mingkun Xie,1 Yajuan Xu,1 Ning Han,1 Qi Chen,3 Hezhou Li,4 Yueli Wu,5 Chunhua Cheng,1 Yuhong Wang,1 Man Zhou,6 Bo Xia,6 Shuhua Guo,1 Shihong Cui11Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 2Department of Obstetrics and Gynecology, The First People’s Hospital in Guangzhou, Guangzhou, 3Department of Pediatric Surgery, 4Department of Ultrasound, 5Department of Genetics Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China; 6Department of Genetics and Biochemistry, Clemson University, Clemson, SC, USA*These authors contributed equally to this workSynopsis: The establishment of a multidisciplinary consultation system is necessary for the diagnosis of complicated fetal anomalies.Purpose: We aimed to investigate the incidences of different types of fetal anomalies and the influence of multidisciplinary consultation on fetal prognosis.Patients and methods: Multidisciplinary specialists include obstetricians, pediatricians, pediatric surgeons, and experts of ultrasound department and genetic counseling. Consultation was done if the fetal ultrasound examinations showed abnormality. Follow-up, assistance, and guidance for the fetus were achieved by phone calls.Results: Ultrasound screening showed that the incidences of central nervous system anomaly and genitourinary anomaly were 25.80% (275/1,066) and 22.05% (235/1,066), respectively. The detection rates of fetal anomalies were 5.07% (54/1,066), 36.12% (385/1,066), and 58.82% (627/1,066) in pregnant women with gestational age of 28 weeks, respectively. In addition, the fetal cerebral ventriculomegaly accounted for 40.73% of central nervous system malformation, while 71.43% cases with fetal cerebral ventriculomegaly were alleviated during the follow-up period. The proportion of hydronephrosis in genitourinary anomalies was 50.64%, and the remission rate of hydronephrosis was 67.23% during the follow-up period.Conclusion: The establishment of a multidisciplinary consultation system is necessary for the diagnosis of complicated fetal anomalies. The central nervous system anomaly and genitourinary anomaly are the most common fetal anomalies. In addition, the remission rates of cerebral ventriculomegaly and fetal hydronephrosis are high during the follow-up period. Keywords: multidisciplinary consultation, fetal anomalies, pregnancy outcome

Maochen Zhang,* Tianyu Zhang,* Liwen Hong, Qiangqiang Wu, Yun Lin, Mengfan Xie, Rong Fan, Zhengting Wang, Jie Zhou, Jie Zhong Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Computed tomography enterography (CTE) and double-balloon enteroscopy (DBE) are widely used in diagnosis of small bowel diseases. Both of these examinations bring discomfort to patients. The aim of this study was to compare patients’ tolerance and preference between CTE and DBE. Methods: From August 1, 2014 to December 31, 2016, patients with suspected or known small bowel diseases who underwent both CTE and DBE were prospectively enrolled in our study. They were asked to fill out a questionnaire evaluating discomfort of the procedure after each examination. Results: One hundred and seven patients completed our study. Abdominal distension, painfulness, tenesmus, general discomfort, prolonged duration, difficulty in completing the test, and discomfort after the examination were significantly lower with CTE than with DBE (P

Liwei Cui,1 Xiuli Ji,2 Mengshuang Xie,1 Shuang Dou,1 Wei Wang,1 Wei Xiao1 1Department of Respiratory Disease, Qilu Hospital, Shandong University, 2Department of Pulmonary Disease, Jinan Traditional Chinese Medicine Hospital, Jinan, People’s Republic of China Background: Since forced expiratory volume in 1 second (FEV1) shows a weak correlation with patients’ symptoms in COPD, some volume parameters may better reflect the change in dyspnea symptoms after treatment. In this article, we investigated the role of inspiratory capacity (IC) on dyspnea evaluation among COPD patients with or without emphysematous lesions.Methods: In this prospective study, 124 patients with stable COPD were recruited. During the baseline visit, patients performed pulmonary function tests and dyspnea evaluation using the modified Medical Research Council (mMRC) scale. Partial patients underwent quantitative computerized tomography scans under physicians’ recommendations, and emphysematous changes were assessed using the emphysema index (EI; low attenuation area [LAA]% −950). These subjects were then divided into the emphysema-predominant group (LAA% −950≥9.9%) and the non-emphysema-predominant group (LAA% −9501 were more likely to exhibit a marked increase in IC (≥300 mL) than those with absolute ∆mMRC ≤1 (74.36% versus 35.29%; odds ratio [OR], 5.317; P0.05).Conclusion: IC could serve as an effective complement to FEV1 in COPD patients undergoing dyspnea evaluation after treatment. For COPD patients with predominant emphysematous lesions, an increase in IC is particularly more suitable for explaining dyspnea relief than FEV1. Keywords: IC, COPD, mMRC score, quantitative computerized tomography, emphysema index

Bai Y, Gao XS, Qin SB, et al. Onco Targets Ther. 2018;11:2571– 2579.Recently the authors found two main errata in the text that need to be corrected.On page 2571, Abstract, Results section, “Two-year overall survival was 55.6%. Two-year local control rate was 85.7%” should read “One-year overall survival was 64.9%. One-year local control rate was 100%”.On page 2574, Response and survival outcomes section, 3rd and 4th sentences, “One-year over-all survival was 88.2%. Two-year overall survival was 55.6% (Figure 2A).” should read “One-year over-all survival was 64.9%. Two-year overall survival was 44.5% (Figure 2A).”On page 2574, Response and survival outcomes section, 10th sentence, “Two-year local control rate was 85.7%. (Figure 2B).” should read “Two-year local control rate was 57.1%. (Figure 2B).”On page 2575, Figure 2 legend, “(A) Kaplan–Meier plots of overall survival for all patients. One-year overall survival was 88.2%. Two-year overall survival was 55.6%. (B) Kaplan–Meier plots of local control for all patients. One-year local control rate was 100%. Two-year local control rate was 85.7%. (C) Patients with B90≥ 65% (n=19) achieved a higher local control rate than those with B90< 65% (n=11) (median survival=15.2 months vs 3.5 months, CI=6.8– 23.6 and 2.2– 4.9 months, respectively; P=0.010). (D) Patients with B80≥ 90% (n=20) achieved a higher local control rate than those with B80< 90% (n=10) (median survival=14.9 months vs 3.5 months, CI=3.4– 26.3 and 1.8– 5.2 months, respectively; P=0.045).” should read “(A) Kaplan–Meier plots of overallsurvival for all patients. One-year overall survival was 64.9%. Two-year overall survival was 44.5%. (B) Kaplan–Meier plots of local control for all patients. One-year local control rate was 100%. Two-year local control rate was 57.1%. (C) Patients with B90≥ 65% (n=19) achieved a higher local control rate than those with B90< 65% (n=11) (median survival=15.2 months vs 3.5 months, CI=6.8– 23.6 and 2.2– 4.9 months, respectively; P=0.010). (D) Patients with B80≥ 90% (n=20) achieved a higher local control rate than those with B80< 90% (n=10) (median survival=14.9 months vs 3.5 months, CI=3.4– 26.3 and 1.8– 5.2 months, respectively; P=0.045).”On page 2576, Discussion section, last sentence “Therefore, daily SABR was applied in our article and the 2-year local control rate was as high as 85.7%, even stage IV NSCLC were 40%.” should read “Therefore, daily SABR was applied in our article and the 1-year local control rate was as high as 100%, even stage IV NSCLC were 40%.”Despite the correction in the text list as above, the Figures of Kaplan–Meier plots of overall survival and local control are correct, and the error doesn`t the change the overall findings reported in the paper. We can still conclude that “This retrospective study suggests that P-SABR is feasible and well tolerated in bulky NSCLC. Local control rate is encouraging, especially for the B90≥ 65% group, which may due to the ability of P-SABR to optimize BED with equivalent toxicity”. The authors apologize for this error.Read the original article

Wei Wang, Mengshuang Xie, Shuang Dou, Liwei Cui, Wei Xiao Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, People’s Republic of China Background: In a previous study, we demonstrated that asthma patients with signs of emphysema on quantitative computed tomography (CT) fulfill the diagnosis of asthma-COPD overlap syndrome (ACOS). However, quantitative CT measurements of emphysema are not routinely available for patients with chronic airway disease, which limits their application. Spirometry was a widely used examination tool in clinical settings and shows emphysema as a sharp angle in the maximum expiratory flow volume (MEFV) curve, called the “angle of collapse (AC)”. The aim of this study was to investigate the value of the AC in the diagnosis of emphysema and ACOS. Methods: This study included 716 participants: 151 asthma patients, 173 COPD patients, and 392 normal control subjects. All the participants underwent pulmonary function tests. COPD and asthma patients also underwent quantitative CT measurements of emphysema. The AC was measured using computer models based on Matlab software. The value of the AC in the diagnosis of emphysema and ACOS was evaluated using receiver-operating characteristic (ROC) curve analysis. Results: The AC of COPD patients was significantly lower than that of asthma patients and control subjects. The AC was significantly negatively correlated with emphysema index (EI; r=-0.666, P

Xiaobin Gu,1 Xian-Shu Gao,1 Wei Xiong,2 Wei Guo,3 Linjun Han,3 Yun Bai,1 Chuan Peng,1 Ming Cui,1 Mu Xie1 1Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, People’s Republic of China; 2Department of Oncology, Tangshan People’s Hospital, Hebei, People’s Republic of China; 3Graduate School of Medicine, Hebei North University, Zhangjiakou, Hebei, People’s Republic of China Purpose: Accumulating studies have investigated the prognostic and clinical significance of programmed death ligand-1 (PD-L1) expression in patients with hepatocellular carcinoma (HCC); however, the results were conflicting and inconclusive. We conducted a meta-analysis to combine controversial data to precisely evaluate this issue.Methods: Relevant studies were thoroughly searched on PubMed, Web of Science, and Embase until April 2016. Eligible studies were evaluated by selection criteria. Hazard ratio (HR) with 95% confidence interval (CI) was used to estimate the prognostic role of PD-L1 for overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS). Odds ratio (OR) with 95% CI were selected to assess the relationship between PD-L1 and clinicopathological features of HCC patients. Publication bias was tested using Begg’s funnel plot.Results: A total of seven studies published from 2009 to 2016 were included for meta-analysis. The data showed that high PD-L1 expression was correlated to shorter OS (HR =2.09, 95% CI: 1.66–2.64, P

Yingcai Yan,1,* Minjie Xie,1,* Linshi Zhang,1 Xiaohu Zhou,1 Haiyang Xie,1 Lin Zhou,1 Shusen Zheng,2,3 Weilin Wang2,31Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, 2Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 3Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The first Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Hepatocellular carcinoma (HCC) is rapidly becoming one of the most prevalent cancers worldwide and is a prominent source of mortality. Ras-related associated with diabetes (RRAD), one of the first members of the 35–39 kDa class of novel Ras-related GTPases, is linked to several types of cancer, although its function in HCC remains unclear. In this study, we observed that RRAD was downregulated in HCC compared with adjacent normal tissues. This change was associated with a poor prognosis. Furthermore, knockdown of RRAD in SK-Hep-1 cells facilitated cell proliferation, accelerated the G1/S transition during the cell cycle, induced cell migration, and reduced apoptosis. In contrast, overexpression of RRAD in Huh7 cells had the opposite effects. Moreover, we demonstrated that RRAD induced cell proliferation through regulation of the cell cycle by downregulating cyclins and cyclin-dependent kinases. RRAD induced tumor cell apoptosis through the mitochondrial apoptosis pathway. In addition, we confirmed that knockdown of RRAD promoted aerobic glycolysis by upregulating glucose transporter 1, whereas overexpression of RRAD inhibited aerobic glycolysis. In conclusion, RRAD plays a pivotal role as a potential tumor suppressor in HCC. An improved understanding of the roles of RRAD in tumor metabolism may provide insights into its potential as a novel molecular target in HCC therapy. Keywords: hepatocellular carcinoma, Ras-related associated with diabetes, aerobic glycolysis, tumorigenicity, glucose transporter 1

Mengshuang Xie, Wei Wang, Shuang Dou, Liwei Cui, Wei Xiao Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, People’s Republic of China Background: The diagnostic criteria of asthma–COPD overlap syndrome (ACOS) are controversial. Emphysema is characteristic of COPD and usually does not exist in typical asthma patients. Emphysema in patients with asthma suggests the coexistence of COPD. Quantitative computed tomography (CT) allows repeated evaluation of emphysema noninvasively. We investigated the value of quantitative CT measurements of emphysema in the diagnosis of ACOS.Methods: This study included 404 participants; 151 asthma patients, 125 COPD patients, and 128 normal control subjects. All the participants underwent pulmonary function tests and a high-resolution CT scan. Emphysema measurements were taken with an Airway Inspector software. The asthma patients were divided into high and low emphysema index (EI) groups based on the percentage of low attenuation areas less than −950 Hounsfield units. The characteristics of asthma patients with high EI were compared with those having low EI or COPD.Results: The normal value of percentage of low attenuation areas less than −950 Hounsfield units in Chinese aged >40 years was 2.79%±2.37%. COPD patients indicated more severe emphysema and more upper-zone-predominant distribution of emphysema than asthma patients or controls. Thirty-two (21.2%) of the 151 asthma patients had high EI. Compared with asthma patients with low EI, those with high EI were significantly older, more likely to be male, had more pack-years of smoking, had more upper-zone-predominant distribution of emphysema, and had greater airflow limitation. There were no significant differences in sex ratios, pack-years of smoking, airflow limitation, or emphysema distribution between asthma patients with high EI and COPD patients. A greater number of acute exacerbations were seen in asthma patients with high EI compared with those with low EI or COPD.Conclusion: Asthma patients with high EI fulfill the features of ACOS, as described in the Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease guidelines. Quantitative CT measurements of emphysema may help in diagnosing ACOS. Keywords: COPD, asthma, quantitative CT, emphysema, overlap syndrome

Zheng Zhao,1,3 Maobin Xie,2 Yi Li,2 Aizheng Chen,4 Gang Li,5 Jing Zhang,2 Huawen Hu,2 Xinyu Wang,1,3 Shipu Li1,31State Key Lab of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, People’s Republic of China; 2Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hong Kong; 3Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan, People’s Republic of China; 4College of Chemical Engineering, Huaqiao University, Xiamen, People’s Republic of China; 5National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, People’s Republic of ChinaAbstract: In order to enhance the bioavailability of poorly water-soluble curcumin, solution-enhanced dispersion by supercritical carbon dioxide (CO2) (SEDS) was employed to prepare curcumin nanoparticles for the first time. A 24 full factorial experiment was designed to determine optimal processing parameters and their influence on the size of the curcumin nanoparticles. Particle size was demonstrated to increase with increased temperature or flow rate of the solution, or with decreased precipitation pressure, under processing conditions with different parameters considered. The single effect of the concentration of the solution on particle size was not significant. Curcumin nanoparticles with a spherical shape and the smallest mean particle size of 325 nm were obtained when the following optimal processing conditions were adopted: P =20 MPa, T =35°C, flow rate of solution =0.5 mL.min-1, concentration of solution =0.5%. Fourier transform infrared (FTIR) spectroscopy measurement revealed that the chemical composition of curcumin basically remained unchanged. Nevertheless, X-ray powder diffraction (XRPD) and thermal analysis indicated that the crystalline state of the original curcumin decreased after the SEDS process. The solubility and dissolution rate of the curcumin nanoparticles were found to be higher than that of the original curcumin powder (approximately 1.4 µg/mL vs 0.2 µg/mL in 180 minutes). This study revealed that supercritical CO2 technologies had a great potential in fabricating nanoparticles and improving the bioavailability of poorly water-soluble drugs.Keywords: curcumin, crystalline sate, dissolution rate, solubility