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Qianyu Bai,1,* Yichi Zhang,1,* Runqiu Cai,1 Haiyan Wu,1 Huiqun Fu,2 Xuemei Zhou,2 Jie Chai,3 Xuepeng Teng,3 Tianlong Liu1 1National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agriculture University, Beijing, People’s Republic of China; 2 101 Institute of the Ministry of Civil Affairs, Beijing, People’s Republic of China; 3Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuemei Zhou, 101 Institute of the Ministry of Civil Affairs, South Fourth Ring West Road No.188, Beijing, 100070, Email zxmcaur@126.com; Tianlong Liu, College of Veterinary Medicine, China Agriculture University, Yuanmingyuan West Road No. 2, Beijing, 100193, Email liutianlong@cau.edu.cnBackground: In the past decades, antimicrobial resistance (AMR) has been a major threat to global public health. Long-term, chronic otitis media is becoming more challenging to treat, thus the novel antibiotic alternative agents are much needed.Methods: ZnO@TiO2@AMP (ATZ NPs) were synthesized through a solvothermal method and subjected to comprehensive characterization. The in vitro and in vivo antibacterial effect and biocompatibility of ATZ NPs were evaluated. For the antibacterial mechanism exploration, we utilized the Electron Paramagnetic Resonance (EPR) Spectrometer to detect and analyze the hydroxyl radicals produced by ATZ NPs.Results: ATZ NPs exhibited a spherical structure of 99.85 nm, the drug-loading rate for ZnO was 20.73%, and AMP within ATZ NPs was 41.86%. Notably, the Minimum Inhibitory Concentration (MIC) value of ATZ NPs against Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae (S. pneumoniae) were 10 μg/mL, and Minimum Bactericidal Concentration (MBC) value of ATZ NPs against S. aureus, and S. pneumoniae were 50 μg/mL. In comparison to the model group, the treatment of otitis media with ATZ NPs significantly reduces inflammatory exudation in the middle ear cavity, with no observable damage to the tympanic membrane. Both in vivo and in vitro toxicity tests indicating the good biocompatibility of ATZ NPs. Moreover, EPR spectroscopy results highlighted the superior ability of ATZ NPs to generate hydroxyl radicals (·OH) compared to ZnO NPs.Conclusion: ATZ NPs exhibited remarkable antibacterial properties both in vivo and in vitro. This innovative application of advanced ATZ NPs, bringing great promise for the treatment of otitis media.Keywords: nanoparticles, otitis media, zinc oxide, mesoporous titanium dioxide, antimicrobial peptide, antimicrobial, hydroxyl radical

Jiahui Ma,1– 4,&ast; Xue Yang,5,&ast; Zhiming Liu,1– 4 Hao Fu,1– 4 Sizhou Fan,1– 4 Kai Wang,1– 4 Yan Li,1– 4 Lvzhen Huang,1– 4 Mingwei Zhao1– 4 1Department of Ophthalmology, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Eye Diseases and Optometry Institute, Peking University People’s Hospital, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, People’s Republic of China; 4College of Optometry, Peking University Health Science Center, Beijing, People’s Republic of China; 5Department of Ophthalmology, Peking University International Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Wang; Yan Li, Email wang_kai@bjmu.edu.cn; 13801153660@163.comPurpose: To investigate the impact of vergence dysfunction on myopia progression in children with Defocus incorporated multiple segments (DIMS) spectacle lenses.Patients and Methods: We retrospectively enrolled children prescribed DIMS spectacle lenses to slow myopic progression. Baseline vergence dysfunction was determined according to phoria at distance and near. Axial length (AL) measurement and cycloplegic subjective refraction were performed before fitting the lenses and at six-month and one-year follow-ups. The six-month and one-year AL and spherical equivalent (SE) change from baseline were calculated and compared in subgroups stratified with the type of vergence dysfunction.Results: Two hundred and ninety-two myopic children were included. Significant AL elongation and SE progression were observed at six months and one year (P < 0.05 for all comparisons). Multiple regression demonstrated that AL elongation at six months (P < 0.001) and one year (P < 0.001) was negatively correlated with age, and SE progression at six months was associated with age (P = 0.002). The AL elongation at six months in children with convergence excess was significantly greater than in normal myopic subjects (P = 0.011) and subjects with convergence insufficiency (P = 0.008), divergence excess (P = 0.007), divergence insufficiency (P = 0.024) and basic esophoria (P = 0.048) at six months.Conclusion: The present research demonstrated that vergence dysfunction influences myopia progression for myopic children with DIMS, and the children with convergence excess suffer from the greatest myopia progression among different types of vergence dysfunction.Keywords: myopia, vergence dysfunction, defocus spectacles, axial length

Fei-Fei Wang,1,&ast; Nan Li,1,&ast; Jing-Jing Wang,1 Nijiti Muyesai,1 Haiyan Fu2 1The People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Emergency Care Center, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China; 2Department of Gastroenterology, Urumqi Friendship Hospital, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiyan Fu, Department of Gastroenterology, Urumqi Friendship Hospital, 558, Shengli Road, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China, Tel/Fax +8618599026892, Email fuhaiyanfhu@126.com Nijiti Muyesai, The People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Emergency Care Center, the People’s Republic of China, No. 91, Tianchi Road, Tianshan District, Urumqi, 830000, People’s Republic of China, Tel/Fax +86 13899955322, Email nijiati0a@126.comObjective: The aim of this study is to examine the distribution and features of gastroscopy in northern Xinjiang, a province in China.Methods: We included a group of 895 patients diagnosed with digestive diseases at Urumqi Friendship Hospital and analyzed their gastroscopic results and baseline data.Results: Among patients aged 12 to 86 years in the specified region, females exhibited a heightened susceptibility to esophageal-gastrointestinal and intestinal disorders compared to males. The mean age for chronic gastritis onset was determined to be 54.79 years. In the context of esophageal-gastric-intestinal disorders, the distribution across various ethnic groups manifested as follows: the Han, Uygur, Hui, and Kazakh populations comprised 53.97%, 23.91%, 7.15%, and 3.46%, respectively. Through principal component-based dimension reduction analysis, we identified chronic non-atrophic gastritis with erosive gastritis, duodenal bulb inflammation, and chronic non-atrophic gastritis (predominantly in the gastric antrum) as pivotal factors contributing to differences in hiatal hernia. Multiple linear regression models were established for different ethnic groups, duodenal bulb inflammation, and hiatal hernia by age. The results revealed a heightened risk of duodenal bulb inflammation (P < 0.01) in Han, Kazakh, Hui, Mongolian, and Uygur women, while the risk of hiatal hernia exhibited a positive correlation with age (P = 0.001).Conclusion: Among patients undergoing gastrointestinal examinations in northern Xinjiang, the most prevalent pathological condition was identified as chronic gastritis. Notably, within this subgroup, the prevalence of duodenal bulb inflammation was found to be greater in women than in men. The ethnic composition within this context encompassed patients from the Han, Kazakh, Hui, and Mongolian ethnic groups. Furthermore, a positive correlation was identified between the incidence of esophageal hiatal hernia and age.Keywords: age, ethnicity, esophageal-gastric-intestinal disease, gastroscopy, gender, northern Xinjiang

Guangyou Duan,1,&ast; Haibo Deng,2,&ast; Hong Fu,3 Lingzhi Wang,4 Hanyu Yang5 1Department of Anesthesiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing City, 400000, People’s Republic of China; 2Department of Anesthesiology, Huizhou Third People’s Hospital, Guangzhou Medical University, Guangzhou, 516002, People’s Republic of China; 3Department of Anesthesiology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing, 400014, People’s Republic of China; 4Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 051026, People’s Republic of China; 5Department of Anesthesiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangyou Duan, Department of Anesthesiology, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Chongqing City, 400000, People’s Republic of China, Email duangy@hospital.cqmu.edu.cnPurpose: This study aimed to compare the electrolyte balance efficacies of two Gelatin-Balanced Crystalloid in clinical applications.Methods: A multi-center, prospective, randomized, single-blind, parallel controlled study was conducted among non-cardiac surgery patients, with clinical registration number ChiCTR2200062999. They were randomized into Succinylated Gelatin, Multiple Electrolytes and Sodium Acetate Injection (SG-MESAI) group (experimental group) and Succinylated Gelatin Injection (SGI) infusion group (control group). The same anesthetic induction technique, anesthetic method, and calculation method for the volume of colloid infusion were used in the two groups. Between-group differences in the changes in base excess (BE), Chloride ion (Cl−), bicarbonate radical (HCO3⁻) and other parameters were recorded at 15 min, 30 min after the infusion relative to the baseline. Hemodynamic indicators were determined at 30 min after colloid infusion. Safety follow-up was conducted by administering the following tests within 48 h± 12 h after surgery.Results: A total of 225 subjects (full analysis set) were finally enrolled, with 110 subjects in the experimental group and 115 subjects in the control group. The baseline data were comparable between the two groups. At 15 min after infusion, the mean changes in BE, Cl− and HCO3⁻ concentration in the experimental group were smaller than those of the control group (P< 0.001). At 30 min after surgery, the mean changes in BE, Cl−, HCO3⁻concentration and pH value were smaller in the experimental group than in the control group (P< 0.05). The incidences of adverse events and adverse reactions in the experimental group was less than the control group, but the difference was not statistically significant (P≥ 0.05). Besides, no serious adverse events or adverse reactions were reported in any subjects.Conclusion: Succinylated Gelatin, Multiple Electrolytes and Sodium Acetate Injection maintained the balance of BE, Cl−, HCO3⁻ and pH value in a better way than Succinylated Gelatin Injection in non-cardiac surgery patients under general anesthesia.Keywords: anesthesia, non-cardiac surgery, fluid therapy, drug clinical trial, succinylated gelatin, multiple electrolytes and sodium acetate injection

Mahipal S Sachdev,1 Rohit Shetty,2 Pooja Khamar,2 Raghav Malik,1 Brian L Schwam,3 Ying Wang,3 Hong Fu,3 Andrew P Voorhees,3 Michal Laron3 1Centre for Sight, New Delhi, India; 2Narayana Nethralaya Eye Hospital, Bangalore, India; 3Johnson and Johnson Surgical Vision, Inc, Milpitas, CA, USACorrespondence: Michal Laron, Johnson and Johnson Surgical Vision, Inc, 510 Cottonwood Drive, Milpitas, CA, 95035, USA, Tel +1 408 273 5802, Email mlaron@its.jnj.comPurpose: To evaluate visual outcomes following the Smooth Incision Lenticular Keratomileusis (SILKTM) procedure for correction of myopic refractive errors with and without astigmatism, using the ELITATM Femtosecond Laser System.Patients and Methods: A prospective, multicenter, single-arm, open-label clinical study was conducted. Eighty-five myopic subjects (n = 170 eyes), aged 18 years or older, with manifest refractive spherical equivalent (MRSE) up to − 12.00 D and astigmatism up to − 6.00 D, were treated binocularly using the ELITA femtosecond laser and followed up for 6 months. Intended correction was emmetropia for all eyes. The primary outcome measures included post-operative uncorrected and corrected distance visual acuity (UDVA and CDVA). Secondary outcome measures included surgeon’s rating for ease of lenticule extraction, predictability, safety, and stability.Results: A total of 170 eyes of 85 patients underwent SILK. Preoperative mean MRSE was − 4.14 D ± 1.32 D (range − 1.38 D to − 8.88 D) and the mean cylinder was − 0.77 D ± 0.62 D. Intraoperative surgeon ease of lenticule dissection was rated as grade 0 or 1 in 85.3% of eyes (no/only mild dissection needed). UDVA at 1 day, 1 week, 1 month, and 6 months was 20/20 or better in 65.9%, 85.4%, 91.5%, and 96% of eyes, respectively. No eyes lost any lines of CDVA at 6 months compared to the preoperative. The postoperative MRSE was stable over time, ranging from − 0.34 D ± 0.24 D at 1 month to − 0.33 D ± 0.23 D at 6 months. MRSE predictability (± 0.50 D) was 93.5% (129/138) at 3 months and 91.1% (113/124) at 6 months. No serious adverse events were noted.Conclusion: The SILK procedure with the ELITA Femtosecond Laser System is safe and effective for the treatment of myopic refractive errors with and without astigmatism. Fast visual recovery was demonstrated, with stability achieved by 3 months.Keywords: smooth incision lenticular keratomileusis, SILK, laser-assisted lenticule extraction, corneal refractive surgery, myopia, keratorefractive lenticule extraction

Shiyu Lin,&ast; Xiaojuan Li,&ast; Yuning Zhang,&ast; Wei Zhang, Gang Shu, Haohuan Li, Funeng Xu, Juchun Lin, Hualin Fu Innovative Engineering Research Center of Veterinary Pharmaceutics, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hualin Fu, Tel +86 28 82691162, Fax +86 28 82652669, Email fuhl2005@sohu.comIntroduction: Biofilm is highly resistant to antibiotics due to its heterogeneity and is implicated in over 80% of chronic infections; these refractory and relapse-prone infections pose a huge medical burden.Methods: In this study, rhamnolipid (RHL), a biosurfactant with antibiofilm activity, was loaded with the antibiotic azithromycin (AZI) to construct a stable nanomicelle (AZI@RHL) that promotes Staphylococcus aureus (S. aureus) biofilm disruption.Results: AZI@RHL micelles made a destruction in biofilms. The biofilm biomasses were reduced significantly by 48.2% (P< 0.05), and the main components polysaccharides and proteins were reduced by 47.5% and 36.8%, respectively. These decreases were about 3.1 (15.9%), 7.3 (6.5%), and 1.9 (19.5%) times higher compared with those reported for free AZI. The disruption of biofilm structure was observed under a confocal microscope with fluorescent labeling, and 48.2% of the cells in the biofilm were killed. By contrast, the clearance rates of cells were only 20% and 17% when treated alone with blank micelles or free AZI. Biofilm formation was inhibited up to 92% in the AZI@RHL group due to effects on cell auto-aggregation and eDNA release. The rates for the other groups were significantly lower, with only 27.7% for the RHL group and 12% for the AZI group (P< 0.05). The low cell survival and great formation inhibition could reduce biofilm recolonization and re-formation.Conclusion: The antibiofilm efficacy of rhamnolipid was improved through micellar nanoparticle effects when loading azithromycin. AZI@RHL provides a one-step solution that covers biofilm disruption, bacteria inactivation, recolonization avoidance, and biofilm re-formation inhibition. Keywords: Staphylococcus aureus, antibiofilm, rhamnolipid, biosurfactant, nanomicelle

Bin Wang,1,&ast; Xiao Zhong,2,&ast; Haojie Fu,3 Haobo Zhang,4 Ruilin Hu,1 Jufen Li,1 Changxia Chen,1 Kexin Wang5 1Southwest University of Science and Technology, Mianyang, Sichuan, People’s Republic of China; 2School of Psychology, Beijing University of Sports, Beijing, People’s Republic of China; 3Shanghai Research Institute for Intelligent Autonomous Systems, Tongji University, Shanghai, People’s Republic of China; 4College of Education Science, Guangxi University for Nationalities, Nanning, Guangxi, People’s Republic of China; 5College of Media and International Culture, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changxia Chen, Southwest University of Science and Technology, No. 59, Middle Section of Qinglong Avenue, Fucheng District, Fucheng District, Mianyang City, Sichuan Province, People’s Republic of China, Email Chenchangxia@swust.edu.cn Kexin Wang, College of Media and International Culture, Zhejiang University, No. 866 Yuhangtang Road, Xihu District, Hangzhou, Zhejiang, People’s Republic of China, Email wangkexin0809@zju.edu.cnPurpose: This study explores the status of pandemic fatigue, predictors, and their mechanisms of action based on a stress-response framework and a parallel model of future-oriented response.Patients and methods: Study 1 investigated 8426 Chinese adult residents’ understanding of and willingness to cooperate with the pandemic prevention and control policies and Study 2 surveyed 1635 Chinese residents on their activeness of pandemic prevention and control (APPC), pandemic risk perception, perceived stress, and future-oriented coping.Results: Study 1 found that public understanding of and willingness to cooperate with prevention policies were significantly lower in 2022 than in 2020 and 2021. Study 2 found that risk perception negatively predicted the APPC; perceived stress and preventive coping significantly mediated the relationship between risk perception and APPC; but perceived stress and proactive coping did not significantly mediate the relationship between risk perception and APPC.Conclusion: This revealed an increase in public fatigue in the third year of the pandemic. Pandemic fatigue can be predicted by pandemic risk perception, but the direct pathway of action is not significant and requires the mediation of perceived stress and preventive coping.Keywords: pandemic fatigue, risk perception, stress, proactive coping, preventive coping

Jiafei Cao,1,2,&ast; Jian Zhu,3,&ast; Yining Xiang,4 Pailan Peng,1,2 Qi Liu,1,2 Hua Fu,1,2 Yan Huang1,2 1Department of Gastroenterology, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 2Department of Gastroenterology, The Guizhou Hospital of the First Affiliated Hospital, Sun Yat-sen University, Guiyang, Guizhou Province, People’s Republic of China; 3Department of Gastroenterology, the Second People’s Hospital of Guiyang, the Affiliated Jinyang Hospital of Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 4Department of Pathology, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Huang, Department of Gastroenterology, the Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Guiyang, Guizhou Province, 550004, People’s Republic of China, Tel +8618108509475, Email 36409351@qq.comAbstract: Gastric syphilis is a rare manifestation of syphilis that occurs in about 1% of cases and is often overlooked due to its non-specific signs and symptoms. We report a case of a 28-year-old Chinese woman who presented with epigastric pain, nausea, vomiting, hematemesis, alopecia, and weight loss. She tested positive for Helicobacter pylori (H. pylori), with rapid plasma reagin (RPR) and Treponema pallidum particle assay (TPPA) tests showing titers of 1:128 and 1:320, respectively. CT imaging revealed thickening of the gastric wall, exudation around the antrum, and multiple lymphadenopathies. Gastroscopy showed multiple irregular ulcers, which resembled lymphoma. However, biopsy results did not support the presence of lymphoma, but immunohistochemistry showed an abundance of syphilis spirochetes in the mucosal lamina propria and glands. This led to a diagnosis of gastric syphilis. The patient received standard treatment for syphilis as well as anti-H. pylori therapy, and her symptoms and endoscopic findings gradually improved and eventually resolved. We hope that this case report can provide valuable insights into the diagnosis and management of gastric syphilis, which can mimic other diseases like lymphoma.Keywords: gastric syphilis, Treponema pallidum, lymphoma, endoscopy, case report

Hao Fu,1 Ping Li,2 Qianchao Xing,3 Hui Jiang,1 Hangshuo Sui4 1Nutrition Department, Affiliated Hospital of Chengde Medical University, Chengde, Heibei, People’s Republic of China; 2Gastroenterology, Affiliated Hospital of Chengde Medical University, Chengde, Heibei People’s Republic of China; 3Radiology Department, Affiliated Hospital of Chengde Medical University, Chengde, Heibei, People’s Republic of China; 4Nutrition Department, Chengde Central Hospital, Chengde, Heibei, People’s Republic of ChinaCorrespondence: Hangshuo Sui, Nutrition Department, Chengde Central Hospital, No. 11, Guangren Street, Chengde, Heibei, 067000, People’s Republic of China, Tel +86 0314 2028780, Email xyjw05@cdmc.edu.cnObjective: The Global Leadership Initiative on Malnutrition (GLIM) has proposed criteria for the diagnosis of malnutrition, one of which is reduced muscle mass. Computed tomography (CT) assessment of psoas muscle area (PMA) has been used to estimate muscle mass in patients, including those with acute pancreatitis (AP). The present study aimed to define the cutoff value of PMA indicative of reduced muscle mass in patients with AP and to assess the impact of reduced muscle mass on the severity and early complications of AP.Methods: Clinical data of 269 patients with AP were analyzed retrospectively. The severity of AP was determined according to the revised Atlanta classification. PMA was evaluated by CT and used to calculate the psoas muscle index (PMI). Cutoff values for reduced muscle mass were calculated and validated. Logistic regression analysis was performed to assess the relationship between PMA and the severity of AP.Results: PMA was a better indicator of reduced muscle mass than PMI, with cutoff values of 11.50 cm2 for men and 8.22 cm2 for women. Rates of local complications, splenic vein thrombosis, and organ failure were significantly higher in AP patients with low than high PMA (all p < 0.05). PMA showed good ability to predict splenic vein thrombosis in women, with an area under the receiver operating characteristic curve of 0.848 (95% confidence interval 0.768– 0.909, sensitivity 100%, specificity 83.64%). Multivariate logistic regression revealed that PMA was an independent risk factor for moderately severe plus severe AP (odds ratio 5.639, p = 0.001) and severe AP (odds ratio 3.995, p = 0.038).Conclusion: PMA is a good predictor of the severity and complications of AP. The PMA cutoff value is a good indicator of reduced muscle mass.Keywords: acute pancreatitis, psoas muscles, sarcopenia, malnutrition, cutoff value

Jiayu Shao, Hangdong Dai, Liwei Xu, Shuilong Zhu, Jufang Zhu, Hangyu Fu, Minxia Ge, Xianhong He Department of Clinical Laboratory, the Third People’s Hospital of Xiaoshan, Hangzhou, People’s Republic of ChinaCorrespondence: Xianhong He; Minxia Ge, Department of Clinical Laboratory, the Third People’s Hospital of Xiaoshan, 76 Zhishan North Road, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 15088760041 ; +86 18057155059, Email miriam1023@163.com; cqmxszj@163.comPurpose: The isolation rate of extended spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing, posing a challenge to clinical anti-infective therapy. This study aims to provide new insight into the genomic characteristics and antimicrobial resistance mechanisms of extended spectrum β-lactamase producing E. coli isolates recovered from a district hospital in China.Methods: A total of 36 ESBL-producing E. coli isolates were collected from body fluid samples from a Chinese district hospital. All isolates were subjected to whole genome sequencing to identify their antimicrobial resistance genes, virulence genes, serotypes, sequence types, and phylogenetic relationships by BacWGSTdb 2.0 webserver.Results: Among these isolates, all were resistant to cefazolin, cefotaxime, ceftriaxone, ampicillin, 24 (66.7%) were resistant to aztreonam, 16 (44.4%) were resistant to cefepime, and 15 were resistant (41.7%) to ceftazidime. The blaCTX-M gene was detected in all ESBL-producing E. coli isolates. Two isolates carrying two different types of blaCTX-M genes simultaneously. The carbapenem resistance gene blaKPC-2 was detected in one (2.8%) isolate. A total of 17 sequence types (STs) were found, with ST131 accounting for the majority (n =13; 36.1%). The most common serotype was O16:H5 associated with seven ST131 strains, followed by O25:H4/ST131 (n = 5) and O75:H5/ST1193 (n = 5). Evaluation of clonal relatedness revealed that all blaCTX-M gene-carrying E. coli had a difference of SNPs range from 7 to 79,198, which could be divided into four clusters. Only 7 SNPs could be found between EC266 and EC622, indicating that they are variants of the same clonal lineage.Conclusion: This study investigated the genomic characteristics of ESBL-producing E. coli isolates recovered from a district hospital in China. Continuous surveillance of ESBL-producing E. coli infections is imperative to create efficient strategies for controlling the transmission of these multi-drug resistant bacteria in clinical and community settings.Keywords: Escherichia coli, ESBLs, antimicrobial resistance, whole genome sequencing

Xianhong He, Liwei Xu, Hangdong Dai, Minxia Ge, Jufang Zhu, Hangyu Fu, Shuilong Zhu, Jiayu Shao Department of Clinical Laboratory, The Third People’s Hospital of Xiaoshan, Hangzhou, People’s Republic of ChinaCorrespondence: Jiayu Shao; Shuilong Zhu, Department of Clinical Laboratory, The Third People’s Hospital of Xiaoshan, 76 Zhishan North Road, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 18505812918 ; +86 18057155360, Email 583744598@qq.com; zslong1976@163.comBackground: The transmission of carbapenem-resistant Enterobacterales pose a significant threat to global public health, which weakens the effectiveness of most antimicrobial agents. The aim of this study is to present the genomic characteristics of a multidrug-resistant Escherichia coli, which contains both blaKPC-2 and blaCTX-M-15 genes, discovered from a respiratory infection in China.Methods: The antimicrobial susceptibility of E. coli isolate 488 was measured by using the broth microdilution method. The Oxford Nanopore MinION and Illumina NovaSeq 6000 platforms were applied to determine the whole-genome sequence of this isolate. De novo assembly of short Illumina reads and long MinION reads were performed by Unicycler. In silico multilocus sequence typing (MLST), antimicrobial resistance genes and plasmid replicon types were determined using the genome sequencing data. Additionally, a pairwise core genome single nucleotide polymorphism (cgSNP) comparison between E. coli 488 and all ST648 E. coli strains retrieved from NCBI GenBank database were conducted using the BacWGSTdb 2.0 server.Results: E. coli 488 was resistant to aztreonam, levofloxacin, cefepime, fosfomycin, amikacin, imipenem, cefotaxime, and meropenem. The complete genome sequence of E. coli 488 (belong to ST648) is made up of eleven contigs totaling 5,573,915 bp, including one chromosome and ten plasmids. Eight antimicrobial resistance genes were identified, including blaKPC-2 located in a 46,161 bp IncI1-type plasmid and the blaCTX-M-15 gene situated in the chromosome. Other two E. coli S617-2 and R616-1 isolates, recovered from China in 2018, are the closest relatives of E. coli 488, with only 52 SNPs difference. The genome also contains at least 57 genomic islands and several IS elements.Conclusion: Our study reveals the first ST648 E. coli isolate containing both blaKPC-2 and blaCTX-M-15 in China. These results could provide valuable insights into the genetic characteristics, antimicrobial resistance mechanisms, and transmission dynamics of carbapenem-resistant Enterobacterales in clinical settings.Keywords: blaKPC-2, blaCTX-M-15, whole genome sequencing, multidrug-resistant, Escherichia coli

Kaifei Wang, Ye Hu, Zhimei Duan, Han Fu, Xingshuo Hu, Ying Zhao, Ruoxuan Wen, Lina Li, Fei Xie College of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Fei Xie, College of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, People’s Republic of China, Tel +86-15001028681, Email xielx301@sina.comBackground: Staphylococcus aureus has been well recognized as an important cause of community-acquired pneumonia (CAP), with non-specific characteristics and poor prognosis. In severe CAP (SCAP) guidelines, β-lactam combined with macrolides or fluoroquinolones therapy was recommended, but the efficacy is not satisfactory due to the continued spread of antimicrobial resistance. Contezolid is a new representative of oxazolidinones in clinical development, but no relevant reports have been reported for the treatment of SCAP. This was the first report of a patient with Staphylococcus aureus SCAP who was successfully treated with contezolid combined with other antibiotics and rehabilitation exercise.Case Presentation: A 44-year-old woman with high blood pressure and diabetes was admitted to our hospital owing to cough, sputum, wheezing for 2 weeks, and aggravation for 2 days. The bronchoscopic alveolar lavage and microorganism-Rapid On Site Evaluation (BAL-mROSE) was used to get pathological data, which were positive for Staphylococcus aureus, in line with blood cultures. During hospitalization, the patient received endotracheal intubation for assisted breathing and anti-infective therapy, including meropenem, linezolid, teicoplanin and tazocin successively. Finally, contezolid obtained excellent result, with platelet recovery to normal levels and significant improvement in pulmonary imaging. Meanwhile, the patient’s swallowing disorder improved after continuous rehabilitation exercise. After discharge, she received contezolid consolidation therapy for 1 week and was free of complaints during the 30-day follow-up without any special treatment for SCAP.Discussion: Treatment with contezolid combined with other antibiotics and rehabilitation exercise for SCAP has shown remarkable efficacy and good safety; hence, this regimen is a promising treatment strategy for this fatal disease.Keywords: severe community-acquired pneumonia, methicillin-sensitive Staphylococcus aureus, antibiotic therapy, contezolid, rehabilitation exercise

Keke Liu, Juan Zhang, Songhui Liu, Jiaoyan Chen, Ya Zhang, Wenxiu Li, Han Fu, Lianguo Fu Department of Child and Adolescent Health, School of Public Health, Bengbu Medical College, Bengbu, Anhui, People’s Republic of ChinaCorrespondence: Lianguo Fu, Tel +86-13195529639, Fax +86-5523175215, Email lianguofu@163.comPurpose: This study aimed to analyze the association pathways of parental stress on children’s appearance, body dissatisfaction, and eating behaviours in Chinese children and adolescents.Patients and Methods: The children aged 8– 15 years were selected from 2 nine-year schools using stratified cluster random sampling. The appearance-related social stress questionnaire and the body dissatisfaction subscale of EDI-1 were used to investigate parental stress on children’s appearance and body dissatisfaction, respectively. The self-administered eating frequency questionnaire was used to investigate children’s eating behaviours.Results: Body dissatisfaction in girls mediated associations between BMI, parental teasing, parental injustice and ignorance, parental encouragement and healthy eating behaviour: BMI → body dissatisfaction → healthy eating behaviour, parental teasing → body dissatisfaction → healthy eating behaviour, parental injustice and ignorance → body dissatisfaction → healthy eating behaviour, parental encouragement → body dissatisfaction → healthy eating behaviour. Parental injustice and ignorance directly and negatively predicted healthy eating behaviour in girls. In boys and girls, parental teasing was a direct predictor factor of unhealthy eating behaviour.Conclusion: Parental teasing, parental injustice and ignorance, parental encouragement, and BMI through body dissatisfaction positively predicted healthy eating behaviour in girls, parental injustice and ignorance directly negatively predicted healthy eating behaviour in girls, and parental teasing directly positively predicted unhealthy eating behaviour in girls and boys. Therefore, parental pressure on children’s appearance may pay important role in children’s eating behaviours.Keywords: parental stress on children’s appearance, body dissatisfaction, eating behaviour, children and adolescents

Haiyao Huang,1,&ast; Lili Gao,1,2,&ast; Xiaopeng Deng,1 Hanliang Fu3 1Department of Construction and Real Estate, School of Civil Engineering, Southeast University, Nanjing, People’s Republic of China; 2Department of Architecture and Civil Engineering, City University of Hong Kong, Hong Kong, People’s Republic of China; 3Laboratory of Neuromanagement in Engineering, Xi’an University of Architecture and Technology, Xi’an, 710055, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaopeng Deng, Department of Construction and Real Estate, School of Civil Engineering, Southeast University, Nanjing, People’s Republic of China, Email dxp@seu.edu.cnPurpose: In the field of construction, it has been shown that individuals with higher emotional intelligence may perform better on the job. However, it is still a question worth exploring about how emotional intelligence affects expatriate performance in international construction projects. Therefore, this study aimed to verify the relationship between expatriates’ emotional intelligence and expatriate performance and explore the mediating role of self-efficacy and psychological resilience.Methods: A cross-sectional study was conducted in June 2021. A non-probability sampling method was used to obtain data. A total of 315 Chinese construction expatriates in 67 countries and regions around the world were evaluated using four scales: the Wong and Law Emotional Intelligence Scale, the General Self-Efficacy Scale, the Connor-Davidson Resilience scale, and the Kraimer’s expatriate’s performance scale. The hypothesis model was tested using Partial Least Squares Structural Equation Modeling (PLS-SEM).Results: The results of the data analysis indicated that self-efficacy (βIndirect effect = 0.175, p< 0.05) and psychological resilience (βIndirect effect = 0.112, p< 0.05) served as fully mediating variables (β Direct effect = 0.177, p=0.101), suggesting a way to explain how emotional intelligence affect the performance of contractor expatriates. The findings also suggest that self-efficacy and psychological resilience also play continuous and multiple mediating roles (βIndirect effect = 0.143, p< 0.05) between emotional intelligence and expatriate performance.Conclusion: This study attempted to investigate the mechanism of emotional intelligence’s influence on expatriate performance from the perspective of individual psychological resources. The results of the study suggest that the emotional intelligence of expatriates may bring about an increase in performance levels by improving self-efficacy and psychological resilience levels. This provides a practical way to improve the performance of expatriates and a new management perspective for human resource management in international construction projects.Keywords: expatriate performance, emotional intelligence, psychological resilience, self-efficacy, sequential mediation model

Kaili Li, Sanle Jiang, Hongxue Fu, Yingting Hao, Shijing Tian, Fachun Zhou Department of Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Shijing Tian; Fachun Zhou, Emergency Department, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong Qu, 17th Floor, Building 1, Chongqing, People’s Republic of China, Tel +86 023-89011756, Email doctortianshijing@163.com; cyzfc1966@126.com; zfc88@126.comBackground: To identify the risk factors and prognosis of carbapenem-resistant organisms (CRO) in patients with acute cholangitis.Methods: This retrospective observational study was conducted to explore the risk factors and prognosis of CRO infection in 503 acute cholangitis patients diagnosed between July 2013 and January 2022 at the First Affiliated Hospital of Chongqing Medical University, who were divided into a CRO group and non-CRO group based on the presence or absence of CRO. Univariate, multivariate analyses, and the proportional hazards model were used to compare the risk factors and prognosis of CRO suffering in patients with acute cholangitis.Results: We identified 35 patients colonized with CRO from 503 acute cholangitis patients. In the multivariate analysis, tumor (OR=7.09, 95% CI=1.11– 45.30, P=0.038) and chronic kidney disease (OR=8.70, 95% CI=2.11– 35.88, P=0.003) were ascertained as the risk factors of the occurrence on CRO infection under the background of acute cholangitis. CRO infection was identified as an independent risk factor for acute cholangitis patient death (HR=5.147, 95% CI=1.475– 17.595, P=0.01) by Cox proportional-hazards regression.Conclusion: Tumor and chronic kidney disease may be risk factors for CRO infection. Patients diagnosed with acute cholangitis further infected with CRO had a poor prognosis and a more severe mortality. Active screening for CRO is expected to facilitate early prevention, diagnosis, and treatment of high-risk patients.Keywords: CRO, acute cholangitis, risk factors, prognosis

Weihao Chen,1– 4 Yanmin Zhao,1– 4 Yi Luo,1– 4 Jian Yu,1– 4 Huarui Fu,1– 4 Xiaoyu Lai,1– 4 Lizhen Liu,1– 4 Yishan Ye,1– 4 Jingsong He,1– 4 Jie Sun,1– 4 Weiyan Zheng,1– 4 Yi Zhao,1– 4 Guoqing Wei,1– 4 Zhen Cai,1– 4 He Huang,1– 4 Jimin Shi1– 4 1Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, People’s Republic of China; 3Institute of Hematology, Zhejiang University, Hangzhou, People’s Republic of China; 4Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, People’s Republic of ChinaCorrespondence: Jimin Shi; He Huang, Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, People’s Republic of China, Tel/Fax +86-0571-87236706, Email shijimin@zju.edu.cn; huanghe@zju.edu.cnBackground: Bloodstream infection (BSI) is a common and serious complication that may lead to high mortality during the different phases after hematopoietic stem cell transplant (HSCT). We investigated BSI in patients undergoing HSCT to provide an appropriate clinical anti-infection experience and improve the prognosis of recipients with BSI after HSCT.Methods: A total of 105 patients with BSI after HSCT at our center from January 2015 to June 2020 were included in this retrospective study. We analyzed the clinical and microbiological data, and the risk factors for mortality at 3 months after BSI.Results: Of the 1141 HSCT recipients, 105 (9.2%) patients presented with 122 episodes of BSI, of which we isolated 85 (65.9%) gram-negative bacteria, 32 (24.8%) gram-positive bacteria and 12 (9.3%) fungi. Multidrug-resistant bacteria (MDR) were more than 70% of all pathogens and carbapenem-resistant organisms (CRO) were 25.6%. There were 55 episodes of BSI in the pre-engraftment phase and 67 episodes in the post-engraftment phase. The mortality of post-engraftment BSI was significantly higher than that of pre-engraftment (56.7% vs 32.7%, p = 0.005). Through multivariate analysis, the independent risk factors for all-cause mortality at 3 months after BSI were higher levels of procalcitonin (PCT), failure to cover appropriate antibiotics timely, and CRO BSI in pre-engraftment period or multidrug-resistant gram-negative bacteria (MDRGNB) BSI in post-engraftment period.Conclusion: Although the incidence of BSI was lower after HSCT, MDR-dominated BSI had a high mortality rate. Rapid identification of infection or pathogens’ classification with various testing methods and the more sensible and timely antibiotic cover are critical to the outcome of BSI after HSCT.Keywords: bloodstream infection, hematopoietic stem cell transplantation, multidrug-resistant bacteria, all-cause mortality

Yuetian Wang,1,&ast; Chun Liu,2,&ast; Huiling Liu,3 Haoyong Fu,1 Chunde Li,1 Lei Yang,3,4 Haolin Sun1 1Department of Orthopedics, Peking University First Hospital, Beijing, People’s Republic of China; 2Medical Research Centre, Changzhou Second People’s Hospital Affiliated to Nanjing Medical University, Jiangsu, People’s Republic of China; 3Institute of Orthopedics, Department of Orthopedics, Soochow University, Suzhou, People’s Republic of China; 4Center for Health Sciences and Engineering (CHSE), School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Yang; Haolin Sun, Tel +86 13681146156, Email ylei@hebut.edu.cn; sunhaolin@vip.163.comPurpose: To evaluate the effect of cement augmentation of cortical bone trajectory (CBT) screws using a novel calcium phosphate–based nanocomposite (CPN).Material and Methods: CBT screws were placed into cadaveric lumbar vertebrae. Depending on the material used for augmentation, they were divided into the following three groups: CPN, polymethylmethacrylate (PMMA), and control. Radiological imaging was used to evaluate the cement dispersion. Biomechanical tests were conducted to measure the stability of CBT screws. A rat cranial defect model was used to evaluate biodegradation and osseointegration of the CPN.Results: After cement augmentation, the CPN tended to disperse into the distal part of the screws, whereas PMMA remained limited to the proximal part of the screws (P < 0.05). As for cement morphology, the CPN tended to form a concentrated mass, whereas PMMA arranged itself as a scattered cement cloud, but the difference was not significant (P > 0.05). The axial pullout test showed that the average maximal pullout force (Fmax) of CPN-augmented CBT screws was similar to that of the PMMA group (CPN, 1639.56 ± 358.21 N vs PMMA, 1778.45 ± 399.83 N; P = 0.745) and was significantly greater than that of the control group (1019.01 ± 371.98 N; P < 0.05). The average torque value in the CPN group was higher than that in the control group (CPN, 1.51 ± 0.78 N∙m vs control, 0.97 ± 0.58 N∙m) and lower than that in the PMMA group (1.93 ± 0.81 N∙m), but there were no statistically significant differences (P > 0.05). The CPN could be biodegraded and gradually replaced by newly formed bone tissue after 12 weeks in a rat cranial defect model.Conclusion: The biocompatible CPN could be a valuable augmentation material to enhance CBT screw stability.Keywords: cement augmentation, CBT screws, osteoporotic spine, PMMA, CPN

Xiaolong Ma,1,&ast; Xiaodong Lv,1,&ast; Sihan Feng,1 Ruishan Liu,2,3 Hao Fu,2 Feng Gao,1 Hao Xu2 1Department of Respiratory Medicine, the First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), Jiaxing, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Laboratory Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Feng Gao, Department of Respiratory Medicine, the First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), No. 1882 South Zhonghuan Road, Jiaxing, 314000, People’s Republic of China, Tel +86 573 825 198 70, Fax +86 573 820 830 06, Email guti-gf@163.com Hao Xu, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qing chun Road, Hangzhou, 310003, People’s Republic of China, Tel +86 571 872 364 23, Fax +86 571 872 364 21, Email xuhao0523@zju.edu.cnPurpose: To investigate the phenotypic and genomic characteristics of the multi-drug resistant and hypervirulent Klebsiella pneumoniae strain recovered from bacteremia.Methods: Antimicrobial susceptibility testing (AST) was performed by the microdilution method. Antimicrobial resistance genes, virulence-associated genes, multilocus sequence typing (MLST), and plasmid replicon were characterized by next-generation sequencing (NGS) and nanopore sequencing. S1 nuclease-pulsed field gel electrophoresis (S1-PFGE) and Southern blotting were performed to characterize the plasmid profile.Results: The hypervirulent colistin- and carbapenem-resistant K. pneumoniae strain DY2009 was identified as ST5571, co-carrying mcr-1, blaNDM-1, and blaOXA-10. In silico analysis found that it was K2 serotype. AST results revealed that DY2009 was resistant to carbapenems, cephalosporins, ciprofloxacin, chloramphenicol, and colistin but remained susceptible to aztreonam, gentamicin, amikacin, and tigecycline. Through the whole-genome analysis, a variety of virulence determinants were identified, including rmpA. Plasmid analysis confirmed that the mcr-1 and blaNDM-1 gene harbored a ∼ 33 kb IncX4 plasmid and a ∼ 44 kb IncX3 plasmid. In contrast, blaOXA-10 was encoded by chromosome.Conclusion: To the best of our knowledge, we first report the clinical hypervirulent K. pneumoniae isolate co-producing MCR-1, NDM-1, and OXA-10 causing bacteremia. We found that mcr-1 and blaNDM-1 genes were located on two self-conjugative epidemic plasmids, contributing to the widespread MCR-1 and NDM-1 in China. The results of this work improve our understanding of the genetic background of colistin- and carbapenem-resistant K. pneumoniae isolate from bacteremia and the resistance mechanisms. Our findings highlight the urgent need for infection control of such strain to prevent it from becoming an extensive-drug resistant clone.Keywords: Klebsiella pneumoniae, NDM-1, MCR-1, OXA-10, rmpA, bacteremia

Shuyue Jiao,1 Xin Zhang,2 Dapeng Wang,3 Hongyong Fu,3 Qingxin Xia3 1Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Pathology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 3Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University; Henan Medical Key Laboratory of Tumor Pathology and Artificial Intelligence Diagnosis, Zhengzhou, People’s Republic of ChinaCorrespondence: Qingxin Xia; Hongyong Fu, Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University; Henan Medical Key Laboratory of Tumor Pathology and Artificial Intelligence Diagnosis, Zhengzhou Key Laboratory of Accurate Pathological Diagnosis of Intractable Tumors, Zhengzhou, 450000, People’s Republic of China, Email tudou414135404@163.com; dlxiaoyong@126.comIntroduction: Small cell lung cancer (SCLC), an aggressive subtype of lung cancer characterized by the development of neuroendocrine tumors, is prone to distant metastasis, resistant to platinum-based drugs and has a poor prognosis. The development of next-generation sequencing technology (NGS) has led to the identification of many genetic alterations in SCLC. Few druggable targeted molecules can be used in clinical practice. Currently, NGS is widely employed in routine clinical practice of non-small cell lung cancer to assist in therapeutic options and prognosis evaluation. This study aims to investigate genes involved in small cell lung cancer (SCLC), their occurrence and their significance in clinical events.Methods: Tumor tissue specimens from 18 Chinese SCLC patients were collected through a 520 cancer‐related genes panel for next-generation sequencing. First, the association between sequence results and clinical outcomes was examined. Subsequently, data on clinical pathology and sequencing results were analyzed.Results: The Kaplan–Meier curve displayed a significant reduction in PFS for SCLC patients with LRP1B or MAP3K13 mutations. Overall survival (OS) of SCLC patients with MSH6 mutation was significantly higher than those with SPEN mutation.Conclusion: Next-generation sequencing demonstrates that the genetic landscape of SCLC. Mutation status of LRP1B, MAP3K13, MSH6 and SPEN has prognostic significance, which might be potential therapeutic targets. We found possible genes and related signaling pathways that affect metastasis. These results can improve our understanding of the mutation characteristics of SCLC and identify potential biomarkers to guide targeted therapies.Keywords: small cell lung cancer, next-generation sequencing, genetic alteration, tumor mutation burden, clinical significance

Yu Fu,1,&ast; Huimin Fu,2,&ast; Yugang Lu,1 Xin Lv1 1Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Anesthesiology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yugang Lu; Xin Lv, Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Tel/Fax +86 021 65115006, Email luyugang@tongji.edu.cn; xinlvg@126.comPurpose: It is pivotal to optimize perioperative analgesia in order to fit a transition in the surgical approach for removing mediastinal tumors, from sternotomy to trans-subxiphoid robotic thymectomy (TRT). Serratus anterior plane block (SAPB) is a safe, effective and easy to perform analgesic technology, which could provide analgesia in thoracic and upper abdominal surgery. However, the efficacy of SAPB analgesia in the patients undergoing TRT is unclear and has never been described in scientific literature. Therefore, this study aimed to determine the effect of ultrasonic-guided low SAPB on analgesia and the quality of recovery (QoR) following the TRT.Study Design and Methods: In this prospective double-blind, randomized controlled design trial, 40 adults scheduled for TRT will be randomly allocated to the low SAPB group (Group S) and placebo control group (Group C). The patient of Group S will be performed SAPB bilaterally at the level of T8–T9 under ultrasound guidance with 40 mL 0.375% ropivacaine after anesthesia induction. Group C will be administered normal saline at the same volume and timing. The primary study outcome is the global Quality of Recovery-40 (QoR-40) score on postoperative days (POD) 1. The secondary endpoints are numeric rating scale (NRS) scores and sufentanil consumption at different time points after surgery, QoR-40 scores on POD 2, 30 and 90, chronic pain at POD 90, and the incidence of perioperative adverse events.Discussion: This is the first prospective trial to shed light on the efficacy of ultrasonic-guided low SAPB on postoperative pain and recovery after TRT. The findings will provide a new strategy of perioperative pain management for TRT.Keywords: serratus anterior plane block, robot-assisted thoracic surgery, subxiphoid, thymectomy, postoperative analgesia

Yuzhi Zhang,1,2 Hao Fu,1,2 Yongtao Zhang,1,2 Dongdong Wang,1,2 Dan Zhao,1– 3 Jiachan Zhang,1– 3 Meng Li,1,2 Changtao Wang1– 3 1Beijing Key Lab of Plant Resource Research and Development, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, People’s Republic of China; 2Institute of Cosmetic Regulatory Science, Beijing Technology and Business University, Beijing, People’s Republic of China; 3Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing, People’s Republic of ChinaCorrespondence: Meng Li; Changtao Wang, Beijing Technology and Business University, Beijing, 100048, People’s Republic of China, Tel +86 10-68984917, Fax +86 10-68984917, Email limeng@btbu.edu.cn; wangct@th.btbu.edu.cnObjective: To evaluate the efficacy of the dandelion fermentation broth in repairing UVB-induced skin inflammation.Methods: Detection of active ingredients in dandelion fermentation broth and water extract. The antioxidant capacity of dandelion fermentation broth was investigated by in vitro antioxidant experiments. The influence of the broth on the content of inflammatory factors interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-1β (IL-1β), and tumor necrosis factor (TNF-α), in human immortalized epidermal cells (HaCaT) is discussed on the basis of a UVB-induced HaCaT damage model. The effects of the broth on the contents of skin barrier-related proteins kallikrein-7 (KLK-7), filaggrin (FLG) and aquaporin (AQP3) in the UVB-induced damage and repair of the HaCaT mechanism are also comprehensively discussed. The effect of DF on the activation of MAPK pathway proteins was detected by PCR. A chicken embryo chorioallantoic membrane test is used to explore the safety of the dandelion fermentation broth.Results: The results show that the dandelion fermentation broth is rich inTotal sugar, with good free radical scavenging ability and antioxidant effects; it can regulate the MAPK pathway, reduce the expression of inflammatory factors, adjust the skin barrier factors and good safety.Conclusion: Dandelion fermentation broth exhibits repairing effect on UVB-induced skin inflammation.Keywords: dandelion fermentation broth, ultraviolet radiation B, human immortalized epidermal cells, inflammation repair, medicine, daily chemical raw materials

Qiuting Mo, 1, 2 Hao Fu, 1, 2 Dan Zhao, 1– 3 Jiachan Zhang, 1– 3 Changtao Wang, 1– 3 Dongdong Wang, 1, 2 Meng Li 1, 2 1Beijing Key Laboratory of Plant Resource Research and Development, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, People’s Republic of China; 2Institute of Cosmetic Regulatory Science, Beijing Technology and Business University, Beijing, People’s Republic of China; 3Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing, People’s Republic of ChinaCorrespondence: Dongdong Wang; Meng Li Tel/Fax +86-010-68984917Email Wdd@btbu.edu.cn; limeng@btbu.edu.cnPurpose: Damage caused by oxidative stress leads to the premature aging of cells. Mogrosides, the main active components of Siraitia grosvenorii, have strong antioxidant activity; however, it is unclear whether mogroside V (MV) exerts these effects in skin cells. This was investigated in the present study by evaluating the protective effects of MV against oxidative damage induced by hydrogen peroxide (H 2O 2) in skin fibroblasts.Methods: Mouse skin fibroblasts (MSFs) were treated with H 2O 2 and cell viability, total antioxidant capacity, reactive oxygen species (ROS) production, malondialdehyde (MDA) content, and antioxidant enzyme activity were assessed.Results: Treatment with MV reduced the ROS level and MDA content in MSFs treated with H 2O 2. This was accompanied by increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities.Conclusion: MV reduces H 2O 2-induced oxidative stress and enhances endogenous antioxidant activity in skin fibroblasts. Thus, MV can potentially be used as an ingredient in anti-aging cosmetic products.Keywords: Siraitia grosvenorii, mogroside V, oxidative stress, antioxidant

Yikun Guo,1 Min Zhang,1 Yan Su,2 Jianfang Liu,1 Hongran Fu,1 Qian Wang,1 Yun Chen1 1Department of Neurology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 2Department of Radiology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of ChinaCorrespondence: Yikun GuoDepartment of Neurology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, 68# Middle Gehu Road, Changzhou, 213000, Jiangsu Province, People’s Republic of ChinaTel +86-519-81087079Fax +86-519-81087711Email guoyikun000@163.comPurpose: Few clinical indicators of a poor outcome have been defined in acute cardioembolic stroke (CES) patients. We would like to explore practical clinical factors that can predict poor outcomes of CES in the early stage.Patients and Methods: In this single-center, retrospective, observational study, 251 consecutive patients with acute CES who did not undergo reperfusion therapy were evaluated. On the basis of the modified Rankin Scale (mRS) score at 3 months, patients were divided into the good functional outcome group (mRS ≤ 2) and the poor functional outcome group (mRS ≥ 3). Risk factors were analyzed and the independent indicators for a poor outcome were identified using a binary logistic regression model.Results: One hundred (39.8%) patients had a poor outcome. Patients in the poor outcome group were significantly older (P = 0.002) and had significantly higher baseline National Institutes of Health Stroke Scale (NIHSS) score compared with those with a good outcome (P < 0.001). After adjusting for potential confounders, the baseline NIHSS score (P < 0.001), moderate to severe leukoaraiosis (P = 0.011), non-symptomatic intracranial hemorrhage (P = 0.019), stroke-associated pneumonia (P = 0.001), and fasting glucose (P = 0.040) were independent risk factors for a poor outcome.Conclusion: The short-term outcome in acute CES patients without reperfusion therapy can be predicted by using five practical clinical factors. These indicators should attract more attention.Keywords: acute cardioembolic stroke, risk factor, functional outcome, reperfusion therapy, leukoaraiosis

Sijia Chen,1,&ast; Wenwen Du,1,&ast; Xiuxiu Zhuang,1,&ast; Qinxue Dai,1 Jingwen Zhu,2 Haifeng Fu,1 Junlu Wang,1 Luping Huang1 1Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Luping HuangDepartments of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaTel +86 13587891399Fax +86 577-55578999-689854Email csj0122@wmu.edu.cnPurpose: To determine the characteristics of the acute pain after laparoscopic-assisted vaginal hysterectomy (LAVH), laparoscopic myomectomy (LM), and laparoscopic adnexectomy (LA) and compare them with each other.Patients and Methods: Patients undergoing LAVH, LM, and LA under general anaesthesia at the First Affiliated Hospital of Wenzhou Medical University between December 2017 and December 2019 were selected. Their data were collected before, during, and after the surgery. We evaluated the degrees of pain in each group of patients and compared them.Results: There were differences in the baseline characteristics of the patients in the LAVH, LM, and LA groups. The severity and incidence of postoperative pain were higher in the LAVH group than in the LM and LA groups, followed by the LM and LA groups. Compared with the LA group, the postoperative pain in the LAVH and LM groups was more complicated. The LA group had the lowest incidence of two or more types of moderate to severe pain. The LAVH and LM groups mainly had visceral pain and low back pain, and the LA group mainly had incisional pain. Shoulder pain had the lowest incidence in the three groups.Conclusion: There were different postoperative pain characteristics after the LAVH, LM, and LA, and we should clinically adjust analgesia programs for different gynaecological laparoscopic surgeries.Keywords: postoperative pain, laparoscope-assisted vaginal hysterectomy, laparoscopic myomectomy, laparoscopic adnexectomy

Jiamin Tu,1 Lei Tu,1 Yinping Jiang,2 Honghao Fu,1 Zijuan Mai,3 Xianglin Wu,4 Bing Xu1 1Department of Proctology, University of Chinese Academy of Science Shenzhen Hospital (GuangMing), Shenzhen, 518100, People’s Republic of China; 2Department of Chinese Medicine, University of Chinese Academy of Science Shenzhen Hospital (GuangMing), Shenzhen, 518100, People’s Republic of China; 3Department of Medical Record Statistics Section, University of Chinese Academy of Science Shenzhen Hospital (GuangMing), Shenzhen, 518100, People’s Republic of China; 4Department of Laboratory, University of Chinese Academy of Science Shenzhen Hospital (GuangMing), Shenzhen, 518100, People’s Republic of ChinaCorrespondence: Jiamin TuDepartment of Proctology, University of Chinese Academy of Science Shenzhen Hospital (GuangMing), No. 4253 Songbai Road, Guangming District, Shenzhen, 518100, People’s Republic of ChinaTel +8615889790570Email jiajiabaxia@126.comBackground: Ralstonia mannitolilytica can cause opportunistic infections. Reports on this pathogen identified in the bloodstream are rare worldwide, especially in China.Case Description: We describe a 48-year-old man who developed sepsis due to bloodstream Ralstonia mannitolilytica infection after surgery for a perianal abscess. His condition deteriorated into multiple organ dysfunction syndromes until susceptible antibiotics (ceftriaxone and levofloxacin) were administrated based on the drug sensitivity test results. The patient had a satisfactory recovery with no complications during a 6-month follow-up period.Conclusion: Ralstonia mannitolilytica blood-borne infection in patients evolves rapidly. The inconsistent sensitivity to antibiotics makes timely treatment difficult and can lead to serious complications. We report the clinical presentations and treatment outcomes for this patient here to remind clinicians about this rare opportunistic pathogen and to highlight the importance of bacterial culture, especially for immunocompromised patients.Keywords: Ralstonia mannitolilytica, sepsis, shock, perianal abscess, multiple organ dysfunction syndrome

Xiulan Peng,1,&ast; Yali Huang,1,&ast; Haifeng Fu,2,&ast; Zhi Zhang,3 Anbing He,1 Renfeng Luo4 1Department of Oncology, The Second Affiliated Hospital of Jianghan University, Wuhan, Hubei, People’s Republic of China; 2Department of Hepatopancreatobiliary Surgery, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Wuhan, Hubei, People’s Republic of China; 3Department of Intensive Care Unit, The Second Affiliated Hospital of Jianghan University, Wuhan, Hubei, People’s Republic of China; 4Department of Diagnostics, JiangHan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiulan PengDepartment of Oncology, The Fifth Hospital of Wuhan, The Second Affiliated Hospital of Jianghan University, 122 Xianzheng Road, Wuhan, Hubei, 430050, People’s Republic of ChinaTel +86027-84830120Email pengxlwh@163.comBackground: We aimed to evaluate the prognostic ability of blood urea nitrogen (BUN) to serum albumin ratio (BAR) to predict in-hospital mortality in patients with lung cancer in the intensive care unit (ICU).Methods: Medical Information Mart for Intensive Care IV (MIMIC-IV v1.0) database was used to identify patients who were diagnosed with lung cancer. The primary outcome was in-hospital mortality. Multivariate COX regression was used to investigate the association between BAR and in-hospital mortality and propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were also used to ensure the robustness of our findings. eICU-CRD database (validation cohort) was also applied to validate our findings.Results: The optimal cut-off value for BAR was 6.8mg/g. Among 1202 patients who were diagnosed with lung cancer, 287 high-BAR group (≥ 6.8mg/g) patients and 287 low-BAR group (< 6.8mg/g) patients, who had similar propensity scores were included in this study. After matching, the high-BAR group had significantly higher in-hospital mortality (hazard ratio, HR, 2.24, 95% confidence index, 95% CI, 1.57– 3.19, P< 0.001) even after adjustment for confounding factors. Moreover, the performance of BAR was superior to that of BUN and serum albumin alone and could add net benefit in predicting in-hospital mortality. Those results were further confirmed in the validation cohort.Conclusion: As an easily accessible and cost-effective parameter, BAR could serve as a good prognostic predictor for lung cancer patients in ICU.Keywords: blood urea nitrogen to serum albumin ratio, lung cancer, intensive care unit, Medical Information Mart for Intensive Care, eICU-CRD, prognosis

Hongling Fu,1,2 Qiu Wang,2,3 Hanmin Liu1,2 1Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Key Laboratory of Birth Defect and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Rehabilitation Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Hanmin LiuDepartment of Pediatrics, West China Second University Hospital, Sichuan University, No. 20, 3rd Section, Ren Min Nan Lu, Chengdu, 610041, People’s Republic of ChinaEmail liuhm@scu.edu.cnAbstract: Pelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive hypomyelinating leukodystrophy with clinical symptoms and imaging manifestations similar to those of Pelizaeus-Merzbacher disease (PMD), an X-linked recessive hypomyelinating leukodystrophy. Typical manifestations of PMLD are nystagmus, dysmyotonia, ataxia, progressive motor dysfunction, and diffuse leukodystrophy on magnetic resonance imaging (MRI). This report identified novel mutations in NCP1 causing PMLD. A 7-month-old male patient was referred to our hospital because he could not lift his head until that time. He had symptoms including congenital nystagmus, hypotonia, and developmental delay. According to the MRI scan, there were signs of leukodystrophy. According to the clinical manifestations and the results of whole-exome sequencing (compound heterozygote mutations in NPC1 (p. G911S, c2731G>A and p. D128H, c382G>C)), the diagnosis of PMLD was considered, and his parents were determined to be carriers of mutant genes. He began rehabilitation training at the age of 1 year old. After 5 years of training, he was still experiencing global developmental delay, equivalent to the developmental level of a nine-month-old child. PMLD is a disease that seriously affects the quality of life of children and can result from mutations in different genes. In this report, we expand the gene spectrum of PMLD and suggest early genetic counselling for suspected patients and their patients.Keywords: PMLD, hypomyelinating leukodystrophy, NPC, compound heterozygote mutations

Huimin Fu, Yu Fu, Xingguo Xu, Yongtao Gao Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of ChinaCorrespondence: Xingguo Xu; Yongtao GaoDepartment of Anesthesiology, Affiliated Hospital of Nantong University, No. 20 Xisi Road, Nantong, Jiangsu 226001, People’s Republic of ChinaTel +86 15162771638; +86 13962988003Fax +86 051381160318Email TDFYXXG@126.com; gyt19700114@sina.comPurpose: In recent years, ultrasound-guided rectus sheath block (RSB) has been widely used in postoperative analgesia of abdominal operation. However, there is no uniform standard for the optimal dose of local anesthetics (LA) under ultrasound-guided rectus sheath block. This study aimed to determine the dose of ropivacaine combined with butorphanol that is effective in 50% (ED50) and 95% (ED95) of subjects for successful pain-free ultrasound-guided RSB in single-incision laparoscopic cholecystectomy (SILC).Patients and Methods: Twenty-four patients scheduled to undergo single-incision laparoscopic cholecystectomy received an ultrasound-guided RSB. The initial dose of ropivacaine injected was 1.7 mg/kg, which was subsequently increased or decreased by 0.2 mg/kg, depending on whether the previous patient was free from pain (numeric rating scale (NRS) score of incisional pain at rest within 12 h after operation ≤ 3). All patients were treated with butorphanol 0.02 mg/kg as preemptive analgesia. The ED50 and ED95 were calculated using a probit regression model.Results: The ED50 and ED95 of ropivacaine combined with butorphanol in ultrasound-guided rectus sheath block for analgesia in SILC, which were calculated by the probit regression model, were 0.719 mg/kg (95% confidence interval (CI), 0.553 mg/kg− 0.873 mg/kg) and 0.967 mg/kg (95% CI, 0.835 mg/kg− 1.91 mg/kg), respectively.Conclusion: As part of a multimodal analgesia strategy, a dose of 0.719 mg/kg ropivacaine provided successful RSB under ultrasound guidance in 50% of the patients who underwent SILC. A dose of 0.967 mg/kg would be successful in 95% of patients.Keywords: ED50, ED95, single-incision laparoscopic cholecystectomy, rectus sheath block

Jun Bian,1– 3 Huijian Fu,4,5 Jia Jin5 1Department of Traffic Information, Zhejiang Expressway Information Engineering Technology CO., LTD, Hangzhou, People’s Republic of China; 2ZEIET Research Institute, Hangzhou, People’s Republic of China; 3Neuromanagement Lab, Zhejiang University, Hangzhou, People’s Republic of China; 4Department of Electronic Commerce, School of Management, Guangdong University of Technology, Guangzhou, People’s Republic of China; 5Academy of Neuroeconomics and Neuromanagement, Ningbo University, Ningbo, People’s Republic of ChinaCorrespondence: Huijian Fu Email huijian_fu@gdut.edu.cnPurpose: Safety signs are widely used to deliver safety-related information. There are many different types of safety signs. Although previous studies have paid attention to the design and effectiveness of safety signs, little attention has been devoted to investigating how people process the information conveyed by different types of safety signs. Accordingly, the current study is intended to explore the neural mechanisms underlying people’s perception of different types of safety signs.Methods: Three types of safety signs (prohibition, mandatory and warning signs) were used in the study. We employed questionnaire and event-related potentials (ERPs) experiment with an implicit paradigm to probe how people perceive these three types of safety signs.Results: Behaviorally, warning signs induced a higher level of perceived hazard than prohibition signs and mandatory signs, and prohibition signs induced a higher level of perceived hazard than mandatory signs. At the brain level, prohibition signs and warning signs led to reduced P2 amplitudes compared to mandatory signs. In addition, warning signs elicited larger N2 and N4 amplitudes than prohibition signs and mandatory signs, and prohibition signs elicited larger N2 and N4 amplitudes than mandatory signs, coinciding with the behavioral results.Conclusion: Different types of safety signs led to significant differences in individuals’ hazard perception. Based on the neural results, we suggest that the processing of safety signs consists of two stages: the rapid detection of hazard information (indicated by P2) and the conscious integration of hazard information in working memory (indicated by N2 and N4).Keywords: safety sign, hazard perception, event-related potentials, P2, N2, N4

Huimin Fu,1 Chaochao Zhong,2 Yu Fu,1 Yongtao Gao,2 Xingguo Xu2 1Nantong University, Nantong, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of ChinaCorrespondence: Xingguo XuDepartment of Anesthesiology, Affiliated Hospital of Nantong University, No. 20 Xisi Road, Nantong, Jiangsu 226001, People’s Republic of ChinaTel +86 15162771638Fax +86 051381160318Email TDFYXXG@126.comPurpose: Pain after single-incision laparoscopic cholecystectomy (SILC), especially visceral pain, often troubles patients and doctors. Whether preemptive butorphanol can relieve visceral pain in patients undergoing SILC remains unknown. The goal of this study was to assess the efficacy of ultrasound-guided bilateral rectus sheath block (RSB) and butorphanol for perioperative analgesia in patients undergoing SILC.Patients and Methods: Fifty-eight patients who met the criteria were randomly divided into two groups, both of which were given preemptive RSB. Patients were given either butorphanol 0.02mg/kg (group B, n=29) or sufentanil 0.1 μg/kg (group S, n=29) as preemptive analgesia. The primary outcome was the cumulative frequency of rescue analgesic request within 24 hours after operation. Secondary outcomes were numeric rating scale (NRS) scores (from 0 to 10) of incisional pain and visceral pain, the length of hospital stay and the incidence of postoperative adverse events.Results: The frequency of postoperative rescue analgesic request of group S was significantly higher than that of group B (P=0.021). The NRS scores for visceral pain were lower in group B at 2, 6 and 12 hours after surgery than in group S (both P< 0.001). The occurrence of postoperative nausea and vomiting (PONV) was significantly higher in group S. There were no significant differences between two groups for other outcomes.Conclusion: Butorphanol can provide sufficient visceral pain treatment after SILC than the dose of sufentanil in equal analgesic effect.Keywords: rectus sheath block, butorphanol, single-incision laparoscopic cholecystectomy, incisional pain, visceral pain, preemptive analgesia

Jiapeng Xu,1,* Yu Zhang,1,* Qing You,1 Hongbing Fu,1 Xiaokai Zhao,2 Kai Lu,2 Ronglin Yan,1 Dejun Yang1 1Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People’s Republic of China; 2Shanghai Yunying Medical Technology Co.Ltd, Shanghai 201600, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ronglin Yan; Dejun YangDepartment of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai 200003, People’s Republic of ChinaEmail yanronglin@smmu.edu.cn; yangdejun@smmu.edu.cnIntroduction: It is worldwide accepted that lncRNA PTCSC3 is a tumor suppressor in glioma and thyroid cancer, whereas its role in the recurrence of gastric cancer is unknown.Patients and Methods: We recruited 80 GC patients (46 males and 34 females, 44 to 68 years, 56.3± 6.7 years) in our study. Two human GC cell lines AGS and SNU-1 were transfected with PTCSC3 and HOXA11-AS expression vectors. Then, qPCR was used to detect the level of relative mRNA. Both invasion and migration assays were performed to detect the effect of the lncRNA on gastric cancer cell motility.Results: In the present study, we showed that PTCSC3 was downregulated in plasma of gastric cancer patients than in plasma of healthy controls. Follow-up study indicated that PTCSC3 was further downregulated in patients with distant-recurrence but not in patients with local recurrence only or non-recurrence. LncRNA HOXA11-AS was upregulated in plasma of gastric cancer cells than in plasma of healthy controls and was inversely correlated with PTCSC3 in plasma of gastric cancer patients. PTCSC3 overexpression mediated the downregulation of HOXA11-AS in gastric cancer cells, while HOXA11-AS overexpression failed to significantly affect PTCSC3. PTCSC3 overexpression led to inhibited, while HOXA11-AS overexpression led to promoted migration and invasion of gastric cancer cells. In addition, HOXA11-AS overexpression reduced the effects of PTCSC3 overexpression.Discussion: Therefore, lncRNA PTCSC3 alleviates in the postoperative distant recurrence of gastric cancer possible by suppression of HOXA11-AS.Keywords: PTCSC3, gastric cancer, distant recurrence, HOXA11-AS

Liming Liang,1 Liang Zhang,2 Jiguang Zhang,3 Shutang Bai,1 Hongdu Fu1 1No.2 Cardiothoracic Surgery, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou City, Hainan Province 570208, People’s Republic of China; 2Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen City 518107, People’s Republic of China; 3Department of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou City, Fujian Province 350001, People’s Republic of ChinaCorrespondence: Liang ZhangDepartment of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, No.628, Zhenyuan Road, Guangming (New) District, Shenzhen City 518107, People’s Republic of ChinaTel/Fax +86-755-81206874Email zhangjack03@163.comBackground: Circular RNAs (circRNAs) were elucidated to act as competing endogenous RNAs (ceRNAs) and to play significant roles in cancer initiation and progression. We aimed to identify the important circRNAs in lung adenocarcinoma and intended to predict the functions of them via the bioinformatics analysis.Methods: We extracted data from three Gene Expression Omnibus (GEO) datasets, GSE101586, GSE101684, and GSE104854, and identified the common differentially expressed circRNAs. Agarose gel electrophoresis and Sanger sequencing were used to verify these significant circRNAs. Then, qRT-PCR was performed to validate the expression through matched tissues and cell lines. Afterwards, a ceRNA network was constructed and functional analysis was performed to predict the potential mechanisms of circRNAs.Results: Five circRNAs (hsa_circ_0072088, hsa_circ_0082564, hsa_circ_0008274, hsa_circ_0000519 and hsa_circ_0003528) were identified differentially expressed in the three datasets. Following the Agarose gel electrophoresis and qRT-PCR validation, hsa_circ_0072088 and hsa_circ_0008274 were chosen for further analysis. A ceRNA network of hsa_circ_0072088 and hsa_circ_0008274 was built based on the CSCD/TargetScan/MiRTarbase/StarBase 3.0. Then, the functional analysis showed that several meaningful terms were identified, such as “epithelial to mesenchymal transition (EMT)”, “Cellular response to TGF-β stimulus”, “MAPK signaling pathway”, and “PI3K-AKT signaling pathway”. Finally, several significant circRNA/miRNA/mRNA regulatory axes, which were predicted relating to cancer progress, were noted from the network.Conclusion: We identified significant circRNAs and meaningful circRNA-miRNA-mRNA networks to provide novel insight into pathogenesis and therapy of lung adenocarcinoma.Keywords: circRNAs, ceRNAs, GEO, lung adenocarcinoma, bioinformatics

Lin-lin Pei,1,* Wen-zhu Yang,1,* Jing-yuan Fu,1,* Meng-xi Liu,1 Ting-ting Zhang,1 Dong-bo Li,1 Ruo-yue Huang,1 Li Zhang,1 Guang-neng Peng,1 Gang Shu,1 Zhi-xiang Yuan,2 Ju-chun Lin,1 Wei Zhang,1 Zhi-jun Zhong,1 Ling Zhao,1 Hua-lin Fu1 1Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, People’s Republic of China; 2College of Pharmacy, Southwest Minzu University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua-lin FuDepartment of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, People’s Republic of ChinaTel +86 028-86291162Email fuhl2005@sohu.comIntroduction: Enrofloxacin is used in the treatment of a wide variety of bacterial infections in mammals. However, its poor solubility limits the clinical use.Methods: In order to improve the solubility of enrofloxacin, the enrofloxacin mesylate (EM) were obtained by a chemical synthesis method. The characterization of EM was carried out using ultraviolet scan (UV), synchronous thermal analysis (SDT), fourier transform infrared spectrometer (FTIR) and mass spectrometry (MS), nuclear magnetic resonance (NMR) and X-ray powder diffraction analysis (XRPD). Acute toxicity of EM in Kunming mice was studied. Besides, pharmacokinetic studies were performed in New Zealand rabbits at a single oral dose of 10 mg/kg, and the antibacterial activity of EM was also evaluated.Results: EM was successfully synthesized and purified. The stoichiometric ratio of mesylate to enrofloxacin was 1:1 and the aqueous solubility of EM was 483.01± 4.06 mg/mL, the solubility of EM was about 2000 times higher than enrofloxacin. The oral lethal dose (LD50) of EM was 1168.364 mg/kg, and the pharmacokinetics indicated that the oral relative bioavailability of EM was about 1.79 times and 1.48 times higher than that of enrofloxacin and enrofloxacin hydrochloride, respectively. In addition, the in vitro antibacterial activity of EM was not significantly changed compared with enrofloxacin and enrofloxacin hydrochloride.Conclusion: EM has higher solubility, low toxicity for oral use, and increases the oral bioavailability in rabbit. This study may be of benefit for the development of new enrofloxacin drugs.Keywords: enrofloxacin mesylate, characterization, antibacterial effect, acute toxicity, pharmacokinetics

Lin Cheng,1 Qiong Jiao,2 Yuchen Jin,1 Hao Fu,1 Huizhen Zhang,2 Libo Chen1 1Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Libo ChenDepartment of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, People’s Republic of ChinaTel +86-21-24058871Fax +86-21-64941720Email lbchen@sjtu.edu.cnAbstract: Preclinical studies have demonstrated that Apatinib, major targeting vascular endothelial growth factor receptor-2 (VEGFR-2), could inhibit the proliferation of anaplastic thyroid carcinoma (ATC) cells in vitro and in vivo. The efficacy and safety in ATC patients, however, remains unknown. Here, we report the case of a 93-year-old female with advanced ATC who initially treated with Apatinib. The tumor shrank notably 4 weeks after the initiation of therapy, which sustained for more than 30 weeks. The cervical CT illuminated a stable disease with a best response of 19.7% of the primary lesion and shrinkage of the metastatic lymph node. Adverse events, including hypertension, dental ulcer, hand-foot syndrome, fatigue, and anorexia, were observed and lightened with supportive treatment and dose reductions. The overall survival of the patient was 41 weeks. This is the first report describing the effectiveness of the VEGFR-2 inhibitor for the treatment of advanced ATC, warranting clinical trials to further ascertain its utility in this challenging setting.Keywords: anaplastic thyroid carcinoma, vascular endothelial growth factor receptor, Apatinib

GuiYuan Liu,1 Yi Pang,1 YaJun Zhang,2 HaiRong Fu,1 Wei Xiong,1 YongHui Zhang11Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing Three Gorges Medical College, Chongqing 404120, People’s Republic of China; 2Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, Chongqing 402160, People’s Republic of ChinaCorrespondence: YongHui ZhangChongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing Three Gorges Medical College, 366 Tianxing Road, Wan Zhou, Chongqing 404120, People’s Republic of ChinaTel +1 858 095 1210Email 304947859@qq.comBackground: Gap junction beta-4 protein (GJB4), or connexin 30.3, a member of integral membrane proteins, has been shown to involve and may function as a tumor promoter in tumorigenesis. However, the role of GJB4 in gastric cancer (GC) is still unclear.Materials and methods: We used Progression-free survival Kaplan-Meier analysis and Western blot analysis to detect the expression of GJB4 in GC tissues and cells. In addition, both in vitro and in vivo assays were used to determine the effect of GJB4 on malignant behavior in GC cells.Results: We found that GJB4 was overexpressed in gastric cancer tissues and cells compared with normal tissues and cells. The high GJB4 expression was significantly associated with poor overall survival of GC patients. Knocking down GJB4 in GC cells significantly suppressed cell proliferation and migration. We found that the effects of GJB4-knockdown on GC cells were associated with downregulation of CTNNB1 and its downstream MYC, MMP7 and CCND1 expression. In addition, we found that the promotive effect of GJB4 overexpression on cell proliferation and migration was negated by XAV-939, which is the inhibitor of Wnt/CTNNB1 pathway. Therefore, we revealed a novel mechanism by which GJB4 could activate the Wnt/CTNNB1 pathway to promote GC cell’s proliferation and migration.Conclusion: This study offer insights into GJB4 function and indicate that GJB4 is a promising biomarker and therapeutic target for gastric cancer patients.Keywords: GJB4, cell proliferation, migration, gastric cancer, CTNNB1

Jianming Li,1–3 Jia Luo,2 Li Liu,2 Hui Fu,2,3 Liang Tang21Department of Neurology, Xiang-ya Hospital, Central South University, Changsha 410219, People’s Republic of China; 2Department of Human Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha, 410219, People’s Republic of China; 3Department of Human Anatomy, School of Basic Medical Science, Changsha Medical University, Changsha, 410219, People’s Republic of ChinaBackground: Different studies have provided some evidence for the association between BST1 polymorphisms and Parkinson’s disease (PD). The extent to which these genetic effects are consistent across different populations is unknown.Methods: A meta-analysis of PD case-control studies using a common set of three variants was conducted. Published reports were obtained from electronic databases including Pubmed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Cochrane Library databases between August 2010 and January 2018.Results: A total of 11 individual studies with 8,725 cases and 17,079 controls were included. The results showed statistically significant association between the dominant model of rs11931532 and PD risk in Asian populations (P=0.006, OR [95% CI]=1.22 [1.06–1.41]). Significant association was also detected between the allelic, dominant, and recessive models of rs4698412 and PD risk in Asian populations (allelic model: P0.05).Conclusion: The meta-analysis suggests that the rs11931532 and rs4698412, but not rs11724635 might be risk factors for PD in Asian populations.Keywords: BST1, Parkinson’s disease, polymorphisms, risk factor

Heli Yang,1 Xiangdong Li,2 Jialun Shi,2 Hao Fu,1 Hao Yang,2 Zhen Liang,1 Hongchao Xiong,1 Hui Wang3 1Department of Thoracic Surgery I, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Haidian, Beijing, People’s Republic of China; 2Department of Cardiothoracic Surgery, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, People’s Republic of China; 3Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China Introduction: This study aimed to develop a practical nomogram to predict prognosis in patients who are undergoing sublobar resection for stage IA non-small-cell lung cancer (NSCLC). Data from Surveillance, Epidemiology, and End Results (SEER) databases were used to construct the nomogram. Methods: Data from patients undergoing sublobar resection for stage IA NSCLC diagnosed between 2004 and 2014 were extracted from the SEER database. Factors that may predict the outcome were identified using the Kaplan–Meier method and the Cox proportional-hazards model. A nomogram was constructed to predict the 3- and 5-year overall survival (OS) and lung cancer-specific survival (LCSS) rates of these patients. The predictive accuracy of the nomogram was measured using the concordance index (C-index) and calibration curve. Results: A total of 4,866 patients were selected for this study. Using univariate and multivariate analyses, eight independent prognostic factors associated with OS were identified, including sex (P

Yushan Han,1,* Xia Zhang,2,* Yishan Lu,3,4 Yan Dong,1 Hong Fu,1 Bin Zhang,1 Yajie Gao1 1Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Department of Oncology, The Fifth People’s Hospital of Dalian, Dalian, People’s Republic of China; 3Queen Mary University of London, London, UK; 4Nanchang University, Nanchang, People’s Republic of China *These authors contributed equally to this work Abstract: CNS metastases are common in patients with non-small-cell lung cancer (NSCLC) and is associated with poor prognosis. In NSCLC patients with EGFR mutations, and ALK fusion oncogene, chemotherapy is ineffective; however, targeted and pulse therapies may be used as alternative treatment options. Elemene can cross the blood–brain barrier and enter the brain tissue. In this paper, treatment consisting of elemene injections in a case of NSCLC with brain metastases, spinal metastases and a possible complication of leptomeningeal metastases is reported, and the efficacy of elemene in treating NSCLC with CNS metastases was investigated. Keywords: NSCLC, CNS metastases, elemene

Siyang Song,1,2,* Hongzhe Fu,2,* Bing He,2 Dan Wang,3 Mengmeng Qin,2 Dan Yang,1,2 Dechun Liu,2 Ge Song,2 Yujie Shi,2 Hua Zhang,2 Xueqing Wang,2 Wenbing Dai,2 Qiang Zhang1,2 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; 2Beijing Key Laboratory of Molecular Pharmaceutics and the State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China; 3Pharmaceutics Department, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China *These authors contributed equally to this work Introduction: Endocytosis of nanomaterials is the first step of nano-bio interaction and current regulation is mostly by nanomaterials but seldom by intracellular signaling proteins. Materials and methods: Herein, we synthesized tubular nanocarbon (oxMWCNT) and lamellar-like nanocarbon (oxGRAPHENE) and formulated their aqueous dispersion. A549 and Caco-2 cells were selected as the models of tumor and intestinal epithelial cells, respectively. After knocking down three members of Rho GTPases (Cdc42, Rac1, RhoA) in these two cell lines, their silencing effects on the uptake pathways of nanomaterials with different morphologies were investigated. Results: An unexpected finding was that the knock-down led to opposite uptake trends in different types of cells. The endocytosis of carbon nanomaterials increased in Caco-2 cells when Rho GTPases were inactivated, while that in A549 cells decreased. For nanomaterials with different shapes, the involved GTPase member of Rho family, or regulating protein molecule, was different. Concretely, Cdc42 and Rac1 were involved in oxMWCNT endocytosis, while all three GTPases participated in oxGRAPHENE internalization. More interestingly, such difference induced different uptake pathways, namely, the cellular uptake of oxMWCNT was clathrin-mediated and oxGRAPHENE was caveolin-modulated, both with the involvement of dynamin. Conclusion: In conclusion, this study provides new insights for the potential intervention in nano-bio interplay. Keywords: shape, cellular uptake, intracellular distribution, nanomaterials, Rho GTPases

Hefan He,1 Weifeng Liu,1 Yingying Zhou,1 Yibin Liu,1 Peiqing Weng,1 Yasong Li,2 Huangde Fu3 1Department of Anesthesia, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, Fujian, China; 2Department of Neurosurgery, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, Fujian, China; 3Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China Background: Sevoflurane post-conditioning exerts nerve-protective effects through inhibiting caspase-dependent neuronal apoptosis after a traumatic brain injury (TBI). Autophagy that is induced by the endoplasmic reticulum stress plays an important role in the secondary neurological dysfunction after a TBI. However, the relationship between autophagy and caspase-dependent apoptosis as well as the underlying nerve protection mechanism that occurs with sevoflurane post-conditioning following a TBI remains unclear. Methods: The Feeney TBI model was used to induce brain injury in rats. Evaluation of the modified neurological severity scores, measurement of brain water content, Nissl staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to determine the neuroprotective effects of the sevoflurane post-conditioning. Both immunofluorescence and Western blot analyses were used to detect the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3-II and Beclin-1, pro-apoptotic factors, as well as the activation of the phosphatidylinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway within the lesioned cortex. Results: Autophagy and neuronal apoptosis were activated in the lesioned cortex following the TBI. Sevoflurane post-conditioning enhanced early autophagy, suppressed neuronal apoptosis, and alleviated brain edema, which improved nerve function after a TBI (all P < 0.05). Sevoflurane post-conditioning induced the activation of PI3K/AKT signaling after the TBI (P < 0.05). The neuroprotective effects of sevoflurane post-conditioning were reversed through the autophagy inhibitor 3-methyladenine treatment. Conclusion: Neuronal apoptosis and the activation of autophagy were involved in the secondary neurological injury following a TBI. Sevoflurane post-conditioning weakened the TBI-induced neuronal apoptosis by regulating autophagy via PI3K/AKT signaling. Keywords: traumatic brain injury, sevoflurane post-conditioning, cell apoptosis, autophagy, PI3K/AKT signaling pathway

Jing Zhou,1 Yangheng Zhang,1 Lingjun Li,1 Huangmei Fu,2 Wenrong Yang,2 Fuhua Yan1 1Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2School of Life and Environmental Science, Centre for Chemistry and Biotechnology, Deakin University, Geelong, VIC, Australia Objective: It is a great challenge to absorb and conduct biophysicochemical interactions at the nano-bio interface. Peptides are emerging as versatile materials whose function can be programmed to perform specific tasks. Peptides combined nanoparticles might be utilized as a new approach of treatment. Human β-defensin 3 (hBD3), possesses both antimicrobial and proregeneration properties. Gold nanoparticles (AuNPs) have shown promising applications in the field of tissue engineering. However, the coordinating effects of AuNPs and hBD3 on human periodontal ligament cells (hPDLCs) remain unknown. In this study, we systematically investigated whether AuNPs and hBD3 would be able to coordinate and enhance the osteogenic differentiation of hPDLCs in inflammatory microenvironments, and the underlying mechanisms was explored. Methods: hPDLCs were stimulated with E. coli-LPS, hBD3 and AuNPs. Alkaline phosphatase (ALP) and alizarin red S staining were used to observe the effects of hBD3 and AuNPs on the osteogenic differentiation of hPDLCs. Real-time PCR and western blot were performed to evaluate the osteogenic differentiation and Wnt/β-catenin signaling pathway related gene and protein expression.Results: In the inflammatory microenvironments stimulated by E. coli-LPS, we found that AuNPs and hBD3 increased the proliferation of hPDLCs slightly. In addition, hBD3-combined AuNPs could significantly enhance ALP activities and mineral deposition in vitro. Meanwhile, we observed that the osteogenic differentiation-related gene and protein expressions of ALP, collagenase-I (COL-1) and runt-related transcription factor 2 (Runx-2) were remarkably upregulated in the presence of hBD3 and AuNPs. Moreover, hBD3-combined AuNPs strongly activated the Wnt/β-catenin signaling pathway and upregulated the gene and protein expression of β-catenin and cyclin D1. Furthermore, hBD3-combined AuNPs induced osteogenesis, which could be reversed by the Wnt/β-catenin signaling pathway inhibitor (ICG-001).Conclusion: The present study demonstrated that hBD3 combined AuNPs could significantly promote the osteogenic differentiation of hPDLCs in inflammatory microenvironments via activating the Wnt/β-catenin signaling pathway. Keywords: hBD3, gold nanoparticles, periodontal ligament cells, osteogenesis, inflammatory microenvironments, Wnt/β-catenin signaling

Zhi-xiang Yuan,1,* Lu Jia,2,* Lee Yong Lim,3 Ju-chun Lin,1 Gang Shu,1 Ling Zhao,1 Gang Ye,1 Xiao-xia Liang,1 Hongming Ji,2 Hua-lin Fu1 1Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 2Department of Neurosurgery, Shanxi Provincial People’ Hospital, Taiyuan, China; 3Pharmacy, Centre for Optimization of Medicines, School of Allied Health, The University of Western Australia, Crawley, Australia *These authors contributed equally to this work Abstract: Previously, 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20)-modified liposomes were reported to specifically target mesangial cells (MCs) in glomeruli. To further gain a better understanding of the characteristics and potential application for glomerular diseases of TRX-20-modified liposomes, we synthesized TRX-20 and prepared TRX-20-modified liposomes (TRX-LPs) with different molar ratios – 6% (6%-TRX-LP), 11% (11%-TRX-LP), and 14% (14%-TRX-LP) – of TRX-20 to total lipid in the present study. All TRX-LPs exhibited concentration-dependent toxicity against the MCs at a lipid concentration ranging from 0.01 to 1.0 mg/mL with IC50 values of 3.45, 1.13, and 0.55 mg/mL, respectively. Comparison of the cell viability of TRX-LPs indicated that high levels of TRX-20 caused severe cell mortality, with 11%-TRX-LP showing the higher cytoplasmic accumulation in the MCs. Triptolide (TP) as a model drug was first loaded into 11%-TRX-LP and the liposomes were further modified with PEG5000 (PEG-TRX-TP-LP) in an attempt to prolong their circulation in blood and enhance TP-mediated immune suppression. Due to specific binding to MCs, PEG-TRX-TP-LP undoubtedly showed better anti-inflammatory action in vitro, evidenced by the inhibition of release of nitric oxide (NO) and tumor necrosis factor-α from lipopolysaccharide-stimulated MCs, compared with free TP at the same dose. In vivo, the PEG-TRX-TP-LP effectively attenuated the symptoms of membranous nephropathic (MN) rats and improved biochemical markers including proteinuria, serum cholesterol, and albumin. Therefore, it can be concluded that the TRX-modified liposome is an effective platform to target the delivery of TP to glomeruli for the treatment of MN. Keywords: triptolide, pegylated liposomes, TRX-20, renal targeting, mesangial cells

Phase field (diffuse interface) models accommodate diffusive triple line motion with variable contact angle, thus allowing for the no-slip boundary condition without the stress singularities. We consider two commonly used classes of phase field models: the compositionally compressible (CC) model with compressibility limited to the fluid mix within the diffuse interface, and the incompressible (IC) model. First, we show that the CC model applied to fluids with dissimilar mass densities exhibits the computational instability leading to the breakup of the triple line. We provide a qualitative physical explanation of this instability and argue that the compositional compressibility within the diffuse interface is inconsistent with the global incompressible flow. Second, we derive the IC model as a systematic approximation to the CC model, based on a suitable choice of continuum velocity field. Third, we benchmark the IC model against sharp interface theory and experimental kinetics. The triple line kinetics is well represented by the triple line mobility parameter. Finally, we investigate the effects of the bulk phase field diffusional mobility parameter on the kinetics of the wetting process and find that within a wide range of magnitudes the bulk mobility does not affect the flow.

Yuliang Pan,1,2 Jun Zhang,1 Huiqun Fu,1 Liangfang Shen2 1Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Oncology Radiotherapy, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China Abstract: Breast cancer is the most common cancer in women worldwide. Local invasion, metastasis, and chemotherapy resistance are the obstacles for treatment of breast cancer. In this study, we aim to investigate the role of miR-144 in breast cancer. We demonstrate that the expression of miR-144 is downregulated in breast cancer and cell lines, and lower miR-144 expression is associated with poor differentiation, higher clinical stage, and lymph node metastasis in patients with breast cancer. The rescue of miR-144 expression is able to inhibit the cell proliferation and the ability of cell migration and invasion. In addition, we show that miR-144 can directly target at 3'-untranslation region of zinc finger E-box-binding homeobox 1 and 2, that is, ZEB1 and ZEB2, and regulate their expression at transcriptional and translational levels. Moreover, we also demonstrate that ectopic expression of miR-144 can inhibit the process of epithelial mesenchymal transition in MCF-7 and MDA-MB-231 cells. Thus, we here demonstrate that miR-144 functions as a tumor suppressor in breast cancer at least partly through inhibiting ZEB1/2-mediated epithelial mesenchymal transition process. Our findings indicate that the miR-144-ZEB1/2 signaling could represent a promising therapeutic target for breast cancer treatment. Keywords: breast cancer, miR-144, ZEB1, ZEB2, epithelial mesenchymal transition

Hui Fu,1,2,* Lisha Qi,2,3,* Lu Chen,1,2 Yuchao He,1,2 Ning Zhang,1,2 Hua Guo1,2 1Department of Tumor Cell Biology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, 2The Key Laboratory of Tianjin Cancer Prevention and Treatment, National Clinical Research Center for Cancer, 3Department of Pathology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Metastasis involves epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition. Ovol2 belongs to the Ovo-like family (Ovol) of evolutionarily conserved zinc-finger transcription factors that regulate gene expression in various differentiation processes. Recent studies have demonstrated that Ovols affect mesenchymal–epithelial transition by inducing the expression of miR-200 in a range of human cancers. Downregulated Ovol2 expression is involved in the invasion and metastasis of breast and prostate cancers, but little is known about its expression and prognostic value in other cancers, including hepatocellular carcinoma (HCC). This study was designed to explore the clinical and prognostic significance of Ovol2 in patients with HCC. The expression of Ovol2 in tumor samples from patients with HCC and HCC cell lines was examined using Western blotting, real-time polymerase chain reaction, and immunohistochemistry. The expression levels of EMT-related markers, including E-cadherin, N-cadherin, and vimentin, were detected in relation to Ovol2 expression. The prognostic significance of Ovol2 in patients with HCC was statistically analyzed by Kaplan–Meier and Cox regression analyses. Ovol2 expression was significantly lower in HCC tissues than in adjacent noncancerous tissues. Low expression of Ovol2 was detected in HCC tissues with poor histological differentiation, microvascular invasion, and cirrhosis. A significant relationship was observed between Ovol2 and EMT marker expression levels. Kaplan–Meier analysis showed that overall survival was significantly worse in patients with HCC with low Ovol2 expression, indicating that Ovol2 deletion was an independent predictor of unfavorable prognosis in patients with HCC. Elevated Ovol2 expression may suppress HCC cell invasion and metastasis via restricting EMT. Keywords: Ovol2, hepatocellular carcinoma, prognosis, epithelial–mesenchymal transition, mesenchymal–epithelial transition