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Wenchao Xie,1,* Wang Liao,1,* Hongming Lin,2 Guanglin He,2 Zhaohai Li,2 Lang Li1 1Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Cardiology, The First People Hospital of Yulin & The Sixth Affiliated Hospital of Guangxi Medical University, Yulin, Guangxi, 537000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lang Li, Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China, Email drlilang1968@126.comPurpose: Our study aimed to establish a prediction model for coronary artery disease (CAD) that integrates immune infiltration and a gene expression signature.Methods: 613 differentially expressed genes (DEGs) and 12 hub genes were screened via the GSE113079 dataset. The pathway enrichment analysis indicated that these genes (613 DEGs and 12 hub genes) were closely associated with the inflammatory and immune responses. Based on the differentially expressed miRNA (DEmiRNA)-DEG regulatory network and immune cell infiltration, the Lasso algorithm constructed a CAD risk prediction model containing the risk score and immune score. Then, ROC-AUC and polymerase chain reaction (PCR) were performed for validation.Results: Six hub genes (PTGER1, PIK3R1, ADRA2A, CORT, CXCL12, and S1PR5) had a high distinguishing capability (AUC > 0.90). In addition, the miRNAs targeting 12 hub genes were predicted and intersected with the DEmiRNAs, and the DEmiRNA-DEG regulatory network was then constructed. Two LASSO models and a novel CAD risk prediction model were constructed through LASSO regression analysis, and they both accurately obtained the risk of CAD. The CAD risk prediction model shows good performance (AUC = 0.988). We also constructed a valid nomogram, and PCR results verified three downregulation hub genes and one upregulation gene in the CAD risk model.Conclusion: We demonstrated the molecular mechanism of the hub genes in CAD and provided a valuable tool for predicting the risk of CAD.Keywords: coronary artery disease, DEmiRNA-DEG regulatory network, nomogram, immune score, immune infiltration

Yu Pan,1,* Lili Cao,2,* Libing Chen,1,* Linjuan Gao,2 Xia Wei,1 Honglei Lin,1 Lei Jiang,1 Yinghui Wang,1,2 Hui Cheng1,2 1Department of Prosthodontics, Institute of Stomatology & Research Center of Dental Esthetics and Biomechanics, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Prosthodontics, Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yinghui Wang; Hui Cheng, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China, Email wyh9519@fjmu.edu.cn; ch.fj@fjmu.edu.cnPurpose: The study was intended to compare the surface properties and the bacterial and biofilm adhesion resistance of two potential antibacterial nanometer titanium dioxide (nano-TiO2) coatings on dental titanium (Ti) abutments prepared by atomic layer deposition (ALD) and the anodic oxidation (AO) techniques.Methods: Nano-TiO₂ coatings were developed using ALD and AO techniques and applied to Ti surfaces. The surface properties and the bacterial and biofilm adhesion resistance of these coatings were evaluated against commonly used Ti and Zirconia (ZrO₂) surfaces. The chemical compositions, crystalline forms, surface topography, roughness and hydrophilicity were characterized. The antibacterial performance was assessed by the scanning electron microscope (SEM), the Colony-forming unit (CFU) assay and the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay using in vitro models of Staphylococcus aureus (S. aureus), Streptococcus mutans (S. mutans), and Porphyromonas gingivalis (P. gingivalis) in both single- and mixed-species bacterial compositions.Results: ALD-prepared nano-TiO₂ coatings resulted in a dense, smooth, and less hydrophilic surface with an anatase phase, significantly reducing the adhesion of the three bacteria by over 50%, comparable to ZrO₂. In contrast, AO-prepared coatings led to a less hydrophilic surface, characterized by various nano-sized pores within the oxide film. This alteration, however, had no impact on the adhesion of the three bacteria. The adhesion patterns for mixed-species bacteria were generally consistent with single-species results.Conclusion: ALD-prepared nano-TiO₂ coatings on Ti abutments demonstrated promising antibacterial properties comparable to ZrO₂ surfaces, suggesting potential in preventing peri-implantitis. However, the bacterial and biofilm adhesion resistance of AO-produced nano-TiO₂ coatings was limited. Keywords: atomic layer deposition, anodic oxidation, titanium dioxide, dental abutment, surface properties, antibacterial effect

Longfei Lin,1,* Yuling Liu,1,* Ruying Tang,1 Shilan Ding,1 Hongmei Lin,2,3 Hui Li1,4 1Institute Chinese Materia Medica China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3National Medical Products Administration Key Laboratory for Research Evaluation of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Li, Institute Chinese Materia Medica China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China, Email lihuizys@126.com Hongmei Lin, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China, Email lhmtcm@126.comAbstract: Evodiamine (EVO) is a tryptamine indole alkaloid and the main active ingredient in Evodia rutaecarpa. In recent years, the antitumor, cardioprotective, anti-inflammatory, and anti-Alzheimer’s disease effects of EVO have been reported. EVO exerts antitumor effects by inhibiting tumor cell activity and proliferation, blocking the cell cycle, promoting apoptosis and autophagy, and inhibiting the formation of the tumor microvasculature. However, EVO has poor solubility and low bioavailability. Several derivatives with high antitumor activity have been discovered through the structural optimization of EVO, and new drug delivery systems have been developed to improve the solubility and bioavailability of EVO. Current research found that EVO could have toxic effects, such as hepatotoxicity, nephrotoxicity, and cardiac toxicity. This article reviews the pharmacological activity, derivatives, drug delivery systems, toxicity, and pharmacokinetics of EVO and provides research ideas and references for its further in-depth development and clinical applications.Keywords: evodiamine, pharmacology, derivatives, drug delivery systems

Chunrong Huang,1,2,* Yulian Gao,1,2,* Hongxia Lin,1– 3,* Qinmei Fan,4,* Ling Chen,1,2 Yun Feng1,2 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, 610000, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First People’s hospital of Jin Zhong, JinZhong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling Chen; Yun Feng, Email co840608@hotmail.com; fy01057@163.comBackground: To evaluate the clinical features of patients with Acinetobacter baumannii bloodstream infection (BSI).Methods: Totally 200 inpatients with Acinetobacter baumannii BSI were included, clinical features of Acinetobacter baumannii BSI inpatients between 90-day survival and 90-day mortality groups, between 30-day survival and 30-day mortality groups, between patients infected with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) were analyzed. The prognostic factors of 90-day mortality were analyzed by univariate logistic regression and multivariate logistic regression. The survival curve in bloodstream infectious patients with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) was analyzed by Kaplan–Meier analysis.Results: The 90-day mortality patients had significantly higher carbapenem-resistant bacterial infection and critical care unit (ICU) admission. The 90-day and 30-day mortality groups showed higher C-reactive protein (CRP) and serum creatinine (Scr) levels and lower red blood cells (RBC) and albumin (ALB) levels than their survival counterparts, respectively. Critical surgery, ICU admission and delayed antibiotic treatment were independently prognostic risk predictors for 90-day mortality in Acinetobacter baumannii BSI patients, while critical surgery and diabetes were independently prognostic risk predictors for 90-day mortality in carbapenem-resistant Acinetobacter baumannii BSI patients. Compared with sensitive group, MDR group showed significantly longer ICU and whole hospital stay, lower levels of lymphocytes, RBC, hemoglobin, lactate dehydrogenase and ALB, higher frequency of infection originating from the skin and skin structure. Moreover, patients in the MDR group had a significantly worse overall survival than the sensitive group.Conclusion: We identified the prognostic factors of Acinetobacter baumannii BSI and carbapenem-resistant Acinetobacter baumannii BSI patients. Critical surgery, ICU admission, delayed antibiotic treatment or diabetes were significantly associated with the mortality of those patients. Moreover, aggressive measures to control MDR Acinetobacter baumannii could lead to improved outcomes. Keywords: Acinetobacter baumannii, bloodstream infection, mortality, prognostic predictors, multidrug-resistance

Jianguo Song,1,* Huanliang Meng,2,* Guoying Deng,1 Haodong Lin1 1Trauma Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, People’s Republic of China; 2Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoying Deng; Haodong Lin, Trauma Center, Shanghai General Hospital, 650 New Songjiang Road, Shanghai, 201620, People’s Republic of China, Email guoying.deng@shgh.cn; haodong.lin@hotmail.comBackground: Inhibiting ROS overproduction is considered a very effective strategy for the treatment of peripheral nerve injuries, and Se has a remarkable antioxidant effect; however, since the difference between the effective concentration of Se and the toxic dose is not large, we synthesized a nanomaterial that can release Se slowly so that it can be used more effectively.Methods: Se@SiO2 NPs were synthesized using a mixture of Cu2-x Se nanocrystals, and the mechanism of action of Se@SiO2 NPs was initially explored by performing sequencing, immunofluorescence staining and Western blotting of cellular experiments. The mechanism of action of Se@SiO2 NPs was further determined by performing behavioral assays after animal experiments and by sampling the material for histological staining, immunofluorescence staining, and ELISA. The effects, mechanisms and biocompatibility of Se@SiO2 NPs for peripheral nerve regeneration were determined.Results: Porous Se@SiO2 was successfully synthesized, had good particle properties, and could release Se slowly. CCK-8 experiments revealed that the optimal experimental doses were 100 μM H2O2 and 200 μg/mL Se@SiO2, and RNA-seq revealed that porous Se@SiO2 was associated with cell proliferation, apoptosis, and the PI3K/AKT pathway. WB showed that porous Se@SiO2 could increase the expression of cell proliferation antigens (PCNA and S100) and antiapoptotic proteins (Bcl-2), decrease the expression of proapoptotic proteins (Bax), and increase the expression of antioxidative stress proteins (Nrf2, HO-1, and SOD2). EdU cell proliferation and ROS fluorescence assays showed that porous Se@SiO2 promoted cell proliferation and reduced ROS levels. The therapeutic effect of LY294002 (a PI3K/AKT pathway inhibitor) was decreased significantly and its effect was lost when it was added simultaneously with porous Se@SiO2. Animal experiments revealed that the regenerated nerve fiber density, myelin thickness, axon area, gastrocnemius muscle wet-to-weight ratio, myofiber area, sciatic nerve function index (SFI), CMAP, apoptotic cell ratio, and levels of antioxidative stress proteins and anti-inflammatory factors were increased following the administration of porous Se@SiO2. The levels of oxidative stress proteins and anti-inflammatory factors were significantly greater in the Se@SiO2 group than in the PNI group, and the effect of LY294002 was decreased significantly and was lost when it was added simultaneously with porous Se@SiO2.Conclusion: Se@SiO2 NPs are promising, economical and effective Se-releasing nanomaterials that can effectively reduce ROS production, inhibit apoptosis and promote cell proliferation after nerve injury via the PI3K/AKT pathway, ultimately accelerating nerve regeneration. These findings could be used to design new, promising drugs for the treatment of peripheral nerve injury. Keywords: Se@SiO2, PI3K/AKT, PNI, antioxidative stress, apoptosis

Junjie Cheng,1,* Yuan Yuan,1,* Jinmeng Li,1 Ruoying Zhang,1 Xudong Fan,1 Zhirou Xu,2 Huirong Lin,3 Xinjun Cai,1 Mingfeng Zheng4 1Department of Pharmacy, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, People’s Republic of China; 2Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, People’s Republic of China; 3Department of Pharmacy, Taizhou Cancer Hospital, Taizhou, People’s Republic of China; 4Department of Orthopaedics, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingfeng Zheng; Xinjun Cai, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang Province, 310003, People’s Republic of China, Email zmfyxz3@163.com; zjtcmcxj@zcmu.edu.cnPurpose: Previous studies have indicated that the development of severe adverse events is associated with linezolid peak concentration (Cmax), but the factors affecting linezolid Cmax and evidences on therapeutic drug monitoring to anticipate toxicity in drug-resistant tuberculosis (DR-TB) patients have not been clarified clearly. This study aimed to explore the factors influencing linezolid Cmax and investigate the association between linezolid concentration and hematological toxicity.Patients and Methods: This study included patients with drug-resistant tuberculosis treated with linezolid from January 2022 to September 2023. We analyzed the factors affecting linezolid Cmax using chi-squared and binary logistic regression. The diagnostic utility of linezolid Cmax in predicting hematological toxicity was evaluated using receiver operating characteristic (ROC) analysis.Results: A total of 76 patients were enrolled in the study. 63.20% met the standard rates for linezolid Cmax. Age (P=0.036), weight (P=0.0016), and creatinine clearance (P=0.0223) significantly correlated with the Cmax. Hematological toxicity was observed in 46.05% (35/76) of patients, characterized by thrombocytopenia (31.58%, 24/76), anemia (6.58%, 5/76), and leukopenia (21.05%, 16/76). ROC curve analysis confirmed the predictive value of linezolid Cmax for thrombocytopenia with an area under curve of 0.728.Conclusion: Suboptimal linezolid Cmax was prevalent among patients with DR-TB, with age, weight, and renal function emerging as influential factors. Elevated linezolid Cmax increases the risk of thrombocytopenia. Meticulous monitoring of linezolid Cmax is imperative during anti-DR-TB therapy to tailor treatment and mitigate hematological toxicity.Keywords: linezolid, therapeutic drug monitoring, influencing factors, hematological toxicity

Hongyuan Liu,1,* Yaodi Wei,1,* Zhenyi Xu,2,* Hao Lin,2,* Yu Zhao,1 Shiyu Wang,1 Fengbao Gao,1 Ninghan Feng,2 Alan J Wolfe,3 Fengping Liu1 1Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Urology, Affiliated Wuxi No. 2 Hospital, Nanjing Medical University, Wuxi, People’s Republic of China; 3Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA*These authors contributed equally to this workCorrespondence: Alan J Wolfe, Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA, Email awolfe@luc.edu Fengping Liu, Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China, Email liulaoshiyc@jiangnan.edu.cnPurpose: Patients with recurrent urinary tract infections face complex management challenges. Fecal microbiota transplantation is a superior treatment for chronic infectious diseases, but limited patient knowledge affects treatment decisions. This study aims to identify factors associated with hesitancy towards fecal microbiota transplantation among patients with recurrent urinary tract infections, to help physicians and nurses in providing accurate and useful information to patients.Patients and Methods: A descriptive qualitative approach was employed, utilizing semi-structured interviews conducted with patients experiencing recurrent urinary tract infections who expressed hesitancy towards fecal microbiota transplantation. The interviews took place between September 2021 and December 2022. Thematic analysis was conducted on the semi-structured interviews to identify perceived facilitators and barriers associated with fecal microbiota transplantation.Results: The analysis included interviews with thirty adult female patients with recurrent urinary tract infections. Four facilitators influencing patients’ decision-making regarding fecal microbiota transplantation were identified: (1) the motivating role of hope and expectations for active patient participation; (2) the influence of healthcare providers, as well as family members and friends on patients’ decisions to pursue fecal microbiota transplantation; (3) the patients’ perception of fecal microbiota transplantation as a low-risk treatment option; and (4) the dedication to the advancement of medical treatments. In contrast, two primary barriers to accepting fecal microbiota transplantation were identified: (1) that conventional treatment controls disease activity, while fecal microbiota transplantation effects remain uncertain; and (2) that safety concerns surrounding fecal microbiota transplantation.Conclusion: Comprehensive information about fecal microbiota transplantation, including donor selection, sample processing, the procedure, and potential discomfort, is essential for patients and families to make informed treatment decisions.Registration: CHiCTR2100048970.Keywords: barriers, decision making, facilitators, fecal microbiota transplantation, qualitative study, recurrent urinary tract infections

Ziting Wu,1– 3 Jiangxia Yu,4 Beini Lyu,2 Haoxiang Lin,2 Shanshan Li,5,6 Gordon G Liu1– 3 1National School of Development, Peking University, Beijing, 100871, People’s Republic of China; 2Institute for Global Health and Development, Peking University, Beijing, 100871, People’s Republic of China; 3PKU China Center for Health Economic Research, Peking University, Beijing, 100871, People’s Republic of China; 4School of Medicine and Health Management, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 5Center for International Cooperation and Disciplinary Innovation of Income Distribution and Public Finance (111 Center), Zhongnan University of Economics and Law, Wuhan, 430073, People’s Republic of China; 6Hubei Finance and Development Research Center, Zhongnan University of Economics and Law, Wuhan, 430073, People’s Republic of ChinaCorrespondence: Shanshan Li, Center for International Cooperation and Disciplinary Innovation of Income Distribution and Public Finance (111 Center), Zhongnan University of Economics and Law, Wuhan, 430073, People’s Republic of China, Email lishanceee@163.com Gordon G Liu, National School of Development, Peking University, Beijing, 100871, People’s Republic of China, Email gordonliu@nsd.pku.edu.cnObjective: Culture and eating habits, which vary greatly across different ethnic groups, have a substantial impact on drinking behavior. This study aimed to examine whether the drinking patterns and reasons differ by ethnic groups, and provide useful insights for multi-ethnic areas that seek to cut down alcohol intake.Methods: We recruited excessive drinkers and collected the drinking patterns and motivations by questionnaire in a multi-ethnic society. Multiple linear regressions were used to evaluate the variations in drinking characteristics among different ethnic groups.Results: We recruited 1287 participants through convenience sampling (a non-probability sampling technique used in research where the researcher selects participants or units for a study based on their accessibility and proximity), among whom 439 excessive drinkers were eligible. The mean age was 38 years for the 439 participants, 92.9% were men, 36.0% were Han, and 64.0% were minorities mainly composed of the Yi. The majority of the participants were married (75.9%) and did physical work (58.1%). Ethnic minorities consumed more alcohol on a single occasion than Han people did (47.3 vs 41.8g/session) while drinking less frequently. For the minority and Han participants, 67% and 42% were not used to drinking with food, respectively. Peer pressure and fostering a good atmosphere were the most common drinking reasons for the minority and Han, respectively.Conclusion: We found substantial differences in drinking patterns and reasons between ethnic minorities and Han ethnicity, attributable to their culture and customs. Findings highlight the importance of drinking habits and motivations in exploring alcohol control education strategies in the context of ethnic integration and population immigration.Keywords: health education, alcohol drinking habits, motivations, ethnic groups

Hongchao Li,1 Wei He,2 Hongbo Lin,3 Angying Du,4 Xue Zhang,5 Han Yang,5 Shuli Qu5 1School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China; 2Fertility and Reproductive Medicine Centre, The Southwest Hospital of AMU, Chongqing, 400038, People’s Republic of China; 3Department of Reproductive Medicine, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China; 4Merck Serono, an Affiliate of Merck KGaA Darmstadt Germany, Beijing, 100016, People’s Republic of China; 5Real-World Solutions, IQVIA, Shanghai, 200041, People’s Republic of ChinaCorrespondence: Shuli Qu, Real-World Solutions, IQVIA, 1359 Yaolong Road, Shanghai, People’s Republic of China, Email shuli.qu1@iqvia.comBackground: To compare the cost-effectiveness of originator (reference) recombinant human follicle stimulating hormone alfa (rhFSH-α) (follitropin alfa, GONAL-f) and its biosimilar (rhFSH, JinSaiHeng) in assisted reproductive technology (ART) from a Chinese patient perspective.Methods: A decision tree model was developed to simulate the treatment pathway of infertile women undergoing ART using GONAL-f or JinSaiHeng. Published clinical and cost data were used to evaluate the cost-effectiveness of the rhFSH-α. The cumulative live birth rate (CLBR), direct medical costs and costs per cumulative live birth were estimated via an analytic decision-tree model.Results: CLBR of GONAL-f was higher than JinSaiHeng preparation (88.3% vs 84.4%), while the cost per cumulative live birth was lower (51,475 vs 52,095 CNY).Conclusion: The originator rhFSH-α was associated with higher CLBR and lower cost per cumulative live birth, with incremental cost per additional live birth of 38,096 CNY (Chinese Yuan).Keywords: recombinant human follicle stimulating hormone, controlled ovarian stimulation, assisted reproductive technology, cost-effectiveness analysis

Tongchao Jiang,1,&ast; Haishuang Sun,2,&ast; Tiankai Xu,1 Shuyu Xue,1 Wen Xia,2 Xiang Xiao,1 Ying Wang,1 Ling Guo,3 Huanxin Lin1 1Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huanxin Lin, Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Email linhx@sysucc.org.cn Ling Guo, Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Email guoling@sysucc.org.cnBackground: The C-reactive protein-albumin-lymphocyte (CALLY) score is a novel indicator associated with inflammation, immunity, and nutrition, utilized for cancer prognostic stratification. This study aimed to evaluate the integrated prognostic significance of the pre-treatment CALLY score and Epstein-Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) patients and to develop prognostic models.Patients and Methods: A total of 1707 NPC patients from September 2015 to December 2017 were retrospectively enrolled. The cut-off point for the CALLY score, determined by maximum selected rank statistics, integrates with the published cut-off point for pre-EBV DNA to develop a comprehensive index. Subsequently, patients were randomly allocated in a 1:1 ratio into training and validation cohorts. Survival analysis was conducted using the Kaplan-Meier method with Log rank tests, and the Cox proportional hazards model was applied to identify independent prognostic factors for constructing predictive nomograms. The predictive ability of the nomograms were assessed through the concordance index (C-index), calibration curves, and decision curve analysis.Results: By integrating CALLY scores and EBV-DNA levels, patients were categorized into three risk clusters. Kaplan-Meier curves reveal significant differences in overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) outcomes among different risk groups (all P values < 0.05). Multivariate analysis revealed that CALLY-EBV DNA index serves as an independent prognostic factor for the OS, DMFS, and LRRFS. The prognostic nomograms based on the CALLY-EBV DNA index provided accurate predictions for 1-year, 3-year, and 5-year OS, DMFS, and LRRFS. Additionally, compared to the traditional TNM staging system, the nomograms exhibited enhanced discriminatory power, calibration capability, and clinical applicability. All results were in agreement with the validation cohort.Conclusion: The CALLY-EBV DNA index is an independent prognostic biomarker. The nomogram prediction models, constructed based on the CALLY-EBV DNA index, demonstrates superior predictive performance compared to the traditional TNM staging.Keywords: CALLY score, EBV DNA, nasopharyngeal carcinoma, biomarker, prognostic model

Yu-Hang Cai,1,&ast; Cheng-Yu Wang,1,&ast; Yu-Bo Fang,1 Hong-Yu Ma,1 Yu-Qing Gao,1 Zhen Wang,2 Junzheng Wu,3 Han Lin,1 Hua-Cheng Liu1 1Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Laboratory Medicine Center, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Anesthesiology, Cincinnati Children’s Hospital, Cincinnati, OH, 45229, USA&ast;These authors contributed equally to this workCorrespondence: Hua-Cheng Liu; Han Lin, Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 West Xueyuan Road, Wenzhou, 325000, People’s Republic of China, Tel +86-13957770577, Fax +86-577-88002925, Email huachengliu@163.com; nanlinhannansh@qq.comPurpose: Remimazolam, an ultra-short-acting and fast-metabolized sedative, has only been sporadically investigated in children. This study was performed to determine the beneficial effects of intranasal remimazolam or dexmedetomidine on preoperative anxiety in children undergoing general surgeries.Patients and Methods: Ninety children were randomly and equally assigned to Group R (intranasal remimazolam 1.5mg kg− 1), Group D (intranasal dexmedetomidine 2 mcg kg− 1), and Group C (intranasal distilled water). The primary outcomes were the preoperative anxiety scores using the modified Yale preoperative anxiety scale (m-Ypas). The secondary outcomes included the cooperation behaviour of intranasal drug application, preoperative sedation levels, parental separation anxiety scores (PSAS), and mask acceptance scores (MAS).Results: Group R showed a significant low anxiety at 10 min after intranasal premedication (vs group C, P=0.010; vs group D, P = 0.002) and at anaesthesia induction (vs group C, P = 0.004). Group D showed a significantly low anxiety score only prior to anaesthesia induction (vs group C, P = 0.005). Most children in group R achieved mild sedation at 10 min (vs group C, P < 0.001; vs group D, P < 0.001), with a few progressing to deep sedation afterwards, while group D tended toward deep sedation. Compared to Group C, patients in Group R performed significantly better on the MAS (P = 0.014) and PSAS (P = 0.008). However, remimazolam did cause poor cooperation behavior to the intranasal application due to its mucosal irritation (vs group C, P = 0.001; vs group D, P = 0.010).Conclusion: Both intranasal remimazolam and dexmedetomidine can effectively alleviate preoperative anxiety in children. While intranasal remimazolam has a rapid onset, it produces only mild sedation and causes substantial nasal irritation.Trial Registration: NCT 04720963, January 22, 2021, ClinicalTrials.Gov.Keywords: dexmedetomidine, paediatrics, preoperative anxiety, premedication, remimazolam

Zhaohui Chen,1,2,* Pengbiao Miao,1,3,* Hongcao Lin,1,2 Yanan Lu1,4 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 2Shenshan Medical Center, Memorial Hospital of Sun Yat-sen University, Shanwei, Guangdong, People’s Republic of China; 3Department of Pancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 4Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanan Lu, Tel +86-020-81332020, Email luynan@mail.sysu.edu.cnPurpose: Pancreatic ductal adenocarcinoma (PDAC) is extremely malignant and rapidly progresses. The overall response rate of PDAC to current treatment methods is still unsatisfactory. Thus, identifying novel targets and clarifying the underlying mechanisms associated with PDAC progression may potentially offer additional treatment strategies. AHNAK2 is aberrantly expressed in a variety of tumors and exerts pro-tumorigenic effects. However, the biological role of AHNAK2 in PDAC remains poorly understood.Methods: The expression of AHNAK2 in PDAC and paired non-tumor tissues was detected by immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR). Lentivirus knockdown was performed to investigate the impact of AHNAK2 on the biological function of pancreatic cancer cells. The subcutaneous cell-derived xenograft (CDX) model and the KPC spontaneous mouse model with AHNAK2 silencing were used to observe the effects of AHNAK2 on tumor growth and prognosis. The expression of c-MET at protein level in response to HGF treatment was assessed using western blot.Results: Our results demonstrated that AHNAK2 was highly expressed in PDAC clinical samples and associated with poor prognosis. Knockdown of AHNAK2 significantly inhibited the proliferation, migration, and invasion of pancreatic cancer cells. AHNAK2 knockdown or knockout resulted in tumor growth suppression and prolonged survival in mice with PDAC. In addition, AHNAK2 and c-MET expression levels showed a significant positive correlation at the post-transcriptional level. Mechanistically, AHNAK2 promoted tumor progression by preventing c-MET degradation and persistently activating the HGF/c-MET signaling pathway.Conclusion: Overall, our study revealed that AHNAK2 plays an important role in PDAC progression by modulating the c-MET signaling pathway, and targeting AHNAK2 may be an effective therapeutic strategy for PDAC. Keywords: pancreatic ductal adenocarcinoma, AHNAK2, c-MET, tumor progression, HGF/c-MET pathway

Tuerhongjian Abudurexiti,1,2,&ast; Abuduwupuer Haibier,1,2,&ast; Alimujiang Yusufu,1,2,&ast; Kutiluke Shoukeer,1,2,&ast; Hang Lin1,2 1Department of Spine surgery, The Sixth Affiliated Hospital of Xinjiang Medical University, Orthopaedic Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China; 2Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tuerhongjian Abudurexiti, Email 267661815@qq.comObjective: This study aims to investigate the clinical efficacy of endoscopic spinal tuberculosis focus removal, posterior pedicle lesion removal, bone grafting, and internal fixation combined with drug chemotherapy in treating thoracolumbar tuberculosis. It also seeks to summarize strategies for preventing complications and provide a reference for clinical treatment.Methods: We retrospectively analyzed 105 patients with spinal tuberculosis treated in our hospital from January 2018 to December 2022. Patients were divided into two groups: Group A (n=38), who underwent endoscopic spinal tuberculosis focus removal, and Group B (n=67), who underwent posterior pedicle lesion removal, bone grafting, and internal fixation. All patients received preoperative quadruple anti-tuberculosis drug chemotherapy (Isoniazid, Rifampicin, Pyrazinamide, Ethambutol) for 2– 4 weeks. We recorded and compared parameters such as operation time, intraoperative blood loss, postoperative drainage, recovery time, hospital stay, blood transfusion, and complications. We also compared pre- and postoperative lumbar VAS, ODI, erythrocyte sedimentation rate, C-reactive protein, Procalcitonin, D-Dimer, Neutrophil to Lymphocyte ratio, hemoglobin, total protein, and Cobb angle to evaluate kyphotic deformity and correction.Results: Preoperative data including age, sex, body mass index, segment involvement, past medical history, smoking history, preoperative erythrocyte sedimentation rate, C-reactive protein, Procalcitonin, D-Dimer, Neutrophil to Lymphocyte ratio, hemoglobin, total protein, lumbar VAS score, lumbar ODI score, and spinal Cobb’s angle showed no significant difference between the groups (P> 0.05). Main postoperative indicators revealed that Group A had significantly lower lumbar VAS scores, higher hemoglobin and total protein levels, and a lower recurrence rate than Group B at the last follow-up (P< 0.05). Secondary postoperative indicators showed that Group A required significantly less blood transfusion, had shorter operative time, less intraoperative blood loss, shorter postoperative hospitalization time, and lower Cobb Angle than Group B (P< 0.05).Conclusion: Endoscopic spinal tuberculosis focus removal can achieve comparable safety to posterior pedicle lesion removal, bone grafting, and internal fixation, with shorter operation time, less intraoperative bleeding, lower postoperative recurrence rate, and less postoperative drainage. This method can effectively improve blood sedimentation, lumbar function, restore Cobb angle, and reduce pain, making it worthy of promotion and application.Keywords: spinal tuberculosis, focus clearance, infectious diseases of spine, drug chemotherapy

Hui Lin,1,2 Lisa Ni,1 Christina Phuong,1 Julian C Hong1,3,4 1Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA; 2UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley and San Francisco, San Francisco, CA, USA; 3Bakar Computational Health Sciences Institute, University of California, San Francisco, CA, USA; 4Joint Program in Computational Precision Health, University of California, Berkeley and San Francisco, Berkeley, CA, USACorrespondence: Julian C Hong, Email julian.hong@ucsf.eduAbstract: Natural language processing (NLP), a technology that translates human language into machine-readable data, is revolutionizing numerous sectors, including cancer care. This review outlines the evolution of NLP and its potential for crafting personalized treatment pathways for cancer patients. Leveraging NLP’s ability to transform unstructured medical data into structured learnable formats, researchers can tap into the potential of big data for clinical and research applications. Significant advancements in NLP have spurred interest in developing tools that automate information extraction from clinical text, potentially transforming medical research and clinical practices in radiation oncology. Applications discussed include symptom and toxicity monitoring, identification of social determinants of health, improving patient-physician communication, patient education, and predictive modeling. However, several challenges impede the full realization of NLP’s benefits, such as privacy and security concerns, biases in NLP models, and the interpretability and generalizability of these models. Overcoming these challenges necessitates a collaborative effort between computer scientists and the radiation oncology community. This paper serves as a comprehensive guide to understanding the intricacies of NLP algorithms, their performance assessment, past research contributions, and the future of NLP in radiation oncology research and clinics.Keywords: artificial intelligence, personalized medicine, radiation therapy, natural language processing

Jiaxu Lu,1,2,&ast; Jiaxian Chen,2,&ast; Junhong Ye,2 Zhen Shi,2 Xiang Gao,1 Peicong Chen,2 Yanzhou Chang,2 Hao Lin,2 Peng Li1 1Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China; 2Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Lin, Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China, Email linhao@gdmu.edu.cn Peng Li, Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China, Email 13763086273@163.comIntroduction: Osteosarcoma is a prevalent and highly malignant primary bone tumor. However, current clinical therapeutic drugs for osteosarcoma are not suitable for long-term use due to significant side effects. Therefore, there is an urgent need to develop new drugs with fewer side effects. Dipsacus asperoides C. Y. Cheng et T. M. Ai, a traditional Chinese medicine, is commonly used for its anti-inflammatory, anti-pain, bone fracture healing, and anti-tumor effects. In this study, we investigated the effects of exosome-like nanoparticles derived from Dipsacus asperoides (DAELNs) on osteosarcoma cells in vitro and in vivo.Methods: DAELNs were isolated and purified from Dipsacus asperoides and their physical and chemical properties were characterized using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The cellular uptake of DAELNs in osteosarcoma cells was analyzed by PKH26 staining. The proliferation, invasion, migration, and apoptosis of osteosarcoma cells were assessed using CCK8 assay, EdU assay, colony-formation assay, transwell assay, wound healing assay, and mitochondrial membrane potential measurement, respectively. The regulatory mechanism of DAELNs inhibiting the progression of osteosarcoma via activating P38/JNK signaling pathway was investigated using Western blotting and immunohistochemistry. Moreover, the therapeutic effects of DAELNs were evaluated using in vivo small animal imaging assay, HE staining, and immunohistochemistry.Results: Our results showed that DAELNs inhibited the proliferation, invasion, migration, and fostered the apoptosis of osteosarcoma cells in vitro and suppressed the tumor growth of osteosarcoma cells in a xenograft nude mouse model. Furthermore, the bio-distribution of DiD-labeled DAELNs showed preferential targeting of osteosarcoma tumors and excellent biosafety in histological analysis of the liver and kidney. Mechanistically, DAELNs activated the P38/JNK signaling pathway-induced apoptosis.Conclusion: Taken together, DAELNs are novel, natural, and osteosarcoma-targeted agents that can serve as safe and effective therapeutic approaches for the treatment of osteosarcoma.Keywords: osteosarcoma, Dipsacus asperoides-derived exosomes-like nanoparticles, P38/JNK signaling pathway

Huizhong Lin,1,&ast; Maosen Lin,1,&ast; Tao Lin,2 Mingfang Ye1 1Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou City, People’s Republic of China; 2Department of Epidemiology and Health Statistics, Fujian Medical University, Fuzhou City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingfang Ye, Email xieheyemingfang@163.comBackground: P-wave terminal force in lead V1 (PtfV1) irregularity has been associated with various cardiovascular conditions, including atrial fibrillation, left ventricular diastolic dysfunction, valvular heart disease, congestive heart failure, stroke, and mortality. However, its prognostic value for unstable angina (UA) has not been extensively studied. To address this knowledge gap, this study aimed to evaluate the long-term predictive significance of PtfV1 at discharge for UA patients.Methods: A total of 707 patients with newly diagnosed UA were included in this study. PtfV1 measurements were recorded at admission and discharge. PtfV1(+) was defined as an absolute value above 0.04mm·s, while PtfV1(-) was defined as an absolute value below 0.04mm·s. Based on their PtfV1 values at discharge, patients were categorized into two groups: PtfV1(-) and PtfV1(+). Univariate and multivariate regression analyses were conducted to identify variables that could potentially contribute to the risk of UA.Results: Univariate analysis revealed a higher incidence of total adverse outcomes and major adverse cardiovascular events (MACE) in the PtfV1(+) group compared to the PtfV1(-) group, with a risk ratio (RR) of 2.006 [95% confidence interval (95% CI): 1.389– 2.896] for total outcomes and an RR of 2.759 (95% CI: 1.870– 4.070) for MACE. After adjusting for confounding factors through multivariate analysis, participants with PtfV1(+) had a 46% increased risk [adjusted hazard ratio (HR): 1.458; 95% CI: 1.010– 2.104]for total adverse outcomes and an 86% increased risk (adjusted HR: 1.863; 95% CI: 1.246– 2.786) for MACE compared to those with PtfV1(-).Conclusion: The presence of PtfV1(+) at discharge is an independent predictor of poor outcomes and provides extended prognostic information for UA patients.Keywords: P wave terminal force in lead V1, PtfV1, unstable angina, UA, prognosis, electrocardiography, major adverse cardiovascular events, MACE

Huan Lin,1 Haiyong Ao,2 Guanghua Guo,1 Mingzhuo Liu1 1Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Jiangxi Key Laboratory of Nanobiomaterials & School of Materials Science and Engineering, East China Jiaotong University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Guanghua Guo; Mingzhuo Liu, Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, No. 17, Yongwai Zheng Street, Nanchang, Jiangxi, People’s Republic of China, Tel +8613007222275 ; +8615879093602, Email ndyfy00655@ncu.edu.cn; ndyfy05397@ncu.edu.cnAbstract: Metformin is a classical drug used to treat type 2 diabetes. With the development of research on metformin, it has been found that metformin also has several advantages aside from its hypoglycemic effect, such as anti-inflammatory, anti-aging, anti-cancer, improving intestinal flora, and other effects. The prevention of inflammation is critical because chronic inflammation is associated with numerous diseases of considerable public health. Therefore, there has been growing interest in the role of metformin in treating various inflammatory conditions. However, the precise anti-inflammatory mechanisms of metformin were inconsistent in the reported studies. Thus, this review aims to summarize various currently known possible mechanisms of metformin involved in inflammatory diseases and provide references for the clinical application of metformin.Keywords: metformin, AMPK, inflammation, mechanisms

Abuduwupuer Haibier,1,2,&ast; Alimujiang Yusufu,1,2,&ast; Hang Lin,1,2 Aiben Kayierhan,1,2 Yimuran Abudukelimu,1,2 Tuerhongjiang Abudurexiti1,2 1Minimally Invasive Spine Surgery, Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2Xinjiang Medical University, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tuerhongjiang Abudurexiti, Email 267661815@qq.comBackground: Low molecular heparin(LMWH) and sodium sulfadiazine heparin(FPX) are commonly used to prevent deep vein thrombosis(DVT) after total hip arthroplasty(THA). In this study, we compared the role of these drugs in preventing DVT after THA.Methods: Patients who underwent unilateral THA at the Sixth Affiliated Hospital of Xinjiang Medical University from April 2020 to December 2022 were retrospectively analyzed for inclusion in this study. According to the anticoagulant drugs used, the patients were divided into LMWH group (n=106) and FPX group (n=97). Changes in perioperative coagulation-related indices, hemoglobin, blood loss And the postoperative complications.Results: The preoperative indexes of the two groups of patients, the difference was not statistically significant (P> 0.05); the indexes of Intraoperative blood loss, Visible blood loss, Hidden blood loss, and Total blood loss of the two groups of patients were compared, and the difference was not significant (P> 0.05); PT activity and INR in the LMWH group were significantly lower than those in the FPX group on the 1st and 5th postoperative days, and the differences were significant (P< 0.05); Platelets, Hemoglobin, Hematocrit, D-dimer, and Fibrinogen were compared between the two groups on the 1st and 5th postoperative days, and the differences were not significant (P< 0.05). The differences were not significant (P> 0.05). The differences in blood transfusion rate and blood volume between the two groups were not significant (P> 0.05); the total hospitalization cost of the LMWH group was significantly lower than that of the FPX group, and the difference was significant (P< 0.05); and the differences in the incidence of postoperative complications between the two groups were not significant (P> 0.05).Conclusion: In this study, we found that the efficacy and safety of FPX and LMWH in preventing VTE after THA were basically the same, and the total cost of hospitalization in the LMWH group was significantly lower than that in the FPX group; however, due to the limited inclusion of the sample size, high-quality, large-sample, long-term follow-up clinical studies are necessary.Keywords: hip osteoarthritis, total Hip arthroplasty, low-molecular-weight heparin, fondaparinux sodium, coagulation indicator, thrombosis

Xiaochun Cheng,1 Huiling Lin2 1School of Social and Behavioral Sciences, Nanjing University, Nanjing, People’s Republic of China; 2School of Law, Huaqiao University, Quanzhou, People’s Republic of ChinaCorrespondence: Huiling Lin, School of Law, Huaqiao University, No. 269, Chenghua North Road, Quanzhou, 362021, Fujian Province, People’s Republic of China, Tel +86-15059749971, Email lhl@hqu.edu.cnPurpose: Academic stress is commonly known to affect adolescents’ subjective well-being, but the influencing mechanisms are rarely investigated in the Chinese context. This study aims to investigate the psychological and behavioral factors operating as pathways between academic stress and adolescents’ subjective well-being.Samples and Methods: A multi-stage cluster random sampling is used to select 1043 adolescents from junior and senior high schools in Jinhu County, Jiangsu Province, China (mean age=14.98 years; 51.1% boys). Structural equation modeling is used to test the direct and indirect effects.Results: Academic stress is significantly correlated with adolescents’ subjective well-being after controlling for gender, grade, hukou, and socioeconomic status. In addition to partially mediating the link between academic stress and subjective well-being, academic burnout and Internet addiction can also operate as chain mediators in this mechanism. Adolescents’ subjective well-being shows significant gender disparities, with boys having a greater degree of subjective well-being than girls. Father’s income is found to have a significant positive association with adolescents’ subjective well-being.Conclusion: The results indicate that academic stress is a significant predictor of academic burnout, which in turn points to a positive association with Internet addiction, thereby explaining low levels of adolescents’ subjective well-being. The present study develops current knowledge and expands our understanding of the underlying mechanisms by which academic stress influences adolescents’ subjective well-being. This can also illuminate the practical ramifications for policymakers and social workers to mitigate academic-related stress and burnout, prevent Internet addiction, and ultimately promote the well-being of adolescent students.Keywords: academic stress, subjective well-being, academic burnout, Internet addiction

Peng Zhang,1,&ast; Hui Lin,1,&ast; Yan Guo,2 Fang Peng,1 Liping Meng1 1Department of Cardiology, Shaoxing People’s Hospital, Shaoxing, Zhejiang, 312000, People’s Republic of China; 2Department of Cardiology, Zhuji hospital of Traditional Chinese Medicine, Shaoxing, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liping Meng; Fang Peng, Department of Cardiology, Shaoxing People’s Hospital, No. 568 Zhongxing North Road, Shaoxing, 312000, Zhejiang, People’s Republic of China, Email mengliping@zju.edu.cn; sxrmyypf@126.comPurpose: Atherosclerosis is still a global public problem with increasing incidence rate and mortality. It has been found that gender factors play an important role in the progression of atherosclerosis. However, few people explore gender related atherosclerosis at the level of genes and immune cells. The purpose of this study was to determine genetic and immune cell differences between male and female samples.Patients and Methods: This study aims to identify differential genes between male and female samples in the GSE43292 dataset. The focus will be on identifying immune-related genes (IRGs) among these differentially expressed genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis will be employed to explore the enrichment of IRGs in biological processes, molecular functions, cellular components, and pathways. Furthermore, a protein-protein interaction (PPI) network for the IRGs will be constructed using Cytoscape software. To estimate the degree of immune cell infiltration, single-sample gene set enrichment analysis (ssGSEA) will be conducted. Moreover, the identified IRGs will be validated using GSE28829 dataset. Finally, we validated in atherosclerotic mice.Results: Seven IRGs (CCL13, IL1RN, FPR2, S100A8, CCL19, CXCL1, CXCL8) were identified as being overexpressed in male atherosclerosis. GO and KEGG analysis revealed that these IRGs are primarily enriched in inflammatory response pathways, cytokine signaling pathways, and cytokine- cytokine receptor interactions. Notably, when compared to females, there was a significant infiltration of immune cells in male specimens. Importantly, all seven IRGs demonstrated high diagnostic value in GSE28829 dataset. The use of animal samples supports our results.Conclusion: This study demonstrates the effectiveness of seven IRGs and reveal sex differences in atherosclerosis. Notably, there is a significant presence of immune cells within the atherosclerotic plaque of men compared to women. These findings have potential implications for the development of personalized treatment approaches targeting gender-related atherosclerosis.Keywords: atherosclerosis, immune related genes, sex related atherosclerosis, bioinformatics, immune infiltration

Hang Lin,1,2 Cui Zhou,1 Kai-Hang Yu,3 Yi-Shuai Lin,1 Ling-Bo Wang,1 Ying Zhang,1 Shi-Xing Liu,1 Wen-Ya Xu,1 Yao Sun,1 Tie-Li Zhou,1 Jian-Ming Cao,4 Jian-Zhong Ye1 1Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2School of the First Clinical Medical Sciences, Wenhzou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 3Pathology Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 4School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Tie-Li Zhou; Jian-Zhong Ye, Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Ouhai District, Wenzhou, 325000, People’s Republic of China, Email wyztli@163.com; jzye89@163.comObjective: Acinetobacter baumannii is a hazardous bacterium that causes hospital-acquired nosocomial infections, and the advent of multidrug-resistant A. baumannii (MDR-AB) strains is concerning. Novel antibacterial therapeutic strategies must be developed. The biological effects of glabridin on MDR-AB were investigated in this study.Methods: The minimum inhibitory concentrations (MICs) of glabridin against eight clinical MDR-AB strains were determined using the broth microdilution technique. Crystal violet staining was used to assess biofilm development, which has significant contribution to bacterial resistance. Swarming motility was measured according to surface growth zone of MDR-AB on LB agar medium. qRT-PCR was used to evaluate the expression of quorum sensing genes abaI and abaR. Glabridin and routinely used therapeutic antimicrobial agents were tested for synergistic action using the checkerboard method.Results: According to our findings, glabridin suppressed MDR-AB growth at high doses (512– 1024 μg/mL). The 1/4 MIC of glabridin significantly decreased MDR-AB biofilm formation by 19.98% (P < 0.05), inhibited MDR-AB motility by 44.27% (P < 0.05), whereas the 1/2 MIC of glabridin dramatically reduced MDR-AB biofilm development by 27.43% (P < 0.01), suppressed MDR-AB motility by 50.64% (P < 0.05). Mechanistically, glabridin substantially downregulated the expression of quorum sensing-related genes abaI and abaR by up to 39.12% (P < 0.001) and 25.19% (P < 0.01), respectively. However, no synergistic effect between glabridin and antibacterial drugs was found.Conclusion: Glabridin might be a quorum sensing inhibitor that inhibits MDR-AB biofilm development and swarming motility.Keywords: Acinetobacter baumannii, multidrug-resistance, glabridin, quorum sensing

Haoran Ding,&ast; Guoqi Zhu,&ast; Hao Lin, Jiapeng Chu, Deqiang Yuan, Yi’an Yao, Yanhua Gao, Fei Chen, Xuebo Liu Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Chen; Xuebo Liu, Email riverapt@126.com; lxb70@hotmail.comBackground: The risk of acute myocardial infarction (AMI) is elevated in patients with systemic lupus erythematosus (SLE), and it is of great clinical value to identify potential molecular mechanisms and diagnostic markers of AMI associated with SLE by analyzing public database data and transcriptome sequencing data.Methods: AMI and SLE-related sequencing datasets GSE62646, GSE60993, GSE50772 and GSE81622 were downloaded from the Gene Expression Omnibus (GEO) database and divided into prediction and validation cohorts. To identify the key genes associated with AMI related to SLE, WGCNA and DEGs analysis were performed for the prediction and validation cohorts, respectively. The related signaling pathways were identified by GO/KEGG enrichment analysis. Peripheral blood mononuclear cells (PBMCs) from patients with AMI were collected for transcriptome sequencing to validate the expression of key genes in patients with AMI. Least absolute shrinkage and selection operator (LASSO) regression analysis was applied to screen diagnostic biomarkers. The diagnostic efficacy of biomarkers was validated by ROC analysis, and the CIBERSORTx platform was used to analyze the composition of immune cells in AMI and SLE.Results: A total of 108 genes closely related to AMI and SLE were identified in the prediction cohort, and GO/KEGG analysis showed significantly enriched signaling pathways. The results of differential analysis in validation cohort were consistent with them. By transcriptional sequencing of PBMCs from peripheral blood of AMI patients, combined with the results of prediction and validation cohort analysis, seven genes were finally screened out. LASSO analysis finally identifies DYSF, LRG1 and CSF3R as diagnostic biomarkers of SLE-related-AMI. CIBERSORTx analysis revealed that the biomarkers were highly correlated with neutrophils.Conclusion: Neutrophil degranulation and NETs formation play important roles in SLE-related AMI, and DYSF, LRG1 and CSF3R were identified as important diagnostic markers for the development and progression of SLE-related AMI.Keywords: myocardial infarction, systemic lupus erythematosus, WGCNA, DEGs, RNA-seq, neutrophil

Zhilu Yao,1,2,&ast; Ning Liu,3,&ast; Hui Lin,1 Yingqun Zhou2,4 1Department of Gastroenterology, Jingan District Zhabei Central Hospital, Shanghai, 200072, People’s Republic of China; 2Clinical Medical College of Shanghai Tenth People’s Hospital, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China; 3Department of Gastroenterology, Changzhou Maternal and Child Health Hospital, Changzhou, 213004, People’s Republic of China; 4Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingqun Zhou; Hui Lin, Email yqzh02@163.com; niliuh@163.comPurpose: Hepatocellular carcinoma (HCC) is a severe global health problem, causing many deaths of patients all over the world. Serine and arginine-rich splicing factor 1 (SRSF1) functions as an important oncogenic role in tumorigenesis and progression in HCC. Therefore, therapies targeting SRSF1 may provide promising therapeutic approaches. MiRNAs are virtually involved at the post-transcriptional level and bind to 3’ untranslated region (3’-UTR) of their target messenger RNA (mRNA) to suppress expression.Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the expression of SRSF1 and miR-1183 in HCC cell lines. CCK8 assay, colony formation assay and wound healing assay were used to detect the function of miR-1183 in HCC cell lines in vitro. Luciferase reporter assay and Western blot were applied to detect the regulation of particular molecules. Xenograft tumor assay was used to detect the function of miR-1183 in HCC cell lines in vivo. Immunohistochemistry (IHC) was used to detect the expression of SRSF1 in HCC tissues and Xenograft tumors.Results: In this study, we identified that miR-1183 was downregulated in HCC cell lines. Functional assays indicated that miR-1183-upregulation cells show weakened proliferation ability and migration ability in vitro and inhibit subcutaneous tumor formation in vivo. With respect to the underlying mechanism, we found that miR-1183 function as a tumor suppressor by specifically binding to SRSF1.Conclusion: This study is the first to demonstrate that miR-1183 function as an important tumor-suppressing role by binding to the 3’-UTR of SRSF1 mRNA and suppressing its protein level in HCC cells in vitro and in vivo. Further, miR-1183 may be a potential target in the prognosis and treatment of HCC.Keywords: SRSF1, miR-1183, HCC, proliferation, migration

Jun Shen,1,&ast; Huanhuan Yan,1,&ast; Congying Yang,2 Haiyue Lin,2 Fan Li,1 Jun Zhou1 1Department of Breast Surgery, The First People’s Hospital of Lianyungang, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, 222002, People’s Republic of China; 2Department of Pathology, The First People’s Hospital of Lianyungang, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, 222002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Zhou, Department of Breast surgery, The First People’s Hospital of Lianyungang, The First Affiliated Hospital of Kangda College of Nanjing Medical University, No. 6 Zhenhua East Road, High-Tech Square, Lianyungang, Jiangsu Province, 222002, People’s Republic of China, Tel +86 18961326373, Email zhoujunzj91@126.comObjective: To explore the validation of a disease-free survival (DFS) model for predicting disease progression based on the combination of ubiquitin-conjugating enzyme E2 C (UBE2C) levels and clinical indicators in breast cancer patients.Methods: We enrolled 121 patients with breast cancer, collected their baseline characteristics and follow-up data, and analyzed the UBE2C levels in tumor tissues. We studied the relationship between UBE2C expression in tumor tissues and disease progression events of patients. We used the Kaplan-Meier method for identifying the disease-free survival rate of patients, and the multivariate Cox regression analysis to study the risk factors affecting the prognosis of patients. We sought to develop and validate a model for predicting disease progression.Results: We found that the level of expression of UBE2C could effectively distinguish the prognosis of patients. In the Receiver Operating Characteristic (ROC) curve analysis, the Area under the ROC Curve (AUC) = 0.826 (0.714– 0.938) indicating that high levels of UBE2C was a high-risk factor for poor prognosis. After evaluating different models using the ROC curve, Concordance index (C-index), calibration curve, Net Reclassification Index (NRI), Integrated Discrimination Improvement Index (IDI), and other methods, we finally developed a model for the expression of Tumor-Node (TN) staging using Ki-67 and UBE2C, which had an AUC=0.870, 95% CI of 0.786– 0.953. The traditional TN model had an AUC=0.717, and 95% CI of 0.581– 0.853. Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) analysis indicated that the model had good clinical benefits and it was relatively simple to use.Conclusion: We found that high levels of UBE2C was a high-risk factor for poor prognosis. The use of UBE2C in addition to other breast cancer-related indicators effectively predicted the possible disease progression, thus providing a reliable basis for clinical decision-making.Keywords: breast cancer, nomograms, prediction model, prognosis, UBE2C

Zhirong Yan,1,&ast; Huifen Lin,2,&ast; Ying Yang,3 Jialin Yang,3 Xueshan Li,2 Yusheng Yao3,4 1Department of Anesthesiology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Anesthesiology, Affiliated Sanming First Hospital of Fujian Medical University, Sanming, People’s Republic of China; 3Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 4Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yusheng Yao, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, No.134 Dongjie Street, Fuzhou, People’s Republic of China, Tel +86-13559939629, Fax +86-591-88217841, Email fjslyys@126.comPurpose: This study aimed to examine the effectiveness of ultrasound-guided thoracic paravertebral block on postoperative quality of recovery in patients undergoing percutaneous nephrolithotomy.Patients and Methods: In this randomized, double-blind, placebo-controlled trial, we enrolled patients scheduled for unilateral percutaneous nephrolithotomy. Patients were randomly allocated to receive thoracic paravertebral block either with 20 mL of 0.5% ropivacaine (PVB group) or an equal volume of saline (control group). The primary outcome was the quality of patient recovery at 24 h postoperatively, assessed using the 15-item Quality of Recovery scale. The secondary outcomes included the area under the curve of pain scores over time, time to first rescue analgesia, and postoperative 24 h morphine consumption.Results: We analyzed the data of 70 recruited participants. The median Quality of Recovery-15 score at 24 h postoperatively was 127 (interquartile range, 117– 133) in the PVB group, which was significantly higher than 114 (interquartile range, 109– 122) in the control group, with a median difference of 10 points (95% confidence interval, 5– 14; P< 0.001). The area under the curve of pain scores over time was lower in patients receiving thoracic PVB than in those receiving saline block (P< 0.001). The median time to first rescue analgesia in the PVB group (10.8 h, interquartile range 7.1– 22.8 h) was longer than that in the control group (1.9 h, interquartile range 0.5– 4.3 h) (P< 0.001). Similarly, the median postoperative 24-hour morphine consumption was nearly half as low in the PVB group as in the control group (P< 0.001). The occurrence of postoperative nausea and vomiting, and pruritus were significantly higher in the control group (P=0.016 and P=0.023, respectively).Conclusion: Preoperative ultrasound-guided single injection of thoracic paravertebral block with ropivacaine improved the postoperative quality of recovery and analgesia in patients undergoing percutaneous nephrolithotomy.Keywords: pain management, quality of recovery, regional anesthesia, ultrasonography

Xiaomin Ren,1 Dingqun Bai,2 Yuan Zhang,3 Haidan Lin,2 Shu Zhang,2 Danyang Li,1 Hui Wei,1 Shouwei Yue1 1Rehabilitation Center, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 2Department of Physical Medicine & Rehabilitation, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Shouwei Yue; Hui Wei, Rehabilitation Center, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China, Tel +18560086655 ; +18560083563, Fax +531 82166115, Email shouweiy@sdu.edu.cn; 83926275@qq.comBackground and Purpose: Epidemiological studies on low back pain in residents living in mountainous areas are scarce. The study was aimed at investigating the prevalence and associated factors of low back pain in Chongqing, relatively impoverished mountainous areas of China.Materials and Methods: This was a cross-sectional study conducted at selected community or village health service centers in Chongqing over a 2-month period (May 2021 to June 2021), which included adults of Chongqing aged > 18 years with or without low back pain (N=1820) chosen by stratified, cluster-sampling. Associated factors of low back pain including sociodemographic characteristics, lifestyle, and occupational features were collected, along with medical history, Oswestry Disability Questionnaire (ODI), and Numerical Rating Scale (NRS) of patients with low back pain, and carried out for at least 20 minutes per respondent. Univariate and multivariate logistic regression models were utilized for statistical analysis.Results: Overall, 30.5% of 1704 respondents presented with low back pain, with 26.3% living in flat areas and 35.6% in mountainous areas. The associated factors of low back pain were mountainous area residence (OR 1.4, 95% CI 1.1– 1.8), advanced age (OR 1.8, 95% CI 1.3– 2.5 for those aged 45– 59 years, OR 2.3, 95% CI 1.6– 3.4 for those aged 60– 74 years, and OR 2.1, 95% CI 1.2– 3.6 for those aged ≥ 75 years), married or remarried (OR 1.9, 95% CI 1.1– 3.2), divorced or widowed (OR 2.7, 95% CI 14– 5.4), moderate labor intensity (OR 1.4, 95% CI 1.1– 1.8), frequent stoop (OR 1.6, 95% CI 1.1– 2.4), and depressed mood (OR 1.6, 95% CI 1.2– 2.1). Residents in the mountainous areas had a higher score on Oswestry Disability Questionnaire (8.3 [SD 6.3] vs 6.2 [SD 4.3]) than those in flat areas.Conclusion: Mountainous areas in Chongqing had higher prevalence of low back pain as 35.6%, compared with 26.3% in flat areas, with more severe dysfunction in low back pain patients. Multifactorial analysis found that the factors associated with low back pain in Chongqing residents included mountain residence, labor intensity, stoop, psychological factors and frequency of exercise.Keywords: low back pain, prevalence, associated factors, China

Xiongjie Jia,&ast; Tao Zhang,&ast; Junjie Sun, Hengxue Lin, Tianliang Bai, Yating Qiao, Yaxin Li, Gang Li, Guicun Li, Xinyu Peng, Aimin Zhang Department of Gastrointestinal Surgery, Affiliated Hospital of Hebei University, Baoding, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aimin Zhang; Xinyu Peng, Department of Gastrointestinal Surgery, Affiliated Hospital of Hebei University, No. 212 Yu-Hua East Road, Baoding City, Hebei Province, People’s Republic of China, Tel +863125983782, Email hdfyzam@126.com; pengxinyu_2012@163.comObjective: Thymidine Phosphorylase (TYMP) gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between TYMP polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy.Methods: A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients were collected for the genotyping of TYMP polymorphism and TYMP mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan–Meier survival analysis, Cox regression analysis was adopted in multivariate analysis. The mRNA expression of TYMP according to genotype status was analyzed using non-parameter test.Results: Prevalence of rs11479 in TYMP among the 218 patients exhibited that minor allele frequency of rs11479 was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which was in accordance with Hardy-Weinberg equilibrium (P=0.825). Association analysis suggested that the median disease-free survival (DFS) of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively (P=0.004). Furthermore, the median overall survival of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively (P=0.033). Multivariate Cox regression analysis exhibited that rs11479 polymorphism was an independent factor for DFS (HR = 1.64, P=0.009). Additionally, of the 65 PBMC specimens, mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of TYMP than that of patients with GG genotype (P< 0.001).Conclusion: Polymorphism rs11479 in TYMP gene might predict the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy through mediation of the mRNA expression of TYMP. The conclusion of this study should be validated in prospective clinical trials subsequently.Keywords: colorectal cancer, adjuvant chemotherapy, capecitabine, prognosis, polymorphism

Xinwei Zhou,1,&ast; Ke Lin,2,&ast; Liangmin Fu,1,&ast; Fei Liu,3,&ast; Hansen Lin,1 Yuhang Chen,1 Bowen Zhuang,2 Hui Liang,4 Qiong Deng,4 Zhu Wang,4 Wei Chen,1 Junhang Luo,1,5 Jiazheng Cao,6 Pengju Li1 1Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Urology, Affiliated Longhua People’s Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 5Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 6Department of Urology, Jiangmen Central Hospital, Jiangmen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengju Li, Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan Road II, Guangzhou, 510080, People’s Republic of China, Tel +86-20-87618227, Email lipj25@mail.sysu.edu.cn Jiazheng Cao, Department of Urology, Jiangmen Central Hospital, Haibang Street 23, Jiangmen, 529030, People’s Republic of China, Tel +86-750-3165500, Email spotatos@163.comBackground: Triggering receptors expressed by myeloid cells-1 (TREM1) is a receptor belonging to the immunoglobulin superfamily and plays an important role in pro-inflammation in acute and chronic inflammatory disorders. However, the understanding of the immunomodulatory roles of TREM1 in the tumor microenvironment remains incomplete.Methods: The expression patterns of TREM1 mRNA in tumors and adjacent normal tissues were compared by analyzing data obtained from the Genotype-Tissue Expression and The Cancer Genome Atlas datasets. Survival analysis was performed to determine the prognostic value of TREM1. Functional enrichment analysis was applied to decipher the discrepancy in biological processes between high- and low-TREM1 groups across various cancers. The correlation between TREM1 and immune cell infiltration determined by using multiple algorithms was evaluated with the Pearson method. Four independent immunotherapy cohorts were adopted to validate the role of TREM1 as a biomarker.Results: TREM1 was elevated in most cancers as verified with clinical samples. Overexpression of TREM1 was linked with undesirable prognosis in patients. Further analysis revealed that TREM1 was positively correlated with immune response, pro-tumor pathways, and myeloid cell infiltration, while being negatively correlated with CD8+ T cell (including infiltration level and biological processes). Concordantly, tumors with high TREM1 levels were more resistant to immunotherapy. Through connective map analysis, therapeutically potential compounds like tozasertib and TPCA-1 were identified, which can be used synergistically with immunotherapy to improve the poor prognosis of patients with high TREM1 levels.Conclusion: Through a systematic and comprehensive pan-cancer analysis, we demonstrated that overexpression of TREM1 in tumors correlated closely with unfavorable outcome, infiltration of immune-suppressive cells, and immune regulation, which highlights its potential use as a tumor prognostic biomarker and a novel target for immunotherapy.Keywords: triggering receptors expressed by myeloid cells-1, pan-cancer, prognostic biomarker, tumor microenvironment, clear cell renal cell carcinoma, immunotherapy

Jie Hu,1,&ast; Huihui Li,1,&ast; Yingshan Zhao,1 Yuancheng Ke,1 Ilva D Rupenthal,2 Hanyu Liu,1 Jinghua Ye,1 Xinyue Han,1 Fan Yang,1 Wei Li,3 Huaqing Lin,1 Dongzhi Hou1 1Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems and Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China; 2Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, 1142, New Zealand; 3Guangzhou Institute for Drug Control, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaqing Lin; Dongzhi Hou, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, 280 Wai Huan Dong Road, Guangzhou, People’s Republic of China, Tel +86 180 2631 2508, Fax +86 20 3935 2117, Email huaqing_@163.net; houdongzhi406@163.comIntroduction: Glaucoma is a chronic disease that requires long-term adherence to treatment. Topical application of conventional eye drops results in substantial drug loss due to rapid tear turnover, with poor drug bioavailability being a major challenge for efficient glaucoma treatment. We aimed to prepare the anti-glaucoma drug betaxolol hydrochloride (BH) as a novel nano-delivery system that prolonged the retention time at the ocular surface and improved bioavailability.Methods: We constructed multifunctional nanoparticles (MMt-BH-HA/CS-ED NPs) by ion cross-linking-solvent evaporation method. The particle size, zeta potential, encapsulation efficiency and drug loading of MMt-BH-HA/CS-ED NPs were physicochemically characterized. The structure of the preparations was characterized by microscopic techniques of SEM, TEM, XPS, XRD, FTIR and TGA, and evaluated for their in vitro release performance as well as adhesion properties. Its safety was investigated using irritation assays of hemolysis experiment, Draize test and histopathology examination. Precorneal retention was examined by in vivo fluorescence tracer method and pharmacokinetics in tear fluid was studied. A model of high IOP successfully induced by injection of compound carbomer solution was used to assess the IOP-lowering efficacy of the formulation, and it was proposed that micro-interactions between the formulation and the tear film would be used to analyze the behavior at the ocular surface.Results: The positively charged MMt-BH-HA/CS-ED NPs were successfully prepared with good two-step release properties, higher viscosity, and slower pre-corneal diffusion rate along with longer precorneal retention time compared to BH solution. The micro-interactions between nanoparticles and tear film converted the drug clearance from being controlled by fast aqueous layer turnover to slow mucin layer turnover, resulting in higher drug concentration on the ocular surface, providing more durable and stable IOP-lowering efficacy.Conclusion: The novel multifunctional MMt-BH-HA/CS-ED NPs can effectively reduce IOP and are suitable for the treatment of chronic disease glaucoma.Graphical Abstract: Keywords: glaucoma, nanoparticles, betaxolol hydrochloride, BH, precorneal retention, micro-interactions

Huang Liu,1,* Zhixing Zhang,2,* Wei Lv,3 Qianyi Li,1 Zhaohui Qing,3 Xiaolin Zhong,4 Shaoqin Peng,3 Hai Lin,1 Houbin Zheng1 1Department of Andrology, NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Human Sperm Bank of Guangdong Province, Guangzhou, People’s Republic of China; 2Department of Ultrasonography, NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Human Sperm Bank of Guangdong Province, Guangzhou, People’s Republic of China; 3Department of Anesthesiology, NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Human Sperm Bank of Guangdong Province, Guangzhou, People’s Republic of China; 4Inpatient Department, NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Human Sperm Bank of Guangdong Province, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Houbin Zheng, Email zhenghoubin@126.comObjective: Microsurgery of andrology always brings unexpected findings. Scrotal calculi are rare and unique, which are easily confused with tumor. To understand its etiology and harm, our study retrospectively analyzed the clinical characteristics of men with scrotal calculi to provide a reference for clinical practice.Methods: The clinical data of patients who underwent microscopic testicular sperm extraction (MTESE) and microscopic epididymal sperm aspiration (MESA) from January 1, 2018 to December 31, 2021 were retrospectively analyzed. Data screening was performed on cases in which calculi were found or not, and the relationship between calculi and spermatogenesis was analyzed.Results: A total of 405 patients were recruited. After screening, 218 nonobstructive azoospermia (NOA), 83 obstructive azoospermia (OA), and 13 cryptozoospermia (CZ) patients were included in the study. Calculi were found in 3 patients [incidence was 0.74% (3/405)], in which 2 patients had obstructive azoospermia (1 was epididymal calculi, 1 was intrascrotal calculi) and 1 patient had cryptozoospermia (intrascrotal calculi). Pathological results showed that chronic granuloma with abscess infiltration appeared in epididymal tissue, basement membrane thickening and fibrosis appeared in seminiferous tubules, and fibrous hyperplasia with calcium deposition was found in scrotal calculus. White blood cells, lymphocytes, red blood cells, abstinence time and urethritis were closely related to the occurrence of calculi. While abstinence time might be a potential predictor, which increased the risk by approximately 1.2 times.Conclusion: Disturbance of the testicular microenvironment caused by lymphocyte infiltration may be the main reason for scrotal calculi and ultimately cause spermatogenesis disorders. Prolonged sexual abstinence was a potential risk.Keywords: intrascrotal calculi, azoospermia, cryptozoospermia, testicular microenvironment, lymphocyte infiltration, prolonged sexual abstinence, tumour

Lanlan Lin1,2 &ast;, Guofu Lin1,2 &ast;, Xiaohui Chen,1,2 Hai Lin,1,2 Qinhui Lin,1,2 Yiming Zeng,1– 3 Yuan Xu1– 3 1Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of China; 2Respiratory Medicine Center of Fujian Province, Quanzhou, People’s Republic of China; 3Clinical Research Center, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuan Xu; Yiming Zeng, Department of Pulmonary and Critical Care Medicine, Clinical Research Center, The Second Affiliated Hospital of Fujian Medical University; Respiratory Medicine Center of Fujian Province, Quanzhou, People’s Republic of China, Email yuan_xu0123@fjmu.edu.cn; zeng_yiming@fjmu.edu.cnBackground: Pulmonary small airway epithelia are the primary site of cellular and histological alterations in chronic obstructive pulmonary disease (COPD), while the potential therapeutic hub genes of pulmonary epithelia are rarely identified to elucidate profound alterations in the progression of the disease.Methods: Microarray dataset of GSE11906 containing small airway epithelia from 34 healthy non-smokers and 33 COPD patients was applied to screen differentially expressed genes (DEGs). Weighted gene correlation network analysis (WGCNA) was further used to identify the hub genes related to clinical features. Moreover, single-cell RNA sequencing data from GSE173896 and GSE167295 dataset were applied to explore the expression and distribution of the hub genes. The expression levels of hub genes in epithelial cells stimulated by cigarette smoke extract (CSE) were detected by RT-qPCR.Results: Ninety-eight DEGs correlated with clinical features of COPD were identified via limma and WGCNA. Eight hub genes (including AKR1C3, ALDH3A1, AKR1C1, CYP1A1, GPX2, CBR3, AKR1B1 and GSR) that might exert an antioxidant role in COPD process were identified. Single-cell transcriptomic analysis indicated that the expressions of AKRAC3, ALDH3A1, GPX2, CBR3 and AKR1B1 were significantly increased in the COPD group when compared with the normal group. Moreover, we found that the expression of ALDH3A1 was the most abundantly expressed in ciliated cells. RT-qPCR results indicated that the majority of candidate novel genes were significantly elevated when the epithelial cells were exposed to CSE.Conclusion: Through integrating limma, WGCNA, and protein-protein interaction (PPI) analysis, a total of eight candidate hub genes of pulmonary airway epithelia were identified in COPD. Moreover, single-cell transcriptomic analysis indicated that ALDH3A1 was enriched in ciliated cells, which may provide a new insight into the pathogenesis and treatment of COPD.Keywords: COPD, pulmonary airway epithelium, hub genes, cigarette smoke

Hongxia Lin,1,2,&ast; Yulian Gao,1,2,&ast; Yanli Qiu,3,&ast; Haixing Zhu,1,2 Shengxiong Zhang,1,2 Hanssa Dwarka Summah,4 Guochao Shi,1,2 Tingting Cheng,5,&ast; Zhitao Yang,6 Yun Feng1,2 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, 20025, People’s Republic of China; 3Department of Anesthesia, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 4Poudre D’Or Chest Hospital, Rivière du Rempart, Mauritius; 5Department of Respiratory and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 20025, People’s Republic of China; 6Department of Emergency, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhitao Yang; Yun Feng, Email yangzhitao@hotmail.fr; fy01057@163.comIntroduction: Elderly patients with immunosuppressive status may have increased risk of mortality. At present, few studies have explored the clinical characteristics of the elderly immunosuppressed population with bloodstream infection. Our objectives were to evaluate the prognostic factors in immunosuppressed elderly patients with bloodstream infection.Methods: Three hundred and seventy-six elderly patients who were diagnosed with bloodstream infection in immunosuppressive status while receiving treatment in our hospital were selected from 2015 to 2019. The demographic data, underlying diseases, comorbidity, inducement, complications, pathogen sources, etiologies and the antibiotic therapy were analyzed between 90-day survival groups and 90-day mortality groups. The prognostic factors of 90-day mortality were evaluated by univariate logistic regression analysis and multivariate logistic regression analysis.Results: The clinical characteristics of 376 immunosuppressed elderly people diagnosed with bloodstream infection were analyzed, and among those people about 111 were 90-day mortality. By univariate logistic regression analysis and multivariate logistic regression analysis, we found ICU admission (OR: 2.052, 95%CI: 1.088– 3.871, p=0.026), the decrease in BMI (OR: 0.307, 95%CI: 0.130– 0.723, p=0.007), coronary heart disease (OR: 2.028, 95%CI: 1.078– 3.816, p=0.028), biliary infection (OR: 4.406, 95%CI: 1.794– 10.821, p=0.001) and the use of tigecycline (OR: 2.480, 95%CI: 1.195– 5.147, p=0.015) were significantly different between the 90-day survival and 90-day mortality groups.Conclusion: ICU admission, coronary heart disease, biliary infection, and the use of tigecycline were the independent prognostic risk factors of 90-day mortality in immunosuppressed elderly people, and the decrease in BMI was the protective factor, which would have the benefit of discriminating the prognostic factors in immunosuppressed elderly people with bloodstream infection.Keywords: bloodstream infection, elderly people, mortality, immunosuppressive states, prognosis

Yulian Gao,1,&ast; Hongxia Lin,1,&ast; Yumin Xu,2,&ast; Yijin Yao,1,&ast; Dake Shi,1 Junjie Li,1 Haixing Zhu,1 Hanssa Dwarka Summah,3 Lei Ni,1 Yun Feng1 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Hospital Infection Management, Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Respiratory, Poudre D’Or Chest Hospital, Rivière du Rempart, Mauritius&ast;These authors contributed equally to this workCorrespondence: Yun Feng; Lei Ni, Email fy01057@163.com; nilei625@139.comPurpose: Carbapenem-resistant Gram-negative bacteria bloodstream infection (CRGNB-BSI) has gradually become a major threat worldwide due to its treatment difficulty and high mortality. This study aimed to determine the risk factors for CRGNB-BSI in immunosuppressed patients.Patients and Methods: A total of 427 immunosuppressed patients with CRGNB-BSI were retrospectively investigated from 2015 to 2021. Both univariate and multivariate logistic regression analyses were applied to evaluate independent risk factors for CRGNB-BSI.Results: The most common etiology was Klebsiella Pneumoniae (50.59%; 216/427), while the Acinetobacillus baumannii infection was associated with the highest mortality (58.25%) among all etiologies. The 60-day mortality of immunosuppressed patients with CRGNB-BSI was 52.48% (224/427). Procalcitonin (PCT) > 0.5 μg/L (OR = 2.32, 95% CI: 1.28– 4.19, P = 0.005) and age > 55 years (OR = 2.06, 95% CI: 1.17– 3.64, P = 0.012) were found to be predictors of 60-day mortality of CRGNB-BSI, and tigecycline regimen (OR = 3.20, 95% CI: 1.81– 5.67, P < 0.001) was associated with higher mortality. Multivariate analysis also revealed that patients who developed acute kidney injury (AKI) (OR = 2.19, 95% CI: 1.11– 4.30, P = 0.023), gastrointestinal bleeding (OR = 3.18, 95% CI: 1.10– 9.16, P = 0.032), multiple organ dysfunction syndrome (MODS) (OR = 12.11, 95% CI: 2.61– 56.19, P = 0.001), and septic shock (OR = 3.24, 95% CI: 1.77– 5.94, P < 0.001) showed worse outcomes. The risk factors were also significantly associated with mortality in the different subgroups.Conclusion: This study demonstrated that PCT > 0.5 μg/L, age > 55 years, and the tigecycline regimen were significantly associated with higher 60-day mortality among immunosuppressed patients with CRGNB- BSI. Patients developing MODS, septic shock, or AKI had worse clinical outcomes.&#x2003Keywords: bloodstream infection, carbapenem-resistant, immunosuppressed patients, subgroups, prognosis

Renhui Huang,1,2,&ast; Qi Shi,1,&ast; Shutian Zhang,1,2 Hong Lin,1,2 Chengzhi Han,1,2 Xinyi Qian,1 Yijun Huang,1 Xiaorong Ren,1 Jiayuan Sun,3 Nana Feng,4 Chunmei Xia,1 Meng Shi5 1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Clinical Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Respiratory Endoscopy, Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China; 4Department of Respiratory and Critical Medicine, Shanghai Eighth People’s Hospital Affiliated to Jiangsu University, Shanghai, People’s Republic of China; 5Department of Thoracic and Cardiovascular Surgery, Huashan Hospital, Affiliated with Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meng Shi, Department of Thoracic and Cardiovascular Surgery, Huashan Hospital, Affiliated with Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, People’s Republic of China, Tel +86 15921527577, Email huashan_heart@sina.cn Chunmei Xia, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 13917406439, Email cmxia@fudan.edu.cnPurpose: Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis of lung ischemia/reperfusion (I/R) injury. Cyclic GMP-AMP synthase (cGAS) is a cytosol dsDNA sensor, coupling with downstream stimulator of interferon genes (STING) located in the ER, which involves innate immune responses. The aim of our present study was to investigate the effects of cGAS on lung I/R injury via regulating ERS.Methods: We used Sprague-Dawley rats to make the lung I/R model by performing left hilum occlusion-reperfusion surgery. cGAS-specific inhibitor RU.521, STING agonist SR-717, and 4-phenylbutyric acid (4-PBA), the ERS inhibitor, were intraperitoneally administered in rats. Double immunofluorescent staining was applied to detect the colocalization of cGAS or BiP, an ERS protein, with alveolar epithelial type II cells (AECIIs) marker. We used transmission electron microscopy to examine the ultrastructure of ER and mitochondria. Apoptosis and oxidative stress in the lungs were assessed, respectively. The profiles of pulmonary edema and lung tissue injury were evaluated. And the pulmonary ventilation function was measured using a spirometer system.Results: In lung I/R rats, the cGAS-STING pathway was upregulated, which implied they were activated. After cGAS-STING pathway was inhibited or activated in lung I/R rats, the ERS was alleviated after cGAS was inhibited, while when STING was activated after lung I/R, ERS was aggravated in the AECIIs, these results suggested that cGAS-STING pathway might trigger ERS responses. Furthermore, activation of cGAS-STING pathway induced increased apoptosis, inflammation, and oxidative stress via regulating ERS and therefore resulted in pulmonary edema and pathological injury in the lungs of I/R rats. Inhibition of cGAS-STING pathway attenuated ERS, therefore attenuated lung injury and promoted pulmonary ventilation function in I/R rats.Conclusion: Inhibition of the cGAS-STING pathway attenuates lung ischemia/reperfusion injury via alleviating endoplasmic reticulum stress in alveolar epithelial type II cells of rats.Graphical Abstract: Keywords: cGAS-STING, endoplasmic reticulum stress, alveolar epithelial type II cells, lung ischemia/reperfusion injury

Huihuang Lin,1,&ast; Huaping Zhang,1,&ast; Dongyong Yang,1,&ast; Xiaoyang Chen,1,&ast; Yunfeng Chen,1,&ast; Duanhong Song,1 Chi Cai,2 Yiming Zeng1 1Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Fujian Medical University, Center of Respiratory Medicine of Fujian Province, Quanzhou, People’s Republic of China; 2Department of Radiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiming Zeng, Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Fujian Medical University, Center of Respiratory Medicine of Fujian Province, No. 34, Zhongshanbei Road, Licheng District, Quanzhou, People’s Republic of China, Tel +86 13515042402, Fax +86 0595 22770258, Email zeng_yi_ming88@163.comPurpose: Surgical bullectomy is the standard treatment of giant emphysematous bulla (GEB). However, bronchoscopic treatment should be considered as an alternative approach for patients who are unfit for surgical treatment. The study aimed to evaluate the clinical efficacy of endobronchial occlusion for the treatment of GEB using silicone plugs.Methods: This retrospective study recruited four patients with GEB who were unsuitable for surgery. Preoperative planning was performed using high-resolution computed tomography and a virtual bronchoscopic navigation system. Customized silicone plugs were then placed in the target airway via bronchoscopy to cause GEB regression and atelectasis.Results: All procedures were completed successfully in four patients. Three months after the procedures, compared with baseline, increases in the mean forced expiratory volume in 1 s (from 1.20 L/s to 1.33 L/s), forced vital capacity (from 2.63 L to 2.90 L), diffusion lung capacity for carbon monoxide (from 29% to 41% of the predicted value) and 6-minute walking test (from 412 m to 474 m) were observed. Additionally, the mean total lung capacity (from 6.80 L to 6.35 L), residual volume (from 3.97 L to 3.52 L), and St. George’s Respiratory Questionnaire scores (from 67 to 45) were all lower than baseline data.Conclusion: Our preliminary results demonstrated that the endobronchial placement of silicone plugs could be a low-cost, safe, and effective choice for the treatment of GEB in surgically unfit patients.Keywords: giant bulla, bronchoscopy, silicone spigot, endobronchial occlusion

Hongxiang Wei,1,&ast; Fei Chen,1,&ast; Jinyuan Chen,2,&ast; Huangfeng Lin,1 Shenglin Wang,1 Yunqing Wang,1 Chaoyang Wu,1 Jianhua Lin,1 Guangxian Zhong1 1Department of Orthopaedics, Fujian Institute of Orthopaedics, the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 2The Centralab, the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangxian Zhong; Jianhua Lin, Tel/Fax +86 591 87981029, Email zhongguangxian@163.com; jianhual@126.comPurpose: The objective of this study was to investigate the antitumor activity, targeting capability, and mechanism of the developed nanodrug consisting of doxorubicin and exosome (Exo-Dox) derived from mesenchymal stem cells in vitro and in vivo.Methods: The exosomes were isolated with Exosome Isolation Kit, and the Exo-Dox was prepared by mixing exosome with Dox-HCl, desalinizing with triethylamine and then dialyzing against PBS overnight. The exosome and Exo-Dox were examined by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). The antitumor activity, targeting capability, and mechanism of the developed Exo-Dox were evaluated by cell viability assay, histological and immunofluorescence analysis and in vivo imaging system.Results: NTA results showed the size of the exosomes had increased from 141.6 nm to 178.1 nm after loading with doxorubicin. Compared with free Dox, the Exo-Dox exhibited higher cytotoxicity against osteosarcoma MG63 cells, HOS cells, and 143B cells than free Dox, the half-maximal inhibitory concentrations (IC50) of Dox, Exo-Dox were calculated to be 0.178 and 0.078 μg mL− 1 in MG63 cells, 0.294 and 0.109μg mL− 1 in HOS cells, 0.315 and 0.123 μg mL− 1 in 143B cells, respectively. The in vivo imaging showed that MSC derived Exo could serve as a highly efficient delivery vehicle for targeted drug delivery. The immunohistochemistry and histology analysis indicated that compared with the free Dox group, the Ki67-positive cells and cardiotoxicity in Exo-Dox group were significantly decreased.Conclusion: Our results suggested that MSC-derived Exo could be excellent nanocarriers used to deliver chemotherapeutic drug Dox specifically and efficiently in osteosarcoma, resulting in enhanced toxicity against osteosarcoma and less toxicity in heart tissue. We further demonstrated the targeting capability of Exo was due to the chemotaxis of MSC-derived exosomes to osteosarcoma cells via SDF1-CXCR4 axis.Keywords: targeted therapy, exosome, doxorubicin, osteosarcoma, nanocarrier

Huiqin Lin,1 Yuting Wu,1 Jinying Wu,2 Qiang Chen,3 Jun Yu,4 Yongjun Lin5 1Department of Geriatrics, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China; 2Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of China; 3Department of General Practice, Fengze Huada Community Medical Center, Quanzhou, People’s Republic of China; 4Outpatient Department, Fujian Military Region Fuzhou No. 9 Cadres Rest and Recuperation Center, Fuzhou, People’s Republic of China; 5Department of General Practice, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, People’s Republic of ChinaCorrespondence: Yongjun Lin, Department of General Practice, The First Hospital of Quanzhou affiliated to Fujian Medical University, Quanzhou, Fujian, People’s Republic of China, Tel +86-15059801280, Email yongjundrlin@outlook.comObjective: This study aims to analyze the prevalence of hypertension and 10-year cardiovascular disease (CVD) risk among older adults living in a coastal region of southeast China.Methods: A population-based cross-sectional survey of 2018 adults was conducted on 60– 98-year-old residents in Quanzhou from September 2016 to March 2018 using multistage stratified cluster random sampling. The 10-year CVD risk was estimated by applying the Chinese model recommended by the Chinese guidelines for CVD prevention.Results: The overall prevalence of hypertension, prehypertension, and normotension among older adults in Quanzhou was 29.0%, 18.7%, and 52.3%, respectively. The percentage of participants with low, moderate, and high 10-year CVD risk was 49.7%, 36.8%, and 13.5%, respectively. Older age, low salt awareness, and low levels of physical activity were significantly correlated with hypertension. The 10-year CVD risk was higher for men than women and increased with age. Higher blood pressure was associated with a greater 10-year CVD risk.Conclusion: More than half of the older adults in Quanzhou surveyed by this study were normotensive, and approximately half the participants had a moderate or high 10-year CVD risk. We recommend the implementation of regionally targeted interventions, such as screening of blood pressure and other risk factors, to reduce blood pressure and CVD risk in Chinese populations.Keywords: prevalence, prediction, hypertension, CVD risk, older adults

Huafang Wang,1 Yuan Chen,2 Huijun Lin,3 Wanmao Ni,4 Qiaolei Zhang,5 Jianping Lan,1 Lai Jin1 1Cancer Center, Department of Hematology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, People’s Republic of China; 2Cancer Center, Department of Pathology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, People’s Republic of China; 3Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, People’s Republic of China; 4Cancer Center, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, People’s Republic of China; 5Department of Hematology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310022, People’s Republic of ChinaCorrespondence: Lai Jin; Jianping Lan, Cancer Center, Department of Hematology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-571-85893497, Email 13586990325@163.com; LANJP@163.comBackground: Mast cell leukemia (MCL) is a highly life-threatening and extremely rare subtype of systemic mastocytosis (SM). MCL often genetically contains one or more somatic mutations, particularly activating mutations of KIT. This study reported on an acute MCL patient who had a rare phenotype and genetic mutants with a history of primary malignant mediastinal germ cell tumor (GCT).Case Presentation: A 30-year-old Asian male patient who underwent two rounds of surgery and chemotherapy with a history of primary mediastinal GCT (PM-GCTs) was admitted to our hospital due to persistent chest pain and severe fatigue. The diagnosis of acute MCL was confirmed via morphology analysis and chemical staining of marrow aspirate, as well as via marrow biopsy, with the addition of C-findings that included splenomegaly and cytopenia. The atypical MCs were phenotypically positive for CD117 and CD9 but weakly positive for CD2 and negative for CD25. Next-generation sequencing of the marrow aspirate identified heterozygous mutations in TP53 P301Qfs&ast;44, FLT3 R973X, SETBP1 N272D, and JAK3 I688F, whereas mutations in KIT were not found. Although the initial therapy of corticosteroids, ruxolitinib, and dasatinib-based regimens was effective, he died of acute respiratory distress syndrome after the first cycle of chemotherapy with cladribine and cytarabine. The patient’s survival time was 2.4 months after the initial presentation of MCL.Conclusion: In this case, MCL preceded by PM-GCTs had similar clinical symptoms and morphological manifestations but distinctly different genetic profiles than primary MCL. The characteristic morphology of MCL provides the most pivotal evidence that led our diagnosis in the correct direction. A competing hypothesis is that there is a common embryonal cancer stem cell between PM-GCTs and secondary MCL, and the latter is gradually developed in the context of additional “driver mutations”.Keywords: case report, mast cell leukemia, germ cell tumor, primary mediastinal, KIT, TP53

Meijun Chen,1 Qingping Yun,1 Haoxiang Lin,1 Shenglan Liu,2 Yihua Liu,1 Yuhui Shi,1 Ying Ji,1 Chun Chang1 1School of Public Health, Peking University, Beijing, People’s Republic of China; 2Department of Social Development, Development Research Center of the State Council, Beijing, People’s Republic of ChinaCorrespondence: Chun Chang School of Public Health, Peking University, Beijing, People’s Republic of China Tel +8613601235974 Email changchunpku@126.comPurpose: Self-management behavior (SMB) plays a significant role in glycemic control. This study aimed to explore the factors related to SMB among patients with type 2 diabetes and how these factors interacted with each other.Patients and Methods: Patients diagnosed with type 2 diabetes were recruited from 18 community healthcare stations (CHSs) from six community healthcare centers (CHCs) in Beijing, China from April to May in 2017. Motivation, competence, autonomy support, social support, self-management skills, adherence to self-monitoring of blood glucose (SMBG) and haemoglobin A1c (HbA1c) measurement were tested by questionnaire. Correlation analysis and path analysis were performed so as to identify the factors associated with patients’ SMB.Results: A total of 532 participants completed this study. Participants who have good compliance to SMBG got higher scores in social support (F = 7.68, p = 0.01), competence (F = 10.47, p = 0.01), and skills (F = 12.34, p < 0.01). Higher competence (β = 0.03, P < 0.001), higher social support (β = 0.01, P < 0.001), better skills(β = 0.01, P < 0.001) directly led to better adherence to SMBG. Social support had a positive effect on autonomy support (β = 0.69, P < 0.001), motivation (β = 0.45, P < 0.001), competence (β = 0.28, P < 0.001), skills (β = 0.14, P < 0.001), which was also indirectly linked to better adherence to SMBG. Better self-management skills directly led to better adherence to HbA1c measurement (β = 0.03, P < 0.001). Social support had a positive effect on autonomy support (β = 0.69, P < 0.001), motivation (β = 0.45, P < 0.001), competence (β = 0.28, P < 0.001), skills (β = 0.14, P < 0.001), which was also indirectly linked to better adherence to HbA1c measurement.Conclusion: Self-determination theory and social support theory were practical in explaining SMB in Chinese population. Competence, motivation and social support played an important role in diabetic self-management. Paying attention to the promotion of individual’s intrinsic motivation and self-efficacy may be able to help patients maintain self-management behavior in the long-term routine.Keywords: self-determination theory, social support theory, self-monitoring of blood glucose, motivation, diabetes

Xiaojun Wang,1,2,&ast; Xuanqi Liu,3,&ast; Yiding Qi,4,&ast; Shuyi Zhang,4 Kailei Shi,4 Huagang Lin,5 Paul Grossfeld,6 Wenhao Wang,1,2 Tao Wu,1,2 Xinkai Qu,4 Jing Xiao,5 Maoqing Ye2,4 1Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 2Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 4Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 5Department of Nephrology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 6Division of Cardiology UCSD School of Medicine, Rady Children’s Hospital of San Diego, La Jolla, CA, 92093, USA&ast;These authors contributed equally to this workCorrespondence: Maoqing Ye, Department of Cardiology, Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China, Tel +86-18930721396, Email yemaoqing@fudan.edu.cn Jing Xiao, Department of Nephrology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China, Tel +86-13817100256, Email jingxiao13@Fudan.edu.cnBackground: Serum uric acid (SUA) is suspected to be associated with atherosclerosis and calcium deposition in atherosclerosis is known to related poor prognosis, yet there is no cohort study on the aged in China. We aimed to investigate the relationships between SUA levels and coronary calcium deposition in the middle-aged and elderly populations in China.Methods: A total of 326 participants between the ages of 50 and 85 who had undergone a coronary CT scan in 2015 at the Huadong Hospital Affiliated to Fudan University (Shanghai, China) were included in this study. Univariate and multivariate binary logistic regression was performed to analyze the correlation between SUA levels and coronary artery calcium score (CACS). The changes in CACS during a five-year follow-up were analyzed through Kaplan–Meier survival and binary cox regression analysis. An observational study was done on another 104 asymptomatic middle-aged and elderly patients to compare relative mRNA expressions of proinflammatory factors in peripheral blood mononuclear cells (PBMCs) from 104 subjects.Results: Based on the first year of follow-up data analysis, the elevation of SUA levels (P< 0.001) is an independent risk factor for the increase of CACS after coordinating the confounding factors. According to five-year follow-up data, cox regression analysis proved that SUA was a risk factor for CACS (HR =5.86, P< 0.001). The mRNA expression of IL-6 and CXCL8 in the HUA and HUA patients with CAC (HUA-CAC) groups was significantly higher than that in the normal control (NC) and coronary calcium deposition (CAC) groups.Conclusion: Taken together, the findings in this study indicate that high SUA levels (P< 0.001) are an independent risk factor for CACS and elevated SUA levels increase the risk of developing coronary calcium deposition among middle-aged and old people in the Chinese population, which may be related to an increase of pro-inflammatory cytokines in the PBMCs.Keywords: serum uric acid, calcium deposition, coronary artery calcium score, monocyte inflammation

Ou L, Lin H, Song Y, et al. Int J Nanomedicine. 2020;15:5131–5146. The Editor and Publisher of International Journal of Nanomedicine are retracting the published article. The authors requested to correct the image used for Figure 8D, p-PTEN, Inhibitor, however it was found the image had been duplicated with that from Figure 7E, p-PTEN, inhibitor from Ou L, Sun T, Liu M, et al. Efficient miRNA Inhibitor Delivery with Graphene Oxide-Polyethylenimine to Inhibit Oral Squamous Cell Carcinoma. Int J Nanomedicine. 2020;15:1569–1583. https://doi.org/10.2147/IJN.S220057. The authors cooperated with our queries and provided some data from their study, but they were unable to provide a satisfactory explanation for the image duplication. As the findings could not be adequately verified the Editor and Publisher made the decision to retract the article. The authors did not agree with this decision. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Background: Powassan virus is an emerging neurotropic arbovirus transmitted by the tick Ixodes scapularis. This systematic review was conducted to aggregate data on its clinical manifestations, diagnostic findings, and complications. Methods: PubMed was searched until August 2023 using the term “Powassan”, to identify all published cases of Powassan virus infections, as per PRISMA guidelines. Results: Among the 380 abstracts identified, 45 studies describing 84 cases (70 adult, 14 pediatric) were included. Cases were reported from the USA and Canada. Complications included paralysis in 44.1% of adult and 42.6% of pediatric cases, cognitive deficits in 33.3% of adult and 25% of pediatric cases, while the mortality rate was 19.1% and 7.1% in the adult and pediatric populations, respectively. Correlation analysis revealed an association between mortality and age (r = 0.264, p = 0.029), development of paralysis (r = 0.252, p = 0.041), or respiratory distress or failure (r = 0.328, p = 0.006). Factors associated with persistent neurological deficits were development of ataxia (r = 0.383, p = 0.006), paralysis (r = 0.278, p = 0.048), speech disorder (r = 0.319, p = 0.022), and cranial nerve involvement (r = 0.322, p = 0.017). Other significant correlations included those between speech disorders and ataxia (r = 0.526, p < 0.001), and between paralysis and respiratory distress or failure (r = 0.349, p = 0.003). Conclusion: Powassan virus infections have significant morbidity and mortality and should be suspected in cases of encephalitis and possible tick exposure. PROSPERO registration number: CRD42023395991.

Ming Gao,1 Haisheng Lin,2 Bingxiao Li,3 Junjie Wen,3 Yingying Wang,1 Zhanhui Zhang,4,&ast; Wenxiong Chen2,&ast; 1Department of Neurology, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, People’s Republic of China; 2Department of Neurology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Department of Pediatrics, First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510630, People’s Republic of China; 4Clinical Medicine Research Institute, First Affiliated Hospital, Jinan University, Guangzhou, 510630, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhanhui ZhangFirst Affiliated Hospital, Jinan University, 613 West Huangpu Avenue, Tianhe, Guangzhou 510630, Guangdong, People’s Republic of China, Tel +86-20-3868-8749, Email zzhaddress@126.comObjective: Tic disorders (TDs) are highly polygenic and heritable neurodevelopmental disorders characterized by the presence of movements (motor tics) and/or vocalizations (phonic tics). SLITRK1 is a pathogenic variation of TD, and in a recent genome-wide association study in those of European ancestry, a single-nucleotide polymorphism (rs2504235) in the FLT3 gene was significantly associated with TDs/Tourette’s syndrome. However, these results need to be proved in different populations. This study aimed to determine whether these two genetic variants were also associated with TD patients in south China.Methods: A total of 116 child TD patients and 114 healthy controls were included. All children underwent peripheral blood sampling for genomic DNA extraction. Gene fragments with two single-nucleotide polymorphisms were amplified by PCR and sequenced by Sanger chain termination before genotype analysis.Results: SLITRK1 var321 was not observed in any of the TD patients or controls. No significant difference was observed in allelic frequencies or genotypic distributions of rs2504235 between TD patients and controls.Conclusion: Our results provide no evidence to support the previous conclusion that SLITRK1 var321 plays a major role in TDs, and FLT3 rs2504235 was not significantly associated with TDs in our cohort.Keywords: tic disorders, Tourette’s syndrome, SLITRK1, SLIT and NTRK like family member 1, FLT3, Fms related receptor tyrosine kinase 3

Xin Hua,1,&ast; Fangfang Duan,1,&ast; Wenyu Zhai,2,&ast; Chenge Song,1 Chang Jiang,1 Li Wang,1 Jiajia Huang,1 Huanxin Lin,3 Zhongyu Yuan1 1Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 2Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 3Department of Radiotherapy, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongyu YuanDepartment of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China, Email yuanzhy@sysucc.org.cnHuanxin LinDepartment of Radiotherapy, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China, Email linhx@sysucc.org.cnPurpose: We attempted to explore the prognostic value of baseline inflammatory and nutritional biomarkers at diagnosis in patients with early-stage breast cancer and develop a novel scoring system, the inflammatory-nutritional prognostic score (INPS).Patients and Methods: We collected clinicopathological and baseline laboratory data of 1259 patients with early-stage breast cancer between December 2010 and November 2012 from Sun Yat-sen University Cancer Center. Eligible patients were randomly divided into training and validation cohorts (n = 883 and 376, respectively) in a 7:3 ratio. We selected the most valuable biomarkers to develop INPS by the least absolute shrinkage and selection operator (LASSO) Cox regression model. A prognostic nomogram incorporating INPS and other independent clinicopathological factors was developed based on the stepwise multivariate Cox regression method. Then, we used the concordance index (C-index), calibration plot, and time-dependent receiver operating characteristic (ROC) analysis to evaluate the prognostic performance and predictive accuracy of the predictive nomogram.Results: Four inflammatory-nutritional biomarkers, including neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), prognostic nutritional index (PNI), and albumin-alkaline phosphatase ratio (AAPR), were selected using the LASSO Cox analysis to construct INPS, which remained an independent prognostic indicator per the multivariate Cox regression analysis. Patients were stratified into low- and high-INPS groups based on the cutoff INPS determined by the maximally selected rank statistics. The prognostic model for overall survival consisting of INPS and other independent clinicopathological indicators showed excellent discrimination with C-indexes of 0.825 (95% confidence interval [CI]: 0.786– 0.864) and 0.740 (95% CI: 0.657– 0.822) in the training and validation cohorts, respectively. The time-dependent ROC curves showed a higher predictive accuracy of our prognostic nomogram than that of traditional tumor-node-metastasis staging.Conclusion: Baseline INPS is an independent indicator of OS in patients with early-stage breast cancer. The INPS-based prognostic nomogram could be used as a practical tool for individualized prognostic predictions.Keywords: early-stage breast cancer, LASSO Cox analysis, inflammatory-nutritional biomarker, prognostic nomograms, overall survival

Yanhong Deng,1,&ast; Lishuo Shi,2,&ast; Jianxia Li,1,&ast; Zhipeng Jiang,3,&ast; Chaojun Xie,4 Shuangling Luo,3 Li Ling,5 Hualiang Lin,6 Zongqiu Chen,4 Yunlong Zhao,7 Liang Kang,3 Jun Yuan,4 Weiping Wen8 1Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangzhou, 510655, People’s Republic of China; 2Clinical Research Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangzhou, 510655, People’s Republic of China; 3Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangzhou, 510655, People’s Republic of China; 4Guangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong Province, 510440, People’s Republic of China; 5Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 6Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 7Medical Department, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangzhou, 510655, People’s Republic of China; 8Department of Otolaryngology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangzhou, 510655, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiping WenDepartment of Otolaryngology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, No. 26 Yuan Cun Er Heng Road, Guangzhou, 510655, People’s Republic of ChinaTel +86-20-87333733Email wenwp@mail.sysu.edu.cnJun YuanGuangzhou Center for Disease Control and Prevention, No. 1, Qide Road of Baiyun District, Guangzhou, Guangdong Province, 510440, People’s Republic of ChinaTel +86-20-36052333-1816Email yuanjuncom@163.comBackground: The quarantine in dedicated hotels has become an inevitable safety measure due to the frequent cross-border travel since the outbreak of COVID-19. The aim of the present study was to explore the trends in the psychological status of individuals entering from high-risk areas of COVID-19 coronavirus while quarantining in dedicated hotels.Methods: A total of 591 individuals who isolated in dedicated hotels were recruited between March and June 2020. Participants self-reported mental symptoms [Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS)] every three days during the quarantine. A mixed-effects linear regression model was used to assess the trends.Results: Participants reporting anxiety and depression symptoms at least one time during quarantine accounted for 4.5% and 18.4%, respectively. Their psychological status was alleviated during some first 9 days, and then it slightly deteriorated, which was suggested by SAS and SDS scores that were negatively correlated with the days of quarantine (T) (adjusted coefficient [β] − 0.81, 95% CI − 1.00 to − 0.62; and β − 0.75, 95% CI − 0.97 to − 0.53, respectively), and were positively correlated with the square of T (β 0.04, 95% CI 0.02 to 0.06; and β 0.04, 95% CI 0.02 to 0.06, respectively). The unemployed and 18∼ 30-year-old participants were prone to greater levels of psychological distress. No significant difference in the trend of mental health was found among different subgroups.Conclusion: The mental health of the people entering Guangzhou from high-risk areas of COVID-19 coronavirus resulted positive during the early period of quarantine in dedicated hotels, after which it deteriorated. The psychological status of individuals should be closely monitored at the beginning and after more than 9 days of quarantine, especially for individuals who are unemployed and 18∼ 30-year-old ones.Keywords: quarantine, dedicated hotels, psychological distress, COVID-19

Jiaqi Xu, Kun Cheng, Hai Lin, Wei Han, Tieying He, Xiaohan Nie, Yonghui Sun, Sulidankazha Qiuman, Yilidan Reheman, Qilong Chen Department of Pancreatic Surgery, Centre of Digestive and Vascular Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, People’s Republic of ChinaCorrespondence: Qilong Chen Email chenqilong651003@sohu.comBackground: Pancreatic cancer (PC) presents a phenomenal disease burden worldwide. The GATA transcription factor family is associated with a variety of human malignancies. However, the relation between GATA family members (GATAs) and PC has not been elucidated.Methods: This study integrates large-scale bioinformatics database resources to analyze the expression patterns of GATAs in PC patients and explore their underlying function mechanism and relevance to immune infiltration and other different cell types in the tumor microenvironment in pancreatic cancer. First, the expression pattern of GATAs in pancreatic cancer was detected by the Oncomine database and the Gene Expression Profile Interaction Analysis (GEPIA2) database and verified through other datasets in the R2 platform. Then, we used the cBioPortal database and the Human Protein Atlas to assess the correlation between GATAs and clinicopathological features of PC. Then, survival analyses were performed to identify candidate prognostic factors in the GATA family in PC patients. Further, we performed gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, protein-protein interaction (PPI) network, immune-infiltration correlation analysis, and cell type analysis of the tumor microenvironment at the single-cell level to explain the function of GATAs in pancreatic cancer.Results: We found that GATA3 and GATA6 were highly expressed in pancreatic cancer, and the expression levels of GATA4 and GATA6 correlated with the pathological stage, differentiation grade, and molecular subtype of pancreatic cancer. The survival analysis revealed that lower GATA4 of PC patients was associated with better outcomes, and higher GATA6 might be associated with longer OS. In addition, GATA3 was associated with immune cell infiltration of PC, and GATA6 was mainly distributed in the epithelial cells with ductal phenotype.Conclusion: This work tentatively identified GATA3, GATA4, and GATA6 in the GATA family associated with pancreatic cancer. GATA4 may serve as a prognostic factor for PC patients, and GATA6 may act as a subtype marker for PC. In addition, GATA3 may reflect the immune-infiltration status of PC.Keywords: pancreatic cancer, GATA transcriptional factor, prognosis, tumor microenvironment, bioinformatics analysis

Guangxian Zhong,1,&ast; Yunqing Wang,1,&ast; Hongxiang Wei,1 Meifang Chen,2 Huangfeng Lin,1 Zhen Huang,1 Jinlong Huang,3 Shenglin Wang,1 Jianhua Lin1 1Department of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, People’s Republic of China; 2The Health Management Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, People’s Republic of China; 3Department of Hematology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, People’s Republic of China&ast;These authors contributed equally to this work.Correspondence: Jianhua Lin; Shenglin Wang Tel/Fax +86 591 87981029Email jianhual@126.com; Shenglinwang0216@163.comPurpose: The aim of this research was to investigate the clinical significance of the expression of flap structure-specific endonuclease 1 (FEN1) in primary osteosarcoma.Methods: The expression of FEN1 was detected by immunohistochemistry analysis. The association of the expression of FEN1 in osteosarcoma with clinicopathological parameters was analyzed by using χ2 test or Fisher’s exact test. Survival analyses were performed by Kaplan–Meier method and Cox proportional hazards regression model.Results: Of the 40 osteosarcoma patients, 19 (47.5%) patients presented with FEN1 high expression, while in the non-neoplastic bone specimens, the FEN1 high expression was observed in 10% (3/30), the positive expression rate in osteosarcoma patients was significantly higher than that of non-neoplastic bone specimens (P< 0.01). Univariate analysis indicated that the progression-free survival (PFS) and overall survival (OS) were correlated with the expression level of FEN1 (PFS, P < 0.001; OS, P = 0.002), Enneking staging (PFS, P = 0.026; OS, P = 0.044) and chemotherapy response (PFS, P = 0.019; OS, P = 0.031). Multivariate analysis demonstrated that FEN1 expression was an independent prognostic factor for the PFS (HR = 4.73, P = 0.002) and OS (HR = 4.01, P = 0.038) of osteosarcoma patients.Conclusion: This study showed that FEN1 was overexpressed in osteosarcoma patients and positively associated with poor prognosis of osteosarcoma patients. Further studies should focus on the relative mechanisms and the targeted FEN1 therapies for osteosarcoma.Keywords: osteosarcoma, flap endonuclease 1, immunohistochemistry, prognosis

Yuhui Ruan,1 Weisin Chen,2 Chenyang Zhuang,2 Hong Lin2,3 1School of International and Public Affairs, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Institute of Medical Science Popularization, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Hong LinDepartment of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaTel +86 13636526656Email lin.hong1@zs-hospital.sh.cnPurpose: This study aimed to elucidate the quality of life of older adults/patients with degenerative lumbar diseases (ODLs) and analyse its association with some of their health-related perceptions.Materials and Methods: This mixed-methods study consisted of a questionnaire survey and an in-depth interview, which was designed within this study. ODLs were recruited from January 12, 2017 to June 27, 2018. The independent sample t-test and grounded theory coding method were employed for data analysis.Results: Of the 125 participants who returned valid questionnaires, 18 were included in the in-depth interviews. ODLs’ quality of life was associated with the following health-related perceptions: “life barriers”, “subjective health status”, and “treatment outcomes” across the domains of physiology, psychology, social relations, and environment.Conclusion: Our findings indicate that ODLs’ quality of life is associated with their health-related perceptions. Thus, to improve older adults’ quality of life, more attention should be paid to enhancing non-medical factors such as their health-related perceptions.Keywords: life barriers, subjective health status, treatment outcomes

Zixiang Wang,1,&ast; Chenyang Zhuang,1,&ast; Weixin Chen,1 Zefang Li,2 Juan Li,1,3 Hong Lin,1,3 Dong Jian1 1Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Orthopedics, Qianjiang Central Hospital of Chongqing, Chongqing, 409000, People’s Republic of China; 3Department of Orthopedics, Shanghai Geriatrics Medical Center, Fudan University, Shanghai, 201100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Lin; Dong JianDepartment of Orthopedics, Zhongshan Hospital, Fudan University, Fenglin Road 180, Shanghai, 200032, People’s Republic of ChinaTel +86-13636526656; +86-13916930859Email lin.hong1@zs-hospital.sh.cn; dong.jian@zs-hospital.sh.cnPurpose: The research aimed to compare the therapeutic effect of teriparatide (TPTD) and zoledronic acid (ZOL) therapy on bone formation and spinal fusion in patients with osteoporosis (OP) who underwent transforaminal lumbar interbody fusion (TLIF).Methods: On the basis of different anti-OP treatment options, the TPTD group was treated daily with TPTD (20 μg. ih. qd) for at least 6 months, while the ZOL group was treated with a single dose of ZOL (5 mg. ivgtt. st) postoperatively. The visual analogue scale (VAS), Oswestry Disability Index (ODI), bone mineral density (BMD), and concentration of bone turnover markers before, 6, and 12 months after surgery were evaluated. X-ray and three-dimensional computed tomography scans were performed at 6 and 12 months postoperatively to assess interbody fusion.Results: The number of patients in the TPTD and ZOL groups was 29 and 38 patients, respectively. The VAS and ODI scores in both groups were significantly reduced at 6 and 12 months after TLIF. Compared with that of baseline, the lumbar spine BMD of TPTD patients increased significantly from 0.716± 0.137 g/cm2 to 0.745± 0.124 g/cm2 and 0.795± 0.123 g/cm2 at 6 and 12 months, respectively, and was significantly higher than that of the ZOL group at 12 months (0.720± 0.128 g/cm2). The bone formation marker, P1NP, in the TPTD group increased significantly (145.48± 66.64 ng/mL and 119.55± 88.27 ng/mL) compared with baseline (44.67± 25.15 ng/mL) and in the ZOL group (28.82± 19.76 ng/mL and 29.94± 20.67 ng/mL) at 6 and 12 months, respectively. The fusion rates in the TPTD and ZOL groups were 57% and 45% at 6 months, without statistical significance. However, TPTD had a more statistically significant positive influence on fusion rate than ZOL at 12 months (86% vs 70%).Conclusion: TPTD was more efficient than ZOL in bone formation and spinal fusion in OP patients who underwent TLIF.Keywords: teriparatide, zoledronic acid, osteoporosis, TLIF

Huijing Lin,1,&ast; Alayi BoLatai,2,&ast; Na Wu1,3 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’ s Republic of China; 2Student Affairs Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’ s Republic of China; 3Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’ s Republic of China&ast;These authors contributed equally to this workCorrespondence: Na WuDepartment of Endocrinology, Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaEmail 3441535223@qq.comAbstract: Diabetic foot is a serious infection of the lower limbs. It is caused by diabetic neuropathy and vascular disease. It is also the primary cause of disability and death in patients with severe diabetes, so prompt treatment is essential for positive outcomes. The clinical use of nano-silver dressings can be considered to further optimize the treatment process and improve the treatment efficacy in diabetic foot patients. Nano-silver dressings have a larger contact surface and a stronger bactericidal effect when compared to ordinary silver dressings. Besides, it can be disinfected repeatedly to better wound infection control and promote wound healing. The current article discusses the pathogenesis of diabetic foot, diabetic foot dressing treatment, the application of nanotechnology in diabetic foot treatment, the efficacy evaluation of different dressings, and the practical prospects of adopting nanotechnology in the treatment of diabetic foot.Keywords: nano-silver, diabetic foot, antibacterial dressings