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Yanting Ma,1 Yongyuan Li,2 Zhanfeng Zhang,3 Guomei Du,4 Ting Huang,1 Zhi Zhong Zhao,5 Shou Liu,1 Zhancui Dang1 1Department of Public Health, Medical College, Qinghai University, Xining, Qinghai, People’s Republic of China; 2Disease Control department, Huangzhong District health Bureau, Xining, Qinghai, People’s Republic of China; 3Huangzhong District, Duoba County Health Services Center, Xining, Qinghai, People’s Republic of China; 4Clinical Laboratory, Qinghai Red Cross Hospital, Xining, Qinghai, People’s Republic of China; 5Disease Control Department, Qinghai Provincial Center for Endemic Disease Control and Prevention, Xining, Qinghai, People’s Republic of ChinaCorrespondence: Shou Liu; Zhancui Dang, Email liushou2004@aliyun.com; yxyyy2019@163.comPurpose: The prevalence of metabolic syndrome (MetS) is increasing worldwide, and early prediction of MetS risk is highly beneficial for health outcomes. This study aimed to develop and validate a nomogram to predict MetS risk in Qinghai Province, China, and it provides a methodological reference for MetS prevention and control in Qinghai Province, China.Patients and Methods: A total of 3073 participants living between 1900 and 3710 meters above sea level in Qinghai Province participated in this study between March 2014 and March 2016. We omitted 12 subjects who were missing diagnostic component data for MetS, ultimately resulting in 3061 research subjects, 70% of the subjects were assigned randomly to the training set, and the remaining subjects were assigned to the validation set. The least absolute shrinkage and selection operator (LASSO) regression analysis method was used for variable selection via running cyclic coordinate descent with 10-fold cross-validation. Multivariable logistic regression was then performed to develop a predictive model and nomogram. The receiver operating characteristic (ROC) curves was used for model evaluation, and calibration plot and decision curve analysis (DCA) were used for model validation.Results: Of 24 variables studied, 6 risk predictors were identified by LASSO regression analysis: hyperlipidaemia, hyperglycemia, abdominal obesity, systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI). A prediction model including these 6 risk factors was constructed and displayed good predictability with an area under the ROC curve of 0.914 for the training set and 0.930 for the validation set. DCA revealed that if the threshold probability of MetS is less than 82%, the application of this nomogram is more beneficial than both the treat-all or treat-none strategies.Conclusion: The nomogram developed in our study demonstrated strong discriminative power and clinical applicability, making it a valuable reference for meets prevention and control in the plateau areas of Qinghai Province.Keywords: metabolic syndrome, nomogram, prediction model, plateau section

Fu-Li Zhu,1,2 Ting Huang,3 Zi-Li Lv,4 Gang Liang,5 Zhen Yao,2 Lian-Cheng Lan,2 Abdul Qadir,2 Xiu-Qi Chen,2 Qing-Wen Shan2 1Department of Pediatrics, the First College of Clinical Medical Science, China Three Gorges University, Yichang Central People’s Hospital, Yichang, Hubei, 443000, People’s Republic of China; 2Department of Pediatrics, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 3Guangxi Key Laboratory of Aquatic Genetic Breeding and Healthy Aquaculture, Guangxi Academy of Fishery Science, Nanning, Guangxi, 530021, People’s Republic of China; 4Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 5Department of Pathophysiology, School of Basic Medical Sciences of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Qing-Wen Shan; Xiu-Qi Chen, Department of Pediatrics, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email shanqw333@163.com; chenxiuqi@gxmu.edu.cnPurpose: To investigate the intestinal inflammatory response and the abundance of intestinal bacteria in rats with high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and assess the intervention effects of taurine (TAU).Methods: Forty male Sprague-Dawley rats were randomly divided into five groups: group I, normal diet and normal saline gavage; group II, normal diet and TAU gavage; group III, HFD and normal saline gavage; group IV, HFD and TAU gavage (from the 1st week); group V, HFD and TAU gavage (from the 10th week). At the end of the 16th week, all the animals were sacrificed. Body weight, liver weight, liver function, and serum lipid levels were measured. The histopathologies of the liver and ileum were observed. The mRNA and protein expression levels of interleukin 17 (IL-17) and IL-10 in the ileum were detected by reverse transcription quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Three types of bacteria were detected in intestinal feces using the 16S rDNA qPCR method.Results: The ileal IL-17 level in group III was significantly higher than those in the other four groups (P < 0.01). The ileal IL-10 mRNA levels in group IV was significantly higher than those in groups III and V (P < 0.05), and IL-10 protein MOD levels in group III was significantly lower than those in the other four groups (P < 0.01). The numbers of Lactobacillus in group III were significantly lower than those in the other four groups (P < 0.01 or P < 0.05). The numbers of Bifidobacteria in groups IV and V were significantly increased compared with that in group III (P < 0.05).Conclusion: TAU may down-regulate the expression of IL-17, up-regulate the expression of IL-10 and regulate the intestinal flora, and alleviate the liver and intestinal damage in rats with HFD-induced NAFLD.Keywords: taurine, non-alcoholic fatty liver disease, interleukin 17, interleukin 10, intestinal barrier, gut microbiota

Xiuwen Zhang,1,&ast; Yibo Zhang,2– 4,&ast; Chen Pu,5 Lehua Wang,5 Yusu Ni,2– 4 Taomin Huang1 1Department of Pharmacy, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Otology and Skull Base Surgery, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China; 3NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai, People’s Republic of China; 4ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China; 5School of Pharmacy, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Taomin Huang, Department of Pharmacy, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China, Tel +86-21-64373955, Email taominhuang@126.com Yusu Ni, Department of Otology and Skull Base Surgery, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China, Tel +86-21-64377134, Email niyusu@aliyun.comPurpose: This study aimed to elucidate the etiologies, microbiological profiles, antibiotic susceptibilities of bacteria and outcomes of patients with auricular perichondritis.Patients and Methods: This was a single-center retrospective study. Inpatients diagnosed with auricular perichondritis at a university teaching hospital in eastern China between January 2013 and December 2022 were included in this study.Results: A total of 127 patients were enrolled, with an average age of 50.6 ± 16.9 years. In addition to cases in which the etiology remained undetermined in 37% of the patients, postoperative infection emerged as the predominant cause (37.8%), followed by trauma (18.1%). Among the 61 cultured isolates, 21.3% were gram-positive bacteria, 55.7% were gram-negative bacteria, and 23.0% were fungal isolates. The most frequent isolate was Pseudomonas aeruginosa (30/61, 49.2%). Notably, the incidence of fungal infections was markedly higher among postoperative patients than among post-traumatic patients (41.7% vs 7.1%, p = 0.03). The proportions of gram-negative bacteria (60.0% vs 50.0%) and fungal isolates (28.6% vs 15.4%) exhibited an increasing trend during the period of 2018– 2022, as compared to the previous period of 2013– 2017. The bacterial isolates exhibited high susceptibility to vancomycin (100%), amikacin (100%), cefepime (94.6%), and ceftazidime (90.9%). In contrast, overall susceptibility to fluoroquinolones was relatively low (65.2– 67.4%), demonstrating a declining trend in the susceptibility of Pseudomonas aeruginosa. Notably, 78.7% of the patients received an initial treatment regimen covering Pseudomonas aeruginosa. Within 30 days of discharge, 8.5% (6/71) experienced an infection recurrence.Conclusion: Auricular perichondritis predominantly originates from iatrogenic (postoperative) infections. Antibiotic therapy covering Pseudomonas aeruginosa is a sensible and appropriate empirical treatment in the majority of patients with auricular perichondritis. However, increased resistance to fluoroquinolones has become a notable concern, suggesting the need to seek new, more aggressive strategies.Keywords: auricular perichondritis, antibiotic sensitivity, Pseudomonas aeruginosa, fluoroquinolones

Tao Huang,1,&ast; Yongling Lv,2,&ast; Wei Wang,1 Yunyao Chen,1 Lixin Fan,1 Zhaowei Teng,3 Xianfeng Zhou,2,4 Hexiao Shen,2 Guang Fu1 1Gastrointestinal Surgery, Wuhan Puren Hospital, Wuhan, People’s Republic of China; 2Maintainbiotech. Ltd. (Wuhan), Wuhan, People’s Republic of China; 3Central Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4School of Life Sciences and Health Engineering, Hubei University of Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hexiao Shen; Guang Fu, Email shenhxmyt@163.com; fuguang71@163.comAbstract: Adverse skin reactions caused by the COVID-19 vaccine have attracted considerable attention. As we all know, the development mechanism of some skin diseases is related to the gut and skin microbiome. A 78-year-old male patient who received the COVID-19 vaccine developed generalized eczema with multiple dense black patches over the body, a widespread rash, erosion, and scabs on his limbs, as well as facial edema. The patient experienced recurrent flare-ups after conventional treatment, but then recovered well without recurrence after undergoing three fecal microbial transplantation (FMT) treatments. This rare case is reported for the first time in this study. This report demonstrates the possible potential of FMT in targeting refractory skin diseases, such as eczema, as well as diseases associated with gut microbiota disturbance after vaccination.Keywords: FMT, eczema, COVID-19 vaccine

Weimin Bai,1,&ast; Taoke Huang,2,&ast; Xinying Li,3,&ast; Weiyang Gao,2 Ji Qin,2 Yongxin Bian,4 Weihao Xu,5 Juan Xu,6 Lijie Qin1 1Department of Emergency, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, 463599, People’s Republic of China; 2Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 3Faculty of Postgraduate Education, Shandong Sport University, Jinan, 250102, People’s Republic of China; 4The First School of Clinical Medicine, Binzhou Medical University, Yantai, 264003, People’s Republic of China; 5Haikou Cadre’s Sanitarium of Hainan Military Region, Haikou, 570203, People’s Republic of China; 6Department of General Surgery, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, 311202, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Xu; Lijie Qin, Email sophia2932@163.com; qinlijie1819@163.comBackground: Frailty is a risk factor for acute myocardial infarction (AMI). This study examined the association between the modified frailty index (MFI) and adverse outcomes in patients with critical AMI.Methods: Data were obtained from the Medical Information Mart for Intensive Care IV database. Logistic and Cox regression models and a competing risk model were applied.Results: Of 5003 patients, 1496 were non-frail and 3507 were frail. Frailty was significantly associated with in-hospital mortality (per point, OR 1.13, 95% CI: 1.05– 1.21; frail vs non-frail, OR 1.31, 95% CI: 1.04– 1.65) and 1-year mortality (per point, HR 1.15, 95% CI: 1.11– 1.20; frail vs non-frail, HR 1.37, 95% CI: 1.20– 1.58). Frailty was significantly associated with post-discharge care needs (per point, OR 1.23, 95% CI: 1.14– 1.33; frail vs non-frail, OR 1.47, 95% CI: 1.22– 1.78). In the competing risk models, frailty was significantly associated with a lower probability of being discharged from the ICU (per point, HR 0.87, 95% CI: 0.85– 0.90; frail vs non-frail, HR 0.73, 95% CI: 0.68– 0.79) and hospital (per point, HR 0.82, 95% CI: 0.80– 0.85; frail vs non-frail, HR 0.62, 95% CI: 0.57– 0.68). Subgroup analyses showed the association of frailty with in-hospital and 1-year mortality was stronger in patients with a SOFA score ≤ 2 than in those with a SOFA score > 2 (both p< 0.05 for interaction).Conclusion: Frailty assessed by the MFI was an independent predictor of adverse outcomes in patients with critical AMI and may be helpful for prognostic risk stratification.Keywords: frailty, modified frailty index, acute myocardial infarction, critically ill patients, prognosis

Tingxuan Huang, Youjia Wu, Lingyi Huang, Renyi Lin, Zhenyue Li, Xiaoxiao Wang, Pingping Wu, Liying Huang School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Liying Huang; Pingping Wu, School of Pharmacy, Fujian Medical University, Xuefu North Road University Town, Fuzhou, Fujian, 350122, People’s Republic of China, Tel +8613860635139 ; +8615980271679, Fax +86059422862016, Email fjmuhly88@sina.com; 631763708@qq.comPurpose: Compound Anoectochilus roxburghii (Wall.) Lindl oral liquid (CAROL) is often as a hepatoprotective agent. The present study aimed to elucidate the protective mechanism of CAROL against alcoholic liver injury in rats by untargeted metabolomics combined with multivariate statistical analysis.Methods: An alcoholic liver disease model was established in sprague-dawley (SD) rats by gavage of alcohol, and CAROL treatment was administered. The hepatoprotective effect of CAROL was evaluated by examining liver tissues changes and detecting biochemical index activities and cytokines in serum and liver homogenates. The metabolites in serum samples were examined using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC–QTOF/MS) and multivariate statistical analysis to screen for differentially expressed metabolites and Kyoto Encyclopedia of Genes and Genomes (KEGG) to assess potential metabolic pathways.Results: CAROL has the potential to downregulate inflammation levels and alleviate oxidative stress. The differential metabolites are mainly engaged in riboflavin metabolism, arginine and proline metabolism, phenylalanine, tyrosine and tryptophan biosynthesis metabolism, phenylalanine metabolism, pyrimidine metabolism, and vitamin B6 metabolism to achieve hepatoprotective effects.Conclusion: CAROL may exhibit beneficial hepatoprotective effects by reducing inflammation, mitigating oxidative stress, and modulating metabolites and their metabolic pathways.This study has important implications for advancing the clinical application of CAROL. Keywords: compound Anoectochilus roxburghii (Wall.) Lindl. oral liquid, alcoholic liver injury, untargeted metabolomics, UHPLC–QTOF/MS, metabolic pathway analysis

The article examines and assesses the phenomenological strength theory of composite materials. A comparative analysis of the theoretical envelopes was conducted for each criterion. A unified form of the phenomenological strength criterion was established. The study specifically examined the effects of altering the interaction parameter on the Tsai-Wu criterion’s theoretical envelope. Based on the available experimental data, the study plotted the failure envelopes of each strength criterion under planar composite stress states. The variation of these envelopes across various stress quadrants was highlighted. As a result of the examinations, four typical phenomenological strength criteria were chosen. The composites’ off-axis tensile and biaxial loading test data were used to evaluate the predictive power objectively. The results showed that not all stress states’ test results agreed with the predictions of the phenomenological strength theory. The criterion proposed by Norris and Tsai-Hill performed better at accounting for the material’s different compressive and tensile characteristics. The other criteria tended to be conservative under particular circumstances. Simultaneously, the Hoffman criterion matched the test data more closely over a broader range of stress states. Overall, this study clarified the limitations and applicability of various strength criteria in composite material strength prediction.

Xiaofeng Zhang,1,&ast; Jiaqi Zhang,1,&ast; Yongzhi Cai,1 Yue Li,1 Shiyun Qin,1 Jingtao Li,1 Decai Zeng,1 Tongtong Huang,1 Liu Liu Huang,2 Yanfen Zhong,1 Lihui Wei,1 Ji Wu1 1Department of Ultrasonic Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Cardiothoracic Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ji Wu, Email gxnnwuji@163.comBackground: Rheumatic mitral stenosis(RMS) may leads to left ventricular remodeling (LVR), which can persist even after valve surgery. Identifying markers for early structure and function in patients with rheumatic heart disease who are at risk for adverse LVR after surgery can help determine the optimal timing of intervention. This study aimed to investigate whether preoperative parameters of global left ventricular long-axis strain (LVGLS) and mechanical discretization (MD) could predict postoperative adverse LVR.Methods: A total of 109 adult patients with RMS and 50 healthy controls were enrolled in this study. Baseline clinical features, conventional echocardiography results, LVGLS, and MD were compared between the two groups. Pre- and post-surgery echocardiography measurements were collected, and adverse LVR was defined as a> 15% increase in left ventricular end-diastolic volume or > 10% decrease in left ventricular ejection fraction. Binary regression analysis was used to determine independent predictors of poor left ventricular remodeling.Results: The variables associated with adverse LVR in this study were LVGLS (P< 0.001, odds ratio: 1.996, 95% CI: 1.394– 2.856) and MD (P=0.011, odds ratio: 1.031, 95% CI: 1.007– 1.055). The poorly reconstructed group had lower absolute values of LVGLS and higher MD than the healthy control group and the non-poorly reconstructed group. A LVGLS cutoff of − 15.0% was the best predictor for patients with poorly reconstructed LVR (sensitivity: 75.7%; specificity: 100.0%; AUC: 0.93), and a MD cutoff of 63.8ms was the best predictor (sensitivity: 63.8%; specificity: 98.6%; AUC: 0.88).Conclusion: Speckle tracking echocardiography has potential value for predicting the progression of adverse LVR and for identifying non-responders among patients with RMS undergoing surgery.Keywords: rheumatic mitral stenosis, left ventricular remodeling, left ventricular global longitudinal strain, mechanical dispersion, speckle tracking echocardiography

Ruting Bo,1,2,&ast; Zhi Xiong,3,&ast; Ting Huang,4 Lingling Liu,4 Zhiqiang Chen2,4 1Department of Ultrasound Tianjin Hospital, Tianjin, 300200, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital of Hainan Medical University, Haikou, 570102, People’s Republic of China; 3Department of Radiology, Xianning Central Hospital, Xianning, 437100, People’s Republic of China; 4Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiqiang Chen, Department of Radiology, The First Affiliated Hospital of Hainan Medical University, No. 31, Longhua Road, Haikou, Hainan Province, 570102, People’s Republic of China, Email zhiqiang_chen99@nyfy.com.cnBackground: Hematoma enlargement (HE) is a common complication following acute intracerebral hemorrhage (ICH) and is associated with early deterioration and unfavorable clinical outcomes. This study aimed to evaluate the predictive performance of a computed tomography (CT) based model that utilizes deep learning features in identifying HE.Methods: A total of 408 patients were retrospectively enrolled between January 2015 and December 2020 from our institution. We designed an automatic model that could mask the hematoma area and fusion features of radiomics, clinical data, and convolutional neural network (CNN) in a hybrid model. We assessed the model’s performance by using confusion matrix metrics (CM), the area under the receiver operating characteristics curve (AUC), and other statistical indicators.Results: After automated masking, 408 patients were randomly divided into two cohorts with 204 patients in the training set and 204 patients in the validation set. The first cohort trained the CNN model, from which we then extracted radiomics, clinical data, and CNN features for the second validation cohort. After feature selection by K-highest score, a support vector machines (SVM) model classification was used to predict HE. Our hybrid model exhibited a high AUC of 0.949, and 0.95 of precision, 0.83 of recall, and 0.94 of average precision (AP). The CM found that only 5 cases were misidentified by the model.Conclusion: The automatic hybrid model we developed is an end-to-end method and can assist in clinical decision-making, thereby facilitating personalized treatment for patients with ICH.Keywords: radiomics, hematoma expansion, prediction, convolutional neural networks, intracerebral hemorrhage

Hua Wu,1 Xiaojun Zhou,1 Fan Zhou,2 Dongliang Huang,3 Tao Huang1 1Department of Laboratory Medicine, Hainan General Hospital, Affiliated Hainan Hospital of Hainan Medical College, Haikou, People’s Republic of China; 2International School of Public Health and One Health, Hainan Medical University, Haikou, People’s Republic of China; 3Emergency Department, Armed Police Hospital of Hainan, Haikou, People’s Republic of ChinaCorrespondence: Tao Huang, Department of Laboratory Medicine, Hainan General Hospital, Affiliated Hainan Hospital of Hainan Medical College, No. 19, Xiuhua Road, Xiuying District, Haikou, 570311, People’s Republic of China, Tel +868986842560, Email 13005080993@163.comAbstract: DL96 Microbial Identification/Antimicrobial Susceptibility Testing (ID/AST) System (Zhuhai DL, Guangdong, China) is one of the most commonly used commercial ID/AST System in China. This study aims to evaluate the performance of DL 96E for Antimicrobial Susceptibility Testing (AST) of 270 Enterobacterales isolates from Hainan general hospital using the broth microdilution method (BMD) as reference method. CLSI M52 criteria was followed when analyzing the evaluation results. Twenty antimicrobial agents were evaluated, and categorical agreement (CA) ranged from 62.8% to 96.5%. Imipenem had the lowest CA (63.9%) and highest very major errors (VME) (52.8%). A total of 103 carbapenem-resistant Enterobacterales were evaluated; DL 96E miss identified 22 isolates, including six carbapenemase-producing Enterobacteriaceae. DL 96E must adjust the Minimum Inhibitory Concentration (MIC) ranges of ciprofloxacin, levofloxacin, and piperacillin-tazobactam to cover Clinical and Laboratory Standards Institute (CLSI) breakpoints, adjust the formulation of some antimicrobial, such as imipenem, and increase the MIC detection range to cover the Quality control (QC) strains’ MIC range.Keywords: antimicrobial susceptibility testing, broth microdilution method, minimum inhibitory concentration, categorical agreement

Xiaohui Wang,1,&ast; Bo Wu,2,&ast; Guogen Sun,3 Wenxi He,4 Jia Gao,1 Teng Huang,1 Jing Liu,1 Qing Zhou,1 Xiaoyu He,5 Shu Zhang,1 Zixiong Zhang,2 He Zhu1 1The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, People’s Republic of China; 2The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Selenium and Human Health Institute, Enshi, Hubei, People’s Republic of China; 3Hubei Selenium and Human Health Institute, Enshi, Hubei, People’s Republic of China; 4Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 5Branch of National Clinical Research Center for Metabolic Diseases, Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zixiong Zhang, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Selenium and Human Health Institute, No. 158, Muyang Avenue, Enshi, Hubei, People’s Republic of China, Email 596099670@qq.com He Zhu, The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei, People’s Republic of China, Email Zhuh@tjh.tjmu.edu.cnPurpose: Pancreatic adenocarcinoma (PAAD) presents an extremely high morbidity and mortality rate. Broccoli has excellent anti-cancer properties. However, the dosage and serious side effects still limit the application of broccoli and its derivatives for cancer therapy. Recently, extracellular vesicles (EVs) derived from plants are emerging as novel therapeutic agents. Thus, we conducted this study to determine the effectiveness of EVs isolated from Se-riched broccoli (Se-BDEVs) and conventional broccoli (cBDEVs) for the treatment of PAAD.Methods: In this study, we first isolated Se-BDEVs and cBDEVs by a differential centrifugation method, and characterized them by using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Then, miRNA-seq was combined with target genes prediction, and functional enrichment analysis to reveal the potential function of Se-BDEVs and cBDEVs. Finally, the functional verification was conducted in PANC-1 cells.Results: Se-BDEVs and cBDEVs exhibited similar characteristics in size and morphology. Subsequent miRNA-seq revealed the expression of miRNAs in Se-BDEVs and cBDEVs. Using a combination of miRNA target prediction and KEGG functional analysis, we found miRNAs in Se-BDEVs and cBDEVs may play an important role in treating pancreatic cancer. Indeed, our in vitro study showed that Se-BDEVs had greater anti-PAAD potency than cBDEVs due to increased bna-miR167a_R-2 (miR167a) expression. Transfection with miR167a mimics significantly induced apoptosis of PANC-1 cells. Mechanistically, further bioinformatics analysis showed that IRS1, which is involved in the PI3K-AKT pathway, is the key target gene of miR167a.Conclusion: This study highlights the role of miR167a transported by Se-BDEVs which could be a new tool for counteracting tumorigenesis.Graphical Abstract: Keywords: selenium, broccoli, extracellular vesicles, apoptosis, pancreatic cancer

Ziyuan Li,1,&ast; Yu Gan,1,&ast; Ting Kang,1,&ast; Yi Zhao,1 Tianguang Huang,2 Yuhao Chen,3 Jin Liu,1 Bowen Ke1 1Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Frontiers Science Center for Disease-Related Molecular Network, Sichuan University West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bowen Ke, Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, People’s Republic of China, Tel +86-28-85422114, Fax +86-28-85582944, Email bowenke@scu.edu.cnBackground: The treatment of neuropathic pain is still a major troublesome clinical problem. The existing therapeutic drugs have limited analgesic effect and obvious adverse reactions, which presents opportunities and challenges for the development of new analgesic drugs. Camphor, a kind of monoterpene, has been shown anti-inflammatory and analgesic effects in traditional Chinese medicine. But we know little about its effect in neuropathic pain. In this article, We have verified the reliable analgesic effect of camphor in the neuropathic pain model caused by different predispositions.Methods: The nociceptive response of mice was induced by transient receptor potential A1 (TRPA1) agonist to verify the effect of camphor on the nociceptive response. Multiple paclitaxel (PTX) injection models, Single oxaliplatin (OXA) injection models, Chronic constriction injury (CCI) models and Streptozotocin-induced (STZ) diabetic neuropathic pain models were used in this study. We verified the analgesic effect of camphor in mice by acetone test and conditioned place aversion test. At the same time, comparing the adverse reaction of nervous system between camphor and pregabalin at equivalent dose in locomotor activity test and rotarod test. Using patch clamp to verify the effect of camphor on dorsal root ganglion (DRG) excitability.Results: In behavioral test, compared with vehicle group, camphor significantly reduced the spontaneous nociception caused by TRPA1 agonist-formalina and allyl isothiocyanate (AITC). Compared with vehicle group, camphor significantly reduced the flinching and licking time in neuropathic pain model mice, including PTX, OXA, STZ and CCI induced peripheral neuralgia models. Compared with vehicle group, pregabalin significantly increased the resting time and reduced the average speed without resting and distance in locomotor activity test, reduced the time stayed on rotarod in rotarod test. In patch clamp test, compared with vehicle group, camphor significantly reduced the action potential (AP) firing frequency of DRG.Conclusion: Camphor can alleviate the symptoms of hyperalgesia in various neuropathic pain models, and has no obvious adverse reactions compared with pregabalin. This effect is related to the down-regulation of DRG neuron excitability.Keywords: camphor, neuropathic pain, TRPA1, hyperalgesia

Hongtao Cheng,1 Zichen Wang,2 Wan-Jie Gu,3 Xin Yang,1 Simeng Song,1 Tao Huang,2 Jun Lyu2,4 1School of Nursing, Jinan University, Guangzhou, People’s Republic of China; 2Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, People’s Republic of ChinaCorrespondence: Jun Lyu, Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China, Tel +86-20-38680061, Email lyujun2020@jnu.edu.cnBackground: Falls are a major public health problem in the older adults that can lead to poor clinical outcomes. There have been few reports on the short-term prognoses of older critically ill patients, and so we sought to determine the impact of falls on elderly patients in intensive care units (ICUs).Patients and Methods: This retrospective study of 4503 patients (aged 65 years or older) analyzed data in the Medical Information Mart for Intensive Care-III critical care database. Of those, 2459 (54.6%) older adults are males, and 2044 (45.4%) older adults are females. Based on information from the medical care record assessment forms, patients were classified into the following two groups based on whether they had a fall within the previous 3 months: falls (n=1142) and nonfalls (n=3361). The primary outcomes of this study were 30- and 90-day mortality. Associations between the results of the Kaplan-Meier (KM) survival analysis, Cox proportional-hazards regression models, and subgroup analysis and its outcomes were analyzed using stabilized inverse probability treatment weighting (IPTW).Results: KM survival curves with stabilized IPTW indicated that 30- and 90-day survival rates were significantly lower in elderly critically ill patients with a history of falls within the previous 3 months than in those patients without a history of falls (all p< 0.001). Multivariate Cox proportional-hazards regression analysis indicated that 30- and 90-day mortality rates were 1.35 times higher (95% confidence interval [CI]=1.16– 1.57, p< 0.001) and 1.36 times higher (95% CI=1.19– 1.55, p< 0.001), respectively, in elderly critically ill patients with a history of falls within the previous 3 months than in those patients without a history of falls.Conclusion: Experience of falls within the previous 3 months prior to ICU admission increased the risk of short-term mortality and affected the prognoses of elderly patients. Falls should therefore receive adequate attention from clinical healthcare providers and management decision-makers.Keywords: accidental falls, older adults, inverse probability treatment weighting, intensive care unit

Jie Li,1,&ast; Siwen Chen,1,&ast; Hui Xue,2,&ast; Haoyi Wang,3,&ast; Tianwei Huang,4 Hongya Xie,5 Jiang He,6 Cai Ke,3 Zhaonan Yu,3 Bin Ni4 1Department of General Medical Ward, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Oncology Medical Ward, Hanzhong Central Hospital, Hanzhong, People’s Republic of China; 3Hangzhou D.A. Medical Laboratory, Hangzhou, People’s Republic of China; 4Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 5Department of Thoracic Surgery, Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 6Department of Thoracic Surgery, Suzhou Wuzhong People’s Hospital, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Ni, Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Tel +86 17774015977, Email bin_ni@163.com Zhaonan Yu, Hangzhou D.A. Medical Laboratory, Hangzhou, People’s Republic of China, Tel +86 15558078770, Email yuzhaonan870213@163.comIntroduction: From an oncologic perspective, genetic detection is becoming a frontline clinical test, used to identify actionable alterations for targeted therapy, monitor molecular clonal tumor evolution, indicate disease progression and prognosis, and predict medication efficacy and resistance. From analysis of both tumor tissue and cell-free DNA from a large cohort of non-small cell lung cancer patients in East-China, we characterized the full spectrum of genomic alterations.Methods: The study comprised 3000 unpaired samples including 1351 tumor tissue DNA (tDNA) and 1649 cell-free circulating tumor DNA (cfDNA) samples, from which 67 cancer-related genes were sequenced and the genetic alteration profiles were depicted. Integrative molecular analyses identified the frequently mutated genes, uncovered co-occurring somatic alterations, described the distribution of hotspot variants, analyzed the frequency of variant alleles, and notably distinguished actionable, novel variants.Results: The most commonly affected genes were EGFR, TP53, KRAS, CDKN2A, and PIK3CA in both tDNA and cfDNA samples. EGFR and CTNNB1, PIK3CA and PTEN, ERBB2 and SMO were found to have frequent co-occurring alterations in tDNA samples, while EGFR and SMO, KRAS and PDGFRA, PIK3CA and KDR were in cfDNA samples. A large number of primary druggable variants were identified in tDNA samples, while numerous drug-resistance variants, rare actionable variants, and non-EGFR actionable variants were detected in cfDNA samples. Novel variants were enriched in KDR, KIT, TP53, ABL1, FGFR1 in tDNA samples while the majority of novel variants were distributed in PDGFRA, EGFR, KIT, ROS1, BRCA2 in cfDNA samples. Variant allele frequency in tDNA samples was significantly (P < 0.001) higher than that in cfDNA samples.Conclusion: The results revealed considerable differences in the alteration characteristics between the two kinds of specimens. To date, this study represents the largest real-world investigation of its kind, derived from the largest number of patients in East-China. It reinforced and expanded the mechanism of molecular analysis of neoplastic genetic profiles.Keywords: real world study, non-small cell lung cancer patients in East-China, tumor tissue DNA, cell-free circulating tumor DNA, next-generation-sequencing, genetic alteration

Minhua Lin,1 Tianxiang Huang,2 Xuan Wang,1 Xuenan Li,3 Jingjiao Ma,3 Lan Su,3 Jun Wu2 1Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Beijing Genetron Health, Co. Ltd, Beijing, 102206, People’s Republic of ChinaCorrespondence: Jun Wu, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China, Tel +86 13508480515, Fax +86 731-89753039, Email junwucs@csu.edu.cnIntroduction: NF-κB signaling is involved in a wide range of biological processes including cell proliferation, cell survival and immunity. Meanwhile, as one of the major oncogenic pathways, its upregulation has been observed in many cancer types. Compared with canonical NF-κB signaling, its non-canonical branch was much less studied in cancerous context.Methods: In this study, we leveraged multi-omics data across multiple platforms to investigate the activity of non-canonical NF-κB signaling in low-grade glioma (LGG) and explore its connection with molecular characteristics of LGG.Results: We found that non-canonical NF-κB signaling could classify LGG patients into subgroups with significant survival difference. Non-canonical NF-κB-low group enriched with oligodendroglioma featured by CIC mutations and 1p19q co-deletion. On the another hand, LGG in non-canonical NF-κB-high group showed high frequency of EGFR mutations but relatively low frequency of IDH mutations. In addition, LGG in this group reflected immunosuppressive environment characterized by high level of cytotoxic T cell exhaustion and macrophage M2 infiltration. More comprehensive evaluation implied that LGG in non-canonical NF-κB-high group reflected significantly higher immunogenicity. Through a series of feature selection technique, we developed a model that can predict the prognosis of LGG patients in a cost-effective way.Conclusion: Our analysis demonstrated the prognostic value of non-canonical NF-κB signaling in LGG. The survival difference between non-canonical NF-κB stratified groups may be explained by their distinct molecular characteristics as well as cellular context. Our prognostic model may help in offering better therapeutic strategy and clinical management.Keywords: lower grade glioma, non-canonical NF-κB signaling, immune microenvironment, T cell exhaustion, M2 macrophages, prognosis

Jie Lin,1,2,&ast; Yanlong Xue,1,2,&ast; Wenyan Su,1,2,&ast; Zan Zhang,1,2 Qiu Wei,1,2 Tianxia Huang1,2 1Department of Respiratory and Critical Care, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 2Department of Respiratory and Critical Care, The First People’s Hospital of Nanning, Nanning, Guangxi, 530022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiu Wei; Tianxia Huang, Department of Respiratory and Critical Care, The Fifth Affiliated Hospital of Guangxi Medical University, 89 Qixing Road, Nanning, Guangxi, 530022, People’s Republic of China, Tel +86 7712636163, Fax +86 7712617892, Email weiqiu2017@163.com; nntianxia620@sina.comPurpose: This study aimed to identify candidate gene markers that may facilitate chronic obstructive pulmonary disease (COPD) diagnosis and treatment.Methods: The GSE47460 and GSE151052 datasets were analyzed to identify differentially expressed mRNAs (DEmRs) between COPD patients and controls. DEmRs that were differentially expressed in the same direction in both datasets were analyzed for functional enrichment and for coexpression. Genes from the largest three modules were tested for their ability to diagnose COPD based on the area under the receiver operating characteristic curve (AUC). Genes with AUC > 0.7 in both datasets were used to perform regression based on the “least absolute shrinkage and selection operator” in order to identify feature genes. We also identified differentially expressed miRNAs (DEmiRs) between COPD patients and controls using the GSE38974 dataset, then constructed a regulatory network. We also examined associations between feature genes and immune cell infiltration in COPD, and we identified methylation markers of COPD using the GSE63704 dataset.Results: A total of 1350 genes differentially regulated in the same direction in the GSE47460 and GSE151052 datasets were found. The genes were significantly enriched in immune-related biological functions. Of 186 modules identified using MEGENA, the largest were C1_ 6, C1_ 3, and C1_ 2. Of the 22 candidate genes screened based on AUC, 11 feature genes emerged from analysis of a subset of GSE47460 data, which we validated using another subset of GSE47460 data as well as the independent GSE151052 dataset. Feature genes correlated significantly with infiltration by immune cells. The feature genes GPC4 and RS1 were predicted to be regulated by miR-374a-3p. We identified 117 candidate methylation markers of COPD, including PRRG4.Conclusion: The feature genes we identified may be potential diagnostic markers and therapeutic targets in COPD. These findings provide new leads for exploring disease mechanisms and targeted treatments.Keywords: chronic obstructive pulmonary disease, bioinformatics analysis, miRNAs, immune response, feature genes

Chunting Liang &ast;, Tongtong Huang &ast;, Xiaofeng Zhang, Huaqing Rao, Zhiru Jin, Xiaoxiong Pan, Jingtao Li, Yingying Mo, Yongzhi Cai, Ji Wu Department of Ultrasonic Medicine, The First Hospital Affiliated to Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ji Wu, Department of Ultrasonic Medicine, The First Hospital Affiliated to Guangxi Medical University, Nanning, 530021, People’s Republic of China, Email gxnnwuji@126.comPurpose: To study the thrombolytic effect and safety of cRGD urokinase liposomes (cRGD-UK-LIP) in rats with acute pulmonary microthromboembolism (APMTE), and explore the application value of echocardiography (ECHO) in animal models.Patients and Methods: Ninety-six SD rats were randomized into 6 groups (16/group): normal control, sham operation, APMTE, normal saline (NS), free urokinase (UK), cRGD-UK-LIP. Four groups (APMTE, NS, UK, cRGD-UK-LIP) of rats were injected with autologous thrombus to induce APMTE. Samples were injected into 3 groups (NS, UK, cRGD-UK-LIP) of rats after modeling. Echocardiography was used to assess right ventricle (RV) function and morphology in rats. Six rats in each group were randomly selected and pulmonary artery pressure (PAP) of them was measured through ECHO-guided transthoracic puncture. Finally, the rats were killed and their tissues were taken for pathological examination.Results: Compared with normal control or sham operation group, rats in APMTE group had enlarged RV, decreased RV function, increased PAP, and lung tissue of them showed postthromboembolic appearance. There was no significant difference between NS group and APMTE group. RV morphology and function of rats in the UK group and cRGD-UK-LIP group were better and vessels with residual thrombus in these 2 groups were less than APMTE group, especially in the cRGD-UK-LIP group. In terms of PAP, only cRGD-UK-LIP group was significantly lower than APMTE group. No hyperemia, bleeding and swelling were observed in heart, liver and kidney of rats in each group.Conclusion: A rat model of APMTE was successfully established. cRGD-UK-LIP has better thrombolytic effect than free urokinase and it is safe. Echocardiography is not merely an important way to evaluate the morphology and function of RV, transthoracic puncture measurement under the guidance of it can be an effective way to monitor PAP in animal models.Keywords: cRGD urokinase liposomes, acute pulmonary microthromboembolism, targeted thrombolysis, right ventricle, echocardiography, pulmonary artery pressure

Sijia Ge,1,* Hua Huang,2,* Wei Huang,1 Ran Ji,1 Jing Chen,1 Shuzhen Wu,1 Liyang Wang,1 Tianxin Huang,1 Yu Sheng,1 Haiou Yan,1 Cuihua Lu,1 Lin Ma3 1Department of Gastroenterology, Affiliated Hospital of Nantong University, Jiangsu, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of Nantong University, Jiangsu, People’s Republic of China; 3Department of Gastroenterology, Affiliated Haian Hospital of Nantong University, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin MaDepartment of Gastroenterology, Affiliated Haian Hospital of Nantong University, Nantong, 226600, Jiangsu, People’s Republic of China, Email 1908397778@qq.comCuihua LuDepartment of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China, Email lch670608@sina.comBackground: As hepatocellular carcinoma (HCC) having the second-highest mortality rate globally, the early diagnosis and prognosis of HCC have always been the focus of various studies. Although PSME4 has been reported to be closely related to several malignancies, its role in HCC remains unclear.Materials and Methods: The TCGA-LIHC database and HCC tissues were used to explore the expression of PSME4 in HCC. Gene set enrichment analysis (GSEA) was used to forecast the biological behavior of HCC cells that PSME4 might be involved in regulation. In addition, CCK-8, colony formation and flow cytometry assays were used to explore the effect of PSME4 on HCC cells. Furthermore, the underlying PSME4-related signaling pathways in HCC were further confirmed using GSEA.Results: We found that the expression of PSME4 in HCC tissues was significantly higher than that in adjacent normal tissues, and patients with high PSME4 expression have a poor prognosis. CCK-8, colony formation and flow cytometry assays shown that knockdown of PSME4 inhibits HCC cell proliferation of HCC cells, promotes cell apoptosis and moves the cell cycle away from the S phase. Mechanistically, PSME4 may promote the development of HCC through mTOR signaling pathway.Conclusion: The high expression of PSME4 in HCC promotes the proliferation of HCC cells via the mTOR signalling pathway. Therefore, PSME4 is an emerging tumour marker for the early diagnosis and prognosis of HCC.Keywords: hepatocellular carcinoma, mTOR signaling, liver cancer prognosis, PSME4

Xiaoyun Hu, Tao Huang, Yun Liu, Lina Zhang, Li Zhu, Xiaohong Peng, Sufang Zhang Department of Pediatrics, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Tao Huang Tel +86 13970012590Email huangtao99@email.cnObjective: The present study aims to investigate the clinical features and diagnostic characteristics of children with Cohen syndrome caused by the vacuolar protein sorting 13 homolog B (VPS13B) gene mutation and to review the relevant literature to provide a reference for genetic counseling and the diagnosis of Cohen syndrome.Methods: The clinical data and molecular genetic test results of a child with Cohen syndrome were retrospectively analyzed and a review of the relevant literature was conducted.Results: A two-year-and-four-month-old boy was referred to the hospital for recurrent fever and shortness of breath. On physical examination, the boy was found to have growth retardation, thick bushy hair, microcephaly, hypertelorism, down-slanting palpebral fissures, and hypotonia. Genetic testing was performed, and the results suggested the presence of exon 20– 32 heterozygous deletion and c.8275 delC (p.R2759 fs&ast;18) heterozygous variant on the VPS13B gene from phenotypically normal parents. These two mutation loci have not been reported in the literature, and they were predicted by relevant software to be pathogenic variants.Conclusion: We identified two novel variants in the VPS13B gene (exon 20– 32 heterozygous deletion and c.8275 delC heterozygous variant) in a boy with Cohen syndrome, thus extending the spectrum of VPS13B gene variants in patients with Cohen syndrome.Keywords: Cohen syndrome, VPS13B gene, heterozygous mutation, heterozygous deletion

Junmu Peng,1,2,&ast; Jie Qin,1,&ast; Tianji Huang,1 Xiaoji Luo,1 Weiyang Zhong,1 Zhengxue Quan1 1Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Orthopedic Surgery, The Ninth People’s Hospital of Chongqing, Chongqing, 400799, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiyang Zhong Email 492467112@qq.comBackground: A retrospective study aimed to introduce a new method for improving the diffusion degree of bone cement and to observe its clinical efficacy in percutaneous vertebroplasty treating osteoporotic vertebral compression fractures (OVCFs).Methods: From January 2019 to March 2020, a total of 83 patients were enrolled and reviewed. The patients were divided into two groups according to the operation method. The clinical and radiographic parameters were recorded and compared between these two groups. Those who received percutaneous vertebroplasty with haemorrhage aspiration were recorded as group A (n=42). In group A, the haemorrhage in the vertebral fracture was aspirated compared with conventional percutaneous vertebroplasty. Patients who underwent conventional percutaneous vertebroplasty were classified as group B (n=41).Results: Visual analogue scale (VAS) values and Oswestry Disability Index (ODI) scores showed no significant difference between the two groups preoperatively, postoperatively or at the final follow-up (FU) (P> 0.05). The intraoperative VAS score (bone cement injection) in group A was significantly lower than that in group B (3.83± 0.79 vs 5.44± 1.32, P < 0.01). The local kyphotic angle (LKA) (final follow-up), LKA loss, fractured vertebral anterior height loss (FVAHL) and anterior vertebral height loss ratio (AVHLR) were significantly lower in group A than in group B. The anterior vertebral height ratio (AVHR) at the final FU in group A was higher than that in group B (P=0.013). The distribution of bone cement was significantly different (P=0.034). By analysing the distribution pattern of bone cement, it was found that the values of LKA loss, FVAHL and AVHLR were superior in the type A bone cement distribution to those in types B and C.Conclusion: Compared with traditional surgical methods, bone haemorrhage aspiration could improve the diffusion degree of bone cement and reduce the height loss and deformity of injured vertebrae. This method provides a feasible new scheme for improving the dispersion of bone cement.Keywords: osteoporotic vertebral compression fractures, percutaneous vertebroplasty, bone cement distribution, fracture haemorrhage aspiration

Changshan Huang, Wei Yu, Qian Wang, Tao Huang, Yuechao Ding Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, People’s Republic of ChinaCorrespondence: Changshan HuangDepartment of Hepato-Biliary-Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450003, People’s Republic of ChinaTel +86 371 65587028Email hnhcs@163.comBackground: Circular RNA (circRNA) is a key regulator for the malignant progression of cancer. However, the role of circRNA anthrax toxin receptor 1 (circANTXR1) in hepatocellular carcinoma (HCC) is still unclear.Methods: Quantitative real-time PCR was performed to detect RNA expression. Cell proliferation, migration and invasion were determined using MTT assay, EdU staining, colony formation assay, wound healing assay and transwell assay. The protein levels of metastasis markers, x-ray repair cross complementing 5 (XRCC5) and exosome markers were examined using Western blot analysis. Xenograft tumor models were built to investigate the role of circANTXR1 in HCC tumorigenesis. The relationship between microRNA (miR)-532-5p and circANTXR1 or XRCC5 was confirmed by dual-luciferase reporter assay and RNA pull-down assay. The identification of exosomes were performed using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA).Results: CircANTXR1 was a stable and highly expressed circRNA in HCC. Silenced circANTXR1 inhibited the proliferation, migration and invasion of HCC cells in vitro, and suppressed HCC tumor growth in vivo. MiR-532-5p could be sponged by circANTXR1, and its inhibitor could reverse the inhibition of circANTXR1 silencing on HCC cells progression. In addition, we discovered that XRCC5 was a target of miR-532-5p. Furthermore, XRCC5 overexpression could reverse the suppressive effect of miR-532-5p overexpression on HCC cell proliferation, migration and invasion. Exosome was involved in the transport of circANTXR1 in HCC cells. Exosome circANTXR1 might be a potential serum biomarker for HCC patients.Conclusion: CircANTXR1 promotes the progression of HCC through the miR-532-5p/XRCC5 axis, which might be a potential serum biomarker and therapeutic target of HCC.Keywords: hepatocellular carcinoma, circANTXR1, miR-532-5p, XRCC5, exosome

Jianlei Ji,&ast; Qinghai Wang,&ast; Tao Huang, Ziyu Wang, Pingli He, Chen Guo, Weijia Xu, Yanwei Cao, Zhen Dong, Hongyang Wang Department of Kidney Transplantation, the Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen Dong; Hongyang WangDepartment of Kidney Transplantation, the Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, 266000, People’s Republic of ChinaTel +8613455263336; +8618661803752Email dong266000@163.com; why19850804@163.comBackground: Trimethoprim/sulfamethoxazole (TMP-SMX) is considered the first-choice treatment for Pneumocystis jirovecii pneumonia (PJP) in recipients of solid organ transplantation. However, this treatment is associated with various severe adverse events that might not be tolerable for some renal transplant recipients, and the optimal dose remains elusive. The present study assessed the efficacy of low-dose TMP-SMX in recipients of a deceased donor kidney.Methods: A total of 37 adult deceased donor kidney recipients who suffered PJP between January 2015 and June 2020 were included. The survival rates of the patients and grafts, the rate of invasive ventilation, and adverse events, including gastrointestinal discomfort, hematologic side effects, hyperkalemia, and renal function impairments, were assessed.Results: The patient and graft survival rates were both 100%. Two patients (5.4%) required invasive ventilation. Eight patients (21.6%) reported gastrointestinal discomfort, but none required dose reduction or discontinued treatment. The frequencies of hematologic side effects, hyperkalemia and impaired kidney function were 5.4% (2/37), 2.7% (1/37), and 2.7% (1/37), respectively.Conclusion: Optimization of TMP-SMX dose may reduce the risk of adverse events without compromising efficacy for the treatment of PJP in deceased donor kidney recipients.Keywords: efficacy, low dose, trimethoprim/sulfamethoxazole, Pneumocystis jirovecii pneumonia, deceased donor kidney recipients

Qinghai Wang,1 Kai Zhao,2 Chen Guo,1 Hong Li,1 Tao Huang,1 Jianlei Ji,1 Xiaoxia Sun,1 Yanwei Cao,1 Zhen Dong,1 Hongyang Wang1 1Department of Kidney Transplantation, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China; 2Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of ChinaCorrespondence: Zhen Dong; Hongyang WangDepartment of Kidney Transplantation, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, 266000, People’s Republic of ChinaTel +8613455263336; +8618661803752Email dong266000@163.com; why19850804@163.comObjective: This study aimed to determine the prevalence of antibiotic resistance and virulence genes of Escherichia coli strains among patients with urinary tract infections (UTIs) after kidney transplantation from deceased donors.Methods: Between January 2014 and June 2018, 64 patients who received kidney transplants from deceased donors at our institution developed a UTI due to E. coli. Polymerase chain reaction was used to detect virulence genes in E. coli strains. The Kirby–Bauer method was used to evaluate the antibiotic susceptibility pattern of the isolates.Results: Among the study cohort, 46 (71.9%) UTIs were community-acquired (CA), and 18 (28.1%) were hospital-acquired (HA). The percentages of isolated E. coli strains that showed antibiotic resistance were as follows: 92.2% to ampicillin, 76.6% to cefalotin, 81.3% to carbenicillin, 29.7% to ciprofloxacin, 62.5% to cotrimoxazole, 35.9% to gentamicin, 34.4% to levofloxacin, 28.1% to norfloxacin, 68.8% to pefloxacin, 57.8% to trimethoprim/sulfamethoxazole, and 20.3% to amikacin. HA E. coli showed higher resistance to ciprofloxacin, cotrimoxazole, trimethoprim/sulfamethoxazole and amikacin, compared with CA E. coli (P< 0.05). The most prevalent virulence genes among the E. coli strains were fim (64.1%), followed by irp2 (56.3%), iroN (46.9%), pap GII (45.3%), sfa (31.3%), pap (25%), iuc (23.4%), pap GI (15.6%), pap GIII (14.1%), hly (9.4%), and cnf (4.7%). The irp2 and iroN genes were found more frequently in the HA E. coli than in the CA E. coli (P< 0.05).Conclusion: The E. coli strains, especially HA E. coli, isolated from UTI patients after kidney transplantation from deceased donors showed resistance to multiple antibiotics and harbored numerous virulence genes. These findings provide insight for genetic characterizations and epidemiological studies of E. coli strains causing UTIs in patients after kidney transplantation from deceased donors.Keywords: Escherichia coli, antimicrobial resistance, virulence genes, urinary tract infections, kidney transplantation

Xiuyuan Zhang, Tingting Huang, Yiming Li, Hong Qiu Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of ChinaCorrespondence: Hong QiuDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People’s Republic of ChinaEmail tjqiuhong@163.comPurpose: Thrombospondin 1 (THBS1) is an endogenous inhibitor of angiogenesis, but it also promotes tumor invasion, metastasis, and immune response in the tumor environment. Previous research has found that THBS1 is highly expressed in many tumors and has a negative correlation with tumor prognosis. However, research on the relationship between THBS1 and immune infiltration in GC is less well documented, and the objective of our study was to investigate the role of THBS1 expression in GC.Patients and Methods: The expression of THBS1 in GC was analyzed by Oncomine, TIMER, TGCA, GEO and IHC staining. Analysis of the signaling pathways associated with THBS1 expression in GC uses GSEA. The relationship between THBS1 expression and immune infiltration was analyzed by the ESTIMATE algorithm, single-cell transcriptome analysis, TIMER2 database and CIBERSORT algorithm. Finally, the relationship between THBS1 expression and drug sensitivity was analyzed by the CellMiner database.Results: THBS1 was overexpressed in GC and was associated with poor prognosis, and high THBS1 expression was an independent risk factor. GSEA results showed that high THBS1 expression in GC was associated with tumorigenesis, adhesion, and significant immune enrichment. THBS1 expression was most strongly correlated with tumor-associated macrophages (TAMs), M2 macrophages and cancer-associated fibroblast (CAFs) in GC. THBS1 expression positively correlates with most immune checkpoint members, suggesting that THBS1 may play an important role in the tumor microenvironment. THBS1 overexpression was negatively correlated with some drug sensitivities, such as Oxaliplatin.Conclusion: Upregulation of THBS1 was positively correlated with poor prognosis and immunosuppression in GC and negatively correlated with anticancer drug sensitivity, suggesting that THBS1 may serve as a potential target for the treatment of GC.Keywords: THBS1, gastric cancer, drug sensitivity, prognosis, tumor microenvironment

Yaqi Jia, Tao Huang Department of Hepatobiliary Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Tao HuangDepartment of Hepatobiliary Surgery, The Affiliated Cancer Hospital of Zhengzhou University, No. 127 Dongming Road, Zhengzhou, 450008, Henan Province, People’s Republic of ChinaTel/Fax +86-371-65587276Email gandansanht@163.comAbstract: Antabuse®, generic name disulfiram, has been extensively used in daily clinical practice to treat alcohol abuse. In vivo and in vitro experiments have demonstrated that disulfiram was capable of inhibiting tumor cell proliferation; clinical studies have indicated that the administration of this drug was associated with favorable survival, whilst in vitro experiments have elucidated the anticancer mechanism of disulfiram. In addition, radiation and cancer biology studies have shown that disulfiram can protect normal cells and sensitize tumor cells during radiotherapy. This review aims at describing the antitumor activity of disulfiram in both preclinical studies and clinical trials, whilst focusing on the advances of this drug in radiation and cancer biology, and the promise of repurposing it as a novel sensitizer to, and protector against, radiation on the incoming clinical studies.Keywords: disulfiram, cancer biology, radiotherapy, overview

Wen Yang,1,* Xia Xu,2,* Ming Xu,1 Jun Zhou,1 Zihan Xi,1 Hui Guo,1 Jie Ming,1 Tao Huang1 1Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao Huang; Jie MingDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No. 1277, Wuhan, Hubei Province, People’s Republic of ChinaTel +8613807112766; +8613905519049Fax +86 27-85726833Email huangtaowh@163.com; mingjiewh@126.comPurpose: Papillary thyroid cancer (PTC) patients could obtain poor prognosis if they have lymph node metastasis, identification of informative and robust biomarkers for predicting cervical lymph node metastasis is critical for improving clinical decision-making and patient prognosis.Materials and Methods: In this study, we analyzed the expression of X box binding protein 1 spliced-form (XBP1s) in 41 PTC tissue samples and extended our findings using public databases, then we investigated how XBP1s’ contributed to PTC progression in vitro.Results: We found that XBP1s’ expression was lower in PTC patients with cervical lymph node metastasis than non-metastasis patients by immunohistochemical analysis. With publicly accessible dataset, we showed that the XBP1 transcription was significantly decreased in thyroid cancer (TC) tissues with lymph node metastasis as compared to that without lymph node metastasis. Moreover, we also found that XBP1 expression was significantly correlated with patients’ gender, T classification, lymph node metastasis and PTC stages, and low XBP1 expression was associated with poor diseases free survival (DFS). In vitro, XBP1s overexpression could inhibit the invasion, migration, and wound healing capacity of PTC cells. Mechanistically, overexpression of XBP1s could enhance the expression of classical epithelial–mesenchymal transition (EMT) markers such as ZO-1 and E-cadherins, and downregulated N-cadherin in BCPAP cells.Conclusion: These findings suggest that XBP1s is a prognostic maker for thyroid carcinoma patients, and sustaining XBP1s expression might be a new strategy to control PTC progression.Keywords: XBP1s, lymph node metastasis, papillary thyroid cancer, EMT

Min Li,1 Tianqing Huang,2 Xiaolan Li,3 Zhiwei Shi,3 Yue Sheng,4 Mimi Hu,3 Kui Song3 1Department of Pharmacy, The First Affiliated Hospital of Jishou University, Jishou, Hunan, 416000, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Jishou University, Jishou, Hunan, 416000, People’s Republic of China; 3Department of Hematology, The First Affiliated Hospital of Jishou University, Jishou, Hunan, 416000, People’s Republic of China; 4Department of Pediatrics, The First Affiliated Hospital of Jishou University, Jishou, Hunan, 416000, People’s Republic of ChinaCorrespondence: Kui SongDepartment of Hematology, The First Affiliated Hospital of Jishou University, Century Avenue, Jishou City, Hunan Province, 416000, People’s Republic of ChinaEmail js_hematology@163.comBackground: Checkpoint kinase 1 (CHK1) plays an important role in DNA damage response and cell cycle progression. Thus, targeting CHK1 is an efficient strategy for cancer therapy.Purpose: The present study aimed to investigate the potential therapeutic effects of GDC-0575, a CHK1-specific inhibitor, in colitis-associated cancer (CAC) and colitis.Methods: We established a DSS-induced acute colitis model and an azoxymethane/dextran sodium sulfate (DSS)-induced CAC model using mice and tested the effect of GDC-0575 on them. Flow cytometry and immunofluorescence were employed to investigate the infiltration of immune cells, and inflammatory cytokine expression in the colon of mice with CAC or colitis was investigated using ELISA and qPCR. We also investigated the correlation between CHK1 and CCL2/CCR2 in human colorectal cancer (CRC) tissues.Results: Administration of GDC-0575 significantly inhibited CHK1 expression in the colon and dramatically impaired the development of CAC and colitis in mice. Moreover, the inhibition of CHK1 expression resulted in efficient inhibition of infiltration by iNOS-positive macrophages, but had no significant effect on CD4 T cells, CD8 T cells, and myeloid-derived suppressor cells (MDSCs). Significant downregulation of TNF-α, IL-6, and IL-1β and dramatic upregulation of IL-10 were observed in the colons of both mice with CAC and colitis treated with GDC-0575. CCL2 expression was also downregulated by GDC-0575 in both mice with CAC and colitis; this was followed by the inhibition of CCR2+ macrophage infiltration in the colon. Furthermore, we report a positive correlation between CHK1 expression and CCL2/CCR2 expression in the malignant tissues of patients with CRC.Conclusion: Taken together, we infer that GDC-0575 impairs the development of CAC and colitis by regulating cytokine expression and inhibiting CCR2+ macrophage infiltration in mice colon.Keywords: colitis, colitis-associated cancer, CHK1, macrophage

Dongfang Tang,1 Tao Huang,2 Qilong Tian,2 Julei Wang2 1Department of Neurosurgery, Henan Provincial People’s Hospital, Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Neurosurgery, The Second Affiliated Hospital of Air Force Military Medical University, Xi’an City, People’s Republic of ChinaCorrespondence: Julei WangDepartment of Neurosurgery, The Second Affiliated Hospital of Air Force Military Medical University, No. 569 Xinsi Road, Baqiao District, Xi’an City, Shaanxi Province, 710038, People’s Republic of ChinaTel +86-29-84777777Email wangjulei_wjl@163.comBackground: The role of Hydroxysafflor Yellow A (HSYA) in glioma is less studied, this research determined the effect of HSYA on glioma cells.Methods: The expressions of MYC and NBS1 in glioma tissues were detected by bioinformatics analysis and verified by RT-qPCR. The target relationship between MYC and NBS1 was predicted by bioinformatics. After treating the cells with HSYA, silenced MYC, or overexpressed NBS1, the viability, apoptosis, proliferation, invasion, migration, and DNA damage of the glioma cells were detected by MTT, flow cytometry, colony formation, transwell, wound healing, and γH2AX immunofluorescence assays, respectively. IC50 of HSYA in glioma cells was analyzed by Probit regression analysis. The expressions of MYC, NBS1, factors related to migration, invasion, apoptosis, and DNA damage of the glioma cells were determined by Western blot or RT-qPCR.Results: MYC and NBS1 were high-expressed in glioma, and NBS1 was targeted by MYC. HSYA and siRNA targeting MYC inhibited the cell viability, proliferation, invasion, migration, and induced the cell apoptosis of glioma cells. HSYA upregulated the expressions of MYC, γH2AX, E-Cadherin, Bax, and Cleaved-PARP1, stimulated the activation of NBS1, MRE11, RAD50, and ATM, and downregulated the expressions of N-Cadherin and Bcl2 in glioma cells. SiMYC decreased the IC50 of HSYA in the glioma cells, enhanced the sensitivity of glioma cells to HSYA, and inhibited the activation of NBS1 and ATM. NBS1 overexpression reversed the effect of siRNA targeting MYC on glioma cells.Conclusion: MYC silencing inhibited the DNA damage response via regulation of NBS1, leading to DNA repair deficiency, and subsequently enhanced the sensitivity of glioma cells to HSYA.Keywords: glioma, hydroxysafflor yellow A, MYC, NBS1, drug sensitivity, DNA repair

Hongying Shi,1,2 Tianyi Huang,3,4 Yanan Ma,5 A Heather Eliassen,2,3 Qi Sun,2– 4 Molin Wang2,3,6 1Department of Epidemiology and Health Statistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; 3Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA; 4Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; 5Department of Biostatistics and Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, People’s Republic of China; 6Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USACorrespondence: Molin WangDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USATel +1 617 525 2202Email mwang@hsph.harvard.eduQi SunDepartment of Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USATel +1 617 432 7490Email qisun@hsph.harvard.eduPurpose: Both short and long sleep durations are associated with higher mortality. This study examined the association between sleep duration and overall health among those who survive to older ages.Participants and Methods: In the Nurses’ Health Study, participants without major chronic diseases in 1986 and survived to age 70 years or older in 1995– 2001 were included. Habitual sleep duration and snoring were self-reported in 1986. Healthy aging was defined as being free of 11 major chronic diseases and having no cognitive impairment, physical impairment, or mental health limitations. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for healthy aging.Results: Of the 12,304 participants, 1354 (11.0%) achieved healthy aging. We observed a non-linear association between sleep duration and the odds of achieving healthy aging. Compared with women sleeping 7 hours per day, women with longer sleep duration were less likely to achieve healthy aging; there was also a suggestion of lower odds of healthy aging for shorter sleepers, although the associations did not reach statistical significance: the multivariate-adjusted ORs (95% CIs) of healthy aging for those sleeping ≤ 5, 6, 8, and ≥ 9 hours were 0.94 (0.70, 1.27), 0.88 (0.76, 1.02), 0.83 (0.72, 0.96), and 0.60 (0.43, 0.84), respectively. Similar non-linear associations were consistently observed for individual dimensions of healthy aging. Regular snoring was associated with 31% lower odds of healthy aging (95% CI: 0.54, 0.88), which was primarily due to lower odds of having no major chronic diseases.Conclusion: Both short and long sleep durations as well as regular snoring at midlife were associated with lower odds of healthy aging in later life.Keywords: sleep, healthy aging, prospective studies, Nurses’ Health Study, snoring

Linlin Yang,1– 3 Yunxia Cui,1– 3 Ting Huang,1– 3 Xiao Sun,1– 3 Yudong Wang1– 3 1Department of Gynecologic Oncology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Shanghai Municipal Key Clinical Specialty, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Embryo Original Disease, Shanghai, People’s Republic of ChinaCorrespondence: Yudong Wang; Xiao Sun Department of Gynecologic OncologyThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 1961 Huashan Road, Shanghai 200060, People’s Republic of ChinaEmail wangyudong6688@126.com; sunxiao000304@163.comPurpose: Progestin resistance is a critical obstacle for endometrial conservative therapy. Therefore, studies to acquire a more comprehensive understanding of the mechanisms are urgent. However, the pivotal molecules are still unexplored.Materials and Methods: We downloaded GSE121367 from the GEO database. The “limma” R language package was applied to identify differentially expressed genes (DEGs). We conducted Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA). Protein–protein interaction was constructed by STRING and visualized in Cytoscape. The tumor immune microenvironment was explored by the TISIDB database. Methylation validation and overall survival analysis were conducted by the TCGA database. In addition, the upstream modulators of hub genes were predicted by miRTarBase and Network Analyst databases. The expression levels of candidate genes were validated by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemical assay (IHC). Cell growth, clone formation, migration, invasion, and wound healing assays were studied to explore the role of MSX1 in progestin resistance in vitro.Results: A total of 3,282 DEGs were identified and they were mostly enriched in the cell adhesion pathway. We screened out ten hub genes whose genomic alteration rates were low based on the current endometrial carcinoma sample sets. Has-miR-335-5p, has-miR-124-3p, MAZ, and TFDP1 were the most prominent upstream regulators. The methylation status of CDH1, JAG1, EPCAM, and MSX1 was decreased, corresponding to their high protein expression, which also predicted better overall survival. The homeobox protein of MSX1 showed significant tissue specificity and better prognostic value and its knockdown inhibited epithelial–mesenchymal transitions (EMT) and enhanced progesterone efficacy.Conclusion: Our study identified that the gene of MSX1 promised to be the specific indicator and therapeutic target for progestin resistance. This would shed new light on the underlying biological mechanism to overcome progestin resistance of endometrial cancer.Keywords: bioinformatic analysis, in vitro experiments, progestin resistance, MSX1, endometrial carcinoma

Feng Wang,* Zhen Xiang,* Teng Huang,* Min Zhang, Wei-Bing Zhou Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei-Bing Zhou Department of OncologyXiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan 410008, People’s Republic of ChinaTel +86-731-89753733Email zhouweibing298@csu.edu.cnBackground: Chemotherapy resistance is the leading cause of cancer treatment failure. This research was conducted to explore a potential link between actin-binding protein anillin (ANLN) and doxorubicin resistance in breast cancer.Materials and Methods: We compared ANLN expression and 50% inhibition concentration (IC50) of doxorubicin in human breast cancer cells (MDA-MB-231) and human breast cancer cells with doxorubicin resistance (MDA-MB-231/ADM). Co-immunoprecipitation was used to investigate the interaction between ANLN and RhoA. The cell viability, apoptosis, gene and protein expression were estimated by MTT, flow cytometry, quantitative real-time PCR and western blot.Results: The doxorubicin resistance in MDA-MB-231/ADM cells (IC50 = 19.40 ± 1.16 μg/mL) was significantly higher than that in MDA-MB-231 cells (IC50 = 1.65 ± 0.23 μg/mL). ANLN was up-regulated in MDA-MB-231/ADM cells compared to MDA-MB-231 cells. Furthermore, ANLN overexpression promoted cell viability and inhibited apoptosis of MDA-MB-231 cells. The gene and protein expression of multidrug resistance (MDR1) and cancer resistance protein (BCRP) were enhanced by ANLN overexpression in MDA-MB-231 cells. ANLN silencing suppressed cell viability and the expression of MDR1 and BCRP and facilitated apoptosis in MDA-MB-231/ADM cells. Moreover, ANLN promoted RhoA activation by interacting with RhoA. ANLN up-regulation enhanced cell viability and the expression of MDR1 and BCRP and decreased apoptosis of MDA-MB-231 cells. The influence conferred by ANLN overexpression was effectively abolished by C3 transferase.Conclusion: This work revealed that ANLN promoted doxorubicin resistance in breast cancer cells by activating RhoA. Thus, our study suggests a novel target for breast cancer treatment.Keywords: ANLN, RhoA, doxorubicin resistance, breast cancer, RhoA, GTPase, patient stratification

Guohong Huang,* Yimei Yang,* Mengxin Lv, Tian Huang, Xiaoyan Zhan, Wei Kang, Jianghou Hou Clinical Research Center of Kunming Maternal and Child Health Hospital, Kunming 650031, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianghou HouClinical Research Center of Kunming Maternal and Child Health Hospital, Kunming 650031, People’s Republic of ChinaEmail houjiangh@126.comBackground: Hepatocellular carcinoma (HCC) is a common malignancy worldwide with a high mortality rate. lncRNA SFTA1P is highly expressed in HCC. We aimed to study the role of SFTA1P in HCC and its relationship with miR-4766-5p.Materials and Methods: The levels of SFTA1P in HCC tissues and cell lines were determined. Relationship between SFTA1P and clinical features and prognosis was studied. The influence of SFTA1P on HCC cell viability, migration, invasion and apoptosis was studied in vitro. Rescue experiments were conducted after the binding site between SFTA1P and miR-4766-5p confirmed by dual-luciferase assay. The protein expression of AKT, p-AKT, mTOR and p-mTOR in HCC cells with knockdown of SFTA1P was determined by Western blotting. A tumor study in nude mice was conducted in order to assess the effects of SFTA1P on tumor growth characteristics.Results: SFTA1P was up-regulated in HCC tissues and cell lines. SFTA1P expression was closely related to tumor size, vascular invasion and TNM stage. Knockdown of SFTA1P inhibited HCC cell viability, migration and invasion and promoted cell apoptosis. MiR-4766-5p was a target of SFTA1P and knockdown of SFTA1P could decrease the protein expression of p-AKT and p-mTOR. Rescue experiments showed that miR-4766-5p mimics could attenuate the promoting role of SFTA1P on HCC cell viability, invasion and migration, and inhibiting role on cell apoptosis. Moreover, we used nude mice models and also found that the knockdown of SFTA1P reduced tumor volume and weight.Conclusion: lncRNA SFTA1P could promote tumor development in HCC by down-regulating miR-4766-5p expression via PI3K/AKT/mTOR signaling pathway. It may be a potential therapeutic target for HCC.Keywords: hepatocellular carcinoma, SFTA1P, miR-4766-5p, PI3K/AKT/mTOR signaling pathway, tumor growth

Tao Huang,1,2 Sushma Kumari,2 Heike Herold,2 Hendrik Bargel,2 Tamara B Aigner,2 Daniel E Heath,1 Neil M O’Brien-Simpson,3 Andrea J O’Connor,1 Thomas Scheibel2,4 1Department of Biomedical Engineering, Melbourne School of Engineering, University of Melbourne, Parkville, VIC 3010, Australia; 2Department for Biomaterials, Faculty of Engineering Science, University of Bayreuth, Prof. Rüdiger Bormann Str. 1, Bayreuth 95447, Germany; 3Melbourne Dental School and the Bio21 Institute of Molecular Science and Biotechnology, The University of Melbourne, Parkville, VIC 3010, Australia; 4Bavarian Polymer Institute (BPI), Bayreuth Center for Material Science and Engineering (BayMAT), Bayreuth Center for Colloids and Interfaces (BZKG), Bayreuth Center for Molecular Biosciences (BZMB), University of Bayreuth, Bayreuth 95447, GermanyCorrespondence: Andrea J O’Connor; Thomas Scheibel Tel +61 3 8344 8962; +49 (0)921/55-6701Email a.oconnor@unimelb.edu.au; thomas.scheibel@bm.uni-bayreuth.dePurpose: Selenium nanoparticles (Se NPs) are promising antibacterial agents to tackle the growing problem of antimicrobial resistance. The aim of this study was to fabricate Se NPs with a net positive charge to enhance their antibacterial efficacy.Methods: Se NPs were coated with a positively charged protein – recombinant spider silk protein eADF4(κ 16) – to give them a net positive surface charge. Their cytotoxicity and antibacterial activity were investigated, with negatively charged polyvinyl alcohol coated Se NPs as a control. Besides, these eADF4(κ 16)-coated Se NPs were immobilized on the spider silk films, and the antibacterial activity of these films was investigated.Results: Compared to the negatively charged polyvinyl alcohol coated Se NPs, the positively charged eADF4(κ 16)-coated Se NPs demonstrated a much higher bactericidal efficacy against the Gram-negative bacteria E. coli, with a minimum bactericidal concentration (MBC) approximately 50 times lower than that of negatively charged Se NPs. Cytotoxicity testing showed that the eADF4(κ 16)-coated Se NPs are safe to both Balb/3T3 mouse embryo fibroblasts and HaCaT human skin keratinocytes up to 31 μg/mL, which is much higher than the MBC of these particles against E. coli (8 ± 1 μg/mL). In addition, antibacterial coatings were created by immobilising the eADF4(κ 16)-coated Se NPs on positively charged spider silk films and these were shown to retain good bactericidal efficacy and overcome the issue of low particle stability in culture broth. It was found that these Se NPs needed to be released from the film surface in order to exert their antibacterial effects and this release can be regulated by the surface charge of the film, such as the change of the spider silk protein used.Conclusion: Overall, eADF4(κ 16)-coated Se NPs are promising new antibacterial agents against life-threatening bacteria.Keywords: Gram-positive, Gram-negative, E. coli, antibacterial film, cytotoxicity

Jun Zhou,* Ming Xu,* Kehao Le, Jie Ming, Hui Guo, Shengnan Ruan, Tao Huang Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao Huang; Shengnan RuanDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of ChinaTel +86-27-85351622Email huangtaowh@163.com; ruanshengnan@yahoo.comBackground: Endocrine therapy plays a key role in estrogen receptor-positive breast cancer patients; but, tamoxifen resistance could be a real difficulty for these patients. Several attempts have been made to explore the mechanism and new therapies for these patients. We intend to clarify the expression change of SRC and SIRT1 in tamoxifen-resistant breast cancer cells and explore their functions on tamoxifen resistance.Methods: SRC and SIRT1 expressions were analyzed by RNA sequencing, qPCR and Western blotting. Loss and gain of function of SRC and SIRT1 were utilized to indicate their oncogenic roles in tamoxifen resistance in vitro and in vivo. Kaplan–Meier analysis and receiver operating characteristic curve were used to evaluate the survival and the predicted effects of SRC and SIRT1 on patients’ prognosis.Results: High expressions of SRC and/or SIRT1 were found in tamoxifen-resistant cells and related to poor overall survival (p< 0.05 for SRC, p< 0.001 for SIRT1, p< 0.001 for SRC and SIRT1) and cancer-specific survival (p< 0.05 for SRC, p< 0.01 for SIRT1, p< 0.01 for SRC and SIRT1) of tamoxifen-treated breast cancer patients. Down-regulation of SRC (p< 0.01) or SIRT1 (p< 0.05) separately reversed the resistance to tamoxifen and the minimal concentration of SRC inhibitor KX-01 (p< 0.05) or SIRT1 inhibitor EX527 (p< 0.001) could also suppress cell proliferation. The expression level of SIRT1 was positively correlated with that of SRC. Overexpression of SRC significantly promotes the cell resistance to tamoxifen inhibited by SIRT1 (p< 0.01). In vivo experiments confirmed the effects of SRC on tumor growth by over- or down-regulating SRC expression (p< 0.001 and p< 0.001, respectively).Conclusion: SRC and SIRT1 are both up-regulated in tamoxifen-resistant breast cancer cells and related to a poor prognosis in tamoxifen-treated breast cancer. Moreover, SRC could promote tamoxifen resistance by up-regulating SIRT1. SRC and SIRT1 might be novel therapeutic targets in tamoxifen-resistant breast cancer and the interaction between SRC and SIRT1 needs to be further explored.Keywords: breast cancer, tamoxifen resistance, SRC, SIRT1, inhibitor

Wenjie Chen,1 Tao Wei,1 Zhihui Li,1 Rixiang Gong,1 Jianyong Lei,1 Jingqiang Zhu,1 Tao Huang2 1Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Breast and Thyroid Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Jingqiang ZhuThyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaTel/Fax +86-28-85422467Email zjqhuaxidoctor@163.comTao HuangDepartment of Breast and Thyroid Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaEmail huangtaowh@163.comBackground: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) have been reported to be prognostic biomarkers in various cancers. Our study evaluated whether the preoperative NLR, PLR and PNI predicted tumor-node-metastasis (TNM) stage and recurrence in papillary thyroid carcinoma (PTC) patients.Methods: A total of 1873 patients with PTC from 9 centers in mainland China were retrospectively assessed. Receiver operating characteristic (ROC) curves were generated, and Kaplan-Meier analyses were performed to evaluate the prognostic value of inflammation-based scores. Univariate and multivariate analyses were conducted to identify risk factors for recurrence.Results: A decreased PNI and an increased PLR were predictive of TNM stage (p=0.005 and p=0.030, respectively), while a decreased NLR was predictive of recurrence (p=0.040). Univariate and multivariate analyses indicated that N1 status (odds ratio (OR), 1.898; 95% confidence interval (CI), 1.253– 2.874; p=0.002), NLR≤ 1.6 (OR, 1.596; 95% CI, 1.207– 2.111; p=0.001) and PNI≤ 53.1 (OR, 1.511; 95% CI, 1.136– 2.009; p=0.005) were independent factors that predicted recurrence.Conclusion: The NLR, PLR and PNI have predictive value for TNM stage and recurrence in patients with PTC, but their predictive efficiency is limited. Caution should be used when considering clinical applications of inflammation-based scores.Keywords: inflammation-based scores, papillary thyroid carcinoma, lymph node metastasis, prognosis

Weiwei Qian, 1, 2 Tingting Huang, 1, 2 Wen Feng 1, 2 1Department of Gynecology, The First People’s Hospital of Lianyungang, Lianyungang 222061, People’s Republic of China; 2Department of Gynecology, Lianyungang Hospital Affiliated to Xuzhou Medical University, Lianyungang 222061, People’s Republic of ChinaCorrespondence: Wen FengDepartment of Gynecology, The First People’s Hospital of Lianyungang, The 6th Zhenhua East Road, Haizhou District, Lianyungang 222061, People’s Republic of ChinaEmail yealf529@163.comBackground: Cervical cancer (CC) is the 4th most common malignancy and cancer-related fatality in women worldwide. Circular RNA is a newly recognized noncoding RNA form. More reports have confirmed their important regulatory functions in diverse physiological and cancer processes. However, the function and mechanisms of circ-HIPK3 in CC remain unknown.Methods: circ-HIPK3 expression status was verified between 45 paired CC and normal adjacent tissues from 45 CC patients, also the 6 CC cell lines and a normal human cervical epithelial End1/E6E7 cell line by qRT-PCR. Effects of circ-HIPK3 silence on CC cell phenotypes were estimated. Circular RNA interactome was applied to forecast binding site between circ-HIPK3 and miRNAs. Pearson correlation analysis was used to confirm the relationship between genes. Point mutation, RNA pull-down, luciferase assay and rescue experiments were applied for molecular mechanism exploration.Results: circ-HIPK3 expression was significantly elevated in CC cells and tissues. circ-HIPK3 silence repressed growth and metastasis, while induced apoptosis in CC cells. circ-HIPK3 sponged miRNA-338-3p (miR-338-3p); miR-338-3p to up-regulate hypoxia-inducible factor-1α (HIF-1α) and CC progress. MiR-338-3p silence or HIF-1α over-expression rescued circ-HIPK3 knockdown caused inhibition of CC malignant characteristics.Conclusion: circ-HIPK3 acts as a competing endogenous RNA of miR-338-3p to promote cell growth and metastasis in CC, via regulating HIF-1α mediated EMT. Therefore, targeting circ-HIPK3/miR-338-3p/HIF-1α axis may be a novel therapeutic strategy for CC.Keywords: cervical cancer, circ-HIPK3, miR-338-3p, HIF-1α, EMT, metastasis

Ting Huang,1 Yiwei Wang,1 Zhihua Wang,1 Yunxia Cui,1 Xiao Sun,2 Yudong Wang3 1Department of Gynecology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Gynecology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Shanghai Key Laboratory of Embryo Original Disease, Shanghai, People’s Republic of China, Shanghai Municipal Key Clinical Specialty, Shanghai, People’s Republic of China; 3Department of Gynecology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Shanghai Public Health Clinical Center, Female Tumor Reproductive Specialty, Shanghai, People’s Republic of ChinaCorrespondence: Yudong Wang; Xiao SunDepartment of Gynecology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, No. 145 Guanyuan Road, Shanghai 200060, People’s Republic of ChinaTel +86-18817819137; +86-18721201446Email wangyudong6688@126.com; sunxiao000304@163.comPurpose: Perineural invasion (PNI) is the neoplastic invasion of nerves by cancer cells, a process that may prove to be another metastatic route besides direct invasion, lymphatic spread, and vascular dissemination. Given the increasing incidence and association with poor prognosis, revealing the pathogenesis of perineural invasion is of great importance.Materials and methods: Four datasets related to PNI were downloaded from the Gene Expression Omnibus database and used to construct weighted gene co-expression network analysis (WGCNA). The intersection of potential pathways obtained from further correlation and enrichment analyses of different datasets was validated by the coculture model of Schwann cells (SCs), flow cytometry and immunohistochemistry (IHC).Results: GSE7055 and GSE86544 datasets were brought into the analysis for there were some significant modules related to PNI, while GSE103479 and GSE102238 datasets were excluded for insignificant differences. In total, 13,841 genes from GSE86544 and 10,809 genes from GSE7055 were used for WGCNA. As a consequence, 19 and 26 modules were generated, respectively. The purple module of GSE86544 and the dark gray module of GSE7055 were positively correlated with perineural invasion. Further correlation and enrichment analyses of genes from the two modules suggested that these genes were mainly enriched in cell cycle processes; especially, the terms S/G2/M phase were enriched. Three kinds of cells grew vigorously after coculture with SCs ex vivo. The Ki67 staining of the cervical cancer samples revealed that the Ki67 index of cancer cells surrounding nerves was higher than of those distant ones.Conclusion: Our work has identified cancer cell proliferation as a common response to neural cancerous microenvironments, proving a foundation for cancer cell colonization and metastasis.Keywords: WGCNA, perineural invasion, proliferation, nerve, cancer

Honglian Huang,* Tao Huang,* Renjie Wei Hechi People’s Hospital, Hechi City, Guangxi Zhuang Autonomous Region, People’s Republic of China*These authors contributed equally to this workCorrespondence: Renjie WeiHechi People’s Hospital, No. 455 Jincheng Middle Road, Jinchengjiang District, Hechi City, Guangxi Zhuang Autonomous Region, 547000, People’s Republic of ChinaTel/Fax +86 778-2281409Email wei77889908@163.com View the original paper by Mrs Huang and colleagues

Man Zou,1,* Yanhui Li,2,* Yuhong Dai,1 Li Sun,1 Tingting Huang,1 Xianglin Yuan,1 Hong Qiu1 1Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 2Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong QiuDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of ChinaTel/Fax +86 278 366 2836Email tjqiuhong@163.comAbstract: Hepatoid adenocarcinoma (HAC) is a group of neoplasms with features resembling hepatocellular carcinoma. The stomach is the most commonly affected organ among the reported primary sites. We report the case of a 28-year-old man with chronic hepatitis B and a complaint of abdominal distension. The patient was examined by PET-CT and magnetic resonance imaging (MRI), which showed diffuse thickening of the peritoneum and omentum but no mass was found in the liver. Pathological examination of a biopsy of the omental nodules was consistent with moderately differentiated hepatocellular carcinoma (HCC); thus, a diagnosis of HAC of the peritoneum and omentum was established. The patient received a chemotherapy regimen consisting of oxaliplatin and capecitabine and gained remarkable effects as the AFP level dropped significantly, and the tumour nearly disappeared. When the patient shifted to the standard multikinase inhibitors, Sorafenib or Lenvatinib, both treatments were ineffective. HAC is a heterogeneous group of prognostically unfavourable tumours mimicking the histological appearance of HCC, and the treatment outcomes are still unclear.Keywords: AFP producing, peritoneal hepatoid carcinoma, XELOX chemotherapy, multikinase inhibitors