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Hui Huang,1– 3,* Qing Ye,1– 4,* Yulan Xu,1– 3,* Baoming Tao,1– 3 Junlan Liu,1– 3 Tian Xie,1– 3 Lingfeng Zha1– 3 1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4School of Nursing, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tian Xie; Lingfeng Zha, Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Tel +86-15972150162 ; +86-15827177185, Email xietian@hust.edu.cn; zhalf@hust.edu.cnPurpose: We investigated the risk factors and characteristic clinical features of peripartum cardiomyopathy (PPCM) to lay the groundwork for early identification, screening, diagnosis, and intervention in high-risk pregnant women.Patients and methods: A retrospective case-control study was conducted to analyze data from 44 patients with PPCM and 226 normal pregnant women from a Chinese population.Results: Significant differences were found between the groups in terms of various factors such as age, body mass index (BMI), heart rate, and medical history. Logistic regression models identified abnormal electrocardiography (OR=18.852), upper respiratory tract infection (OR=41.822), gestational hypertension (OR=18.188), and cesarean section (OR=8.394) as risk factors for PPCM. Common clinical features observed in patients with PPCM included cough, wheezing, and chest tightness (68.18%), left heart enlargement (56.82%) and valvular insufficiency (81.82%). Additionally, cardiotropic virus was detected in a subset of patients (43.18%) and NT-proBNP was elevated ≥ 400 pg/mL (81.82%).Conclusion: In the Chinese population, the presence of abnormal electrocardiograms during pregnancy, history of upper respiratory tract infection, gestational hypertension, and maternal choice of cesarean section suggest the possibility of PPCM development. Factors such as advanced age, family history of cardiovascular disease, gestational diabetes mellitus, eclampsia, anemia, and hypoproteinemia should be considered. Clinically, patients present with cough, wheezing, chest tightness, enlarged left heart, valvular insufficiency and NT-proBNP elevated ≥ 400 pg/mL. This study could serve as a valuable reference for medical practitioners for the early identification and screening of patients with PPCM.Keywords: peripartum cardiomyopathy, risk factors, clinical features, early identification

Xundi Bao,1 Shuo Liang,1 Jun Li,1 Qian Ye,1 Dandan Wu,1 Shu Wang,2 Yue Li,1 Yunsheng Ding,1 Jie Liu3 1Clinical Laboratory, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of China; 2Department of Science and Education, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of China; 3Tuberculosis Control Institute, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of ChinaCorrespondence: Xundi Bao, Clinical laboratory, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), No. 397, Jixi Road, Shushan District, Hefei, Anhui, People’s Republic of China, Tel +86-13866774716, Email baoxundi@163.comObjective: To preliminarily assess the prevalence and control effect of tuberculosis and drug-resistant tuberculosis (TB) in Anhui province, and analyze the trends in the changing drug resistance spectrum of Mycobacterium tuberculosis (Mtb) isolated in Anhui province from 2016 to 2022.Methods: From 2016 to 2022, a total of 2336 culture-positive tuberculosis strains were collected from four drug resistance monitoring sites. Patient demographic information was collected and drug susceptibility testing was conducted.Results: Among the 2336 Mycobacterium tuberculosis complex strains, 1788 (76.54%) were from male patients and 548 (23.46%) were from female patients. The majority were of Han ethnicity, from rural areas, and employed in agriculture, with 12.54% (285/2273) having diabetes. A total of 1893 (81.04%) strains were sensitive to all six anti-TB drugs tested, and 443 (18.96%) strains were resistant to at least one or more anti-TB drugs. The drug resistance rate for patients undergoing initial treatment was 16.80% (348/2071), and 35.85% (95/265) for those receiving retreatment. Among the six anti-TB drugs, the resistance rates from highest to lowest were: INH (10.55%, 236/2336), SM (8.18%, 183/2336), OFX (6.53%, 146/2336), RFP (5.95%, 133/2336), EMB (2.37%, 53/2336), KM (1.97%, 44/2336). Significant differences were observed in MDR strains across different ages, types, with or without diabetes, and geographical sources (χ 2=14.895,76.534,6.032,5.109, all P< 0.05).Conclusion: The tuberculosis prevention and control measures have controlled the drug resistance rate of Mycobacterium tuberculosis to a certain extent. However, there are still statistical differences in drug resistance rates among TB patients with different categories, age groups, regions, and diabetic diseases. Early detection and prompt treatment of patients with drug-resistant TB remain critical to controlling the spread of this disease.Keywords: tuberculosis, mycobacterium, drug resistance, surveillance, population distribution, characteristic analysis

Qiang Ye,1 Guoping Huang,1 Qin Hu,1 Qin Man,2 Xiaoying Hao,3 Liangyan Liu,4 Qiang Zhong,1 Zhao Jin2 1Department of Clinical Laboratory, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, Zigong, Sichuan, 643000, People’s Republic of China; 2Department of Prenatal Diagnosis Center, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, Zigong, Sichuan, 643000, People’s Republic of China; 3Department of Ultrasound, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, Zigong, Sichuan, 643000, People’s Republic of China; 4Department of Obstetrics, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, Zigong, Sichuan, 643000, People’s Republic of ChinaCorrespondence: Zhao Jin, Department of Prenatal Diagnosis Center, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, No. 49 Da Huang Tong Road, Da’an District, Zigong, Sichuan, 643000, People’s Republic of China, Tel +86-13990094008, Email Jinzhao_work@163.comObjective: This study was to evaluate the performance of noninvasive prenatal testing (NIPT) in detecting fetal chromosome disorders in pregnant women.Methods: From October 1st, 2017, to December 31th, 2022, a total of 15,304 plasma cell free DNA-NIPT samples were collected for fetal chromosome disorders screening. The results of NIPT were validated by confirmatory invasive testing or clinical outcome follow-up. Further, NIPT performance between low-risk and high-risk groups, as well as singleton pregnancy and twin pregnancy groups was compared. Besides, analysis of 111 false-positive cases was performed.Results: Totally, NIPT was performed on 15,086 eligible venous blood samples, of which 179 (1.19%) showed positive NIPT results and 68 were further validated to be true positive samples via confirmatory invasive testing or follow-up of clinical outcomes. For common chromosome aneuploidies, sex chromosome abnormalities (SCA) and other chromosomal aneuploidies, the detection sensitivities of NIPT were all 100%, the specificities were 99.87%, 99.70%, and 99.68% and the positive predictive values (PPVs) were 65.45%, 31.82%, and 10.91%, respectively. No statistically significant variance in detection performance was observed among 2987 high-risk and 12,099 low-risk subjects, as well as singleton and twin pregnancy subjects. The concentration of cell-free fetal DNA of 111 false-positive cases ranged from 5.5% to 33.7%, which was higher than the minimum requirement of NIPT.Conclusion: With stringent protocol, NIPT shows high sensitivity and specificity for detecting fetal chromosome disorders in a large-scale clinical service, helping improving overall pregnancy management.Keywords: noninvasive prenatal testing, fetal chromosome disorders, high risk, twin pregnancy, performance evaluation

Xu-Fu Yuan,1 Yu-Qin Ji,2 Teng-Xiao Zhang,3 Hong-Bin Xiang,4 Zhuo-Yan Ye,5 Qiang Ye3 1School of Sports Training, Nanjing Sport Institute, Nanjing, Jiangsu, People’s Republic of China; 2School of Sport and Human Science, Nanjing Sport Institute, Nanjing, Jiangsu, People’s Republic of China; 3School of Physical Education and Humanities, Nanjing Sport Institute, Nanjing, Jiangsu, People’s Republic of China; 4School of Sport, Exercise and Health Sciences, Loughborough University, Leicestershire, UK; 5Nanjing Foreign Language School Xianlin Campus, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Qiang Ye, School of Physical Education and Humanities, Nanjing Sport Institute, No. 8 Linggusi Road, Xuanwu, Nanjing, Jiangsu Province, People’s Republic of China, Tel +86-19962033966, Fax +86-84755161, Email yeqiang@nsi.edu.cnBackground/Objective: In the post-epidemic era, an increasing number of individuals were accustomed to learning sports and physical activity knowledge online for fitness and health demands. However, most previous studies have examined the influence of e-learning materials and resources on learners and have neglected intrinsic factors such as experience and physiological characteristics. Therefore, we conducted a study to investigate the effect of exercise habits and gender on sports e-learning behavior via eye-tracking technology.Methods: We recruited a sample of 60 undergraduate students (mean age = 19.6) from a university in Nanjing, China. They were randomly assigned into 4 groups based on 2 genders × 2 exercise habits. Their gaze behavior was collected by an eye-tracking device during the experiment. The cognitive Load Test and Learning Effect Test were conducted at the end of the individual experiment.Results: (1) Compared to the non-exercise habit group, the exercise habit group had a higher fixation count (P< 0.05), a shorter average fixation duration (P< 0.05), a smaller average pupil diameter (P< 0.05), and a lower subjective cognitive load (P< 0.05) and better learning outcome (P< 0.05). (2) Male participants showed a greater tendency to process information from the video area of interest (AOIs), and had lower subjective cognitive load (P < 0.05) and better learning outcomes (P < 0.05). (3) There was no interaction effect between exercise habits and gender for any of the indicators (P > 0.05).Conclusion: Our results indicate that exercise habits effectively enhance sports e-learning outcomes and reduce cognitive load. The exercise habits group showed significant improvements in fixation counts, average fixation duration, and average pupil diameter. Furthermore, male subjects exhibited superior learning outcomes, experienced lower cognitive load, and demonstrated greater attentiveness to dynamic visual information. These conclusions are expected to improve sports e-learning success and address educational inequality.Keywords: e-learning, exercise habit, eye-tracking, gaze behavior, gender

Linyuan Gui,1,&ast; Qingyuan Ye,2,&ast; Lu Yu,3 Geng Dou,1 Yang Zhou,1 Yang Liu,4 Yanqi Zhang,5 Xiaoshan Yang,1,6 Fang Jin,5 Shiyu Liu,1 Yan Jin,1 Lili Ren1 1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 2State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Digital Dentistry Center, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 3Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, 250012, People’s Republic of China; 4Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 5State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 6Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lili Ren; Yan Jin, State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China, Email lanyangddgy@qq.com; yanjin@fmmu.edu.cnBackground: Osteoporosis is a highly prevalent disease that causes fractures and loss of motor function. Current drugs targeted for osteoporosis often have inevitable side effects. Bone marrow mesenchymal stem cell (BMSCs)-derived apoptotic extracellular vesicles (ApoEVs) are nanoscale extracellular vesicles, which has been shown to promote bone regeneration with low immunogenicity and high biological compatibility. However, natural ApoEVs cannot inherently target bones, and are often eliminated by macrophages in the liver and spleen. Thus, our study aimed to reconstruct ApoEVs to enhance their bone-targeting capabilities and bone-promoting function and to provide a new method for osteoporosis treatment.Methods: We conjugated a bone-targeting peptide, (Asp-Ser-Ser)6 ((DSS)6), onto the surface of ApoEVs using standard carbodiimide chemistry with DSPE-PEG-COOH serving as the linker. The bone-targeting ability of (DSS)6-ApoEVs was determined using an in vivo imaging system and confocal laser scanning microscopy (CLSM). We then loaded ubiquitin ligase RING finger protein146 (RNF146) into BMSCs via adenovirus transduction to obtain functional ApoEVs. The bone-promoting abilities of (DSS)6-ApoEVs and (DSS)6-ApoEVsRNF146 were measured in vitro and in vivo.Results: Our study successfully synthesized bone-targeting and gained functional (DSS)6-ApoEVsRNF146 and found that engineered ApoEVs could promote osteogenesis in vitro and exert significant bone-targeting and osteogenesis-promoting effects to alleviate osteoporosis in a mouse model.Conclusion: To promote the bone-targeting ability of natural ApoEVs, we successfully synthesized engineered ApoEVs, (DSS)6-ApoEVsRNF146 and found that they could significantly promote osteogenesis and alleviate osteoporosis compared with natural ApoEVs, which holds great promise for the treatment of osteoporosis. Keywords: osteoporosis, mesenchymal stem cells, apoptotic extracellular vesicles, bone-targeting, bone regeneration

Qinglin Ye,1,&ast; Guiling Xu,1,&ast; Hao Yuan,2,3 Junhao Mi,2,3 Yuli Xie,2,3 Haoyu Li,1 Zhejun Li,1 Guanwen Huang,1 Xuesong Chen,1 Wei Li,1 Rirong Yang2,3 1Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, People’s Republic of China; 2Centre for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Department of Immunology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rirong Yang, Centre for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Department of Immunology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Fax +86 0771 5317061, Email yangrirong@sr.gxmu.edu.cn; 520yrr@163.com Wei Li, Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, People’s Republic of China, Email liwei030514@126.comBackground: Diabetic kidney disease (DKD) is a chronic renal disease which could eventually develop into renal failure. Though albuminuria and estimated glomerular filtration rate (eGFR) are helpful for the diagnosis of DKD, the lack of specific biomarkers reduces the efficiency of therapeutic interventions.Methods: Based on bulk-seq of 56 urine samples collected at different time points (including 11 acquired from DKD patients and 11 from healthy controls), in corporation of scRNA-seq data of urine samples and snRNA-seq data of renal punctures from DKD patients (retrieved from NCBI GEO Omnibus), urine-kidney specific genes were identified by Multiple Biological Information methods.Results: Forty urine-kidney specific genes/differentially expressed genes (DEGs) were identified to be highly related to kidney injury and proteinuria for the DKD patients. Most of these genes participate in regulating glucagon and apoptosis, among which, urinary PART1 (mainly derived from distal tubular cells) and PLA2R1 (podocyte cell surface marker) could be used together for the early diagnosis of DKD. Moreover, urinary PART1 was significantly associated with multiple clinical indicators, and remained stable over time in urine.Conclusion: Urinary PART1 and PLA2R1 could be shed lights on the discovery and development of non-invasive diagnostic method for DKD, especially in early stages. Keywords: diabetic kidney disease, urine, non-invasive, diagnosis, biomarker

Qing Ye,1,2 Huaiyong Wang3 1School of Education, Shanghai Normal University, Shanghai, People’s Republic of China; 2School of Foreign Languages, East China Normal University, Shanghai, People’s Republic of China; 3School of Psychology, Shanghai Normal University, Shanghai, People’s Republic of ChinaCorrespondence: Huaiyong Wang, School of Psychology, Shanghai Normal University, 100 Guilin Road, Shanghai, 200234, People’s Republic of China, Tel +86-13661679853, Fax +86-21-64323908, Email hywang98431@126.com; hywang@shnu.edu.cnBackground: Tuition-free normal university students (TFNUS) have become an important group in Chinese normal university. The subjective well-being of TFNUS not only affects their own mental health, and decisions to stay in the teaching profession, but also can significantly influence their future student’s perception of stress, learning motivation and academic achievement. However, little attention has been paid to the relationship between positive factors and TFNUS’s subjective well-being and the underlying mechanism and boundary condition. The purpose of this study is to examine whether, how and when profession-related support from different sources influences TFNUS’s subjective well-being.Methods: Based on the Conservation of Resource Theory and Self-Determination Theory, a time-lagged design was used to collect two wave data (N=526), and we use dominance analysis to examine the relative importance of profession-related support from significant others (eg, government, teachers, and parents) in relation to subjective well-being among Chinese tuition-free normal university students, and propose a moderated mediation model to reveal the mediating (intrinsic motivation for teaching) and moderating (dispositional gratitude) effects of this relation.Results: Profession-related government, teacher, and parent support were all positively related to subjective well-being, in a descending order of relative importance were as follows: teacher, parent and government. Furthermore, intrinsic motivation for teaching mediated the relationship between profession-related support and subjective well-being. In addition, dispositional gratitude only moderated the relationship between two sources (teacher and parent, respectively) of profession-related support and intrinsic motivation for teaching. Moreover, dispositional gratitude moderated the strength of the indirect effect of profession-related teacher support and parent support on subjective well-being (through intrinsic motivation for teaching), and the mediated relationship was stronger for those with high (vs low) dispositional gratitude.Conclusion: The profession-related support had positive direct effect on tuition-free normal university students’ subjective well-being, as well as indirect effect through intrinsic motivation for teaching. Dispositional gratitude moderated the relationship between of profession-related teacher, parent support and intrinsic motivation for teaching, and the strength of the indirect effect of this support on subjective well-being.Keywords: profession-related support, subjective well-being, Chinese tuition-free normal university students, intrinsic motivation for teaching, dispositional gratitude

Danuta Kielar,1 Andrew M Jones,2 Xia Wang,3 Heide Stirnadel-Farrant,1 Rohit K Katial,4 Abhinav Bansal,5 Manu Garg,5 Chandrakant Sharma,5 Shubhankar Thakar,5 Qin Ye5 1BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 2Late-Stage Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 3Data Science & AI, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 4BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 5ZS, Philadelphia, PA, USACorrespondence: Danuta Kielar, AstraZeneca, Academy House, 136 Hills Road, Cambridge, CB2 8PA, UK, Tel +44 7384905053, Email danuta.kielar@astrazeneca.comBackground: Blood eosinophils can increase in response to infection, inflammation, and hypersensitivity reactions, yet their involvement in the progression of chronic kidney disease (CKD) is poorly understood. This study explores the relationship between blood eosinophils and CKD progression among patients in a real-world setting.Methods: This retrospective study analyzed data obtained from the Optum® de-identified electronic health records dataset in the United States. Patients diagnosed with CKD stage 3 or 4 (International Classification of Diseases diagnosis code or estimated glomerular filtration rate [eGFR] < 60 mL/min) between January 2011 and March 2018 were included and followed until progression to the next CKD stage, death, or dropout. The primary objective of this study was to assess the relationship between blood eosinophil counts (bEOS) and CKD progression, adjusting for clinical and demographic features as well as known risk factors for CKD stages 3– 4. The primary outcomes were CKD progression and all-cause mortality.Results: We found that high eosinophilic levels (bEOS ≥ 300 cells/μL) were associated with CKD progression from stage 3 to stages 4 or 5 (hazard ratio [HR] ranging from 1.30 to 1.50) and from stages 4 to 5 (HR ranging from 1.28 to 1.50). Among patients with CKD progression, those with blood eosinophils ≥ 300 cells/μL appeared to have a relatively lower eGFR, higher all-cause mortality, and reduced time to CKD progression and death than those with < 300 cells/μL. Factors including sex, race, hypertension, anemia, and treatments for cardiovascular and hematopoietic drugs were associated with CKD progression.Conclusion: Elevated eosinophils may increase the risk for CKD progression. Larger studies are needed to assess whether the risk of mortality is increased among patients with elevated eosinophils.Keywords: eosinophilic inflammation, renal insufficiency, glomerular filtration rate

Jingwei Wang,1,2,&ast; Bowen Xia,3,&ast; Ruimin Ma,1 Qiao Ye1,2 1Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Occupational Medicine and Toxicology, Clinical Center for Interstitial Lung Diseases, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiao Ye, Department of Occupational Medicine and Toxicology, Clinical Center for Interstitial Lung Diseases, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Worker’s Stadium, Chaoyang District, Beijing, 100020, People’s Republic of China, Email yeqiao_chaoyang@sina.comPurpose: Chronic obstructive pulmonary disease (COPD) is the main cause of mortality world widely. Non-coding RNAs (lncRNAs) and associated competitive endogenous RNAs (ceRNAs) networks were recently proved to lead to mRNA gene expression downregulation but were still unclear in COPD. This study aims to investigate and elucidate the mechanisms underlying the involvement of ceRNA co-expression networks in COPD pathogenesis.Methods: Obtained expression signature of data from the Gene Expression Omnibus database and compared the differentially expression of mRNAs and miRNAs between COPD patients and healthy smokers. Predicted the miRNA–lncRNA and miRNA–mRNA interaction using online library and employed CIBERSORT to measure the proportions of the 22 immune cells in the COPD and control groups.Results: Established a ceRNA-network comprising 11 lncRNAs, 5 miRNAs, and 16 mRNAs. Using the weighted correlation network analysis method, we identified hub genes and hub miRNAs and obtained one core sub-network, XIST, FGD5-AS1, KCNQ1OT1, HOXA11-AS, LINC00667, H19, PRKCQ-AS1, NUTM2A-AS1/has-mir-454-3p/ZNF678, PRRG4. COPD patients had different proportions of immune cells than controls, and these variations were associated with the magnitude of pulmonary function parameters.Conclusion: The ceRNA-network, particularly the core sub-network, may be a putative goal for COPD, in which specific immune cells were involved.Keywords: chronic obstructive pulmonary disease, competing endogenous RNA network, microRNAs, miRNAs, CIBERSORT algorithm, gene expression omnibus

Qinglin Ye,&ast; Guiling Xu,&ast; Haizhen Huang,&ast; Shuting Pang, Boji Xie, Bingmei Feng, Peng Liang, Yijie Qin, Siji Li, Yin Luo, Chao Xue, Wei Li Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Chao Xue, Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email liwei030514@126.com; xccqh@126.comPurpose: Chronic kidney disease (CKD) progression is complex. There are not standardized methods for predicting the prognosis of CKD. Nicotinamide N-methyltransferase (NNMT) has been shown to be associated with renal fibrosis. This study aimed to validate NNMT as a prognostic biomarker of progressive CKD.Patients and Methods: We explored the relationship between NNMT expression and CKD-related outcome variables using the NephroseqV5 and GEO databases. Additionally, a validation set of 37 CKD patients was enrolled to measure the correlation between NNMT expression levels and CKD outcomes. Furthermore, single-cell RNA sequencing data and the Human Protein Atlas were reanalyzed to investigate the expression specificity of NNMT in the kidney. Finally, to detect the status of NNMT expression with tubular fibrosis in vivo, we constructed a unilateral ureteral obstruction (UUO) mouse treated with an NNMT inhibitor.Results: Analyzing the datasets showed that NNMT was expressed mainly in proximal tubule compartments. And patients with high NNMT expression levels had a significantly lower overall survival rate compared to those with low NNMT expression levels (P = 0.013). NNMT was independent of prognosis factors in the multivariate Cox regression model, and the AUCs for CKD progression at 1, 3, and 5 years were 0.849, 0.775, and 0.877, respectively. Pathway enrichment analysis indicated that NNMT regulates the biological processes of tubulointerstitial fibrosis (TIF). In the validation group, NNMT levels were significantly higher in the CKD group combined with interstitial fibrosis. In vivo, NNMT was a high expression in the UUO group, peaking at postoperative day 21. Treatment with an NNMT inhibitor improved renal tubular interstitial fibrosis, and expression levels of FN, α-SMA, VIM, and TGF-β 1 were decreased compared with UUO (P < 0.05).Conclusion: NNMT was expressed mainly in tubular renal compartments, and associated with CKD prognosis. It holds potential as a diagnostic biomarker for tubular fibrosis in CKD.Graphical Abstract: Keywords: nicotinamide N-methyl transferase, tubular fibrosis, chronic kidney disease, biomarker diagnosis

Jiequn Huang,1 Changzhi Liu,1 Zhujiang Zhou,1 Han Xia,2 Zhensheng Zhu,2 Jianhai Lu,1 Jingcheng Lin,1 Zhen Chen,1 Qimei Ye,1 Liuer Zuo1 1Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan), Foshan, Guangdong, People’s Republic of China; 2Department of Scientific Affairs, Hugobiotech Co, Ltd, Beijing, People’s Republic of ChinaCorrespondence: Liuer Zuo, Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde, Foshan), Foshan, Guangdong, People’s Republic of China, Email 13500276597@163.comBackground: Pneumonia infected by Chlamydia abortus (C. abortus) is rare, especially complicated with severe acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS).Case Presentation: We presented the clinical details of a 44-year-old male who was diagnosed with C. abortus pneumonia, which rapidly progressed and ultimately led to ARDS, sepsis and MODS. Although he was initially diagnosed with pneumonia upon admission, no pathogenic bacteria were detected in sputum by conventional tests. Empirical intravenous infusion of meropenem and moxifloxacin was administered, but unfortunately, his condition deteriorated rapidly, especially respiratory status. On Day 2 after extracorporeal membrane oxygenation (ECMO) initiation, metagenomic next-generation sequencing (mNGS) was performed on the patient’s bronchoalveolar lavage fluid, which indicated an infection with C. abortus. The patient’s antimicrobial therapy was adjusted to oral doxycycline (0.1g every 12h), intravenous azithromycin (0.5g every day), and imipenem and cilastatin sodium (1g every 6h). The patient’s condition improved clinically and biologically. However, the patient was discharged due to financial reasons and unfortunately passed away eight hours later.Conclusion: Infections with C. abortus can result in severe ARDS and serious visceral complications which necessitate prompt diagnosis and active intervention by clinicians. The case highlights the significance of mNGS as an essential diagnostic tool for uncommon pathogens. Tetracyclines, macrolides or their combinations are effective choices for treatment of C. abortus pneumonia. Further study is needed to explore the transmission routes of C. abortus pneumonia and establish precise guidelines for antibiotic treatment.Keywords: Chlamydia abortus, ECMO, pneumonia, acute respiratory distress syndrome, metagenomic next-generation sequencing

Jiaoquan Chen,&ast; Yuwu Luo,&ast; Nanji Yu, Yan Yang, Xin Zhou, Shujuan Zhang, Qianru Ye, Huilan Zhu Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, Guangdong, 510095, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huilan Zhu, Department of Dermatology Guangzhou Institute of Dermatology 56 Hengfu Road, Guangzhou, Guangdong, 510095, People’s Republic of China, Email zhlhuilan@126.comAbstract: Subcorneal pustular dermatosis (SPD) is a rare, chronic pustular dermatosis. The pathogenesis of SPD has not been fully elucidated, but some studies have found that tumor necrosis factor (TNF)-α may be associated with its pathogenesis. Some patients with multidrug-resistant SPD have improved significantly after treatment with the anti-TNF-α agent (adalimumab). We present a case of a 28-year-old female with severe SPD who responded rapidly to adalimumab (80mg/week) in combination with acitretin and methylprednisolone within a week. With adalimumab (40 mg next week and followed by 40mg every two weeks) and gradually ceasing other systemic medication, the patient’s condition continued to improve without relapse or side effects. The outcome of this case suggests that adalimumab might be an effective treatment option against multidrug-resistant SPD.Keywords: subcorneal pustular dermatosis, anti-TNF-α agent, adalimumab

Mengxiong Li,1,&ast; Zhi Zeng,2,&ast; Aiqing Zhang,3 Qingjian Ye,4 Shujun Su,4 Tingting Xia5 1Department of Obstetrics and Gynecology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 518107, People’s Republic of China; 2The Department of Reproductive Medicine Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510000, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 4Department of Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 5Center for Reproductive Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingting Xia Tel +86-020-85256032Email xiatting@mail.sysu.edu.cnObjective: Dysfunction of cumulus granulosa cells has been suggested as a contributor to abnormal folliculogenesis and the development of polycystic ovary syndrome (PCOS), but the underlying molecular mechanisms remain unclear. Recent studies indicate that circular RNAs (circRNAs) exert important roles for diseases. We aimed to screen crucial circRNAs of PCOS patients and predict their functions.Methods: The high-throughput datasets of circRNAs (GSE145296), microRNAs (miRNAs; GSE72274) and messenger RNAs (mRNAs; GSE155489) in cumulus cells of PCOS patients and controls were collected from the Gene Expression Omnibus database. Differentially expressed circRNAs (DECs), miRNAs (DEMs) and protein-coding genes (DEGs) were identified by the limma method. The weighted correlation network analysis (WGCNA) was conducted using the DECs to mine PCOS-associated modules. Hub DECs in modules were defined as both of |gene significance| and |module membership| > 0.8. The downstream effectors of hub DECs were predicted by constructing DEC-DEM-DEG ceRNA and DEC-RNA binding protein (RBP) networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to explore the functions of circRNAs.Results: A total of 3614 DECs, 3544 DEGs and 1469 DEMs were identified between PCOS and controls. WGCNA analysis yielded five PCOS-related modules, of which 190 DECs were hub circRNAs. Seventeen hub DECs, nine DEMs, and 315 DEGs were identified to construct the ceRNA network, while 56 hub DECs and two DEGs (MBNL2, RBPMS) constituted the circRNA-RBP network. Five hub DECs (hsa_circ_0063309, hsa_circ_0054275, hsa_circ_0056196, hsa_circ_0018108 and hsa_circ_0070987) were overlapped between ceRNA and DEC-MBNL2 regulatory networks and thus they may be pivotal for PCOS. Furthermore, hsa_circ_0099109 could interact with the RBP gene RBPMS. Function analyses showed these circRNAs were inflammation-, apoptosis- or steroidogenesis-related.Conclusion: Aberrant expression of six circRNAs that function as RBP regulators or miRNA sponges may be possible mechanisms underlying the pathogenesis of PCOS by affecting apoptosis and steroidogenesis in cumulus cells.Keywords: circular RNAs, competitive endogenous RNAs, polycystic ovary syndrome, RNA-binding proteins, weighted gene co-expression network analysis

Xiaohua Zhang,1,&ast; Xinguo Liu,2,&ast; Qiongxiang Ye,2 Xunbao Wang,2 Jinjun Chen,2 Zhiyong Wang,2 Pengfei Zhao,2 Baozhou Tao,2 Guoping Xu,2 Wanfeng Xu,2 Kan Wu,2 Yao Xiao,3 Li Yang,1 Junqiang Tian,1 Juan Wang,1 Zhilong Dong,1 Zhiping Wang1 1Institute of Urology, Lanzhou University Second Hospital; Key Laboratory of Gansu Province for Urological Diseases; Gansu Nephro-Urological Clinical Center, Lanzhou, Gansu Province, People’s Republic of China; 2Department of Urology, Susong County People’s Hospital, Susong, Anhui Province, People’s Republic of China; 3Department of Pediatrics, Lanzhou University Second Hospital, Lanzhou, Gansu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiping Wang Email wangzplzu@163.comObjective: To compare the analgesic efficacy and safety of acupuncture and lornoxicam in acute renal colic (ARC).Design, Setting, Participant: A randomized, double-blind, parallel-controlled, single-centered trial was conducted at Susong County People’s Hospital from October 2019 to November 2020. Eighty-four patients with ARC were randomly divided into lornoxicam group (Group L) and acupuncture group (Group A). Group A was treated with acupuncture at Sanyinjiao (SP6), Yinlingquan (SP9) and normal saline, and Group L was treated with sham acupuncture at SP6, SP9 and lornoxicam.Main Outcome Measures: Visual analogue scale (VAS) scores and adverse reactions such as nausea and dizziness were recorded within 5, 10, 15, 20 and 40 minutes after treatment. The main outcome of this study was the short-term effective (STE) rate, the secondary outcome was the onset time, and the safety index was incidence of adverse reactions.Results: A total of 80 patients completed this study, including 41 patients (21 males and 20 females) in Group L and 39 patients (21 males and 18 females) in Group A. Group A exhibited lower scores versus group L after treatment (P < 0.05). The overall STE of group L was 61.00% (25/41), significantly lower than group A [84.62% (33/39)] (P < 0.001). There was no difference in the incidence of adverse reactions between group A [2.6% (1/39)] and group L [7.3% (3/41)] (P = 0.616). The ordered logistic regression analysis showed patients receiving acupuncture therapy are more likely to be cured [OR = 2.887, 95% CI: (1.190, 7.000), P = 0.019].Conclusion: Acupuncture at SP6, SP9 and intramuscular injection of lornoxicam can effectively and safely relieve ARC, but the former has faster and better analgesic effect. Moreover, the incidence of adverse reactions was similar between the two treatments. This acupuncture therapy is recommended as a complementary therapy for ARC.Keywords: acupuncture, lornoxicam, renal colic, analgesia

Qian Ye, Ke-Jun Chen, Meng Jia, Sheng Fang Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Sheng FangDepartment of Dermatology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaEmail fangshengderm@163.comObjective: The aim of this study was to describe the clinical and histopathological characteristics of seborrheic keratosis (SK) with secondary tumor and identify associated factors.Methods: This study was a monocentric retrospective case-control study describing the factors associated with the development of tumors in SK. A total of 1365 patients with SK were admitted to our department between 2018 and 2021. All of the histopathological specimens and medical records of these patients were reviewed. We compared the data of 36 patients with tumors arising in SK with those of the remaining 1329 patients with only SK, which were designated the control group.Results: The incidence of tumors arising in SK that were biopsied was 2.6%. The tumor types included squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and keratoacanthoma (KA). Compared with other patients with SK, elderly patients with immunosuppression, patients presenting surrounding erythema or ulceration, and those with SK in exposed areas had an increased possibility of developing a secondary tumor. Tumors arising within SK have the histopathological features of ulceration, cytologic atypia, mitosis, “malignant horn”, trabecular cell cords, solar elastosis and severe inflammatory infiltration in the dermis.Conclusion: SK can show malignant progression in a small fraction of SK cases that are biopsied. This study is the first report on the clinical and histopathological characteristics of tumors arising in SK and identifies relevant factors in an Asian population.Keywords: seborrheic keratosis, tumor, clinical, histopathological

Qian Ye, Junying Guo, Yansong Chen, Zhaolei Cui, Yan Chen Department of Laboratory Medicine, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou City, Fujian Province, 350014, People’s Republic of ChinaCorrespondence: Zhaolei Cui; Yan ChenDepartment of Laboratory Medicine, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, No. 420 Fuma Road, Jin’an District, Fuzhou City, Fujian Province, 350014, People’s Republic of ChinaEmail cuileidizi@163.com; chenyan220422@fjmu.edu.cnObjective: The aim of this study was to evaluate the effectiveness of Epstein–Barr virus (EBV) VCA-IgA antibody, EBV DNA and HSP90α alone or in combinations for the diagnosis and prognostic prediction of nasopharyngeal carcinoma (NPC).Methods: A total of 113 treatment-naïve patients with NPC and 40 healthy controls were enrolled. Plasma HSP90α and serum EBV VCA IgA antibody were detected using ELISA, and plasma EBV DNA was quantified using qPCR assay. The effectiveness of plasma HSP90α level, serum EBV VCA IgA antibody and plasma EBV DNA was examined in the diagnosis and prognosis prediction of NPC.Results: Higher plasma HSP90α, serum EBV VCA IgA antibody and plasma viral load of EBV DNA were detected in NPC patients than in healthy controls (P < 0.001). The plasma HSP90α levels, serum EBV VCA IgA antibody titers and plasma viral load of EBV DNA were significantly greater in NPC patients with stages III and IV than in those with stages I and II (P < 0.001), and significantly lower plasma HSP90α levels, serum EBV VCA IgA antibody titers and plasma viral load of EBV DNA were found in the good prognosis group than in the poor prognosis group post-treatment (P < 0.05). The area under representative operating curves (AUCs) of plasma HSP90α, serum EBV VCA IgA antibody and plasma EBV DNA alone and in combination were 0.884, 0.841, 0.934 and 0.954 for the diagnosis of NPC, respectively. Univariate and multivariate Cox proportional hazards regression analyses identified HSP90α as an independent prognostic factor for NPC.Conclusion: The combination of plasma HSP90α, serum EBV VCA IgA antibody and plasma EBV DNA shows high diagnostic performance for NPC, and plasma HSP90α may be a potential marker for diagnosis and prognosis prediction of NPC.Keywords: nasopharyngeal carcinoma, EBV VCA-IgA antibody, EBV DNA, HSP90α, diagnostic performance, prognosis prediction

Meng Jia, Feng-Zeng Li, Qian Ye, Ke-Jun Chen, Sheng Fang Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Sheng FangDepartment of Dermatology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaEmail fangshengderm@163.comBackground: Heat shock proteins (HSPs), a group of heat stress proteins, are characterized by highly conserved properties. Malignant transformation is a cellular stress, and the expression of HSPs may be affected during this process. Heat shock protein 105 (HSP105) is a protective protein that has long been observed in many cancer types, but little attention has been given to cutaneous squamous cell carcinoma (CSCC). As such, the objectives of this study were to observe the expression of HSP105 on CSCC and evaluate its correlation with clinicopathological characteristics.Methods: This retrospective study enrolled 60 patients with CSCC. The patients’ clinical data, including sex, age, tumor location, tumor type, and degree of pathological differentiation, were collected. The expression of HSP105 was measured by Western blot and immunohistochemical staining.Results: HSP105 expression was decreased in CSCC (HSCORE=0.65 (0.30, 1.98)) compared with normal skin (HSCORE=2.20 (1.50, 2.80)) (P< 0.001). These results were consistent with the Western blot analysis. HSP105 immunostaining of Bowen disease (HSCORE=1.28 (1.08, 2.40)) revealed higher expression than in verrucous carcinoma (HSCORE=0.30 (0.23, 0.85)), keratoacanthoma (HSCORE=0.53 (0.29, 0.93)) and acantholytic squamous cell carcinoma (HSCORE=0.53 (0.41, 0.68) (P< 0.01)). Poorly differentiated CSCC showed significantly higher expression of HSP105.Conclusion: Our study reveals for the first time that the expression of HSP105 is decreased in CSCC. We suggest that the molecular mechanisms underlying the differential expression of HSP deserve a more rigorous future study, the results of which might explain its role in carcinogenesis and its potential as a target for selective tumor therapy.Keywords: heat shock protein 105, cutaneous, squamous cell carcinoma, expression

Qing Ye,1,* Qiqiang Zhang,1,* Huijuan Yao,1,* Ajing Xu,1 Yan Liu,1 Jia Qi,1 Hai Zhang,2 Jian Zhang1 1Department of Pharmacy, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 200092, People’s Republic of China; 2Department of Pharmacy, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201204, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian ZhangDepartment of Pharmacy, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, People’s Republic of ChinaTel/Fax +86 21-25077150Email zhangjian@xinhuamed.com.cnHai ZhangDepartment of Pharmacy, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 2699 High Tech West Road, Pudong New Area, Shanghai, 201204, People’s Republic of ChinaTel/Fax +86 21-20261401Email zhxdks2005@126.comBackground: Shegan Mixture (SGM) is a traditional Chinese medicine that has anti-inflammatory and therapeutic effects on asthma. However, its active ingredients and combined action mechanism have not been fully elucidated so far. The purpose of this study was to screen the effective ingredients and targets and elucidate the synergistic action mechanism of SGM in asthma mice using the network pharmacological approach.Methods: A mouse model of asthma model was used in this study. Mice were orally administered SGM at three doses for 4 weeks and the effect of SGM on asthma was evaluated. The active ingredients and their targets of SGM were identified by searching databases, such as Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). The main active ingredients were selected with parameters OB and DL. The synergistic action mechanisms of SGM in asthma were studied through key active ingredient-target interaction network and verified using surface plasmon resonance assay (SPR).Results: SGM exerts anti-asthmatic effects by reducing lung tissue damage and inflammatory factors (IFN-γ, IL-4, IL-5, and IL-13) in asthmatic mice. Twenty ingredients and 45 related proteins were selected as potential nodes using enrichment analysis and network analysis. Inflammation and smooth muscle regulation-related pathways were considered to be the main pharmacological mechanisms of SGM in the treatment of asthma. Especially, 5 molecule-target pairs (including 3 ingredients and 4 proteins) were well docked with each other and the SPR assay revealed that glabridin-PTGS2 had good binding with 44.5 μM Kd value.Conclusion: SGM exerts the synergistic anti-asthma effects by virtue of reducing lung-tissue damage and inflammatory factors in asthmatic mice, which explains the theoretical basis for the traditional Chinese medicine, SGM, to treat asthma. Our study thus sheds light on a variety of options including Chinese medicine that could potentially be used in the clinical treatment of asthma.Keywords: Shegan mixture, asthma, network pharmacology, surface plasmon resonance, traditional Chinese medicine

Yanlei Zhang,1 Zusen Ye,1 Yun Fu,2 Zheng Zhang,1 Qiang Ye,1 Feichi Chen,1 Jianhua Cheng1 1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, People’s Republic of China; 2Department of Cardiac Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, People’s Republic of ChinaCorrespondence: Jianhua ChengDepartment of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Wenzhou 325000, Zhejiang Province, People’s Republic of ChinaTel +86 577 55579365Fax +86 577 55578999Email chengjianhua@wmu.edu.cnBackground: Cardiac myxoma is the most common primary cardiac tumor. Even though it rarely causes a stroke, it is an important risk factor. Here, we compared our clinical experience in managing myxoma patients who developed stroke complications with those who did not present with this condition at the First Affiliated Hospital of Wenzhou Medical University.Patients and Methods: The medical records were reviewed of 160 cardiac myxoma patients who were treated in our facility from January 2006 to December 2019. They were separated into either a stroke group or non-stroke group.Results: Cardiac obstructive symptoms, embolic events and constitutional symptoms were observed in 92 (57.7%), 25 (15.6%) and 18 (11.2%) patients, respectively. Among 23 cardiac myxoma ischemic stroke patients, hypoesthesia (60.9%), hemiparesis (56.5%) and facial paresis (47.8%) were the three most common neurological symptoms. The middle cerebral artery (82.6%) was the most commonly affected vessel, whereas 73.9% of the ischemic patients had multiple stroke lesions. Binary logistic regression analysis showed that coronary heart disease and tumor sizes were independently associated in the stroke group (p < 0.05). The 10 years cumulative survival rate was 87.9% for all patients after surgical intervention. There was no significant difference in the 10 years cumulative survival rate between the two groups (80.0% vs 88.9%, p =0.274 > 0.05).Conclusion: The three most common neurological symptoms (hypoesthesia, hemiparesis and facial paresis), the middle cerebral artery and multiple lesions involvements were the definitive markers of patients afflicted with cardiac myxoma stroke. Small tumor sizes were independently associated with these patients. Surgical resection is a relatively safe procedure for treating both the stroke and non-stroke patients.Keywords: cardiac myxoma, embolic complication, ischemic stroke, surgery

Fei Yang,* Rigao Chen,* Dangwei Gu, Qingqing Ye, Wei Liu, Jianhua Qi, Kai Xu, Xiaohong Fan Department of Spine Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohong Fan Email 173787798@qq.comPurpose: Although lumbar spinal stenosis (LSS) is the most common spinal disease in the elderly, there is still a confusion about the appropriate surgical treatment strategy. The aim of this study was to compare the safety and efficacy of full-endoscopic and microscopic unilateral laminotomy for bilateral decompression (ULBD) for LSS in elderly patients.Patients and Methods: A retrospective analysis of 61 consecutive elderly patients with LSS who underwent either full-endoscopic (FE group) or microscopic (Micro group) unilateral laminotomy for bilateral decompression was performed. Clinical data were assessed before 2 weeks, 3 months, 6 months and 12 months after surgery using the Visual Analog Scale (VAS), the Oswestry Disability Index (ODI) and the modified MacNab criteria.Results: There are no significant differences in VAS (back and leg) and ODI between the two groups. However, the VAS back pain in the FE group was significantly improved compared to the Micro group at 2 weeks. The rate of excellent or good outcomes was 87.88% and 85.71% in the FE and Micro group, respectively (P> 0.05). The hospital stay and early ambulation in FE group were shorter than those in Micro group, but the operation time was longer (P< 0.05). The complications between the FE group (18.18%) and the Micro group (17.86%) were minor (P> 0.05).Conclusion: Both full-endoscopic and microscopic decompression have achieved favorable clinical results in treating elderly lumbar spinal stenosis, and the complications are minor. Full-endoscopic decompression has the advantages of small incision and rapid recovery, which can be used as an alternative for the treatment of lumbar spinal stenosis, especially the elderly with comorbidities.Keywords: central stenosis, minimally invasive spinal surgery, MISS, comorbidity, complication

Xiaozhou Liang,1 Xuchao Miao,1 Weijin Xiao,2 Qin Ye,3 Sisi Wang,4 Juqiang Lin,1 Chao Li,2,5,6 Zufang Huang1 1Fujian Normal University, Ministry of Education, Key Laboratory of Optoelectronic Science and Technology for Medicine, Fujian Provincial Key Laboratory for Photonics Technology, Fuzhou, People’s Republic of China; 2Department of Pathology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Head and Neck Surgery, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, People’s Republic of China; 4Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 5Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, People’s Republic of China; 6Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, People’s Republic of ChinaCorrespondence: Zufang Huang Tel +86 591 834 65373Email zfhuang@fjnu.edu.cnObjective: The objective of this study is to evaluate the performance and feasibility of surface-enhanced Raman spectroscopy coupled with a filter membrane and advanced multivariate data analysis on identifying and differentiating benign and malignant thyroid tumors from blood plasma.Patients and Methods: We proposed a membrane filter SERS technology for the differentiation between benign thyroid tumor and thyroid cancer. That is to say, by using filter membranes with optimal pore size, the blood plasma samples from thyroid tumor patients were pretreated with the macromolecular proteins being filtered out prior to SERS measurement. The SERS spectra of blood plasma ultrafiltrate obtained using filter membranes from 102 patients with thyroid tumors (70 thyroid cancers and 32 benign thyroid tumors) were then analyzed and compared. Two multivariate statistical analyses, principal component analysis-linear discriminate analysis (PCA-LDA) and Lasso-partial least squares-discriminant analysis (Lasso-PLS-DA), were performed on the SERS spectral data after background subtraction and normalization, as well as the first derivative processing, to analyze and compare the differential diagnosis of benign thyroid tumors and thyroid cancer.Results: SERS measurements were performed in blood plasma acquired from a total of 102 thyroid tumor patients (benign thyroid tumor N=32; thyroid cancer N=70). By using filter membranes, the macromolecular proteins in blood plasma were effectively filtered out to yield high-quality SERS spectra. 84.3% discrimination accuracy between benign and malignant thyroid tumor was achieved using PCA-LDA method, while Lasso-PLS-DA yields a discrimination accuracy of 90.2%.Conclusion: Our results demonstrate that SERS spectroscopy, coupled with ultrafiltration and multivariate analysis has the potential of providing a non-invasive, rapid, and objective detection and differentiation of benign and malignant thyroid tumors.Keywords: surface-enhanced Raman spectroscopy, thyroid tumor, filter membrane, silver nanoparticles, blood plasma

Yan Zeng1, Cheng-Long Wang2, Jie Xian1, Qian Ye3, Xue Qin1, Yi-Wen Tan1, You-De Cao1 1Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Pathology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, People’s Republic of China; 3Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: You-De CaoDepartment of Pathology, College of Basic Medicine, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel +86 236 848 5789Email 420306100@qq.comPurpose: Tumors with high mutation load tend to have a stronger immune response in some tumors. The correlation between expression of programmed death ligand-1 (PD-L1), a biomarker of immune response in tumors, and p53, accepted as the most frequently mutated gene in many cancers, in triple-negative breast cancer (TNBC) has not been fully investigated in cancer patients.Materials and methods: 132 cases of TNBC and 32 cases of non-TNBC paraffin-embedded tissue sections were selected to detect the expression of PD-L1 and p53 by immunohistochemistry, and results were correlated with clinical data and survival outcomes. The staining of PD-L1 in tumor cells (TCs) and tumor-associated immune cells (TAICs) was assessed separately.Results: Strong positive correlations were observed between expression of p53 and PD-L1 both in TCs (r=0.338, P=0.000) and TAICs (r=0.186, P=0.033). The same positive correlation was found in the expression of PD-L1 in TCs and TAICs (r=0.764, P=0.000). Like p53 (P=0.024), positive rate of PD-L1 in TCs was significantly higher in TNBC than in non-TNBC (P=0.02). PD-L1 and p53 in TCs staining were significantly associated with histological grade, tumor size and Ki67 index (P

Haijun Shen,1 Qianqian Gao,1 Qi Ye,1 Shiyun Yang,1 Yuqian Wu,1 Qin Huang,1 Xiaona Wang,2 Zhenhua Sun3 1Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China; 2Department of Internal Medicine of Jiangsu University Hospital Workers, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China; 3Department of Thyroid and Breast Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China Background and purpose: Nanoparticle-loaded hydrogels – localized drug delivery devices containing a combination of therapeutic nanoparticles and implantable hydrogel – have been recipients of increased focus and interest for cancer treatment. However, it is difficult for the released nanoparticles to penetrate deeply into tumors because of the dense collagen network in the tumor extracellular matrix, which greatly limits their antitumor effect. We hypothesized that the implantation of a hydrogel loaded with both nanoparticles and losartan (Los) might enhance penetration because Los has been proven to effectively reduce collagen levels in various tumors. Herein, we developed a nanoparticle/Los-loaded hydrogel system and evaluated the intratumoral distribution and anticancer effect after peritumoral implantation of nanoparticles. Methods: Fluorescent polystyrene nanoparticles (FPNPs, size ~100 nm) and Los were simultaneously encapsulated in a polyethylene glycol (PEG) hydrogel to form the FPNP/Los-loaded hydrogel. After peritumoral implantation in 4T1 tumor-bearing mice for 2 weeks, intratumoral distributions of FPNPs and collagen level were determined. Based on the results, liposomal doxorubicin (Doxil, ~100 nm) was subsequently substituted for FPNPs in the hydrogel. The cellular uptake and cytotoxicity of the Doxil/Los-loaded hydrogel were studied, and the in vivo antitumor efficacy after peritumoral implantation was evaluated. Results: Compared with a standard FPNP-loaded hydrogel, the FPNP/Los-loaded hydrogel resulted in enhanced penetration and reduced collagen levels after implantation. Thereafter, the potential of a Doxil/Los-loaded hydrogel for cancer treatment was studied. Doxorubicin was released from the hydrogel and induced effective cytotoxicity against 4T1 cells. The Doxil/Los-loaded hydrogel showed synergistic antitumor effects in 4T1 tumor-bearing mice and was more effective at tumor inhibition than the Doxil-loaded hydrogel. Conclusion: This study provides a proof of principle that the implantation of nanoparticles/Los-loaded hydrogel can increase the intratumoral distribution and antitumor efficacy of nanoparticles, owing to collagen depletion by Los. Future studies may build on this strategy for enhanced tumor penetration of nanoparticles. Keywords: localized drug delivery, tumor penetration, tumor extracellular matrix, collagen, matrix metalloproteinase, breast cancer

Saibin Wang,1,2 Qian Ye,3 Junwei Tu,1 Yong Song2 1Department of Respiratory Medicine, Jinhua Municipal Central Hospital, Jinhua, Zhejiang Province, China; 2Department of Respiratory Medicine, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, China; 3Department of Medical Records Quality Management, Jinhua Municipal Central Hospital, Jinhua, Zhejiang Province, China Background: Several risk factors have been proposed for bleeding during bronchoscopy, including immunosuppression, thrombocytopenia, pulmonary arterial hypertension, and mechanical ventilation. However, research on bronchoscopic biopsy-induced bleeding in the population of lung cancer without these “proposed risk factors” remains lacking. Patients and methods: A total of 531 lung cancer patients with endobronchial biopsy (EBB) were enrolled in this retrospective observational study. Patients were divided into biopsy-induced bleeding group (n=162) and non-bleeding group (n=369). Using multiple logistic regression, independent risk factors for EBB bleeding were identified. Results: The location, histologic type, and stage of lung cancer were independently associated with EBB bleeding, as assessed by multiple logistic regression (p

Qidong Ye,1 Pan Fu,2 Jiaying Dou,2 Nina Wang2 1Department of Pediatrics, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, People’s Republic of China; 2Department of Hematology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Introduction: Acute myeloid leukemia (AML) is a common malignancy of the hematopoietic system. In bone marrow samples of AML patients, PDIA3 expression was higher than that in the samples of healthy controls. We aimed at exploring the effect of PDIA3 siRNA on proliferation, apoptosis, migration, and invasion of AML HL-60 and HEL cells.Materials and methods: RT-PCR was performed to identify PDIA3 expression. Cell proliferation was assessed by MTT. Flow cytometry analysis and transwell were used to detect cell apoptosis, migration and invasion. Gene set enrich-ment analysis (GSEA) was employed to explore the PDIA 3-associated pathways in AML. Western blotting was used for protein expression detection.Results: PDIA3 siRNA significantly inhibited the proliferation of AML cells at 24 and 48 h. PDIA3 siRNA notably enhanced the percentage of apoptotic cells. The migration and invasion abilities of HL-60 and HEL cells in the PDIA3 siRNA group were significantly suppressed compared with those in the control and siNC groups. GSEA of the Cancer Genome Atlas dataset showed that Kyoto Encyclopedia of Genes and Genomes oxidative phosphorylation and amino sugar and nucleotide sugar metabolism pathways could be correlated with PDIA3 expression; this was further confirmed in AML cells by Western blotting. MAPK signaling was also blocked by PDIA3 siRNA. Conclusion: PDIA3 siRNA effectively enhanced apoptosis, and suppressed proliferation, invasion, and migration of AML cells by regulating oxidative phosphorylation and amino sugar and nucleotide sugar metabolism pathways, and MAPK signaling, which can provide novel therapeutic targets for AML. Keywords: PDIA3, acute myeloid leukemia, migration, invasion, gene set enrichment analysis, MAPK pathway

Weiwei Tan,1,* Meihong Pan,1,* Hui Liu,1 Hequn Tian,1 Qing Ye,1 Hongda Liu2 1Department of Traditional Chinese Medicine, Yidu Central Hospital of Weifang, Weifang, Shandong, China; 2Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China *These authors contributed equally to this work Abstract: Ergosterol peroxide (EP), a sterol derived from medicinal mushrooms, has been reported to exert antitumor activity in several tumor types. However, the role of EP toward ovarian cancer cells has not been investigated. In this study, we analyzed the cytotoxicity of EP in various cell lines representing high-grade serous ovarian cancer and low-grade serous ovarian cancer, respectively. Although EP showed no significant inhibition of the viability of normal ovarian surface epithelial cells, it impaired the proliferation and invasion capacities of tumor cells in a dose-dependent manner. We further figured out key modulators involved in its antitumor effects by quantitative reverse transcription polymerase chain reaction, ELISA, and Western blot. The nuclear β-catenin was down-regulated upon EP treatment, subsequently reducing the Cyclin D1 and c-Myc expression levels. Meanwhile, the protein level of protein tyrosine phosphatase SHP2 was up-regulated in EP treated cells, whereas Src kinase activity was inhibited. Both activation of SHP2 phosphatase and inhibition of Src kinase decreased the phosphorylation level of transducer and activator of STAT3 protein, which was implicated in oncogenesis. On the other hand, EP remarkably inhibited the expression and secretion of VEGF-C, implying its involvement in counteracting tumor angiogenesis. Moreover, EP treatment showed comparable cytotoxic effect with β-catenin knock-down or STAT3 inhibition. Taken together, our results demonstrated that EP showed antitumor effects toward ovarian cancer cells through both β-catenin and STAT3 signaling pathways, making it a promising candidate for drug development. Keywords: β-catenin, ergosterol peroxide, ovarian cancer, STAT3

Gao F, Ye Q, Wan Q, Liu S, Zhou J. Ther Clin Risk Manag. 2020;16:347. Due to a processing error the link for the British Medical Journal Open (BMJ Open) article described was missing. The link for the BMJ Open article has been provided here: http://dx.doi.org/10.1136/bmjopen-2018-024473. Read the original article Read the Expression of Concern

Hongda Ma,1 Yao Yao,2 Changli Wang,1 Liyu Zhang,3 Long Cheng,4 Yiren Wang,5 Tao Wang,6 Erguang Liang,6 Hui Jia,1 Qinong Ye,4 Mingxiao Hou,1 Fan Feng11Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang, 2Department of Pharmacy, Women & Infants Hospital of Zhengzhou, Zhengzhou, 3Shaanxi Institute of Pediatric Disease, Xi’an Children’s Hospital, Xi’an, 4Institute of Biotechnology, Chinese Military Medical Science Academy, Beijing, 5School of Life Science, Shenyang Pharmaceutical University, Shenyang, 6Institute of Toxicology and Pharmacology, Chinese Military Medical Science Academy, Beijing, People’s Republic of ChinaAbstract: Many kinds of endocrine-disrupting chemicals (EDCs), for example, the environmental estrogens bisphenol A and nonylphenol, may regulate the activity of estrogen receptor α (ERα) and therefore induce potential disruption of normal endocrine function. However, the involvement of EDCs in human cancers, especially in endocrine-related cancer neuroblastoma regulation, is not very clear. In this work, results showed that upon bisphenol A or nonylphenol treatment, the transcription factor activity of ERα was significantly increased in neuroblastoma cell line SH-SY5Y. Bisphenol A and nonylphenol could enhance ERα activity via recruiting it to the target gene promoter. Furthermore, treatment of bisphenol A and nonylphenol enhanced the in vitro proliferation, invasion, and migration ability of neuroblastoma cells. By investigating the role of EDC-induced ERα upregulation, our data extend the understanding of the function of EDCs and further suggest that ERα might be a potential therapeutic target in human neuroblastoma treatment.Keywords: neuroblastoma, endocrine-disrupting chemicals, environmental estrogens, bisphenol A and nonylphenol, proliferation and metastasis

Brenda S Bohaty,1,2 Qiang Ye,3 Anil Misra,3,4 Fabio Sene,6 Paulette Spencer3,51Department of Pediatric Dentistry, University of Missouri-Kansas City School of Dentistry, Kansas City, MO, USA; 2Department of Pediatric Dentistry, Children's Mercy Hospital, Kansas City, MO, USA; 3Bioengineering Research Center, 4Department of Civil, Environmental, and Architectural Engineering, 5Department of Mechanical Engineering, University of Kansas, Lawrence, KS, USA; 6Department of Restorative Dentistry, State University of Londrina, School of Dentistry, Londrina, BrazilAbstract: Restoring posterior teeth with resin-based composite materials continues to gain popularity among clinicians, and the demand for such aesthetic restorations is increasing. Indeed, the most common aesthetic alternative to dental amalgam is resin composite. Moderate to large posterior composite restorations, however, have higher failure rates, more recurrent caries, and increased frequency of replacement. Investigators across the globe are researching new materials and techniques that will improve the clinical performance, handling characteristics, and mechanical and physical properties of composite resin restorative materials. Despite such attention, large to moderate posterior composite restorations continue to have a clinical lifetime that is approximately one-half that of the dental amalgam. While there are numerous recommendations regarding preparation design, restoration placement, and polymerization technique, current research indicates that restoration longevity depends on several variables that may be difficult for the dentist to control. These variables include the patient's caries risk, tooth position, patient habits, number of restored surfaces, the quality of the tooth–restoration bond, and the ability of the restorative material to produce a sealed tooth–restoration interface. Although clinicians tend to focus on tooth form when evaluating the success and failure of posterior composite restorations, the emphasis must remain on advancing our understanding of the clinical variables that impact the formation of a durable seal at the restoration–tooth interface. This paper presents an update of existing technology and underscores the mechanisms that negatively impact the durability of posterior composite restorations in permanent teeth.Keywords: composites, bonding, dental restorations

Sustainable development in the building sector requires the integration of energy efficiency and renewable energy utilization in buildings. In recent years, the concept of net zero energy buildings (NZEBs) has become a potential plausible solution to improve efficiency and reduce energy consumption in buildings. To achieve an NZEB goal, building systems and design strategies must be integrated and optimized based on local climatic conditions. This paper provides a comprehensive review of NZEBs and their current development in hot and humid regions. Through investigating 34 NZEB cases around the world, this study summarized NZEB key design strategies, technology choices and energy performance. The study found that passive design and technologies such as daylighting and natural ventilation are often adopted for NZEBs in hot and humid climates, together with other energy efficient and renewable energy technologies. Most NZEB cases demonstrated site annual energy consumption intensity less than 100 kW-hours (kWh) per square meter of floor space, and some buildings even achieved “net-positive energy” (that is, they generate more energy locally than they consume). However, the analysis also shows that not all NZEBs are energy efficient buildings, and buildings with ample renewable energy adoption can still achieve NZEB status even with high energy use intensity. This paper provides in-depth case-study-driven analysis to evaluate NZEB energy performance and summarize best practices for high performance NZEBs. This review provides critical technical information as well as policy recommendations for net zero energy building development in hot and humid climates.