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Peng Chen,1 Dongsheng Lin,2 Chen Wang,2 Cuiwen Song,1 Wenjing Wang,1 Jinglian Qu,1 Zhibing Wu2 1Basic Medical School, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, People’s Republic of China; 2First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Zhibing WuDepartment of Neurology, First Clinical Medical College of Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 020 36585577Email wuzhibing2021@126.comBackground: Neuropathic pain (NP) is a syndrome of pain mediated by distinct pathophysiological processes, and current treatments are not fully satisfactory. Emodin is an effective component of Chinese traditional medicine and has an alleviating effect on NP, but the pharmacological mechanism is not clear.Methods: We used isobaric tags for relative and absolute quantitation (iTRAQ) technique integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify potential targets of emodin in a rat peripheral nerve chronic constriction injury (CCI) model.Results: A total of 177 differentially expressed proteins were identified among the sham group, CCI group, and emodin group, with a threshold of 1.2-fold change and a P value ≤ 0.05. Among them, 100 differentially expressed proteins (51 up-regulated and 49 down-regulated) were identified in the CCI group compared with sham group. Moreover, 108 differentially expressed proteins (65 up-regulated and 43 down-regulated) were identified in the emodin group with the CCI group as reference. The enrichment analysis of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed an important role of calcium signaling pathway, neurotransmitter regulation, and long-term potentiation (LTP) in emodin-treated CCI model. Real-time quantitative fluorescence PCR (qRT-PCR) and Western blot analysis revealed that emodin decreased expression of calcium signaling related proteins, including calmodulin (CaM) dependent protein kinase II (CaMK II), phospholipase Cβ 1 (PLCβ 1), protein kinase C (PKC), protein kinase C (PKA), and tropomyosin-related kinase B (TrkB), compared with the CCI group.Conclusion: Overall, these findings indicated that emodin might alleviate NP by regulating the calcium signaling pathway.Keywords: neuropathic pain, emodin, CCI, iTRAQ, KEGG

Tingting Yang,1,* Yanyan Huang,2,3,* Xinghui Li,1 Mengying Li,1 Suisui Ma,4 Guo Xuan,5 Yihua Jiang,5 Shuangyuan Sun,6 Yinghua Yang,7 Zhuochun Wu,1 Xiangyun Li,2 Ying Wang1,8 1School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2Department of Geriatrics, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Tian Qiao and Chrissy Chen Institute Clinic Translational Research Center, Shanghai, People’s Republic of China; 4Yuluo Management Consultation Co. Ltd of Shanghai, Shanghai, People’s Republic of China; 5Medicine-Mental Health Center of Minhang District/Minhang Branch, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 6Shanghai Municipal Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 7Shanghai Center for Clinical Laboratory, Shanghai, People’s Republic of China; 8Key Laboratory of Health Technology Assessment, National Health and Family Planning Commission of the People’s Republic of China, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Wang Email wangying1013@fudan.edu.cnXiangyun Li Email ccwlxy.cool@163.comBackground: China has the largest population of patients with dementia worldwide, no assessment of illiterate old population’s dementia knowledge, attitudes, stigma have been conducted so far in China.Aim: This study focused on the impact of education on knowledge, attitudes, and stigma related to dementia.Methods: The community-based sample used in this study was recruited using multi-stage random sampling from residents aged ≥ 60 years registered in Shanghai. We used the Geriatric Depression Scale (GDS-30) to identify depression, and the Ascertain Dementia 8 questionnaire (AD8) for evaluating participants’ cognitive impairment. Knowledge, Attitude, Belief, and Practice scale, Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM-PC) were used for measuring dementia knowledge, attitudes, stigma. We separated the population into illiterate and literate group, propensity score matching based on age, sex, depression, and cognitive impairment. We calculated the difference of knowledge, attitudes, and stigma related to dementia between illiterate and literate groups.Results: Two thousand five hundred and eighteen participants completed the survey. After propensity score matching, 186 pairs of matched participants left. The overall correct rate of dementia knowledge was 70.34%. The illiterate group had a lower percentage of correct answers for each knowledge item. The item “Dementia is not a disease, it is forgetfulness due to aging” had the lowest accuracy rate in both groups (38.71% vs. 50.54%, p=0.022). Illiterate older adults were less accepting of dementia than literate older adults. The majority of participants did not agree that: “There is no need to visit a doctor when older people have memory loss, difficulty communicating, or finding words” (56.99% vs. 68.28%). Illiterate older adults had higher scores for the items assessing stigma toward dementia than literate older adults.Conclusion: Dementia-related knowledge and attitudes among community-dwelling older adults in Shanghai may be related to literacy.Keywords: knowledge, attitudes, stigma, dementia, illiterate elderly

Zhuang Wu,1,* Hang Xu,2,* Sha Zhu,1 Ruxin Gu,1 Min Zhong,1 Xu Jiang,1 Bo Shen,1 Jun Zhu,1 Yang Pan,1 Jingde Dong,1 Jun Yan,1 Wenbin Zhang,3 Li Zhang1 1Department of Geriatric Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neurology, The Yancheng Clinical College of Xuzhou Medical University, Yancheng, People’s Republic of China; 3Department of Neurosurgery, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Zhang; Jun Yan Email neuro_zhangli@163.com; 2519002414@qq.comBackground and Purpose: Gait analysis and the effects of levodopa on the gait characteristics in Mild parkinsonian signs (MPS) are rarely published. The present research aimed to (1) analyze the gait characteristics in MPS; (2) explore the effects of levodopa on the gait performance of MPS.Methods: We enrolled 22 inpatients with MPS and 20 healthy control subjects (HC) from Nanjing Brain Hospital. The Unified Parkinson’s Disease Rating Scale was used to evaluate motor symptoms. Acute levodopa challenge test was performed to explore the effects of levodopa on the gait performance of MPS. The instrumented stand and walk test was conducted for each participant and the JiBuEn gait analysis system was used to collect gait data.Results: For spatiotemporal parameters: Compared with HC, the state before taking levodopa/benserazide in MPS group (meds-off) demonstrated a decrease in stride length (SL) (p≤ 0.001), an increase in SL variability (p≤ 0.001), and swing phase time variability (p=0.016). Compared with meds-off, the state after 1 hour of taking levodopa/benserazide in MPS group (meds-on) exhibited an increase in SL (p≤ 0.001), a decrease in SL variability (p≤ 0.001). For kinematic parameters: Compared with HC, meds-off demonstrated a decrease in heel strike angle (p=0.008), range of motion (ROM) of knee joint (p=0.011) and ROM of hip joint (p=0.007). Compared with meds-off, meds-on exhibited an increase in HS (p≤ 0.001). Bradykinesia and rigidity scores were significantly correlated with gait parameters.Conclusion: Although the clinical symptoms of the MPS group are mild, their gait damage is obvious and they exhibited a decreased SL and joints movement, and a more variable gait pattern. Levodopa had little effect on the gait performance of those individuals.Keywords: elderly, mild parkinsonian signs, gait, levodopa challenge test

Wencui Wan,1,* Zhen Wu,2,* Jia Lu,2,* Weiwei Wan,1 Jing Gao,3 Hongxia Su,4 Wei Zhu5 1Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Ear, Nose, and Throat, Changshu No. 2 People’s Hospital, Changshu, People’s Republic of China; 3Department of Ophthalmology, First Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, People’s Republic of China; 4Department of Rhinology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 5Department of Ophthalmology, Changshu No. 2 People’s Hospital, Changshu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongxia SuDepartment of Rhinology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaTel +86-137726129234Email hxs_ent@163.comWei ZhuDepartment of Ophthalmology, Changshu No. 2 People’s Hospital, No. 99, Xiannan Street, Changshu, Jiangsu, 215000, People’s Republic of ChinaTel +86-13776212565Email shzhuwei0722@163.comBackground: Retinal vein occlusion (RVO) was a vision-threatening retinal vascular disorder, however, the relationship between obstructive sleep apnea (OSA) and RVO risk remained unclear.Methods: A total of 45 RVO cases and 45 controls between April 2018 and April 2020 were included. All the participants underwent full-night polysomnography (PSG) and thus detected the severity of OSA. Besides, the relationship between the apnea–hypopnea index (AHI) and oxidative and inflammatory biomarkers, including 8-hydroxy-2 deoxyguanosine (8-OHdG), C-reactive protein (CRP), interleukin 1 beta (IL1β), interleukin 6 (IL6) and tumor necrosis factor alpha (TNFα) were detected. The incidences of macular edema (ME) and neovascular glaucoma (NVG) were detected in a three-months follow-up.Results: In this case–control study, it was found that OSA incidence was increased in the RVO cases comparing with the cataract controls. Advanced analyses about the RVO subtypes demonstrated that incidence of OSA was higher in the central RVO (CRVO) cases comparing with branch RVO (BRVO) cases. Plasma samples from OSA cases demonstrated relatively higher concentrations of oxidative stress parameters and inflammatory biomarkers, including 8-OHdG, CRP, IL1β, and IL6, in the RVO cases. Significant linear correlations between AHI and oxidative/inflammatory biomarkers were detected, and advanced analyses on the OSA subtypes demonstrated that these biomarkers were significantly higher in cases with later stages of OSA. In a three months follow-up, an impaired visual activity improvement rate and increased ME incidence in the OSA group among all the RVO cases were detected.Conclusion: OSA was related with an increased incidence of RVO. Besides, OSA would lead to increased oxidative and inflammatory biomarkers concentrations in the RVO cases. OSA could be used as a harmful prognostic factor of visual activity improvement and ME incidences. These findings highlighted the role of OSA in the development of RVO.Keywords: obstructive sleep apnea, retinal vein occlusion, risk factor, prognosis, oxidative stress

Yusi Gao, Fangfang Fan, Jia Jia, Yimeng Jiang, Danmei He, Zhongli Wu, Yong Huo, Jing Zhou, Yan Zhang Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jing ZhouDepartment of Cardiology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of ChinaTel +86-10-83575728Fax +86-10-66551383Email zhoujing123@yahoo.comIntroduction: Elevated heart rate is linked with poor prognosis and has been shown to accelerate the progress of atherosclerosis. However, the association between heart rate and new-onset PAD is unknown.Methods: A total of 3463 participants without PAD at baseline from a community-based cohort in Beijing were included and followed up for 2.3 years. PAD was defined as ankle–brachial index (ABI) ≤ 0.9. We used multivariate logistic regression models to investigate the association of heart rate and the risk of new-onset PAD.Results: Participants were 56.67 ± 8.54 years old, and 36.12% were men. The baseline ABI was 1.11 ± 0.08, and the incidence of new-onset PAD was 2.97%. Multivariate regression models, adjusted for sex, age, risk factor of atherosclerosis, medications, and baseline ABI, showed that heart rate was significantly associated with incidence of PAD (odds ratio [OR] = 1.22, 95% confidence interval [CI]: 1.03– 1.43, P = 0.020); every increase of 10 heart beats per minute (bpm) was associated with a 22% increase in the odds of developing new-onset PAD. Respondents in the higher-heart rate group (≥ 80 bpm) had an increased risk of new-onset PAD, compared with those in the lower-heart rate group (< 80 bpm) (OR = 1.73, 95% CI: 1.14– 2.63, P = 0.010). Subgroup analyses revealed no significant heterogeneity among the analyzed subgroups.Conclusion: Elevated heart rate was independently associated with the risk of new-onset PAD in a community-based population in Beijing. Heart rate management should be considered for the purpose of PAD prevention.Keywords: cohort studies, heart rate, peripheral arterial disease, ankle–brachial index

Xiaoliang Zeng,* Jihua Feng,* Yanli Yang, Ruzhi Zhao, Qiao Yu, Han Qin, Lile Wei, Pan Ji, Hongyuan Li, Zimeng Wu, Jianfeng Zhang Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zimeng Wu; Jianfeng ZhangThe Second Affiliated Hospital of Guangxi Medical University, No. 166 Daxuedong Road, Nanning, Guangxi, 530007, People’s Republic of ChinaTel +867713277166Fax +867713277285Email wzm19950214@126.com; drzhangjf@163.comObjective: Sepsis is a disease associated with high mortality. We performed bioinformatic analysis to identify key biomarkers associated with sepsis and septic shock.Methods: The top 20% of genes showing the greatest variance between sepsis and controls in the GSE13904 dataset (children) were screened by co-expression network analysis. The differentially expressed genes (DEGs) were identified through analyzing differential gene expression between sepsis patients and control in the GSE13904 (children) and GSE154918 (adult) data sets. Intersection analysis of module genes and DEGs was performed to identify common DEGs for enrichment analysis, protein-protein interaction network (PPI network) analysis, and Short Time-series Expression Miner (STEM) analysis. The PPI network genes were ranked by degree of connectivity, and the top 100 sepsis-associated genes were identified based on the area under the receiver operating characteristic curve (AUC). In addition, we evaluated differences in immune cell infiltration between sepsis patients and controls in children (GSE13904, GSE25504) and adults (GSE9960, GSE154918). Finally, we analyzed differences in DNA methylation levels between sepsis patients and controls in GSE138074 (adults).Results: The common genes were associated mainly with up-regulated inflammatory and metabolic responses, as well as down-regulated immune responses. Sepsis patients showed lower infiltration by most types of immune cells. Genes in the PPI network with AUC values greater than 0.9 in both GSE13904 (children) and GSE154918 (adults) were screened as key genes for diagnosis. These key genes (MAPK14, FGR, RHOG, LAT, PRKACB, UBE2Q2, ITK, IL2RB, and CD247) were also identified in STEM analysis to be progressively dysregulated across controls, sepsis patients and patients with septic shock. In addition, the expression of MAPK14, FGR, and CD247 was modified by methylation.Conclusion: This study identified several potential diagnostic genes and inflammatory and metabolic responses mechanisms associated with the development of sepsis.Keywords: sepsis, septic shock, bioinformatics, diagnosis, immunosuppression

Hailong Si,1 Huiling Wang,1 Haijuan Xiao,2 Yu Fang,1 Zhaoli Wu2 1First School of Clinical Medical, Shaanxi University of Traditional Chinese Medicine, Xianyang, 712000, People’s Republic of China; 2Department of Oncology, Affiliated Hospital of the Shaanxi University of Traditional Chinese Medicine, Xianyang, 712000, People’s Republic of ChinaCorrespondence: Zhaoli WuDepartment of Oncology, Affiliated Hospital of the Shaanxi University of Traditional Chinese Medicine, No. 2, Weiyang West Road, Xianyang, 712000, Shaanxi Province, People’s Republic of ChinaTel +86-29-32087707Email zb37jl9@163.comBackground: Celastrol is a potential anti-tumor agent in hepatocellular carcinoma (HCC). Identifying the molecular determinants of the anti-HCC effect of celastrol is still challenging. In this study, we undertook to associate circular RNAs (circRNAs) with the anti-HCC molecular determinants of celastrol.Methods: Cell colony formation, proliferation, migration, invasion and apoptosis were determined using the colony formation, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide (MTS), transwell and flow cytometry assays, respectively. The levels of circRNA slit guidance ligand 3 (circ_SLIT3), miR-223-3p and C-X-C motif chemokine receptor 4 (CXCR4) were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Ribonuclease R (RNase R) and actinomycin D assays were performed to assess the stability of circ_SLIT3. Targeted relationships among circ_SLIT3, miR-223-3p and CXCR4 were confirmed by the dual-luciferase reporter assay. In vivo assays were performed to detect the roles of celastrol and circ_SLIT3 on tumor growth in vivo.Results: Celastrol repressed HCC cell proliferation, migration, invasion, and enhanced apoptosis in vitro and suppressed tumor growth in vivo. Celastrol down-regulated circ_SLIT3 expression in HCC cells, and celastrol exerted an anti-tumor effect on HCC in vitro and in vivo by down-regulating circ_SLIT3. Mechanistically, circ_SLIT3 directly interacted with miR-223-3p, and circ_SLIT3 controlled CXCR4 expression by sponging miR-223-3p. Moreover, miR-223-3p was involved in the celastrol/circ_SLIT3-mediated regulation on HCC progression. Furthermore, celastrol exerted the anti-HCC effect in vitro through the miR-223-3p/CXCR4 axis.Conclusion: Our present work first identified the circ_SLIT3/miR-223-3p/CXCR4 axis as a novel mechanism of the anti-HCC effect of celastrol, providing a new insight into the involvement of circRNAs in the anti-tumor molecular determinants of celastrol.Keywords: hepatocellular carcinoma, celastrol, circ_SLIT3, miR-223-3p, CXCR4

Huining Zhou,1,* Zhengyi Wu,1,* Hui Wang,1 Wenya Yu,1 Jiaoling Huang,1 Liang Zhou,1 Dehua Yu,2 Tianchun Hou,1 Yipeng Lv,1 Chen Chen,3 Li Luo,4 Jianwei Shi,1,5 Zhaoxin Wang1,6 1School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of General Practice, Yangpu Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Jing‘an District Jiangning Road Community Health Service Center, Shanghai, People’s Republic of China; 4School of Public Health, Fudan University, Shanghai, People’s Republic of China; 5Shanghai General Practice and Community Health Development Research Center, Shanghai, People’s Republic of China; 6General Practice Center, Nanhai Hospital, Southern Medical University, Foshan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianwei Shi; Zhaoxin WangSchool of Public Health, Shanghai Jiaotong University School of Medicine, 227 South Chongqing Road, Shanghai 200025, People’s Republic of ChinaTel +86 188 1820 9852; +86 139 1853 7473Email shijianwei_amy@126.com; supercell002@sina.comPurpose: The purpose of this study was to use the hospital information system to analyze the cancer profile and compare demographics, hospitalization, status of surgery and treatment cost of various cancer categories based on the electronic health record (EHR) of outpatient children with tumors in Shanghai, China.Patients and Methods: Information was collected from 3834 inpatients aged 0– 18 who were diagnosed with malignant tumors in all 17 hospitals with pediatric wards in the Pudong New District of Shanghai from 2011 to 2016. All patients were classified according to the International Classification of Childhood Cancer-3 (ICCC-3). The chi-squared test was used to compare demographics, hospitalization information, status of surgery and treatment cost according to inpatients’ cancer category.Results: In both the malignant non-solid tumor and solid tumor groups, males and those aged 0– 4 years were the dominant groups. Lymphocytic leukemia was the most common cancer in all inpatients (n=994, 25.93%), and the acute myeloid leukemia had the longest length of stay of inpatients (median=26.00 days). In both the non-solid and solid tumor groups, patients who received only one type of surgery had an advantage. The highest proportion of patients who had undergone surgery was found in non-Hodgkin lymphoma patients. In terms of total cost, surgical cost and medicine cost, the expenditure of central nervous system tumor patients was the highest. Astrocytoma had the highest total cost.Conclusion: Leukemia is common in children with cancer in Pudong and should be given attention. Because the highest financial burden falls on patients with central nervous system tumors and acute myeloid leukemias, the government should take immediate and targeted measures for these cancers in particular.Keywords: malignant tumors, disease burden, demographics, hospitalization information, epidemiology

Zhen Wu,1 Wei Zhao,1 Zhen Yang,1 Yue Ming Wang,2 Yu Dai,1 Liang-An Chen1,2 1Respiratory Department of Chinese PLA General Hospital, Beijing, People’s Republic of China; 2School of Medicine, Nankai University, Tianjin, People’s Republic of ChinaCorrespondence: Liang-An Chen IMB 16th Floor, Room 16-104, 28 Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of ChinaTel +86 10-66936184Email chenliangan301@163.comPurpose: Molecular-based targeted therapy has improved life expectancy for advanced non-small cell lung cancer (NSCLC). However, it does not have to be inevitable that patients receiving third-generation EGFR-TKIs become drug resistant. EGFR C797S and MET amplification are common mechanisms of osimertinib. However, a large part of these potential drug mechanisms remains unknown, and further research is needed.Methods: Tumour and blood samples from forty advanced NSCLC patients were identified as acquired drug resistant to osimertinib. The NGS panel was applied to detect EGFR C797S and MET amplification in tumour tissues or plasma samples. Whole-exome sequencing was conducted in five pairs of tumour tissues obtained before osimertinib administration and after osimertinib resistance in patients without C797S/cMET amplification.Results: The overall C797S mutation rate was 20%, and MET amplification was detected in six out of sixteen C797S-negative samples. PDGFRA in the PI3K-AKT-mTOR signalling pathway, RASAL2, RIN3 and SOS2 in the RAS-Raf-ERK signalling pathway, PTK2 in the ERBB signalling pathway and ABCC1 and ABCB5 in the ABC membrane pump system were identified as candidate crucial genes of drug resistance to osimertinib.Conclusion: EGFR C797S mutation and MET amplification are leading mechanisms for osimertinib resistance in lung cancer. The crucial potential mutated genes defined in our present study may need further validation in a considerable number of lung cancer patients.Keywords: osimertinib, drug resistance, whole-exome sequencing, lung cancer, targeted therapy

Juliang He,* Jian Guan,* Shian Liao, Zhenjie Wu, Bin Liu, Hao Mo, Zhenchao Yuan Department of Bone and Soft Tissue Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hao Mo; Zhenchao Yuan Email mohaogxzlyy@163.com; yzccwhyzw@163.comPurpose: The long noncoding RNA CCDC144NL antisense RNA 1 (CCDC144NL-AS1) exhibits important functions in gastric cancer. In this study, we aimed to investigate the roles of CCDC144NL-AS1 in modulating the phenotype of osteosarcoma (OS) cells in vitro and in vivo and elucidate its underlying mechanisms.Methods: Reverse transcription quantitative polymerase chain reaction (PCR) was performed to determine the expression level of CCDC144NL-AS1 in OS tissues and cell lines. The proliferation, apoptosis, migration, and invasion in vitro as well as tumor growth in vivo were determined in OS cells using the Cell Counting Kit 8 assay, flow cytometric analysis, transwell migration and invasion assays, and xenograft experiments, respectively. Bioinformatics analysis was performed to identify the potential microRNA targets of CCDC144NL-AS1, which were subsequently confirmed using the luciferase reporter assay, RNA immunoprecipitation assay, reverse transcription quantitative PCR, Western blotting, and rescue experiments.Results: CCDC144NL-AS1 expression was upregulated in OS tissues and cell lines. Patients with OS who exhibited high CCDC144NL-AS1 expression had shorter overall survival than those who exhibited low CCDC144NL-AS1 expression. Functionally, interference in CCDC144NL-AS1 expression led to a notable decrease in the proliferation, migration, and invasion of OS cells and an increase in cell apoptosis in vitro. Furthermore, CCDC144NL-AS1 knockdown impaired OS tumor growth in vivo. Mechanistically, CCDC144NL-AS1 directly bound to miR-490-3p in OS cells, where it functioned as a molecular sponge and subsequently increased the expression of high-mobility group AT-hook 2 (HMGA2). Rescue experiments further demonstrated that miR-490-3p suppression or HMGA2 restoration abated CCDC144NL-AS1 deficiency-induced cancer-inhibitory actions in OS cells.Conclusion: CCDC144NL-AS1 exhibits pro-oncogenic roles in OS by functioning as a sponge for miR-490-3p and increasing HMGA2 expression. Our findings suggest that greater understanding of the CCDC144NL-AS1/miR-490-3p/HMGA2 pathway can provide useful information for OS diagnosis, prognosis, and therapy.Keywords: long noncoding RNA, microRNA, competitive endogenous RNA, high-mobility group AT-hook 2

Xuedong Li,1,2,* Xixi Lin,1,2,* Zuoxing Wu,3 Yuangang Su,1,2 Jiamin Liang,1,2 Runfeng Chen,1,2 Xue Yang,1,2 Lei Hou,4 Jinmin Zhao,1,5 Qian Liu,5 Feng Xu1,2,6 1Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 2Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 3School of Medicine, Xiamen University, Xiamen, Fujian 361102, People’s Republic of China; 4Department of Cardiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 5Research Centre for Regenerative Medicine, Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 6Department of Subject Planning Shanghai, Ninth People’s Hospital Shanghai, Jiaotong University School of Medicine, Shanghai 200011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng XuDepartment of Subject Planning Shanghai, Ninth People’s Hospital Shanghai, Jiaotong University School of Medicine, Shanghai, People’s Republic of ChinaEmail xufenghhou@163.comQian LiuResearch Centre for Regenerative Medicine, Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of ChinaEmail luoboqian@hotmail.comIntroduction: Osteoporosis is an osteolytic bone condition characterized by decreased bone strength and increased bone fragility. It is the result of elevated formation or activity of bone-resorbing osteoclasts. Although current therapeutic agents are efficacious against osteoclast-mediated bone loss, detrimental side effects preclude the long-term use of these agents. Pristimerin (PRI) is a naturally occurring quinone-methide triterpenoid that has been revealed to exert anti-inflammatory and anti-tumor effects via regulating various signaling cascades including NF-κB and MAPK activation.Methods: The bone marrow macrophages were used to confirm the anti-osteoclastic and anti-resorptive functions of PRI in vitro. An in vivo ovariectomy (OVX) model was applied to verify the function of PRI protecting bone loss.Results: PRI abolished the early activation of NF-κB and ERK MAPK signal cascades thereby thwarting the downstream expression of c-Fos and NFATc1, which prevented the production of mature osteoclasts. In vivo, PRI protects mice against ovariectomy (OVX)-mediated bone loss by diminishing osteoclast formation and bone resorptive activity.Conclusion: Our study shows that PRI demonstrates therapeutic potential in the effective treatment against osteoclast-induced osteolytic diseases like osteoporosis.Keywords: osteoporosis, osteoclast, pristimerin, ERK, NF-κB

Chunliang Shang,1 Yuan Li,1 Zhangxin Wu,1 Qin Han,1 Yuan Zhu,2 Tianhui He,1 Hongyan Guo1,3 1Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, People’s Republic of ChinaCorrespondence: Hongyan GuoDepartment of Obstetrics and Gynecology, Peking University Third Hospital, No. 49 Huayuan North Road, Haidian District, Beijing 100191, People’s Republic of ChinaTel +86-17301281996Fax +86 1082267842Email bysyghy@163.comBackground: To depict the prognostic landscape of gynecological cancers from the perspective of DNA methylation, alternative splicing (AS) and polyadenylation (APA) events and investigate their correlation with immune infiltrates.Methods: Methylation and RNA-seq data and corresponding clinical information regarding gynecologic cancers were used to explore the relationships between changes in DNA methylation, AS and APA events and gynecologic cancer prognosis. QRT-PCR and multiple bioinformatics tools were employed to construct a gene interaction network and explore immune infiltrates.Results: Only the mRNA levels of CIRBP and INPP5K were simultaneously significantly decreased in gynecologic cancers and negatively associated with overall survival, which verified by qrt-PCR. We also identified that CIRBP or INPP5K DNA methylation, AS and APA events are prognostic indicators of gynecologic cancers. The activation of T cells might be the main signaling pathway by which these genes modulate cancer progression. CIRBP/INPP5K expression is positively associated with immune infiltration and is a major risk factor of survival, especially among uterine corpus endometrial carcinoma (UCEC) patients.Conclusion: According to these findings, the DNA methylation, AS and APA events of CIRBP and INPP5K may serve as important prognostic biomarkers and targets in gynecological cancers by modulating T cell infiltration.Keywords: DNA methylation, alternative splicing, alternative polyadenylation, activation of T cells, immune infiltration

Jihua Feng,* Jielong Pang,* Dan He,* Zimeng Wu, Qian Li, Pan Ji, Cuiying He, Zhimei Zhong, Hongyuan Li, Jianfeng Zhang Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianfeng ZhangDepartment of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, People’s Republic of ChinaEmail drzhangjf@163.comPurpose: Early diagnosis of sepsis-induced acute respiratory distress syndrome (ARDS) is critical for effective treatment. We aimed to identify early stage biomarkers.Materials and Methods: Differentially expressed genes were identified in whole blood samples from patients with sepsis or ARDS based on the Gene Expression Omnibus (GEO) datasets GSE32707, GSE54514 and GSE10361. Functional enrichment analysis explored the biological characteristics of differentially expressed genes. Genes with high functional connectivity based on a protein-protein interaction network were marked as hub genes, which were validated using the GEO dataset GSE76293, and a gene set variation analysis index (GSVA) was assigned. Diagnostic and predictive ability of the hub genes were assessed by receiver operating characteristic (ROC) curve analysis. DNA methylation levels of hub genes were quantified using the GEO dataset GSE67530.Results: Forty-one differentially expressed genes were shared between sepsis-specific and ARDS-specific datasets. MAP2K2 and IRF7 functional activity was highly connected in sepsis-induced ARDS. Hub genes included RETN, MVP, DEFA4, CTSG, AZU1, FMNL1, RBBP7, POLD4, RIN3, IRF7. ROC curve analysis of the hub gene GSVA index showed good diagnostic ability in sepsis or ARDS. Among genes related to sepsis-induced ARDS, 17 were differentially methylated. Principal component analysis and heatmaps indicated that gene methylation patterns differed significantly between ARDS patients and controls.Conclusion: We identified a genetic profile specific to early-stage sepsis-induced ARDS. The abnormal expression of these genes may be caused by hypomethylation, which may serve as a biomarker for early diagnosis of ARDS.Keywords: acute respiratory distress syndrome, ARDS, sepsis-induced ARDS, hub genes, methylation, gene set variation analysis

Xiaonan Xu, Zimu Wu, Hongyan Qiu, Jun Wu Department of Neurology, Peking University Shenzhen Hospital, Shenzhen 518000, Guangdong Province, People’s Republic of ChinaCorrespondence: Jun Wu Email junwu_2000@126.comObjective: Brain microvascular endothelial cells (BMECs) are involved in brain vascular dysfunction in ischemic stroke. Abnormal expression of circular RNAs regulate physiological and pathophysiological processes in the central nervous system. The aim of the present study was to investigate profile circRNAs in human BMECs after oxygen glucose deprivation (OGD), which was an in vitro model of ischemic stroke, and find promising biomarkers in ischemic stroke.Methods: RNA sequencing (RNA-seq) technology was conducted to analyze the differential expression of circRNAs between BMECs after OGD and non-OGD treated BMECs. RT-qPCR, cell proliferation, cell apoptosis and dual-luciferase assay, and so on, were used to investigate the functions and molecular mechanisms of hsa_circ_0001360 (named circPHC3 in this study) in ischemic stroke.Results: CircPHC3 was highly expressed in human BMECs after OGD. Knockdown of circPHC3 inhibited cell death and apoptosis in human BMECs treated with OGD. Mechanistically, circPHC3 acted as miR-455-5p sponge to activate TRAF3 to promote cell death and apoptosis in human BMECs after OGD.Conclusion: In short, circPHC3 promotes cell death and apoptosis in ischemic stroke in vitro model, which might be a novel molecular target for acute cerebrovascular protection.Keywords: ischemic stroke, circPHC3, TRAF3, miR-455-5p

Shujuan Wang,1,* Yu Zhang,1,* Yajun Liu,2 Ruyue Zheng,1 Zhenzhen Wu,1 Yi Fan,1 Mengya Li,1 Menglin Li,1 Tao Li,1 Yafei Li,1 Zhongxing Jiang,1 Chong Wang,1 Yanfang Liu1 1Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Orthopaedics, Brown University, Warren Alpert Medical School/Rhode Island Hospital, Rhode Island, RI, USA*These authors contributed equally to this workCorrespondence: Yanfang Liu; Chong WangDepartment of Hematology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou 450052, People’s Republic of ChinaEmail fccliuyf1@zzu.edu.cn; fccwangc@zzu.edu.cnBackground: Relapse is a major obstacle in the treatment of acute myeloid leukemia (AML). Refinement of risk stratification may aid the identification of patients who are likely to relapse. Abnormal cysteine and glycine-rich protein 2 (CSRP2) has been implicated in various cancers, but its function remains unclear. The purpose of this study was to explore the role of CSRP2 in predicting adult AML recurrence.Methods: RT-PCR was used to detect the expression of CSRP2 in 193 newly diagnosed adult AML patients and 44 healthy controls. The competitive risk model was used to calculate the cumulative incidence of relapse rate (CIR), Kaplan–Meier to calculate the relapse-free survival rate (RFS), and the Cox regression model to perform multivariate analysis. Viral transfection was used to construct AML cell lines with stable knockdown of CSRP2, CCK8 to detect proliferation and drug resistance, flow cytometry to detect cell cycle and apoptosis, and Western blot to detect key molecules in signaling pathways.Results: CSRP2 transcript levels were higher in 193 adult AML compared with 44 healthy controls. In 149 patients who achieved complete remission, those with high CSRP2 transcript levels displayed a lower 2-year CIR and higher 2-year RFS, especially when receiving only chemotherapy. In multivariate analysis, a high CSRP2 transcript level was independently associated with a better RFS. Knockdown of CSRP2 promoted proliferation and cell cycle progression, and reduced chemosensitivity. Western blot analysis showed upregulation of p-AKT and p-CREB in CSRP2-knockdown AML cell lines. Inhibition assays suggested these two signaling pathways participated in the CSRP2-mediated proliferation effects in AML cell lines.Conclusion: In summary, CSRP2 correlates with relapse in adult AML. Down-regulation of CSRP2 could promote the proliferation of AML cell lines by regulating the AKT and CREB signaling pathways. Therefore, CSRP2 may provide prognostic significance and potential therapeutic targets in the management of AML.Keywords: acute myeloid leukemia, relapse, cysteine and glycine-rich protein 2, proliferation, cAMP-regulatory element-binding protein

Si-Lan Gu,1,* Yiwen Gong,1,* Jiaying Zhang,1,* Yunbo Chen,1 Zhengjie Wu,1 Qiaomai Xu,1 Yunhui Fang,1 Jingxia Wang,1 Ling-Ling Tang2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, People’s Republic of China; 2Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Shulan International Medical College, Hangzhou 310000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling-Ling TangShulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Shulan International Medical College, Hangzhou 310000, People’s Republic of ChinaEmail 1196040@zju.edu.cnBackground: Antibiotics play an important role in the treatment of infectious diseases. However, the overuse of antibiotics increases the spread of drug-resistant bacteria and causes dysbiosis of the intestinal microbiota. Few studies have addressed the longitudinal effects of antibiotics on the microbiome and host immunity.Materials and Methods: In this study, the short-term effect of fluoroquinolone (levofloxacin) and β-lactam antibiotics (meropenem, cefoperazone/sulbactam, and aztreonam) on the gut microbiota of mice was evaluated by 16S rRNA gene sequencing. The susceptibility of Bifidobacterium longum, Lactobacillus lactis, Enterococcus faecium, and Clostridium butyricum to these antimicrobial agents was assessed using the disc diffusion method.Results: Our results showed that 4-day antibiotic exposure significantly reduced the alpha and beta diversity of gut bacteria and increased serum inflammatory cytokines, and these changes persisted long after antibiotic withdrawal and did not return to pre-treatment levels. Nonetheless, the bacterial community composition tended to return to pre-treatment levels after discontinuing treatment. The tested probiotic strains were resistant to aztreonam but were sensitive to meropenem and cefoperazone/sulbactam.Conclusion: Short-term antibiotic treatment led to significant changes in the intestinal flora with a tendency to recover. The antibiotics had different effects on the intestinal microbial community and probiotic strains. This study provides guidance for the concomitant use of probiotics and antibiotics, and the results emphasize the importance of using broad-spectrum antibiotics responsibly to prevent the long-term disruption of the native microbiota.Keywords: antibiotics, gut microbiota, 16S rRNA gene sequencing, probiotics

Li Zhang,1,* Zhijie Ma,2 Zhe Wu,3 Mu Jin,1 Lixin An,1 Fushan Xue1,* 1Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, People’s Republic of China; 2Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University, Beijing 100012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Zhang; Fushan XueDepartment of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong’an Road, Xicheng District, Beijing 100050, People’s Republic of ChinaEmail zhangli8828@163.com; xuefushan@aliyun.comBackground: Depression is a prevalent and complex psychiatric disorder with high incidence in patients with chronic pain. The underlying pathogenesis of chronic pain-induced depression is complicated and remains largely unclear. An integrated analysis of endogenous substance-related metabolisms would help to understand the molecular mechanism of chronic pain-induced depression. Curcumin was reported to exert various health benefits, such as anti-depression, antioxidant, antineoplastic, analgesia, and anti-inflammation.Objective: The aim of this study was to analyze the biomarkers related to depression in serum and to evaluate the anti-depression properties of curcumin in a chronic pain-induced depression model of rats.Design: This is a randomized, controlled experiment.Setting: This study was conducted at the Experimental Animal Center, Beijing Friendship Hospital, Capital Medical University.Methods: Trigeminal neuralgia (TN) was produced by injecting 4 μL, 10% cobra venom saline solution into the infraorbital nerve (ION). Curcumin was administered by gavage twice a day from post-operation day (POD) 15 to POD 42. Mechanical allodynia was assessed using von Frey filaments. Sucrose preference and forced swimming tests were performed to evaluate depression-like behaviors. The metabolomics analysis was preceded by LCMS-IT-TOF and multivariate statistical methods for sample detection and biomarker screening.Results: Cobra venom intra-ION injection led to chronic mechanical allodynia, reduced sucrose preference, and prolonged immobility during forced swimming. Curcumin treatment alleviated chronic mechanical allodynia, regained sucrose preference, and reduced immobility time. Differential analysis identified 30 potential metabolites changed under TN condition. The integrated analyses further revealed two major metabolic changes by comparing the serums from sham operated rats, TN rats, and TN rats treated with curcumin: 1) ether lipid metabolism; and 2) glycerophospholipid metabolism, and suggested that curcumin may improve chronic pain-induced depression by regulating these two types of lipid metabolisms.Conclusion: Ether lipid and glycerophospholipid metabolism might be two of the pathways with the most potential related to chronic pain induced-depression; and curcumin could alleviate chronic pain induced-depression by modulating these two pathways. These results provide further insights into the mechanisms of chronic pain-induced depression and may help to identify potential targets for anti-depression properties of curcumin.Keywords: curcumin, depression, chronic pain, trigeminal neuralgia, metabolomics

Zhiyuan Wu,1,* Yongqin Yu,1,* Lanyan Fu,2 Hanran Mai,2 Li Huang,1 Di Che,2 Jianping Tao,1 Xiaoqiong Gu2– 4 1Department of Pediatric Intensive Care Unit, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, People’s Republic of China; 2Department of Clinical Biological Resource Bank, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, People’s Republic of China; 3Department of Blood Transfusion, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, People’s Republic of China; 4Department of Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoqiong Gu; Jianping Tao Email guxiaoqiong@gwcmc.org; golou6354@163.comBackground: Sepsis in children is one of the main causes of death in pediatric intensive care units (PICUs); however, the pathogenesis of sepsis is not fully clear. Previous studies revealed that many genetic variations were related to sepsis susceptibility. A long non-coding RNA SOX2 overlapping transcript (SOX2OT) may play a role in mitochondrial homeostasis and antioxidative activity, but the relationship between the lncRNA SOX2OT polymorphism and sepsis susceptibility has not been reported.Methods: In this study, 474 pediatric sepsis patients and 678 healthy controls were recruited from southern China. After genotyping, the strength of the associations was evaluated through odds ratios (ORs) and 95% confidence intervals (CIs).Results: The SOX2OT rs9839776 T allele was associated with decreased susceptibility to sepsis in southern Chinese children (TT/CT vs CC adjusted OR = 0.778, 95% CI = 0.610– 0.992; P = 0.0431). Moreover, the difference in susceptibility was greater in children of age > 60 months (adjusted OR = 0.458, 95% CI = 0.234– 0.896; P = 0.0225), survivors (adjusted OR = 0.758, 95% CI = 0.585– 0.972; P = 0.0358), males (adjusted OR = 0.655, 95% CI = 0.479– 0.894; P = 0.0077) and the sepsis subgroup (adjusted OR = 0.548, 95% CI = 0.343– 0.876; P = 0.0120).Conclusion: The rs9839776 T allele may contribute to decreased sepsis risk in Chinese children. Future studies with a larger sample size are needed to verify these results.Keywords: sepsis, SOX2OT, rs9839776, susceptibility, polymorphism

Xuemeng Dong,1 Zehao Wu,1 Xiuping Li,1 Liyan Xiao,1 Man Yang,1,2 Yang Li,1,2 Junchao Duan,1,2 Zhiwei Sun1,2 1School of Public Health, Capital Medical University, Beijing 100069, People’s Republic of China; 2Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, People’s Republic of ChinaCorrespondence: Zhiwei Sun; Yang LiBeijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, People’s Republic of ChinaTel/Fax +86 010 83911507; +86 010 83911868Email zwsun@ccmu.edu.cn; li_yang@ccmu.edu.cnAbstract: With the increasing production and application of engineered amorphous silica nanoparticles (aSiNPs), people have more opportunities to be exposed to aSiNPs. However, the knowledge of its adverse health effects and related mechanisms is still limited, compared with the well-studied crystalline micron-sized silica. Since small differences in the physical–chemical properties of nanoparticles could cause significant differences in the toxic effect, it is important to distinguish how these variations influence the outcoming toxicity. Notably, particle size, as one of the essential characterizations of aSiNPs, is relevant to its biological activities. Thus, the aim of this systematic review was to summarize the relationship between the particle size of aSiNPs and its adverse biological effects. In order to avoid the influence of complicated in vivo experimental conditions on the toxic outcome, only in vitro toxicity studies which reported on the cytotoxic effect of different sizes aSiNPs were included. After the systematic literature retrieval, selection, and quality assessment process, 76 eligible scientific papers were finally included in this review. There were 76% of the studies that concluded a size-dependent cytotoxicity of aSiNPs, in which smaller-sized aSiNPs possessed greater toxicity. However, this trend could be modified by certain influence factors, such as the synthetic method of aSiNPs, particle aggregation state in cell culture medium, toxicity endpoint detection method, and some other experimental conditions. The effects of these influence factors on the size-dependent cytotoxicity of aSiNPs were also discussed in detail in the present review.Keywords: silica nanoparticles, particle size, cytotoxicity, cell death, nanotoxicology, influence factors

Chenglong Zhao,* Yao Wang,* Xiaopan Cai,* Wei Xu,* Dongsheng Wang, Ting Wang, Qi Jia, Haiyi Gong, Haitao Sun, Zhipeng Wu, Jianru Xiao Spine Tumor Center, Department of Orthopedic Oncology, Changzheng Hospital, Navy Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianru Xiao; Zhipeng WuSpine Tumor Center, Department of Orthopedic Oncology, Changzheng Hospital, Navy Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai, People’s Republic of ChinaTel +86-21-81886843Fax +86-21-63520020Email cz_xiaojianru@163.com; eaglewzp@163.comBackground: Surgery remains the mainstay of treatment for breast cancer spinal metastasis (BCSM) to relieve symptoms and improve the quality of life of BCSM patients. Therefore, it is important to effectively predict the prognosis of patients to determine whether they can undergo surgical operation. However, the prevalent methods for prognosis evaluation lack specificity and sensitivity for indicated malignancies like breast cancer because they are built on a relatively small number of heterogeneous types of primary tumors. The aim of the present study was to explore a novel predictive model based on the clinical, pathological and blood parameters obtained from BCSM patients before they received surgical intervention.Methods: Altogether, 144 patients were included in this study. Univariate and multivariate analyses were performed to investigate the significance of preoperative parameters and identify independent factors for prognostic prediction of BCSM. A nomogram for survival prediction was then established and validated. Time-dependent ROC (TDROC) curves were graphed to evaluate the accuracy of the novel model vs other scoring systems including Tomita Score, revised Tokuhashi Score, modified Bauer Score and New England Spinal Metastasis Score. P values < 0.05 were considered statistically significant.Results: Independent factors, including preoperative postmenopausal (P=0.034), visceral metastasIs (P=0.021), preoperative Frankel Score (P=0.001), estrogen receptor status (P=0.014), platelet-to-lymphocyte ratio (P=0.012), lymphocyte-monocyte ratio (P< 0.001) and albumin-globulin ratio (P=0.017), were selected into the nomogram model with the C-index of 0.834 (95% CI, 0.789– 0.890). TDROC curves showed that the Changzheng Hospital (CZ) Score system had the best performance and exhibited the largest IAUC value in comparison with the other scoring systems.Conclusion: We constructed a nomogram model known as CZ Score based on the significant factors to predict the prognosis for BCSM patients. The result showed that CZ Score had a better value for prognostic evaluation and surgical decision-making as compared with the other scoring systems.Keywords: breast cancer, spine metastases, nomogram, scoring system, prognosis

Yanhong Wang,1,* Yang Mi,2,* Jihua Tian,1,* Xi Qiao,3 Xiaole Su,3 Jing Kang,1 Zhijing Wu,1 Guiqing Wang,1 Xiaoshuang Zhou,4 Yun Zhou,4 Rongshan Li4 1Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Urology, Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital, Taiyuan, Shanxi, People’s Republic of China; 3Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 4Department of Nephrology, The Affiliated People’s Hospital of Shanxi Medical University, Shanxi Provincial People’s Hospital, Shanxi Kidney Disease Institute, Taiyuan, Shanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun ZhouDepartment of Nephrology, The Affiliated People’s Hospital of Shanxi Medical University, Shanxi Provincial People’s Hospital, No. 29 Shuang Ta East Street, Taiyuan, Shanxi 030012, People’s Republic of ChinaEmail zhouyun_sx@163.comRongshan LiDepartment of Nephrology, The Affiliated People’s Hospital of Shanxi Medical University, Shanxi Provincial People’s Hospital, No. 29 Shuang Ta East Street, Taiyuan 030012, People’s Republic of ChinaEmail rongshanli13@163.comBackground: Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and increases the risk of subsequently developing chronic kidney disease. Angiogenesis has been shown to play an important role in reducing renal injury after ischemia reperfusion. In this study, we investigated whether IMD could reduce renal IRI by promoting angiogenesis.Methods: The kidneys of Wistar rats were subjected to 45 min of warm ischemia followed by 24 h of reperfusion. IMD was overexpressed in vivo using the vector pcDNA3.1-IMD transfected by an ultrasound-mediated system. The renal injury after ischemia reperfusion was assessed by detection of the serum creatinine concentration and histologic examinations of renal tissues stained by PAS and H&E. Real-time PCR and Western blotting were used to determine the mRNA and protein levels, respectively. Histological examinations were used to assess the expression of CD31, MMP2, MMP9, ET-1, VEGF and VEGFR2 in tissues.Results: Renal function and renal histological damage were significantly ameliorated in IMD-transfected rats after ischemia reperfusion. Compared to the IRI, IMD significantly promoted angiogenesis. IMD also upregulated the protein and mRNA expression levels of VEGF and VEGFR2 and downregulated the expression level of MMP2, MMP9 and ET-1.Conclusion: IMD could protect the kidney after renal ischemia-reperfusion injury by promoting angiogenesis and reducing the destruction of the perivascular matrix.Keywords: intermedin, ischemia-reperfusion injury, kidney, angiogenesis, VEGF, VEGFR2, MMP2, MMP9, ET-1

Hang Xue, Ziyi Wu, Jiaxin Yao, Anqi Zhao, Lanlan Zheng, Xiao Yin, Fang Wang, Ping Zhao Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang 110004, People’s Republic of ChinaCorrespondence: Ping ZhaoDepartment of Anesthesiology, Shengjing Hospital, China Medical University, 36 Sanhao Street, Shenyang, People’s Republic of China, 110004 Tel +86-18940258971Fax + 86-24-23269477Email zhaoping_sj@163.comPurpose: The physiologic transition from a fetus to a neonate is composed of a series of complex processes that include changes in cerebral tissue oxygenation saturation (cSO2). Monitoring this process is of great importance. This study aimed to define the cSO2 reference interval in neonates without medical support, extending the measurements until 1 hour after birth, and to determine the incidence of abnormally low or high regional cerebral oxygenation during the neonatal transition.Patients and Methods: A total of 418 neonates delivered by cesarean section were enrolled. Near-infrared spectroscopy was used to monitor cerebral oxygenation.Results: We found that cSO2 of the non-oxygen-inhaled intrathecal anesthesia in neonates without medical support increased from about 49.0% in the second minute. Most of them reached cSO2 relative stabilization at 55.7– 81.0% between 7 and 8 minutes after birth. One hour after birth, newborn cSO2 was maintained at 78.0– 87.0%. The low cSO2 rate among babies born under intrathecal anesthesia with and without maternal oxygen inhalation during cesarean sections was approximately 4.5% and 9.0%, respectively.Conclusion: We reported the trend in cSO2 from 2 minutes after birth to 1 hour in the neonatal nursing room and determined the incidence of abnormal regional cSO2 during this neonatal transition period. Anesthesiologists should pay special attention to the risk of cSO2 abnormalities in newborns when managing pregnant women with comorbidities.Keywords: cerebral oxygenation saturation, transitional period after birth, cesarean section, anesthetic monitoring

Shixue Chen,1,2,* Ziwei Huang,2,3,* Wangping Jia,1,4,* Haitao Tao,2 Sujie Zhang,2 Junxun Ma,2 Zhefeng Liu,2 Jinliang Wang,2 Lijie Wang,2 Pengfei Cui,1,2 Zhibo Zhang,1,2 Di Huang,2,3 Zhaozhen Wu,2,3 Xuan Zheng,1,2 Yi Hu2 1Department of Graduate Administration, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Medical Oncology, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3School of Medicine, Nankai University, Tianjin, People’s Republic of China; 4Institute of Geriatrics, Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatrics Diseases, Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi HuDepartment of Medical Oncology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian, Beijing, People’s Republic of ChinaEmail huyi0401301@sina.comPurpose: At present, there are no validated biomarkers that can predict whether patients with advanced hepatocellular carcinoma (aHCC) are likely to benefit from anti-PD-1 therapy. We aimed to determine whether lung immune prognostic index (LIPI) is associated with outcomes in patients with aHCC treated with PD-1 inhibitors.Patients and Methods: Patients undergoing initial treatment with PD-1 inhibitors for aHCC at a single center from January 1, 2015 to August 31, 2019 were included. The patients were stratified according to pretreatment LIPI based on a derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) ≥ 3 and a lactate dehydrogenase (LDH) level ≥ the upper limit of normal (ULN). Kaplan–Meier analysis and the Log rank test were used to calculate and compare survival between good LIPI and intermediate/poor LIPI scores. The prognostic values of LIPI for survival and disease control rate were evaluated using Cox proportional hazard and logistic regression models, respectively.Results: Of the 108 study patients, 53 (49%) had a good LIPI (dNLR < 3 and LDH normal) and 55 (51%) had intermediate/poor LIPI (dNLR ≥ 3 or/and LDH ≥ ULN). With a median follow-up of 12.4 months, intermediate/poor LIPI was independently associated with shorter overall survival (OS) (hazard ratio [HR] 4.00; 95% CI, 2.00– 8.03) and progression-free survival (PFS) (HR 2.65; 95% CI, 1.61– 4.37). The median OS for good and intermediate/poor LIPI was not reached and was 13.7 (95% CI, 8.2– 19.1) months, respectively, and the median PFS was 10.9 (95% CI, 8.9– 12.9) and 4.0 (95% CI, 2.2– 5.8) months (both P < 0.001), respectively.Conclusion: Pretreatment LIPI combined with a dNLR ≥ 3 and/or LDH ≥ ULN is associated with poor outcomes in patients with aHCC treated with PD-1 inhibitors. Further validation in large, prospective studies are warranted.Keywords: PD-1 inhibitor, hepatocellular carcinoma, biomarker, LIPI, dNLR, LDH

Zhuang Wu,1 Min Zhong,1 Xu Jiang,1 Bo Shen,1 Jun Zhu,1 Yang Pan,1 Jingde Dong,1 Jun Yan,1 Pingyi Xu,2 Wenbin Zhang,3 Yang Gao,4 Li Zhang1 1Department of Geriatric Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neurology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Neurosurgery, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Computer Science and Technology, Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Li Zhang Email neuro_zhangli@163.comPurpose: Gait impairment is a common clinical symptom of patients with Parkinson’s disease (PD). Detecting specific gait parameters’ changes in order to guide clinical intervention is at present lacking. The present study aimed to (1) quantify gait impairments in different PD subtypes and (2) explore whether the results of quantitative gait analysis are beneficial to clinical treatment.Patients and Methods: We enrolled 86 patients with PD (48 men, and 38 women) from the Department of Geriatrics of the Affiliated Brain Hospital of Nanjing Medical University. Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn-Yahr Scale were used to evaluate the motor symptoms of PD. All patients stopped anti-Parkinsonian medication for 24 hours (72 hours for controlled release medicine). The patients were divided into two subtypes, namely, postural instability gait difficulty (PIGD; n=56) and tremor dominant (TD; n=30) subtypes according to UPDRS. All patients completed the instrumented stand and walk test, and a set of JiBuEn gait analysis system was used in gait data collection.Results: We observed a shorter stride length (p=0.021), a longer stride time (p=0.036), a faster cadence (p=0.036), and a more variable stride length (p=0.012) in the PIGD group compared with the TD group. In addition, compared with the TD group, we found that the toe-off angle (p=0.005) and the range of motion of ankle joint (p=0.009) decreased in the PIGD group.Conclusion: Our study demonstrated that the gait performance of patients with PIGD is worse than those with TD from the perspective of quantitative gait analysis. We extended previous research and found the PIGD group exhibited severe gait impairments in some specific spatiotemporal and kinematic gait parameters. The different manifestations of these gait impairments may guide in choosing appropriate treatment of patients with different PD subtypes.Keywords: Parkinson’s disease, postural instability gait difficulty, tremor, wearable sensors, gait

Di Wu,1 Lin Kang,2 Jingjing Tian,2 Yuanhao Wu,2 Jieying Liu,2 Zhengyao Li,1 Xiangdong Wu,1 Yue Huang,1 Bo Gao,3 Hai Wang,1 Zhihong Wu,2,4 Guixing Qiu1 1Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 2Medical Science Research Center (MRC), Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 3Umibio (Shanghai) Co. Ltd, Shanghai 201210, People’s Republic of China; 4Beijing Key Laboratory for Genetic Research of Bone and Joint Disease, Beijing 100730, People’s Republic of ChinaCorrespondence: Hai WangDepartment of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Beijing 100730, People’s Republic of ChinaEmail wanghai907@hotmail.comZhihong WuMedical Science Research Center (MRC), Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Beijing 100730, People’s Republic of ChinaEmail wuzh3000@126.comBackground: Both magnetic nanoparticles (MNPs) and exosomes derived from bone mesenchymal stem cells (BMSC-Exos) have been reported to improve wound healing. In this study, novel exosomes (mag-BMSC-Exos) would be fabricated from BMSCs with the stimulation of MNPs and a static magnetic field (SMF) to further enhance wound repair.Methods: Mag-BMSC-Exos, namely, exosomes derived from BMSCs preconditioned with Fe3O4 nanoparticles and a SMF, together with BMSC-Exos were both first isolated by ultracentrifugation, respectively. Afterwards, we conducted in vitro experiments, including scratch wound assays, transwell assays, and tube formation assays, and established an in vivo wound healing model. The miRNA expression profiles were compared between BMSC-Exos and mag-BMSC-Exos to detect the potential mechanism of improving wound healing. At last, the function of exosomal miR-21-5p during wound healing was confirmed by utilizing a series of gain- and loss-of-function experiments in vitro.Results: The optimal working magnetic condition was 50 μg/mL Fe3O4 nanoparticles combined with 100 mT SMF. In vitro, mag-BMSC-Exo administration promoted proliferation, migration and angiogenesis to a greater extent than BMSC-Exo administration. Local transplantation of mag-BMSC-Exos into rat skin wounds resulted in accelerated wound closure, narrower scar widths and enhanced angiogenesis compared with BMSC-Exo transplantation. Notably, miR-21-5p was found to be highly enriched in mag-BMSC-Exos and served as a critical mediator in mag-BMSC-Exo-induced regulatory effects through inhibition of SPRY2 and activation of the PI3K/AKT and ERK1/2 signaling pathways.Conclusion: Mag-BMSC-Exos can further enhance wound healing than BMSC-Exos by improving angiogenesis and fibroblast function, and miR-21-5p upregulation in mag-BMSC-Exos might be the potential mechanism. This work offers an effective and promising protocol to improve wound healing in clinic.Keywords: exosomes, wound healing, miR-21-5p, angiogenesis, fibroblast function

linbin Lu,1,* Yan Zhang,1,* Peichan Zheng,2,* Zhixian Wu,3 Xuewen Wang,1 Yaying Chen,1 Xiong Chen1 1Department of Oncology, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzong Clinical College of Fujian Medical University, Fuzhou, Fujian 350025, People’s Republic of China; 2Fujian Center for Safety Evaluation of New Drug, Fujian Medical University, Fuzhou, Fujian 350122, People’s Republic of China; 3Department of Hepatobiliary, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzong Clinical College of Fujian Medical University, Fuzhou, Fujian 350025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiong ChenDepartment of Oncology, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzong Clinical College of Fujian Medical University, 156 Xierhuan Northern Road, Fuzhou, Fujian 350025, People’s Republic of ChinaTel +86 1-216-612-2438Fax +86-591-24937089Email cxiongzpc@fjmu.edu.cnBackground: Platelet count (PLT) has been proved as an essential biomarker for the survival of hepatocellular carcinoma (HCC). However, the prognostic value of PLT change (ΔPLT) is still uncertain. The aim of this study was to explore the relationship between ΔPLT and HCC survival after transarterial chemoembolization (TACE) treatment.Methods: Cox proportional hazard regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for HCC. The non-linear relationship between ΔPLT and OS was estimated through a restricted cubic spline regression analysis, and a two-piece-wise Cox proportional hazard model was further performed to calculate the threshold effect.Results: A total of 597 HCC patients treated with TACE were selected for the secondary analysis. Compared with the ΔPLT within ± 20 (× 109/L), ΔPLT≥ 20 (× 109/L) was significantly associated with an 64% increase in risk of death (HR, 1.64; 95% CI: 1.21 to 2.22) after adjustment for confounding variables, but the association was not significant in the group of ΔPLT≤-20 (HR, 1.23; 95% CI: 0.92 to 1.63). We also found a U-shape relationship between ΔPLT and HCC survival at the turning point of ΔPLT as 0 (20× 109/L). The HR for the death was 1.12 (95% CI: 1.06, 1.18) with ΔPLT≥ 0 (20× 109/L) while 0.95 (95% CI: 0.92, 0.98) with ΔPLT< 0 (20× 109/L). After potential confounding factors were adjusted, the non-linear relationship between ΔPLT and OS was still significant (P=0.013). Besides, ΔPLT≥ 20 (× 109/L) was associated with new lesions (OR, 2.74; 95% CI: 1.38 to 5.45).Conclusion: Elevated PLT was associated with poor overall survival of HCC patients after TACE treatment.Keywords: hepatocellular carcinoma, transarterial chemoembolization, platelet count, prognosis, real-world study

Guofeng Xiong,1,2 Jiaming Chen,1 Zhen Wu,1 Shizhi He,1 Meng Lian,1 Jugao Fang1 1Department of Otorhinolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People’s Republic of China; 2Department of Otolaryngology, Head and Neck Surgery, Wenzhou Central Hospital, Wenzhou 325000, People’s Republic of ChinaCorrespondence: Meng Lian; Jugao Fang Department of OtorhinolaryngologyHead and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, No. 8 Chongwenmen Inner Street, Dongcheng District (East District), Beijing 100730, People’s Republic of ChinaTel/Fax +86-010-58266699Email lianmeng_3@163.com; jugaofang03162@163.comBackground: Long non-coding RNA (lncRNA) LUCAT1 has recently been recognized as an oncogene in several malignancies. This study was launched to probe its role in thyroid carcinoma (TC) development and the implicated molecules.Methods: LUCAT1 expression in TC cell lines and in normal thyroid follicular epithelial cell line Nthy-ori3-1 was determined by RT-qPCR. Binding relationships between LUCAT1 and microRNA (miR)-493, and between miR-493 and a disintegrin and metalloproteinase-10 (ADAM10) were predicted on a bioinformatics system and then validated through luciferase reporter gene assays. Expression of miR-493 and ADAM10 in TC cells was determined. Gain- and loss-of functions of LUCAT1, miR-493 and ADAM10 were performed to explore their influences on the behaviors of TC cells. Xenograft tumors were induced in nude mice for in vivo studies.Results: LUCAT1 and ADAM10 were highly expressed, while miR-493 was poorly expressed in TC cell lines. LUCAT1 served as a miR-493 sponge to upregulate ADAM10 expression. Silencing of LUCAT1 discouraged proliferation, invasion, and migration but triggered apoptosis of TC cells. By contrast, these changes were abrogated by further miR-493 inhibition or ADAM10 upregulation. The in vitro experiment results were reproduced in vivo. In addition, miR-493 inhibition or ADAM10 overexpression was found to increase the phosphorylation of STAT3 in cells.Conclusion: This study evidenced that LUCAT1 increases ADAM10 expression through sequestering miR-493, leading to JAK-STAT activation and TC cell growth and metastasis. LUCAT1 and ADAM10 may serve as therapeutic targets for TC treatment.Keywords: long non-coding RNA LUCAT1, microRNA-493, ADAM10, thyroid carcinoma, JAK-STAT signaling pathway

Chunyu Yang,1– 4,* Xiaomei Zhong,2,4,* Huarong Zhou,2,4 Zhangying Wu,2,4 Min Zhang,2,4 Yuping Ning1,2,4 1The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 3The Third People’s Hospital of Zhongshan, Zhongshan, Guangdong, People’s Republic of China; 4Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuping NingThe Affiliated Brain Hospital of Guangzhou Medical University, Mingxin Road #36, Liwan District, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 20-8126-8720Fax +86 20-8189-1391Email ningjeny@126.comBackground: In people with psychosis, physical comorbidities are highly widespread and leading contributors to the untimely death encountered. Readmission rates in psychiatric patients are very high. Somatic comorbidities could be one of the considerable risk factors for psychiatric rehospitalization. Nevertheless, much less is known about the relation between physical comorbidities and psychiatric readmission. We aimed to investigate the association between physical comorbidities and psychiatric readmission in Han Chinese patients with psychiatric disorders.Methods: We used administrative data for January 1, 2009 to December 31, 2018 from the headquarters of the Affiliated Brain Hospital of Guangzhou Medical University to identify adults with schizophrenia, unipolar depression or bipolar disorder discharged from hospital. Data were extracted on sociodemographic and clinical characteristics. The Charlson comorbidity index (CCI) was used to assess the existence of significant physical comorbidity. Cox proportional hazards regression estimated rehospitalization risk after discharge.Results: A total of 15,620 individuals were included in this study, with the mean age of 35.1 years (SD = 12.8), and readmission occurred for 23.6% of participants. Survival analysis showed that physical comorbidities were statistically and significantly associated with psychiatric readmission, even after the adjustment for the number of psychiatric comorbidities, other sociodemographic and clinical variables.Conclusion: Our results suggest that somatic comorbidities are related with higher rates of psychiatric readmission. Hence, to treat psychosis more effectively and to reduce rehospitalization, it is crucial to treat physical comorbidities promptly and adequately. It is absolutely necessary to bring somatic comorbidities to the forefront of psychiatric treatment and research.Keywords: psychiatric disorder, physical comorbidity, readmission, survival analysis

Hua-chun Rao,1,* Zhao-ke Wu,1,* Si-da Wei,1 Yun Jiang,1 Qing-xin Guo,1 Jia-wen Wang,1 Chang-xian Chen,1 Hui-yong Yang2 1Quanzhou Orthopedic-Traumatological Hospital, Fengze District, Quanzhou, Fujian, People’s Republic of China; 2School of Medicine, Institute of Molecular Medicine, Huaqiao University, Quanzhou, People’s Republic of China*These authors contributed equally to this work.Correspondence: Chang-xian Chen Tel +86 13636913112Email ccx6070@qq.comHui-yong Yang Tel +86 15359531722Email shyhy@hqu.edu.cnPurpose: Moesin-ezrin-radixin-like protein (Merlin) has been identified as a tumor suppressor in several types of cancers. However, the biological function of Merlin in osteosarcoma remains unclear. MicroRNAs (miRNAs) can influence cancer progression by targeting oncogenes or anti-oncogenes. In this study, we sought to evaluate the regulation of Merlin expression by miR-25-3p and the role of the miR-25-3p/Merlin axis in osteosarcoma progression, with the aim of identifying a potential therapeutic target for osteosarcoma.Materials and Methods: TCGA (The Cancer Genome Atlas) database was used to analyze the correlation between Merlin expression and prognosis. RT-qPCR and Western blotting analyses were performed to compare Merlin expression between normal and malignant cells. A dual-luciferase reporter assay was performed to evaluate the direct targeting of Merlin by miR-25-3p. We overexpressed miR-25-3p, or/and Merlin, in U-2 OS and 143B cells, and studied their cellular functions in vitro. MTT and colony formation assays were performed to determine the effects on cell growth. EdU and cell cycle assays were performed to analyze the effects in cell replication. We used annexin V-fluorescein isothiocyanate and propidium iodide to stain apoptotic cells, and analyzed the cells using flow cytometry. The effects on cell metastasis were studied in wound healing and transwell assays. Lastly, the underlying mechanism was determined in RT-qPCR and Western blotting experiments.Results: Low Merlin expression was linked to poor prognosis. miR-25-3p was observed to directly target Merlin and downregulate its expression. miR-25-3p promoted cell growth, migration, and invasion, and inhibited apoptosis induced by cisplatin. Moreover, the overexpression of Merlin reversed the abovementioned effects of miR-25-3p. Further, the miR-25-3p/Merlin axis was observed to play an important role in the Hippo pathway, and regulated the expression of genes such as BIRC5, CTGF, and CYR61.Conclusion: miR-25-3p functions as an oncogenic microRNA in osteosarcoma by targeting Merlin, and may serve as a potential therapeutic target for osteosarcoma.Keywords: Merlin, miR-25-3p, osteosarcoma, proliferation, apoptosis, metastasis

Tao Wang,1,* Xin Gao,1,* Kun Zhang,1,* Jian Yang,1,* Zheyu Wu,1,2 Tielong Liu,1 Qi Jia,1 Jianru Xiao1 1Department of Orthopaedic Oncology, Spinal Tumor Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, People’s Republic of China; 2Department of Orthopaedics, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianru Xiao; Qi Jia Tel +86-021-81886999Email xiaojianru1908@163.com; 15821055604@163.comPurpose: Spinal metastasis from urothelial carcinoma (UC) is relatively uncommon. The aim of the present study is to explore the clinicopathological features, surgical treatments and outcomes of this rare disease.Patients and Methods: Fifteen patients with UC spinal metastasis who received surgery in our center between 2009 and 2018 were retrospectively investigated. Clinical data, treatment options, and outcomes were analyzed.Results: For the 15 patients (9 men and 6 women), the primary tumors were located in the upper urothelial tract in ten and lower urothelial tract in five. UC mainly metastasized to the lumbar spine in seven cases, followed by the thoracic spine in five. Pathologic fracture and soft tissue mass with dura mater compression were observed in 66.7% and 93.3% cases, respectively. Palliative resection was performed in nine cases and excisional resection in six. Eleven patients received postoperative chemotherapy, including three with a preoperative ECOG score > 2. Bisphosphonates were administered in all patients. Pain was relieved remarkably in all patients, and both the neurological function and general status were improved significantly after surgery. The median overall survival was 14 months. Log rank test showed that patients receiving postoperative chemotherapy survived longer than those without chemotherapy (p=0.037). WHO grade 3 was also correlated with poorer prognosis (p=0.012).Conclusion: Pathological fracture and soft tissue mass with dura mater compression is frequently observed on radiological images in patients with UC spinal metastasis. Surgery is useful to prevent deterioration of performance status and improve quality of life, which provide an opportunity for further systematic therapy. Multimodal treatments, including surgery, postoperative chemotherapy and bisphosphonates are recommended. WHO grade 2 and receiving postoperative chemotherapy were favorable prognostic factors for the overall survival of patients with UC spinal metastasis.Keywords: urothelial carcinoma, upper tract urothelial carcinoma, spine metastasis, bisphosphonates, prognosis, WHO grade

Peng Xue,1 Ziyu Wu,2 Kunpen Wang,1 Guojun Gao,3 Min Zhuang,4 Miao Yan4 1Department of Urology, First People Hospital of Lianyungang, Lianyungang, Jiangsu Province, People’s Republic of China; 2Department of Urology, NO 2 Hospital of Huaian, Huaian, Jiangsu Province, People’s Republic of China; 3Department of Urology, The Affiliated Hospital of Weifang Medical College, Weifang, Shandong Province, People’s Republic of China; 4Department of Oncology, First People Hospital of Lianyungang, Lianyungang, Jiangsu Province, People’s Republic of ChinaCorrespondence: Miao YanDepartment of Oncology, First People Hospital of Lianyungang, Zhenghua Road 6, Lianyungang, Jiangsu Province 222002, People’s Republic of ChinaTel +86051885605016Email yanmiao_ym@126.comBackground: The current standard of care for metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT) with or without anti-androgen and chemotherapy. The aim of this study was to evaluate the efficacy and safety of a multimodal approach including local primary tumor therapy, metastasis-directed therapy (MDT), and hormonal therapy in patients with oligometastatic prostate cancer (PCa).Methods: We reviewed data of patients with PCa and bone oligometastases at diagnosis treated in three institutions with ADT followed by cytoreductive surgery with or without metastases-directed radiotherapy. Oligometastases were defined as the presence of five or fewer metastatic lesions with the absence of visceral metastases. In this retrospective cohort study, 58 patients underwent cytoreductive radical prostatectomy and ADT. Of these, 26 patients (45%) received stereotactic body radiation therapy (SBRT) to all metastatic sites as a MDT. Oncological outcomes were analyzed using the Kaplan–Meier method.Results: The median follow-up period was 46.2 months. Of the 58 patients, the 3-year castration-resistant prostate cancer (CRPC)-free survival and cancer-specific survival was 75.9% and 91.4%, respectively. Pre- or post-treatment predictive factors for progression to CRPC, including prostate-specific antigen (PSA) level at diagnosis ≥ 20 ng/mL, Gleason grade groups 5, clinical T stage cT3b-4, PSA nadir level of ≥ 0.05 ng/mL, and no MDT with SBRT, were significantly associated with progression to CRPC. Subgroup analysis showed that the MDT group had significantly better CRPC-free survival than the non-MDT group with Gleason grade groups 1– 4 (HR=0.228; 95% CI= 0.056– 0.926). A total of 3.4% of the patients had grade 2 acute genitourinary toxicities and 5.2% had grade 2 acute gastrointestinal toxicities. No late grade > 2 adverse events were observed.Conclusion: This multi-center, retrospective cohort study revealed the feasibility of combining cytoreductive prostatectomy and metastasis-directed radiotherapy for newly-diagnosed oligometastatic PCa. This treatment strategy has the potential to delay the progression to CRPC.Keywords: oligometastases, prostate cancer, stereotactic body radiotherapy, androgen deprivation therapy, radical prostatectomy, metastasis-directed therapy

Chuanben Chen,1,* Qinyan Chen,2,* Yuanji Xu,1 Wei Zheng,1 Zhizhong Lin,1 Zijie Wu,2 Wangzhong Ye,2 Xinyi Huang,2 Xiurong Lin,1 Penggang Bai1 1Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou 350014, Fujian Province, People’s Republic of China; 2Graduate School, Fujian Medical University, Fuzhou 350000, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuanben Chen Tel +86 591-83660011Fax +86 591-83928767Email chenchuanben2010@126.comPurpose: To investigate whether juvenile patients with nasopharyngeal carcinoma (NPC) in China have better prognosis than their adult counterparts in the intensity-modulated radiation therapy (IMRT) era, after controlling for potential confounding variables.Methods: Data pertaining to 1139 patients with newly diagnosed NPC without metastasis, who were treated with IMRT at our hospital, were retrospectively analyzed. Of these, 60 patients were juvenile (age ≤ 18 years) diagnosed between January 2003 and December 2018, while 1079 patients were adults (≤ 65 years) diagnosed between January 2013 and December 2014. To minimize the influence of selection and confounding bias, 1:2 propensity score matching (PSM) was used. Overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated using the Kaplan–Meier method and between-group differences assessed using the Log rank test. The long-term toxicity of the juvenile patients was evaluated according to the criteria of the Radiation Therapy Oncology Group (RTOG) and the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.Results: Five-year OS of juvenile and adult patients were 88.07% and 85.08%, respectively. Before PSM, OS, PFS, DMFS, or LRFS were comparable in the two groups (all P > 0.05). After PSM, OS, DFS, and LRFS in the juvenile group were markedly longer than that in adults (P = 0.005, P = 0.027, and P = 0.024, respectively). With respect to long-term toxicity, the most common adverse effects in juvenile patients were cervix fibrosis, ototoxicity, and xerostomia. However, except for two patients who developed grade 3 ototoxicity, all adverse effects were within grade 2.Conclusion: In the IMRT era, juvenile Chinese patients with NPC had better 5-year OS, DFS, and LRFS than their adult counterparts. The adverse events in the juvenile cohort were relatively mild; however, the risk of severe ototoxicity should not be neglected.Keywords: juvenile nasopharyngeal carcinoma, intensity-modulated radiotherapy, prognosis

Yongkun Wang,1,* Zhen Wu,1,* Yingxue Li,2 Zheng Zheng,2 Jinqiang Yan,2 Shuyan Tian,2 Lin Han2 1Department of Thyroid Surgery, Liaocheng People’s Hospital (Clinical Hospital of Shandong First Medical University) Liaocheng, Shandong, People’s Republic of China; 2Department of Pathology, Liaocheng People’s Hospital (Clinical Hospital of Shandong First Medical University) Liaocheng, Shandong, People’s Republic of China*These authors contributed equally to this work.Correspondence: Lin Han Tel + 86-0635-8273132Email defhme@163.comBackground: Breast cancer is one of the most common cancers worldwide. Long non-coding RNAs and microRNAs act as important regulators in human cancers. This study aims to explore the molecular mechanism among H19, miR-491-5p and zinc finger 703 (ZNF703) in breast cancer.Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression of H19, miR-491-5p and ZNF703. Cell Counting Kit 8 (CCK-8) assay was performed to evaluate cell proliferation. Cell apoptosis was assessed by flow cytometry assay. The number of migrated and invaded cells was counted by transwell assay. Dual luciferase reporter assay was carried out to test luciferase activity. Protein level of ZNF703 was measured by Western blot assay.Results: H19 was highly expressed in breast tissues and cells. H19 knockdown inhibited proliferation, induced apoptosis and blocked migration and invasion. Moreover, H19 bound to miR-491-5p and negatively regulated miR-491-5p expression. MiR-491-5p inhibition abrogated the activities of proliferation, apoptosis, migration and invasion affected by H19 knockdown. Furthermore, miR-491-5p directly targeted ZNF703 and inversely modulated ZNF703 expression. ZNF703 up-regulation rescued the effects of miR-491-5p overexpression on proliferation, apoptosis, migration and invasion. In addition, H19 knockdown reduced ZNF703 expression by targeting miR-491-5p/ZNF703 axis.Conclusion: H19 promoted proliferation, migration and invasion and retarded apoptosis of breast cancer cells via sponging miR-491-5p to down-regulate ZNF703 expression.Keywords: breast cancer, H19, miR-491-5p, ZNF703

Tingting Yang,1,* Fen Li,2,* Bifan Zhu,2 Yuqian Chen,2 Duo Chen,2 Changying Wang,2 Zhiying Hou,2 Jiajie Xu,2 Shuwei Gu,3 Jiefeng Liu,4 Zhuochun Wu,1 Ying Wang,1 Chunlin Jin2 1School of Public Health/ Key Laboratory of Health Technology Assessment, National Health and Family Planning Commission of the People’s Republic of China, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Health Development Research Center, Shanghai Medical Information Center, Shanghai, People’s Republic of China; 3Jiangxi University of Traditional Chinese Medicine, School of Economics and Management, Nanchang, Jiangxi, People’s Republic of China; 4Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunlin Jin; Ying Wang Email jinchunlin@shdrc.org; wangying1013@fudan.edu.cnBackground: The value of identifying and targeting population demographics at high risk of stroke based on patient-reported outcomes (PROs) with electronic health records (EHRs) in Shanghai is largely undiscovered.Aim: To test the hypothesis that establishing an evidence-based support system composed of PROs integrated with EHRs could be effective at identifying individuals at high risk of suffering from stroke.Methods: The patients included in this study joined the hypertensive patient management system from 2014 to 2018. We merged the Hypertension Patients Management Database and the Diabetes Mellitus Patients Management Database of Shanghai Jiading district, then kept the hypertension patients with or without diabetes. We subsequently performed a screen analysis utilizing EHRs to target the population with any risk factor for stroke, namely, hypertension, diabetes mellitus, obesity, smoking and physical inactivity. We also calculated the distribution of each risk factor and the combinations of risk factors.Results: In the Jiading District of Shanghai, 46,580 hypertensive patients with complete baseline information joined the hypertensive patient management system from 2014 to 2018. The majority of the patients were aged above 60 years old. Physical inactivity (83.24%), smoking (24.07%), diabetes (16.87%), and obesity (12.23%) were highly prevalent in hypertensive participants. Approximately 4377 patients were diagnosed with hypertension exclusively, accounting for 9.70% of the total number of patients in this study. Meanwhile, approximately 52.47% of the patients were diagnosed with two concurrent risk factors, and 38.13% of the patients had hypertension, meaning that 17,762 patients could be labeled as the high-risk population for stroke according to the criteria established by the National Stroke Screening Survey.Conclusion: Our exploratory findings demonstrate the feasibility of pinpointing and targeting populations at high risk of stroke using the EHRs of hypertensive patients.Keywords: hypertension, electronic health records, EHRs, stroke risk factors

Shaocheng Qi,1 Yongbin Hu,1 Chaoqi Dai,1 Peiqin Chen,1 Zhendong Wu,1 Thomas J Webster,2 Mingzhi Dai1,3 1Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, People’s Republic of China; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 3Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of ChinaCorrespondence: Thomas J Webster Department of Chemical EngineeringNortheastern University, Boston, MA, USAEmail th.webster@neu.eduMingzhi DaiNingbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, People’s Republic of ChinaEmail daimz@nimte.ac.cnBackground: As a key component in artificial intelligence computing, a transistor design is updated here as a potential alternative candidate for artificial synaptic behavior implementation. However, further updates are needed to better control artificial synaptic behavior. Here, an updated channel-electrode transistor design is proposed as an artificial synapse device; this structure is different from previously published designs by other groups.Methods: A semiconductor characterization system was used in order to simulate the artificial synaptic behavior and a scanning electron microscope was used to characterize the device structure.Results: It was found that the electrode added to the transistor channel had a strong impact on the representative transmission behavior of such artificial synaptic devices, such as excitatory postsynaptic current (EPSC) and the paired-pulse facilitation (PPF) index.Conclusion: These behaviors were tuned effectively and the impact of the channel electrode is explained by the combined effects of the joint channel electrode and conventional gate. The voltage dependence of such oxide devices suggests more capability to emulate various synaptic behaviors for numerous medical and non-medical applications. This is extremely helpful for future neuromorphic computational system implementation.Keywords: artificial synapse, thin-film transistor, channel-electrode transistor, neuron behavior control

Run Tang1 ,* Zeming Wu1 ,* Feng Lu,1 Cheng Wang,1 Bo Wu,1 Jianqing Wang,2 Yingxiang Zhu1 1Department of Urology, The People’s Hospital of Suzhou New District, Suzhou, Jiangsu, People’s Republic of China; 2Department of Urology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingxiang Zhu Email trian123@126.comJianqing Wang Email jqwang14@fudan.edu.cnBackground: Prostate cancer is one of the most common malignancies in urology, especially in developed countries. Our previous studies showed that Lanthionine synthase C-like protein 1 (LanCL1) can promote the proliferation of prostate cancer cells and protect cells from oxidative stress. Also, LanCL1 protects cells by inhibiting the JNK signaling pathway after H2O2 treatment.Materials and Methods: In our study, we analyzed the data of RNA-seq to identify the DEGs after LanCL1 overexpression. We performed a functional enrichment analysis with gene set enrichment analysis (GSEA) and a database for annotation, visualization, and integrated discovery (DAVID). We also identified the critical hub gene correlated with disease prognosis by Cox regression analysis.Results: A total of 8928 DEGs were identified. Through the analysis of GO and KEGG, we found that DEGs are significantly enriched in categories related to metabolism, cancer-related signaling pathways, and inflammation. The top 15 hub genes were then identified and ranked by degree from the protein–protein interaction network. Survival analysis showed 4 hub genes related to disease prognosis and ICAM1 expression is an independent risk factor for the prognosis.Conclusion: Our results suggest the critical genes and pathways that might play key roles after LanCL1 overexpression in prostate cancer. We also provide candidate gene targets that might play important roles in prostate cancer development.Keywords: prostate cancer, RNA sequencing, LanCL1

Xu-Lei Huo,1,* Bo Wang,1,* Gui-Jun Zhang,2,* Jun-Peng Ma,1 Liang Wang,1 Li-Wei Zhang,1 Xiao-Ying Xu,1 Xiao-Jie Li,1 Huan Li,1 Da Li,1 Jun-Ting Zhang,1 Zhen Wu1 1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen Wu Tel +86-10-59976514Fax +86-10-59771377Email wuzhen1966@aliyun.comObjective: Intracranial pineoblastomas are rare neoplasms with poor prognosis. The aim of this study was to describe the independent prognostic factors and treatment strategies for overall survival in pediatric and adult patients.Methods: Sixty-four patients were surgically treated between January 2012 and December 2018.Results: The series included 37 (57.8%) males and 27 (42.2%) females. Gross total resection was achieved in 41 (64.1%) cases, and the 1-, 3-, and 5-year rates of overall survival were 86.3, 52.3, and 36.6%, respectively. In the pediatric group (n=42), 28 patients (66.7%) were male, with the median, and the mean age was 4 and 6.2± 4.7 years, respectively. After a median follow-up of 25.0 months, twenty-six patients (61.9%) died, and the 1-, 3-, and 5-year rates of overall survival were 84.9, 46.4, and 26.7%, respectively. Postoperative radiotherapy (p=0.058) and postoperative chemotherapy (p=0.183) had a positive influence on the increased overall survival. Meanwhile, postoperative radiotherapy combined with chemotherapy following surgery had a positive impact on overall survival (p=0.174, Log rank). In the adult group, the mean overall survival was 67.3± 9.3 months (range, 0.8– 95.3 months), and the 1-, 3-, and 5-year rates of overall survival were 89.5, 64.4, and 64.4%, respectively. In this group, no statistical association was observed between clinical factors and outcomes. However, patients who received postoperative radiotherapy (60.7 vs 57.6 month, mean survival; p=0.510, Log rank) or chemotherapy (63.0 vs 59.9 month, mean survival; p=0.404, Log rank) had better survival rates compared with those who declined.Conclusion: In the pediatric group, surgery with postoperative radiotherapy and chemotherapy was a favorable factor for overall survival. In the adult group, a positive trend in overall survival was found when patients received radiation and/or chemotherapy following surgery.Keywords: pediatric patients, adult patients, treatment strategy, overall survival

Liang Ding,1 Jianjun Yin,2 Wenbo Zhang,3 Ziqiang Wu,4 Shulei Chen4 1Department of Physical Education, Southeast University, Nanjing, People’s Republic of China; 2Department of Physical Education, Guangdong University of Finance and Economics, Guangzhou, People’s Republic of China; 3Department of Physical Education, Changchun Institute of Education, Changchun, People’s Republic of China; 4Department of Physical Education, Dalian Institute of Science and Technology, Dalian, People’s Republic of ChinaCorrespondence: Liang DingDepartment of Physical Education, Southeast University, 2 Sipailou, Nanjing 210009, People’s Republic of ChinaEmail dlseu1980@163.comPurpose: Poor eating behaviors are associated with imbalances in energy and food intake, which may directly or indirectly contribute to muscle strength loss. This study aimed to investigate the association between eating behaviors and hand grip strength in Chinese adults.Materials and Methods: We designed and conducted a cross-sectional study of 2009 Chinese individuals aged 25– 65 years in 2017. Eating behaviors, including breakfast consumption, snacking after dinner, and eating rate, were assessed using a self-administered questionnaire. Hand grip strength was assessed using a digital grip dynamometer. Age, sex, BMI, physical activity, educational level, occupation, living status, sleep duration, smoking and drinking status, hypertension, diabetes, and depressive symptoms were used as confounding factors.Results: After final adjustments for confounding factors, grip strength was measured as 35.2 (95% confidence interval [CI]: 34.7– 35.8), 36.0 (95% CI: 35.6– 36.4), and 36.9 (95% CI: 36.6– 37.3) for those who skipped, occasionally ate, and regularly ate breakfast, respectively (p for trend < 0.001). Those who always, sometimes, and seldom snacked after dinner (p for trend < 0.001) reported the following grip strength: 34.7 (95% CI: 34.0– 35.3), 36.2 (95% CI: 35.8– 36.6), and 36.9 (95% CI: 36.6– 37.2), respectively. Significant associations were not found between eating rate and grip strength.Conclusion: This study showed that higher frequency of breakfast consumption and lower frequency of snacking after dinner were associated with higher grip strength in Chinese adults. Therefore, eating behaviors may be involved in muscle function.Keywords: breakfast consumption, eating rate, snacking after dinner, grip strength, adult population

Gaohong Di,1 Chengkun Xia,1 Shanglong Yao,1 Xiangdong Chen,1 Zhilin Wu,1 Ling Hu,2 Jie Wang1 1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Anesthesiology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Jie Wang; Chengkun Xia Department of Anesthesiology of Wuhan Union Hospital, No. 1277 Jiefang Avenue, Hankou, Wuhan, Hubei, People’s Republic of ChinaTel/ Fax +86 27-85726834Email gatogiratorio@gmail.com; xiayulong_2001@163.comBackground: The rapid spread of COVID-19 has expanded into a pandemic, for which the main containment strategies to reduce transmission are social distancing and isolation of ill persons. Thousands of medical staff have been infected worldwide. Coronavirus testing kits have been in short supply, and early diagnostic reagents did not have high sensitivity. The aim of this study was to describe the characteristics of patients requiring emergency surgery in a COVID-19 outbreak area.Methods: We assessed medical data regarding all patients who underwent emergency surgery at the main campus of Wuhan Union Hospital from January 23, 2020, to February 15, 2020. We classified patients based on suspicion of COVID-19 infection (suspected vs not suspected) before they were admitted to the operating room. We used descriptive statistics to analyze the data. Outcomes included the incidence of confirmed COVID-19 infection and length of stay, which were followed until March 25, 2020.Results: Among the 88 emergency patients included in this study, the mean age was 37 years. Twenty-five patients presented with abnormalities observed on chest CT scans and 16 presented with fever. The median wait time for surgery was one day. The median preparation time and median time until short orientation memory concentration test (SOMCT) recovery from anesthesia were 44.0 min and 23.0 min, respectively. The median postoperative length of stay was five days. Compared with patients not suspected of COVID-19 infection, six patients were confirmed to be infected with COVID-19 in the suspected group. No health care workers were infected during this study period.Conclusion: Simple identification using temperature screening of patients, respiratory symptoms, and chest CT scans before being admitted for emergency surgery was rapid and effective. Shortened contact times might reduce the risk of infection. Additional investigations with larger samples and improved designs are needed to confirm these observations.Keywords: COVID-19, emergency, cross-infection

Zijian Wu, Zhijie Wang, Zhaoxu Zheng, Jianjun Bi, Xishan Wang, Qiang Feng Department of Colorectal Surgery, 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 ChinaCorrespondence: Qiang Feng Department of Colorectal SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan South Road, Chaoyang District, Beijing 100021, People’s Republic of ChinaEmail fengqiang2008@vip.sina.comObjective: The aim of our study was to analyze the factors affecting lymph node metastasis (LNM) and the prognosis of colorectal neuroendocrine tumors (NETs).Patients and Methods: A retrospective analysis was conducted to collect the clinical data of 135 patients with colorectal NETs from January 2000 to December 2018, including clinical manifestations, pathological results, treatment methods, etc. Follow-up was regularly performed to observe the recurrence and metastasis of tumors and to identify the clinical and pathological features of colorectal NETs, risk factors for LNM and survival outcomes.Results: Among 135 patients, there were 57 (42.2) patients with LNM, and the independent risk factors for LNM in the multivariable analyses were tumor diameter ≥ 2 cm (P= 0.040) and tumor grade G3 (P=0.001). Patients were followed up for 1 to 190 months, and of the 133 patients who were successfully followed up, the 5-year OS was 71.7%, and the 5-year PFS was 69.0%. The multivariate analysis for survival outcomes showed that age ≥ 65 years (P=0.002/< 0.001) and lymph node metastasis (P=0.018/0.025) were independent risk factors affecting 5-year PFS and OS in colorectal neuroendocrine tumors. Tumors in the colon (P=0.022), moderately positive (++) CgA (P=0.010) and strongly positive (+++) CgA (P=0.007) were independent risk factors for poor 5-year PFS in patients with colorectal NETs.Conclusion: Rectal NETs have a better prognosis than colonic neuroendocrine tumors. Tumor diameter and tumor grade are independent risk factors for LNM in colorectal neuroendocrine tumors. Age, tumor location, lymph node status and a positive level of the neuroendocrine marker CgA are independent risk factors that affect the prognosis of colorectal NETs.Keywords: colorectal neoplasms, neuroendocrine neoplasms, lymph node metastasis, prognosis, survival analysis