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Yanyu Zhong,1,&ast; Nan Wang,1,&ast; Sihui Lu,2 Yaqian Lu,2 Xin Pan,3 Ying Zhou1 1Reproductive Medicine Centre, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Zhou, Reproductive Medicine Centre, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Gusu District, Suzhou, Jiangsu Province, 215008, People’s Republic of China, Tel +86-0512-67973182, Email zhouyingzzzyyy@163.com Xin Pan, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Gusu District, Suzhou, Jiangsu Province, 215008, People’s Republic of China, Tel +86-0512-67973182, Email panxinxin9@outlook.comObjective: This study aimed to analyze uterine artery and spiral artery hemodynamics in patients with unexplained recurrent pregnancy loss (URPL) with varying pregnancy outcomes.Methods: 174 pregnant women with URPL and 144 pregnant women without adverse pregnancy histories were enrolled in this retrospective study. Based on pregnancy outcomes, these patients were divided into two groups: normal pregnancy outcomes (URPL-N, n=138) and adverse pregnancy outcomes (URPL-A, n=36). Control group participants were categorized into normal pregnancy outcomes (CON-N, n=129) and adverse pregnancy outcomes (CON-A, n=15). We compared uterine artery and spiral artery hemodynamics during different stages of gestation and the predictive value of these parameters for pregnancy outcomes.Results: URPL-N group had fewer pregnancy losses and lower BMI compared to URPL-A group (P< 0.05). Spiral artery hemodynamics in URPL-N and CON-N groups were lower than those in URPL-A and CON-A groups during the mid-luteal phase, 11– 13 weeks, 15– 17 weeks, and 19– 21 weeks of gestation, respectively. Uterine artery hemodynamics ((Pulsatility index (mPI), resistive index (mRI), and systolic-to-diastolic ratio (mS/D)) in the mid-luteal period were lower in URPL-N group than URPL-A group. Similarly, in CON-N group were lower than CON-A group. The URPL-A and CON-A groups had higher uterine artery and spiral artery hemodynamics when compared to the URPL-N and CON-N groups. Spiral artery hemodynamics exhibited larger areas under the ROC curve compared to uterine artery parameters.Conclusion: Abnormal hemodynamics in these arteries may contribute to URPL and adverse pregnancy outcomes. Spiral artery hemodynamics are more reliable predictors of pregnancy outcomes than uterine artery parameters.Keywords: unexplained recurrent pregnancy loss, spiral artery, uterine artery, blood flow, pregnancy outcome

Yijia Guo,1– 3,&ast; Ruyun Zhang,4,&ast; Xinling Gan,5 Erli Wang,6 Shuihua Lu,7 Hui Jiang,3 Hongfei Duan,8 Zhengzhou Yuan,9 Weimin Li,2,3,10 Yong Liu1 1Department of Neurology, Chengdu Medical College, The First Affiliated Hospital, Chengdu, People’s Republic of China; 2Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Emergency, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Department of Radiology, The First People’s Hospital of Longquanyi District, Chengdu, People’s Republic of China; 7National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, Shenzhen Third People’s Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 8Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 9Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 10National Tuberculosis Clinical Laboratory of China, Beijing Key Laboratory in Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this work as first authorsCorrespondence: Yong Liu, Chengdu Medical College, The First Affiliated Hospital, No. 278, Middle Section, Baoguang Avenue, Xindu District, Chengdu, 610500, People’s Republic of China, Email 410578100@qq.comBackground: The predictors associated with clinical outcomes in patients with tuberculous meningitis (TBM) remain unclear. We aimed to analyse the relationship between systemic inflammation and clinical outcomes, as well as to explore whether systemic inflammation level influences the effectiveness of dexamethasone on treatment.Methods: Between January 2011 and December 2021, TBM patients admitted to five hospitals were observed consecutively. Baseline and post-treatment systemic inflammation levels were calculated using the neutrophil-lymphocyte-ratio (NLR). Generalized linear mixed models were employed to identify predictors of clinical outcomes. Propensity score matching and subgroup analyses were conducted to evaluate the effect of dexamethasone on treatment outcomes across different NLR levels.Results: A total of 1203 TBM patients were included in the study. During the follow-up, 144 (13.6%) participants experienced early neurological deterioration within 7 days after admission, and 345 (28.67%) exhibited poor functional outcome at the 12-month follow-up. Multivariate analysis revealed that post-treatment NLR was significantly associated with early neurological deterioration (OR=1.25; 95% CI, 1.14– 1.33; P< 0.001), and poor outcome (OR=1.34; 95% CI, 1.26– 1.45; P< 0.001). After propensity score matching, dexamethasone treatment was not associated with early neurological deterioration (OR=0.83; 95% CI, 0.42– 1.66; P=0.610) or poor outcome (OR=1.22; 95% CI, 0.49– 2.11; P=0.490) in the highest quartile of post-treatment NLR. The effect of dexamethasone on treatment outcomes did not significantly vary with disease severity stratification.Conclusion: Elevated systemic inflammation is an independent risk factor for neurological outcome in TBM patients. Further studies are required to investigate systemic inflammation in more severely affected population to better predict the outcomes following anti-inflammatory therapies.Keywords: tuberculous meningitis, systemic inflammation, neurological outcome

Yongjiao Zhang,1,2 Xiaolei Xuan,2 Diwen Ye,1,2 Dong Liu,2 Yufan Song,2 Fei Gao,2 Sumei Lu2 1School of Medical Laboratory, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Sumei Lu; Fei Gao, Email lsmqianyi@126.com; 448617003@qq.comAbstract: Absent in melanoma 2 (AIM2) is a protein encoded by the AIM2 gene located on human chromosomes, AIM2 can recognize and bind to double stranded DNA (dsDNA), leading to the assembly of the AIM2 inflammasome. The AIM2 inflammasome plays important proinflammation role in many diseases, and can induce pyroptotic cell death. It has also been closely linked to the development and progression of metabolic diseases and can be activated in obesity, diabetes, nonalcoholic fatty liver disease, and atherosclerosis. In this article, we mainly review the role of AIM2 in glucose metabolism, especially in obesity-related disorders of glucose and lipid metabolism, and provide insights to better understand the role of AIM2 in the pathogenesis, and clinical treatment of metabolic disease.Keywords: AIM2, obesity, metabolic diseases, diabetes, glucose metabolism disorders

Wenyu Li,1 Yanqiu Hou,1 Jiayu An,1 Linxuan Chen,1 Shan Lu1,2 1School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Research Centre for Rural Health Service, Key Research Institute of Humanities & Social Sciences of Hubei Provincial Department of Education, Wuhan, People’s Republic of ChinaCorrespondence: Shan Lu, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Hang Kong Road 13, Wuhan, 430030, People’s Republic of China, Tel +86 15827079650, Email shanlu@hust.edu.cnPurpose: The objective of this study was to explore the connection between family doctor contract services and preventable hospitalizations. Additionally, we sought to examine the role of primary health care quality as a mediating factor in the link between family doctor contract services and preventable hospitalizations among patients with hypertension.Patients and Methods: This cross-sectional study was performed in Dangyang (Hubei Province, Central China) and Xishui (Guizhou Province, Western China) counties in July–August 2023. Participants comprised 625 patients selected via a multi-stage sampling method. Causal mediation analysis was conducted to explore the effect of family doctor contract services on preventable hospitalizations and the mediating effect of primary healthcare quality on this relationship.Results: Utilization rate of family doctor contract services of hypertensive patients was 58.6%, score of primary health service quality was 70.75 and incidence of preventable hospitalizations was 28.2%. Amongst hypertensive patients, utilization of family doctor contract services decreased the occurrence of preventable hospitalizations, with a total effect of − 0.22 (p < 0.001). Primary healthcare quality mediates the association, with a mediate effect of − 0.05 (p < 0.001), explaining 22.73% of the total effect.Conclusion: Improving the utilization of family doctor contract services and primary healthcare quality may result in lower rates of preventable hospitalizations amongst hypertensive patients.Keywords: family doctor contract services, preventable hospitalizations, primary healthcare quality, hypertension, mediation analysis

Gang Deng, Yuanyuan Yang, Song Lu, Lin Ma, Guohua Wu College of Biotechnology and Sericultural Research Institute, Jiangsu University of Science and Technology, Zhenjiang, 212100, People’s Republic of ChinaCorrespondence: Guohua Wu, Email ghwu@just.edu.cnIntroduction: With the development of technology, personal heat management has become a focus of attention. Phase change fabrics, as intelligent materials, are expected to be widely used in multiple fields, bringing comfortable, intelligent and convenient living experience.Methods: In this study, miniature phase change microcapsules (MPCM) with n-octadecane as core and poly(methyl methacrylate) as shell were successfully prepared. Using the in-situ reduction property of polydopamine, gold nanoparticles were deposited on the surface of the microcapsules, which retained the heat storage function and imparted photothermal and antibacterial properties. The MPCM with photothermal conversion function was modified on the surface of silk fabric using aqueous polyurethane after verified by comprehensive material characterisation techniques.Results: Under the near infrared light of 808 nm wavelength and 0.134 W/cm² irradiation intensity, the MPCM@PDA@Au modified silk fabrics showed excellent photothermal conversion performance, which could be increased from 25°C to 60°C in 50s. After the light source was cut off, the fabrics showed good heat release ability, with melting enthalpy and crystallisation enthalpy reaching 41.58 J/g and 43.3 J/g, respectively, which were not changed after repeated cycles. After the light source is cut off, the fabric has good heat release ability, and the enthalpy of melting and crystallisation reaches 41.58 J/g and 43.3 J/g, respectively, and the photothermal efficiency remains unchanged after many cycles of use, which proves that it has excellent durability and stability. The antimicrobial test shows that the fabric has significant antibacterial effect on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus).Discussion: MPCM@PDA@Au silk fabrics bring new possibilities for the future of personal thermal management and antimicrobial protection in the field of medical health, outdoor sports and other areas of broad application prospects, heralding the birth of a series of innovative applications and solutions.Keywords: photothermal conversion, phase change material, thermal energy storage, functional textile

Yibin Lin,1,2 Lehua Liu,1 Siyang Lu,1 Linqi Fan,1 Huaqi Hu,1 Xuanyin Wang,1 Jichao Zhu,3 Xinhua Qiang,4 Jie He,5 Hongchang Zhou,1,2,6 Shengwen Shao,1,6 Gaoming Zheng7 1School of Medicine, Huzhou University, Huzhou, 313000, People’s Republic of China; 2Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, 31300, People’s Republic of China; 3Clinical Laboratory, Huzhou Central Hospital, Huzhou, 313000, People’s Republic of China; 4Clinical Laboratory, First People’s Hospital Affiliated to Huzhou University, Huzhou, 313000, People’s Republic of China; 5Infectious Diseases Department, First People’s Hospital Affiliated to Huzhou University, Huzhou, 313000, People’s Republic of China; 6Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, Huzhou University, Huzhou, 313000, People’s Republic of China; 7Clinical Laboratory, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, People’s Republic of ChinaCorrespondence: Gaoming Zheng; Shengwen Shao, Email zheng151031@sina.com; shaoshw@zjhu.edu.cnBackground: Bacillus cereus is a common bacterium found in the environment. Some strains can cause food poisoning, and very few can cause clinically severe infections, leading to death. Here, we characterized the genome sequence of B. cereus LIN78 isolated from teeth with deep caries and compared it with those of 25 other related species.Methods: Third-generation sequencing technology, bacteriological analyses, biochemistry, and mass spectrometry were applied to characterize the drug-resistance genes and virulence factors of B. cereus LIN78.Results: The complete genome sequence of B. cereus Lin78 consists of 5647 genes distributed on a circular chromosome, a 393 kbp plasmid, and 928 pseudogenes (37.4% of whole-genome DNA). The LIN78 genome contains 14 sets of 16s, 23s, and 5s ribosomal RNA operons; 106 tRNA genes, one tmRNA, 12 genomic islands, six prophases, 64 repeats; 37 antibiotic-resistant genes; and 1119 putative virulence genes, including enterotoxins and cytolysins. The B. cereus LIN78 genome carries multiple copies of non-ribosomal polypeptide synthetase (NRPS) and post-translationally modified peptides (RiPPs). Phylogenetic analysis of the 26 B. cereus strains showed that B. cereus LIN78 is evolutionarily closely related to B. thuringiensis ATCC 10792 and B. cereus ATCC 14579.Conclusion: The newly isolated B. cereus carries many virulence genes, including enterotoxins and hemolysins, similar to B. anthracis, and multiple antibiotic resistance genes. These findings suggest that the strain has a potential risk of causing disease. Our studies are vital for further exploration of the evolution of B. cereus, its pathogenic mechanisms, and the control and treatment of bacterial infections.Keywords: bacillus cereus, whole-genome DNA sequencing, virulence factor, drug resistance gene, human teeth

Chao Ma,1,&ast; Haoyu Li,2,3,&ast; Shuwen Lu,4 Xian Li5,6 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Hunan Clinical Research Centre of Ophthalmic Disease, Changsha, Hunan, People’s Republic of China; 4Department of Ophthalmology, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 5Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK; 6Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK&ast;These authors contributed equally to this workCorrespondence: Chao Ma, Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86-371-66278091, Email gmchao219@163.comAbstract: Degenerative fundus disease encompasses a spectrum of ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), which are major contributors to visual impairment and blindness worldwide. The development and implementation of effective strategies for managing and preventing the onset and progression of these diseases are crucial for preserving patients’ visual acuity. Melatonin, a neurohormone primarily produced by the pineal gland, exhibits properties such as circadian rhythm modulation, antioxidant activity, anti-inflammatory effects, and neuroprotection within the ocular environment. Furthermore, melatonin has been shown to suppress neovascularization and reduce vascular leakage, both of which are critical in the pathogenesis of degenerative fundus lesions. Consequently, melatonin emerges as a promising therapeutic candidate for degenerative ocular diseases. This review provides a comprehensive overview of melatonin synthesis, its localization within ocular tissues, and its mechanisms of action, particularly in regulating melatonin production, thereby underscoring its potential as a therapeutic agent for degenerative fundus diseases.Keywords: melatonin, fundus degeneration, oxidative stress, inflammation, anti-apoptotic

Wenxue Liu,1 Yapeng Wang,2 Yi Jiang,2 Shan Lu,1 Jiawei Zhu,3 Yuhuan Tian,2 Jun Pan,1 Zhenjun Xu,1 Dongjin Wang1 1Institute of Cardiothoracic Vascular Disease, Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 2Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, People’s Republic of China; 3Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Dongjin Wang; Zhenjun Xu, Institute of Cardiothoracic Vascular Disease, Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China, Email wangdongjin@njglyy.com; xzj881225@163.comBackground: Postoperative delirium (POD) significantly impacts patient outcomes after acute type A aortic dissection (ATAAD) surgeries. This study investigates the role of Neuronal Pentraxin 2 (NPTX2) as a potential biomarker for POD in ATAAD patients.Methods: This secondary analysis involved ATAAD patients from a prospective observational study. Serum NPTX2 levels were measured preoperatively and immediately postoperatively using Enzyme-Linked Immunosorbent Assay (ELISA). Delirium was assessed using the Confusion Assessment Method (CAM) or CAM for the ICU (CAM-ICU). Statistical analyses included the Pearson Correlation Coefficient and multivariate logistic regression to evaluate the association between NPTX2 levels and POD.Results: Among the 62 patients included, 46.77% developed POD. Patients with POD had significantly lower preoperative and postoperative serum NPTX2 levels. The Receiver Operating Characteristic (ROC) curve analysis showed that postoperative NPTX2 had a strong predictive capability for POD (AUC = 0.895). The optimal cutoff for postoperative NPTX2 in predicting POD was less than 421.4 pg/mL. Preoperative NPTX2 also demonstrated predictive value, albeit weaker (AUC = 0.683).Conclusion: Serum NPTX2 levels, both preoperatively and postoperatively, are promising biomarkers for predicting POD in ATAAD patients. These findings suggest that NPTX2 could be instrumental in early POD detection and intervention strategies.Keywords: acute type a aortic dissection, postoperative delirium, NPTX2, biomarker

Zhe Xiong,1,2 Ying Fang,1,2 Shuangshuang Lu,1 Qiuyue Sun,1,3 Yuhui Sun,1,3 Pengcheng Yang,4,&ast; Jin Huang1,&ast; 1Department of Gastroenterology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 2Graduate School of Dalian Medical University, Dalian, Liaoning Province, China; 3Graduate School of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 4Department of Gastroenterology, Hengshanqiao People’s Hospital, Changzhou, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengcheng Yang; Jin Huang, Email 496808936@qq.com; hj042153@hotmail.comBackground: Ulcerative colitis (UC) is a nonspecific inflammatory disease confined to the intestinal mucosa and submucosa, and its prevalence significantly increases each year. Disulfidptosis is a recently discovered new form of cell death that has been suggested to be involved in multiple diseases. The aim of this study was to explore the relevance of disulfidptosis in UC.Methods: First, the UC datasets were downloaded from the Gene Expression Omnibus (GEO) database, and UC samples were typed based on upregulated disulfidptosis-related genes (DRGs). Then, weighted gene co-expression network analysis (WGCNA) was performed on the datasets and molecular subtypes of UC, respectively, to obtain candidate signature genes. After validation of the validation set and qRT-PCR, we constructed a nomogram model by signature genes to predict the risk of UC. Finally, single-cell sequencing analysis was used to study the heterogeneity of UC and to demonstrate the expression of DRGs and signature genes at the single-cell level.Results: A total of 7 DRGs were significantly upregulated in the expression profiles of UC, and 180 UC samples were divided into two subtypes based on these DRGs. Five candidate signature genes were obtained by intersecting two key gene modules selected by WGCNA. After evaluation, four signature genes with diagnostic relevance (COL4A1, PRRX1, NNMT, and PECAM1) were eventually identified. The nomogram model showed excellent prediction ability. Finally, in the single-cell analysis, there were eight cell types (including B cells, T cells, monocyte, smooth muscle cells, epithelial cells, neutrophil, endothelial cells and NK cells) were identified. The signature genes were significantly expressed mainly in endothelial cells and smooth muscle cells.Conclusion: In this study, subtypes related to disulfidptosis were identified, and single-cell analysis was performed to understand the pathogenesis of UC from a new perspective. Four signature genes were screened and a prediction model with high accuracy was established. This provides novel insights for early diagnosis and therapeutic targets in UC.Keywords: ulcerative colitis, disulfidptosis, molecular clusters, WGCNA, nomogram

Yue Chen,1,&ast; Aili Gao,1,&ast; Yanan Ke,1 Xin Zhou,1 Li Lin,2 Sha Lu,2 Yumei Liu1 1Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, 510095, People’s Republic of China; 2Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumei Liu, Director of Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, People’s Republic of China, Tel/Fax +86- 20-83593472, Email liuyumei1109@163.comAbstract: Protothecosis, an infrequent human infection, is caused by achlorophyllic algae belonging to the genus Prototheca, particularly Prototheca wickerhamii. The skin stands as the most commonly affected organ. This report documents a case involving an 82-year-old male with Protothecosis. Histopathological analysis revealed granulomatous inflammation in the dermis, exhibiting necrotic features and hosting numerous non-budding spherical organisms. These organisms were positively stained using methenamine silver and periodic acid–Schiff stains, confirming identification as P. wickerhamii after validation through tissue culture and sequencing procedures. Initially, the patient received oral itraconazole at a dosage of 200 mg daily, accompanied by topical 1% naftifine-0.25% ketoconazole cream for a duration of 4 weeks, resulting in significant improvement. Subsequently, due to gastrointestinal discomfort presumably linked to itraconazole, terbinafine was administered. Over a span of 3 months, the patient received oral terbinafine at a dosage of 250 mg/day alongside the application of topical 1% naftifine-0.25% ketoconazole cream, leading to complete healing of the skin lesion, leaving behind a fibrotic scar.Keywords: protothecosis, Prototheca wickerhamii, terbinafine

Xian Li,1,&ast; Hong Lai,2,&ast; Peng Wang,3 Shuai Feng,4 Xuexin Feng,4 Chao Kong,3 Dewei Wu,5 Chunlin Yin,5 Jianghua Shen,6 Suying Yan,6 Rui Han,7 Jia Liu,7 Xiaoyi Ren,8 Ying Li,8 Lu Tang,9 Dong Xue,9 Ying Zhao,9 Hao Huang,10 Xiaoying Li,10 Yanhong Zhang,10 Xue Wang,11 Chunxiu Wang,12 Ping Jin,13 Shibao Lu,3 Tianlong Wang,4 Guoguang Zhao,14 Chaodong Wang1 On behalf of the APPLE-MDT Research Team, Xuanwu Hospital, Capital Medical University and National Clinical Research Center for Geriatric Diseases1Department of Neurology & Neurobiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China; 3Department of Orthopedic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 4Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 5Department of Cardiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 6Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 7Department of Gerontology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 8Department of Nutrition, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 9Department of Oral Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 10Department of Medical Administration, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 11Department of Medical Library, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 12Center for Evidence-Based Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 13Center for Medical Information, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 14Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaodong Wang, Department of Neurology, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, No. 45 Changchun Street, Beijing, 100053, People’s Republic of China, Tel/Fax +86-10-8319-8677, Email cdongwang@xwhosp.orgPurpose: We aimed to identify the risk factors for postoperative cognitive decline (POCD) by evaluating the outcomes from preoperative comprehensive geriatric assessment (CGA) and intraoperative anesthetic interventions.Patients and Methods: Data used in the study were obtained from the Aged Patient Perioperative Longitudinal Evaluation–Multidisciplinary Trial (APPLE-MDT) cohort recruited from the Department of Orthopedics in Xuanwu Hospital, Capital Medical University between March, 2019 and June, 2022. All patients accepted preoperative CGA by the multidisciplinary team using 13 common scales across 15 domains reflecting the multi-organ functions. The variables included demographic data, scales in CGA, comorbidities, laboratory tests and intraoperative anesthetic data. Cognitive function was assessed by Montreal Cognitive Assessment scale within 48 hours after admission and after surgery. Dropping of ≥ 1 point between the preoperative and postoperative scale was defined as POCD.Results: We enrolled 119 patients. The median age was 80.00 years [IQR, 77.00, 82.00] and 68 patients (57.1%) were female. Forty-two patients (35.3%) developed POCD. Three cognitive domains including calculation (P = 0.046), recall (P = 0.047) and attention (P = 0.007) were significantly worsened after surgery. Univariate analysis showed that disability of instrumental activity of daily living, incidence rate of postoperative respiratory failure (PRF) ≥ 4.2%, STOP-Bang scale score, Caprini risk scale score and Sufentanil for maintenance of anesthesia were different between the POCD and non-POCD patients. In the multivariable logistic regression analysis, PRF ≥ 4.2% (odds ratio [OR] = 2.343; 95% confidence interval [CI]: 1.028– 5.551; P = 0.046) and Sufentanil for maintenance of anesthesia (OR = 0.260; 95% CI: 0.057– 0.859; P = 0.044) was independently associated with POCD as risk and protective factors, respectively.Conclusion: Our study suggests that POCD is frequent among older patients undergoing elective orthopedic surgery, in which decline of calculation, recall and attention was predominant. Preoperative comprehensive geriatric assessments are important to identify the high-risk individuals of POCD.Keywords: cognitive dysfunction, postoperative cognitive complications, orthopedic surgery, comprehensive geriatric assessment, risk factors

O artigo apresenta em detalhe a gênese do Fundo Monteiro Lobato, no CEDAE/Unicamp, abrangendo desde o projeto inicial até o desenvolvimento do Acervo ao longo dos anos. Algumas seções são mais explicitadas, como cartas (algumas transcritas), fotografias, livros e presença na mídia. Destaca seu papel para o conhecimento mais completo das plateias e bastidores da história literária brasileira dos inícios do século XX, para além dos estereótipos correntes sobre o escritor.

Zongfeng Zhao,1,&ast; Jie Cheng,2,&ast; Wanqun Sun,1 Jian Zhu,3 Sheng Lu,3 Yanyan Feng,4 Zhendong Song,5 Yali Yang,6 Xiujuan Wu3 1Department of Scientific Research, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Urology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Dermatology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 4Chengdu Second People’s Hospital, Chengdu, Sichuan Province, People’s Republic of China; 5WLSA Shanghai Academy, Shanghai, People’s Republic of China; 6Department of Dermatology, Shanghai Ninth Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yali Yang, Department of Dermatology, Shanghai Ninth Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, No. 639, Manufacturing Bureau Road, Huangpu District, Shanghai, 200011, People’s Republic of China, Email ky7812@126.com Xiujuan Wu, Department of Dermatology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, No. 966, Huaihai Middle Road, Xuhui District, Shanghai, 200031, People’s Republic of China, Email xjwuxj@sina.comPurpose: Psoriasis is an incurable chronic inflammatory skin disease. The exact function and regulatory mechanism of non-coding RNA upregulation in psoriasis remains to be elucidated. The aim of this study was to analyse the role of the lncRNA-miRNA-mRNA network of psoriasis and LINC01176 in the pathogenesis of psoriasis.Patients and Methods: We performed miRNA, lncRNA, and mRNA sequencing analysis in pretreatment and treatment psoriatic tissues and normal tissues, constructed an lncRNA-miRNA-mRNA coexpression network and screened mRNA-associated pathways using bioinformatics analysis. We further validated the regulatory role of LINC01176-miR-218-5p on the proliferation and inflammation of the psoriatic model by dual-luciferase reporter assay, cell transfection, CCK-8 method, TUNEL staining and animal model construction method. An lncRNA-miRNA-mRNA coexpression network was successfully constructed by RNA-seq data analysis.Results: We obtained the relationship between LINC01176, miR-218-5p and IL36-G. Analysis of the apoptotic and proliferative capacity of the transfected cells showed that miR-218-5p up-regulation significantly inhibited cell proliferation and promoted apoptosis. A mouse model of psoriasis was successfully established. Phenotypic observations revealed that keratin-forming cells in mice coated with LINC01176-shRNA emulsifier were significantly lower than those in the model group and close to those in the normal group. HE and immunohistochemical experiments were performed, and the results showed the role and mechanism of action of LINC01176-shRNA. Suppression of LINC01176 significantly inhibited the expression of IL-36G in psoriatic tissues. LINC01176 showed a targeting and positive correlation with IL36-G expression.Conclusion: Our study shows that LINC01176 promotes the proliferation and invasion of keratinocytes and inhibits apoptosis by targeting miR-218-5p, which acts as a repressor of the psoriasis-associated IL-36G. The shRNA-LINC01176 emulsion showed potential treatment capability in alleviating symptoms of psoriasis.Keywords: psoriasis, LINC01176, IL-36G, inflammation

Wanchun Cheng,1 Mohammad Mofatteh,2 José Fidel Baizabal-Carvallo,3,4 Shaohuan Lu,1 Ping Su,1 Yimin Chen,5,6 Luoming Li,1 Lizhi Qin,1 Xingmei Zuo,1 Yifeng Lan,7 Yue Huang,8 Zhihui Yu,9 Zirui Luo,10,&ast; Gang Chen10,&ast; 1Department of Neurology and National Stroke Center, The 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China; 2School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK; 3Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA; 4Department of Sciences and Engineering, University of Guanajuato, León, Mexico; 5Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People’s Hospital, Foshan, People’s Republic of China; 6Neuro International Collaboration (NIC), Foshan, People’s Republic of China; 7Department of Radiology, the 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China; 8Department of Emergency, the 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China; 9Department of Laboratory Medicine, the 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China; 10Dean’s Office, the 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zirui Luo; Gang Chen, Dean’s Office, the 5th People’s Hospital of Foshan City, Foshan, Guangdong Province, 528211, People’s Republic of China, Email ziruiluo@126.com; vikingsaga@163.comPurpose: Intravenous thrombolysis has emerged as an effective approach to improve the long-term survival and functional status of patients with ischemic stroke. The aim of this study was to assess the impact of a national stroke project on the door-to-needle-time (DNT).Patients and Methods: The patients were divided into pre-construction and construction periods. Construction Measures were performed during the construction period. The DNT and onset-to-needle time (ONT) were compared in two period groups.Results: After participating in the National Stroke Center Project and effective measurements, the thrombolysis treatment metrics were improved significantly. The DNT (IQR) was shortened from 65.0 (54.5,85.0) minutes in the Pre-Construction period to 40.0 (33.0,53.0) minutes in the Construction period (p < 0.001). Similarly, the ONT was reduced from 157.0 (IQR) (115.0,184.0) minutes to 116.0 (87.8,170.0) minutes (p = 0.035).Conclusion: The DNT time and ONT time can be shortened by National Stroke Center Construction projects. More suitable hospitals should be encouraged to participate as the National Stroke Center.Keywords: acute ischemic stroke, intravenous thrombolysis, door-to-needle time, onset-to-needle time

Zhe Xiong,1,2 Ying Fang,1,2 Shuangshuang Lu,1 Qiuyue Sun,1,3 Jin Huang1 1Department of Gastroenterology, the Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 2Graduate School of Dalian Medical University, Dalian, Liaoning Province, People’s Republic of China; 3Graduate School of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Jin Huang, Email hj042153@hotmail.comBackground: Inflammatory bowel disease (IBD) and periodontitis (PD) are correlated, although the pathogenic mechanism behind their correlation has not been clarified. This study aims to explore the common signature genes and potential therapeutic targets of IBD and PD using transcriptomic analysis.Methods: The GEO database was used to download datasets of IBD and PD, and differential expression analysis was used to identify DEGs. We then conducted GO and KEGG enrichment analyses of the shared genes. Next, we applied 4 machine learning (ML) algorithms (GLM, RF, GBM, and SVM) to select the best prediction model for diagnosing the disease and obtained the hub genes of IBD and PD. The diagnostic value of the signature genes was verified by a validation set and qRT‒PCR experiments. Subsequently, immune cell infiltration in IBD samples and PD samples was analyzed by ssGSEA. Finally, we investigated and validated the response of hub genes to infliximab therapy.Results: We identified 43 upregulated genes as shared genes by intersecting the DEGs of IBD and PD. Functional enrichment analysis suggested that the shared genes were closely associated with immunity and inflammation. The ML algorithm and qRT‒PCR results indicated that IGKC and COL4A1 were the hub genes with the most diagnostic value for IBD and PD. Subsequently, through immune infiltration analysis, CD4 T cells, NK cells and neutrophils were identified to play crucial roles in the pathogenesis of IBD and PD. Finally, through in vivo and in vitro experiments, we found that IGKC and COL4A1 were significantly downregulated during the treatment of patients with IBD using infliximab.Conclusion: We investigated the potential association between IBD and PD using transcriptomic analysis. The IGKC and COL4A1 genes were identified as characteristic genes and novel intervention targets for these two diseases. Infliximab may be used to treat or prevent IBD and PD.Keywords: Inflammatory bowel disease, periodontitis, machine learning, ssGSEA, infliximab, IGKC, COL4A1

Peng Wang,1– 3,&ast; Chao Kong,1– 3,&ast; Ze Teng,4 Sitao Zhang,1– 3 Peng Cui,1– 3 Shuaikang Wang,1– 3 Guoguang Zhao,2,3 Shibao Lu1– 3 1Department of Orthopedics, Xuanwu Hospital of Capital Medical University, Beijing, 100053, People’s Republic of China; 2National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China; 3Beijing Municipal Geriatric Medical Research Center, Beijing, 100053, People’s Republic of China; 4Department of Radiology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, 100021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shibao Lu, Department of Orthopedics, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Xicheng, Beijing, 100053, People’s Republic of China, Email shibaoluspine@sina.com Guoguang Zhao, National Clinical Research Center for Geriatric Diseases, 45 Changchun Street, Xicheng, Beijing, 100053, People’s Republic of China, Email cmuzhaogg@163.comBackground: Enhanced recovery after surgery (ERAS) is currently widely used in many surgical specialties, but there is still a lack of concern about the cervical ERAS program for old patients (> 60 years old). We aimed to determine whether our ERAS program significantly improved satisfaction and outcomes in old patients (> 60 years old) with anterior cervical discectomy and fusion (ACDF).Methods: This is a retrospective cohort study. The study enrolled patients if they were over the age of 60 years old underwent ACDF from July 2019 and June 2021 (ERAS group) and from January 2018 and June 2019 (non-ERAS group). Data including demographic, comorbidity, and surgical information were collected. We also evaluated ERAS process compliance, primary outcome, surgical complication, and length of stay (LOS).Results: There were 135 patients in the ERAS group, and 122 patients in the non-ERAS group were included. A comparison of the demographic data revealed that there were no statistically significant intergroup differences observed between the group. Overall, ERAS pathway compliance was 91.9%. There were no significant differences in the fusion levels, operative time, intraoperative blood loss, postoperative VAS score, and complications between the ERAS and non-ERAS groups. In addition, there was no significant difference in readmission and mortality at 30-day follow-up between the two groups. However, we observed a statistically significant decrease in the LOS in the ERAS group (8.68± 2.34 of ERAS group versus 10.43± 4.05 in non-ERAS group, p=0.013).Conclusion: This report describes the first ERAS protocol used in old patients with ACDF. Our ERAS program is safe and associated with incremental benefits with respect to LOS in old patients with ACDF.Keywords: enhanced recovery after surgery, old, anterior cervical discectomy and fusion

Wenying Cai,1,&ast; Qianqian Ruan,2– 4,&ast; Jiahao Li,1 Li Lin,1 Liyan Xi,1,5 Jiufeng Sun,2,3 Sha Lu1 1Department of Dermatology and Venereology, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Institute of Public Health, Guangzhou, People’s Republic of China; 3Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, People’s Republic of China; 4School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 5Dermatology Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sha Lu, Department of Dermatology and Venereology, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, 107 West Yanjiang Road, Guangzhou, People’s Republic of China, Email lush7@mail.sysu.edu.cn Jiufeng Sun, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Guangzhou, People’s Republic of China, Email sunjiuf@163.comBackground: Deep fungal infection has become an important cause of infection and death in hospitalized patients, and this has worsened with increasing antifungal drug resistance.Objective: A 3-year retrospective study was conducted to investigate the clinical characteristics, pathogen spectrum, and drug resistance of deep fungal infection in a regional hospital of Guangzhou, China.Methods: Non-duplicate fungi isolates recovered from blood and other sterile body fluids of in-patients of the clinical department were identified using biochemical tests of pure culture with the API20C AUX and CHROMagar medium. Antifungal susceptibilities were determined by Sensititre YeastOne® panel trays.Results: In this study, 525 patients (283 female, 242 male) with deep fungal infection were included, half of them were elderly patients (≥ 60 years) (54.67%, n=286). A total of 605 non-repetitive fungi were finally isolated from sterile samples, of which urine specimens accounted for 66.12% (n=400). Surgery, ICU, and internal medicine were the top three departments that fungi were frequently detected. The mainly isolated fungal species were Candida albicans (43.97%, n=266), Candida glabrata (20.00%, n=121), and Candida tropicalis (17.02%, n=103), which contributed to over 80% of fungal infection. The susceptibility of the Candida spp. to echinocandins, 5-fluorocytosine, and amphotericin B remained above 95%, while C. glabrata and C. tropicalis to itraconazole were about 95%, and the dose-dependent susceptibility of C. glabrata to fluconazole was more than 90%. The echinocandins had no antifungal activity against Trichosporon asahi in vitro (MIC90> 8 μg/mL), but azole drugs were good, especially voriconazole and itraconazole (MIC90 = 0.25 μg/mL).Conclusion: The main causative agents of fungal infection were still the genus of Candida. Echinocandins were the first choice for clinical therapy of Candida infection, followed with 5-fluorocytosine and amphotericin B. Azole antifungal agents should be used with caution in Candida glabrata and Candida tropicalis infections.Keywords: fungal infection, species distribution, antifungal drugs, drug susceptibility, drug resistance

Kang Huang,1,&ast; Tianyi Ma,1,&ast; Qiang Li,1 Yilei Zhou,2 Ting Qin,1 Zanrui Zhong,1 Shilin Tang,1 Wei Zhang,1 Jianghua Zhong,1 Shijuan Lu1 1Department of Cardiovascular Medicine, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, People’s Republic of China; 2Medical College, Jingchu University of Technology, Jingmen, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shijuan Lu, Department of Cardiovascular Medicine, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, No. 43, Renmin Avenue, Haidian Island, Haikou, Hainan, 570100, People’s Republic of China, Tel/Fax +86-13005013999, Email lushijuan122@163.comBackground: The pathophysiological mechanism of ischemic stroke is complex. Traditional risk factors cannot fully or only partially explain the occurrence and development of IS. Genetic factors are getting more and more attention. Our study aimed to explore the association between CYP4F2 gene polymorphism and susceptibility to IS.Methods: A total of 1322 volunteers were enrolled to perform an association analysis through SNPStats online software. Using FPRP (false-positive report probability) to detect whether the result is a noteworthy finding. The interaction of SNP-SNP in IS risk was assessed by multi-factor dimensionality reduction. Statistical analysis of this study was mainly completed by SPSS 22.0 software.Results: Mutant allele “A” (OR = 1.24) and genotype “AA” (OR = 1.49) or “GA” (OR = 1.26) of CYP4F2-rs2108622 are risk genetic factors for IS. Rs2108622 is significantly associated with an increased risk of IS among subjects who are females, aging > 60 years old, with BMI ≥ 24 kg/m2, and smoking or drinking volunteers. CYP4F2-rs3093106 and -rs3093105 are associated with susceptibility to IS among smoking, drinking subjects, or IS patients complicated with hypertension.Conclusion: CYP4F2-rs2108622, -rs3093106, and -rs3093105 are associated with an increased risk of IS.Keywords: ischemic stroke, susceptibility, CYP4F2, genetic variants, association analysis

Kang Huang,1 Tianyi Ma,1 Qiang Li,1 Zanrui Zhong,1 Ting Qin,1 Yilei Zhou,2 Wei Zhang,1 Shilin Tang,1 Jianghua Zhong,1 Shijuan Lu1 1Department of Cardiology, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, Hainan, 570100, People’s Republic of China; 2Jingchu University of Technology, School of Medicine, Jingmen, Hubei, 448000, People’s Republic of ChinaCorrespondence: Shijuan Lu, Department of Cardiology, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, No. 43, Renmin Avenue, Haidian Island, Haikou, 570100, Hainan, People’s Republic of China, Tel +86-13005013999, Email Lu_shijuan@163.com Jianghua Zhong, Jingchu University of Technology, School of Medicine, No. 33, Xiangshan Avenue, Jingmen, Hubei, 448000, People’s Republic of China, Tel +86-13322003882, Email zhong3882@163.comIntroduction: Ischemic stroke (IS) is a multifactorial and polygenic disease, which is affected by genetic factors. In this study, we explored the role of CYP19A1 single nucleotide polymorphisms (SNPs) in IS in the Chinese population.Methods: 1302 subjects (651 controls and 651 cases) were recruited in this case–control study. Four candidate SNPs (rs28757157 C/T, rs3751592 C/T, rs3751591 G/A, rs59429575 C/T) of CYP19A1 were selected by the 1000 genomes project database. The association between CYP19A1 SNPs and IS risk was assessed using logistic regression analysis with odds ratio (OR) and 95% confidence intervals (CIs). False-positive report probability (FPRP) analysis further verified the positive results. The interaction of SNP-SNP was analyzed by multi-factor dimensionality reduction (MDR) to predict is risk.Results: In the research, CYP19A1 loci (rs28757157 and rs3751591) were associated with the occurrence of IS. The two variants conferred an increased susceptibility to IS in the subjects aged over 60 years old, smokers and drinkers. Rs28757157 was related to the risk of IS in females, non-smokers and subjects with BMI less than 24, while rs59429575 was related to the risk of IS in males and subjects with BMI greater than 24.Conclusion: The study revealed that there is a significant association between CYP19A1 loci (rs28757157 and rs3751591) and IS risk in the Chinese Han population, providing a theoretical basis for further exploring its specific role in the pathogenesis of IS.Keywords: ischemic stroke, risk, CYP19A1, single nucleotide polymorphisms, case-control study, Chinese Han population

Wei Lu,1– 3 Zhaowei Teng,1,2 Jiayu Chen,1– 3 Rongmao Shi,4 Tiannan Zou,1– 3 Ming Gao,1– 3 Weichao Li,1– 3 Zhi Peng,1– 3 Long Wang,1– 3 Yonghui Zhao,1– 3 Sheng Lu1– 3 1Yunnan Key Laboratory of Digital Orthopedics, the First People’s Hospital of Yunnan Province, Kunming, People’s Republic of China; 2Department of Orthopedics, the First People’s Hospital of Yunnan Province, Kunming, People’s Republic of China; 3Department of Orthopedics, the Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, People’s Republic of China; 4Department of Orthopedics, Clinical College of the 920th Hospital of Joint Logistics Support Force of Kunming Medical University, Kunming, People’s Republic of ChinaCorrespondence: Sheng Lu, Department of Orthopedics, the First People’s Hospital of Yunnan Province, No. 157 Jinbi Road, Kunming, 650032, People’s Republic of China, Tel +86-0871-63633071, Fax +86-0871-63633071, Email drlusheng@163.comPurpose: The objective of this study was to analyze the clinical characteristics and the therapeutic effects of treatment at our spinal center in OVCF patients associated with referred pain. The underlying goals were to deepen the understanding of referred pain caused by OVCFs, improve the currently low early diagnosis rate of OVCFs, and improve the effectiveness of treatment.Methods: The patients who had referred pain from OVCFs and met the inclusion criteria were retrospectively analyzed. All patients were treated with percutaneous kyphoplasty (PKP). Visual analog scale (VAS) scores and Oswestry Disability Index (ODI) were used to evaluate the therapeutic effect at different time points.Results: There were 11 males (19.6%) and 45 females (80.4%). Their corresponding mean bone mineral density (BMD) value was − 3.3 ± 0.4. The regression coefficient of BMD in the linear regression equation was − 4.51 (P< 0.001). According to the classification system for referred pain in OVCFs, there were 27 cases of type A (48.2%), 12 cases of type B (21.2%), 8 cases of type C (14.3%), 3 cases of type D (5.4%), and 6 cases of type E (10.7%). All patients were followed up for at least 6 months, and both VAS scores and ODI were found to be significantly better postoperatively than preoperatively (P< 0.001). There was no significant difference in VAS scores and ODI between different types preoperatively or 6 months postoperatively (P > 0.05). Within each type, there were significant differences in VAS scores and ODI between the pre- and postoperative timepoints (P < 0.05).Conclusion: Attention should be paid to referred pain in OVCF patients, which is not uncommon in clinical practice. Our summary of the characteristics of referred pain caused by OVCFs can improve the early diagnosis rate of OVCFs patients and provide a reference for their prognosis after PKP.Keywords: referred pain, radicular pain, vertebral fracture, percutaneous kyphoplasty, osteoporosis, spinal fracture

Yuxin Zhang,1– 3,&ast; Zhigang Wu,1,&ast; Shenji Lu,2 Minghui Lin,1 Xiaokun Yue,4 Zengguang Wang,4 Bin Cai1,2 1Department of Rehabilitation Medicine, Hainan Western Central Hospital, Danzhou, Hainan, People’s Republic of China; 2Department of Rehabilitation Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Oral Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, People’s Republic of China; 4Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuxin Zhang; Bin Cai, Department of Rehabilitation Medicine, Hainan Western Central Hospital, No. 2, Fubo East Road, Nada Town, Danzhou, Hainan, 571700, People’s Republic of China, Tel +86-21-53315248, Email yuxinzhang0129@163.com; caib1138@sh9hospital.org.cnObjective: This study aimed to characterize the gene expression profile at the early stages of the healing process of post-traumatic joint contracture (PTJC).Methods: Twelve rats were used for PTJC model establishment and were divided into four groups according to the sampling time: S0d, S3d, S7d and S2w. Transcriptome sequencing was performed on fibrotic joint capsule samples in four groups followed by bioinformatics analyses including differentially expressed genes (DEGs) screening, Short Time-series Expression Miner (STEM) analysis, network construction, and pathway analysis. Five important genes were validated by qRT-PCR.Results: A total of 1171, 1052 and 793 DEGs were screened in S3d vs S0d, S7d vs S0d, and S2w vs S0d comparison groups, respectively. A total of 383 overlapping genes were screened out, which were significantly enriched in some inflammatory functions and pathways. Through STEM analysis, three clusters were identified, including 105, 57 and 57 DEGs, respectively. Then, based on the cluster genes, 10 genes, such as Il6, Timp1, Cxcl1, Cxcr4 and Mmp3, were further selected after PPI and pathway analyses. The expression levels of Il6, Timp1, Cxcl1, Cxcr4 and Mmp3 were validated by qRT-PCR.Conclusion: The present study screened out several genes with significant changes in expression levels at the early stages of the healing process in PTJC, such as Il6, Timp1, Cxcl1, Cxcr4 and Mmp3. Our study offers a valuable contribution to the understanding pathomechanism of PTJC.Keywords: post-traumatic joint contracture, transcriptome sequencing, Short Time-series Expression Miner analysis, joint capsule fibrosis

Chao Ma,1,&ast; Haoyu Li,2,3,&ast; Shuwen Lu,4 Xian Li,5,6 Shuai Wang,1 Wenzhan Wang1 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Ophthalmology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3Hunan Clinical Research Centre of Ophthalmic Disease, Changsha, Hunan, People’s Republic of China; 4Department of Ophthalmology, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 5Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK; 6Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, the University of Manchester, Manchester, UK&ast;These authors contributed equally to this workCorrespondence: Wenzhan Wang, Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +0371-66278091, Email 18003857188@189.cnAbstract: Ocular injuries caused by inflammation, surgery or accidents are subject to a physiological healing process that ultimately restores the structure and function of the damaged tissue. Tryptase and trypsin are essential component of this process and they play a role in promoting and reducing the inflammatory response of tissues, respectively. Following injury, tryptase is endogenously produced by mast cells and can exacerbate the inflammatory response both by stimulating neutrophil secretion, and through its agonist action on proteinase-activated receptor 2 (PAR2). In contrast, exogenously introduced trypsin promotes wound healing by attenuating inflammatory responses, reducing oedema and protecting against infection. Thus, trypsin may help resolve ocular inflammatory symptoms and promote faster recovery from acute tissue injury associated with ophthalmic diseases. This article describes the roles of tryptase and exogenous trypsin in affected tissues after onset of ocular injury, and the clinical applications of trypsin injection.Keywords: trypsin, tryptase, inflammation, proteinase-activated receptor 2, ophthalmology, therapeutic

Rui Zhong,&ast; Gang Yu,&ast; Yingming Wang,&ast; Chao Fang, Shuai Lu, Zhilin Liu, Jingyu Gao, Chengyuan Yan, Qichun Zhao Department of Sports Medicine, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, 230001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qichun Zhao, Department of Sports Medicine, The Affiliated Provincial Hospital of Anhui Medical University, No. 17 Lujiang Road, Luyang District, Hefei, 230001, People’s Republic of China, Tel/Fax +86 13965050622, Email qichzhao@163.comPurpose: To compare the effects of an allogeneic bone graft and a non-filled bone graft on the rate of osteotomy gap union in medial opening wedge high tibial osteotomy (MOWHTO) with an opening width less than 10 mm.Methods: A total of 65 patients undergoing MOWHTO between January 2018 and December 2020 were enrolled in this retrospective study. The patients were divided into two groups: the allograft group (MOWHTO with allogeneic bone grafting, 30 patients) and the non-filling group (MOWHTO without bone void fillers, 35 patients). The clinical outcomes, including the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC), Lysholm score, and post-operative complications, were compared. The radiographic evaluation included changes in hip–knee–ankle angle (HKA), medial proximal tibial angle (MPTA), femorotibial angle (FTA), and weight-bearing line ratio (WBLR) at pre-operation, at two-day post-operation, and the last follow-up. Radiographs were obtained at three, six and twelve months post-surgery, and at the time of the last follow-up to assess the fill area of the osteotomy gap. The union rate of the osteotomy gap was calculated and compared, and risk factors that may affect the rate of osteotomy gap union were also discussed.Results: The rate of osteotomy gap union at 3 and 6 months after the operation in the allograft group was significantly higher compared with the non-filling group (all P< 0.05), while no significant difference was found after the 1-year post-operative and at the last follow-up. Also, the WOMAC and Lysholm scores of the allograft group were significantly higher than those of the non-filling group (all P< 0.05), and there was no significant difference between the two groups at the last follow-up.Conclusion: Filling the gaps with the allograft bones may accelerate the union of osteotomy gap, improve clinical outcomes, and have important implications for patient rehabilitation in the early post-operative course. Bone grafting did not affect the final rate of osteotomy gap union and the clinical score of patients.Keywords: MOWHTO, osteotomy gap, bone union, allogenic bone graft

Chao Ma,1,&ast; Haoyu Li,2,3,&ast; Shuwen Lu,4 Xian Li,5,6 Shuai Wang,1 Wenzhan Wang1 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Ophthalmology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3Hunan Clinical Research Centre of Ophthalmic Disease, Changsha, Hunan, People’s Republic of China; 4Department of Ophthalmology, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 5Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, England; 6School of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, the University of Manchester, Manchester, England&ast;These authors contributed equally to this workCorrespondence: Wenzhan Wang, Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 371-66278091, Email 18003857188@189.cnAbstract: Ocular lesions due to Brucella infection are uncommon and easily overlooked in clinical management, but must be differentiated from non-infectious eye diseases and treated promptly to protect the patient’s vision. We reviewed the relevant literature and identified 47 patients with ocular complications of Brucella infection. Among them, 28 showed ocular neuropathy, 15 presented with uveitis, and four patients displayed other ocular symptoms. Ocular symptoms accompanying Brucella infection require prompt diagnosis and treatment. The main methods of diagnosis are intraocular fluid tests and blood tests. Early diagnosis and treatment with suitable antibiotics are central to protecting the patient’s vision. Notably, in terms of mechanism of injury, Brucella infection is chronic and cannot be eliminated by phagocytes, and can cause damage to the eye by inducing autoimmune reactions, antigen-antibody complex production, release of endogenous and exogenous toxins, and bacterial production of septic thrombi in the tissues. In this review, we summarize the ocular symptoms, diagnosis, treatment and prognosis of Brucella infection, and discuss the mechanisms of Brucella in ocular lesions, providing a reference for the diagnosis and treatment of Brucella ocular lesions.Keywords: Brucella, infection mechanism, ocular, ocular neuropathy, uveitis

Peng Cui,1,2,&ast; Peng Wang,1,2,&ast; Xinli Hu,1,2,&ast; Chao Kong,1,2 Shibao Lu1,2 1Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2National Clinical Research Center for Geriatric Diseases, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Kong; Shibao Lu, Email kong988500@163.com; spinelu@xwhosp.orgBackground: There were exponentially increased studies focused on revealing the satisfactory outcomes after implementing enhanced recovery after surgery (ERAS) in patients undergoing lumbar fusion surgery. However, little attention has been paid to the impact of chronologic age alone on perioperative outcomes.Methods: In the present study, patients were dichotomized into two groups: young-old (65– 79 years), and old-old (80 years and older). Given the heterogeneity and age-related comorbidities in this population and the need to compare similar groups, we performed propensity score matching for gender, body mass index (BMI), operation time, American Society of Anesthesiologists (ASA) grade, Charlson Comorbidity Index (CCI), fusion levels and frail status. Perioperative outcomes were compared between two groups.Results: In our study, we found there were significant discrepancies in length of stay (LOS) (7.17 ± 2.81 vs 8.11 ± 3.57 days, p = 0.031) and postoperative nausea and vomiting (3.7% vs 11.0%, p = 0.038); however, there were no significant differences in C-reactive protein (21.50 ± 26.52 vs 19.22 ± 22.04 mg/L, p = 0.490), overall complication rates (24.8% vs 33.0%, p = 0.179), ambulation time (2.89 ± 1.34 vs 2.55 ± 1.49 days, p = 0.078) or removal of urinary catheter time (2.47 ± 1.44 vs 2.32 ± 1.40 days, p = 0.446).Conclusion: There were few differences in perioperative outcomes between young-old and old-old groups. Despite similar postoperative complication rates, the old-old group might experience longer LOS when complications occur. More importantly, current outcomes suggested that chronologic age alone does not appear to have the capacity to reflect the tolerance of elderly patients to surgery.Keywords: enhanced recovery after surgery, propensity score matching, lumbar fusion surgery, elderly, postoperative outcomes

Ahmed O Kaseb,1 Yinghui Guan,2,&ast; Betul Gok Yavuz,1,&ast; Alexander R Abbas,2 Shan Lu,2 Elshad Hasanov,3 Han Chong Toh,4 Wendy Verret,5 Yulei Wang2 1Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Oncology Biomarker Development, Genentech Inc, South San Francisco, CA, USA; 3Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore; 5Product Development, Genentech Inc, South San Francisco, CA, USA&ast;These authors contributed equally to this workCorrespondence: Yulei Wang, Department of Oncology Biomarker Development, Genentech Inc, 1 DNA Way, South San Francisco, CA, 94080, USA, Tel +1 650 255 9698, Email wang.yulei@gene.com Ahmed O Kaseb, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 426, Houston, TX, 77030, USA, Tel +1 713 792 2828, Email akaseb@mdanderson.orgPurpose: Child-Turcotte-Pugh class A (CTP-A) in unresectable hepatocellular carcinoma (HCC) is the standard criterion for active therapy and clinical trial enrollment. We hypothesized that insulin-like growth factor-1 (IGF-1) derived scores may provide improved survival prediction over CTP classification. This study aimed to evaluate the potential prognostic and predictive effects of IGF-1 derived scores in the phase III IMbrave150 study.Patients and Methods: Baseline and on-treatment serum IGF-1 levels from 371 patients were subjected to central analysis. Patients’ IGF-1 score (1/2/3) and IGF-CTP score (A/B/C) were determined based on pre-specified cutoffs. Outcomes were analyzed by baseline and by on-treatment changes of the IGF-1 and IGF-CTP scores within and between the two treatment arms. The interaction between these scores and outcomes was assessed using univariate and multivariate analyses.Results: Baseline IGF-CTP score (A vs B/C) showed prognostic significance for OS in both the atezolizumab-bevacizumab (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.20– 0.56; P< 0.001) and sorafenib (HR, 0.32; 95% CI, 0.16– 0.65; P=0.002) arms. Baseline IGF-1 score (1 vs 2/3) also showed prognostic significance for OS in both the atezolizumab-bevacizumab (HR, 0.33; 95% CI, 0.20– 0.55; P< 0.001) and sorafenib (HR, 0.48; 95% CI, 0.26– 0.89; P=0.02) arms. HRs for PFS were consistent with those for OS. No significant predictive effects were observed for either score between the two arms. Kinetic analysis revealed that patients with increased IGF-1 score (1-> 2/3) at 3 weeks post treatment had shorter OS than patients with stable IGF-1 score of 1 in both the atezolizumab-bevacizumab (HR, 3.70; 95% CI, 1.56– 8.77; P=0.003) and sorafenib (HR, 5.83; 95% CI, 1.88– 18.12; P=0.0023) arms.Conclusion: Baseline and kinetic change of IGF-CTP and IGF-1 scores are independent prognostic factors for patients with unresectable HCC treated with atezolizumab-bevacizumab or sorafenib. These novel scores may provide improved patient stratification in future HCC clinical trials. IMbrave150 ClincialTrials.gov number, NCT03434379.Keywords: IGF-CTP score, prognostic biomarker, immunotherapy, HCC

Xiaofeng Zhou,1 Bingzhi Wang,2 Yu Liu,1 Zicheng Wang,2 Xuehui Zhao,2 Fanxiao Liu,2 Shun Lu,2 Weicheng Xu,2 Lianxin Li,1,2 Jinlei Dong2 1Department of Orthopaedics Surgery, Shandong Provincial Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Orthopaedics Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Lianxin Li, Department of Orthopaedics, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China, Tel +8613505312449, Email lilianxin@hotmail.com Jinlei Dong, Department of Orthopaedics, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China, Tel +861509874540, Email dongjinlei@163.comPurpose: The conventional lateral approach is widely used to treat radial head fractures with screws. However, the traditional incision may have shortcomings, including excessive exposure and significant scarring. We propose an innovative method – a mini-open lateral approach of less than 2.5 cm for surgical treatment of radial head fractures with screws.Methods: From Jan 2017 to Dec 2020, 34 patients diagnosed with closed radial head fracture were treated with open reduction and internal fixation (ORIF) in this study. The novel group (mini-open group) included 15 patients, and the other 19 patients were in the traditional group. The time of operation and the blood loss during operation were recorded. Postoperative clinical outcomes and radiographic results were recorded and compared between the two groups. The range of motion (ROM) in the elbow, the Visual Analogue Scale (VAS), the Mayo Elbow Performance Score (MEPS), Rating Scale of the American Shoulder and Elbow Surgeons (ASES), and the Shortened Disabilities of the Arm, Shoulder and Hand Questionnaire (Q-DASH) score and complications, such as wound infection, vascular and nerve damage, and fragment redisplacement were observed in the two groups.Results: In the comparison between the two groups, there was no significant difference in age, sex, cause of radial head fracture, or other basic information. The operation time, intraoperative blood loss, and VAS score at 3 days postoperation were significantly reduced in the novel group (p < 0.05). The follow-up results showed that there was no significant difference in MEPS, ASES, or Q-DASH scores between the two groups.Conclusion: The mini-open approach reduced intraoperative blood loss, shortened operation time, relieved patient pain, and achieved a satisfactory postoperative clinical result, which demonstrates that the novel approach is a safe and effective option for treating radial head fractures.Keywords: radial head, mini-open, fracture, screw, clinical efficacy

Ting Liang,1– 6 Ding Xiao,2,3,7 Shanshan Lu,2,3 Xu Ye,8 Zhiqiang Xiao1– 3 1National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 2Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 3Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 4Department of Hematology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 5Hunan Hematology Oncology Clinical Medical Research Center, Changsha, 410008, People’s Republic of China; 6National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 7Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 8Department of Radiation Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410008, People’s Republic of ChinaCorrespondence: Zhiqiang Xiao, National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, 410008, People’s Republic of China, Tel +86-13873146236, Email zqxiao2001@hotmail.comPurpose: To evaluate the prognostic value of interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), leukemia inhibitory factor (LIF), and macrophage migration inhibitory factor (MIF) in non-metastatic nasopharyngeal carcinoma (NPC) patients undergoing radical radiotherapy.Patients and Methods: A serum panel compromising the inflammatory factors was analyzed in 372 NPC patients before and after radiotherapy. Independent prognostic factors were screened out using multivariate Cox regression analysis. A prediction model was built based on the training set data and validated using the test set data. The prognostic value of these factors was evaluated using the time-dependent receiver operating characteristic (ROC) curve and an integrated time-averaged area under the curve (AUC).Results: The baseline levels of IL-6, GM-CSF, and MIF were independent factors associated with poor OS and DMFS. A predictive model base established combining the baseline levels of these factors. The AUC values for the test set were 0.9828, 0.9968, and 0.9571 at 1, 3, and 5 years, respectively, compared to 0.9978, 0.9981, and 0.9222 for the training set, respectively. The AUC values for DMFS at 1, 3, and 5-years for the training set were 0.8744, 0.8951, and 0.9358, respectively, compared to 0.9525, 0.9663, and 0.9625 for the test set, respectively. The combination of post-treatment levels of IL-6, GM-CSF, and LIF also had good predictive value for OS with an AUC value > 0.85 during follow-up.Conclusion: IL-6, GM-CSF, and MIF baseline levels are powerful prognostic factors for non-metastatic NPC patients. The combination of these factors effectively predicts OS and DMFS in non-metastatic NPC patients.Keywords: nasopharyngeal carcinoma, inflammatory factor, radical radiotherapy, prognostic value, overall survival

Guiping Li,1 Kamran Ali,2 Xiujun Gao,1 Sha Lu,1 Weiqin xu,1 Xiaoying Zhu1 1Mental Health Center Affiliated Hangzhou Seventh People’s Hospital Zhejiang University School of Medicine, Hangzhou, 310013, People’s Republic of China; 2Department of Dermatology, International Education College of Zhejiang Chinese Medical University, Hangzhou, 310006, People’s Republic of ChinaCorrespondence: Xiaoying Zhu, Mental Health Center Affiliated Hangzhou Seventh People’s Hospital Zhejiang University School of Medicine, Hangzhou, 310013, People’s Republic of China, Email m18957118053_2@163.comBackground/Objectives: Neurosyphilis is a disease caused by Treponema pallidum when it invades the central nervous system. Asymptomatic neurosyphilis (ANS) is one of the most common types of neurosyphilis, however it is often misdiagnosed. This study aimed to explore the impact of ANS on patient’s quality of life and social stigma.Methods: A total of 159 ANS patients were diagnosed by their serology and cerebrospinal fluid. These patients’ stigma and quality of life were assessed separately through the Social Impact Scale (SIS) and the Easy Response Questionnaire.Results: The average age was 36.25± 8.36 years old, and 114 patients were males (71.69%). The serum syphilis test of 159 selected patients was positive, and the indicators of nucleus cells, protein quantification, and syphilis antibodies in the cerebrospinal fluid met the criteria for ANS. The total stigma score was (40.23 ± 10.12), with the scores of the different entries being clearly differentiated, with the highest being the 15th entry (I feel I need to keep my illness a secret), with an average score of 3.15/4.Conclusion: Patients with asymptomatic neurosyphilis may feel social stigma and are more negative when facing their disease. Health-care workers should be aware of the particular aspects of their condition and pay special attention to the need for patient privacy.Keywords: neurosyphilis, asymptomatic neurosyphilis, social stigma, quality of life, social impact scale, sexually transmitted diseases

Zhigang Liu,1,2,&ast; Baisheng Fu,2,&ast; Weicheng Xu,2 Fanxiao Liu,2 Jinlei Dong,2 Lianxin Li,2 Dongsheng Zhou,2 Zhenhai Hao,2 Shun Lu2 1Department of Orthopaedics Surgery, Haining People’s Hospital, Jiaxing, People’s Republic of China; 2Department of Orthopaedics Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shun Lu, Department of Orthopaedics Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +8618653189700, Email sdqdpdlushun@163.comPurpose: Traumatic sciatic nerve injury is one of the most serious consequences of acetabular fracture. However, reports on this type of injury are rare. In this study, we investigated the demographics of acetabular fracture with traumatic sciatic nerve injury, the clinical characteristics of patients with these injuries, and potential risk factors.Patients and Methods: We retrospectively reviewed patients diagnosed to have acetabular fracture at our trauma center between January 2014 and June 2021. Data on patient demographics, characteristics of the acetabular fracture, whether or not sciatic nerve injury occurred, types of sciatic nerve injury, and risk factors were analyzed.Results: A total of 195 patients met the diagnostic criteria for acetabular fractures. The average Injury Severity Score was 25.9 and the average Abbreviated Injury Scale score was 12.4. Road traffic accidents and falls from height were the main causes. Chest injuries and lower extremity fractures were the most common associated injuries. Posterior wall fractures were the most common fracture type. After exclusion of spinal cord and iatrogenic sciatic nerve injuries, 18 patients with acetabular fractures had traumatic sciatic nerve injury. Four of the 19 sides with traumatic sciatic nerve injury involved the common peroneal nerve division and 15 involved both the common peroneal and tibial nerve divisions. Logistic regression analysis identified a higher AIS score, posterior column fracture, and posterior hip dislocation to be predictors of traumatic sciatic nerve injury.Conclusion: Acetabular fractures were mostly high-energy injuries. Posterior wall fractures were the most common acetabular fracture types. Most patients sustained injury to the sciatic nerve as well as injury to the common peroneal and tibial nerve divisions. A higher AIS score, posterior column fracture, and posterior hip dislocation were predictors of acetabular fracture combined with traumatic sciatic nerve injury.Keywords: acetabular fractures, traumatic sciatic nerve injury, posterior hip dislocation

Shun Lu,1 Fanxiao Liu,1 Weicheng Xu,1 Xiaofeng Zhou,2 Lianxin Li,1 Dongsheng Zhou,1 Qinghu Li,1 Jinlei Dong1 1Department of Orthopaedics Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan City, Shandong Providence, People’s Republic of China; 2Department of Orthopaedics Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan City, Shandong Providence, People’s Republic of ChinaCorrespondence: Qinghu Li; Jinlei Dong, Department of Orthopaedics, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan City, Shandong Providence, People’s Republic of China, Tel +8613402214695 ; +861509874540, Email sdliqinghu@163.com; dongjinlei@163.comBackground: Open Tile C pelvic fractures are particularly severe. However, reports on their management and outcomes are relatively rare. This study analyzed the demographic and clinical characteristics of patients with open Tile C pelvic fractures and describes our management and outcomes of these injuries.Methods: This retrospective review included all patients with open Tile C pelvic fractures treated in our department between January 2014 and June 2021. Data on patient demographics, characteristics of the injuries, surgical management, and outcomes were analyzed.Results: Thirty patients with a mean age of 34.0 years met the diagnostic criteria. The average Injury Severity Score was 40.3. According to the Tile fracture classification, 6 patients sustained type C1.1, 12 sustained type C1.2, 3 sustained type C1.3, 5 sustained C2 and 4 sustained type C3. Most patients had soft tissue injuries in multiple zones. All patients sustained associated injuries. Management consisted of bed rest in 8 cases, external fixation as the final strategy in 14, conversion from external fixation to internal fixation in 3, open reduction with internal fixation in 5, and amputation in 6. The average amount of packed red blood cells transfused was 33.3 units, the average intensive care unit stay was 11.3 days, the mean number of operations required was 6.2, and the mean length of hospital stay was 81.8 days. The main complications were early soft tissue infections and venous thrombosis. One patient died of sepsis and multi-organ failure. Soft tissue injuries in multiple zones increased utilization of hospital resources whereas anorectal injuries did not. Vascular damage accompanying truck crush injuries had a high amputation rate.Conclusion: Open Tile C pelvic fractures require multidisciplinary diagnosis and management and consume considerable hospital resources. More emphasis needs to be placed on this complex injury.Keywords: open tile C fractures, management, outcomes

Peng Cui,1,2,&ast; Peng Wang,1,2,&ast; Jialin Wang,1,2 Xu Liu,1,2 Chao Kong,1,2 Shibao Lu1,2 1Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2National Clinical Research Center for Geriatric Diseases, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Kong; Shibao Lu, Email kong988500@163.com; spinelu@xwhosp.orgBackground: There are many studies on the impact of frailty on postoperative complications; however, there are few studies focusing on stepwise propensity score matching (PSM) to offset the influence of age.Methods: We gathered data for patients undergoing short-level posterior lumbar interbody fusion from January to December 2021. According to the Fried frailty phenotype, we categorized patients into non-frail, pre-frail, and frail groups, then, stepwise PSM for age, sex, American Society of Anesthesiologists (ASA) and fusion levels were performed to keep comparable clinical data between groups. Univariate and multivariate logistic regressions were used to determine the impact of clinical demographics on postoperative complications.Results: A total of 559 consecutive patients with complete medical records were enrolled (237 males and 322 females; mean age 72.55 ± 5.86 years). After PSM, we found that pre-frail patients were more vulnerable to develop urinary retention (p = 0.031) and surgical site infections (p = 0.021) than non-frail patients. Longer length of stay (LOS), delayed ambulation and removal of urinary catheter times were observed in pre-frail patients. However, there was a significant difference only in LOS between pre-frail and frail patients. Binary logistic regression revealed that C-reactive protein (CRP) and frail status were independently associated with postoperative complications between non-frail and pre-frail patients, while only CRP was independently correlated with complications between pre-frail and frail patients.Conclusion: After PSM, we found higher rates of urinary retention and surgical site infections in pre-frail patients than in non-frail patients. CRP was independently related to postoperative complications, while frail status was only independently associated with postoperative complications between pre-frail and non-frail patients. Pre-frail/frail patients tended to have more severe stress responses than non-frail patients.Keywords: frail, propensity score matching, lumbar, postoperative complications

Tingting Chen,1,2,&ast; Bingxiang Ma,1,2,&ast; Shi Lu,1,2 Lupeng Zeng,1,2 Huaying Wang,1,2 Wanhua Shi,1,2 Linying Zhou,3 Yaokun Xia,4 Xi Zhang,1 Jing Zhang,5 Jinghua Chen1 1School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 2Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 3Electron Microscopy Facility, Public Technology Service Center, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 4Key Laboratory of the Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 5Department of Chemical Biology, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, 350002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinghua Chen, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China, Tel +86 591-22862016, Fax +86 591-22862016, Email cjh_huaxue@126.com; xz@fjmu.edu.cnPurpose: In recent years, a variety of nanoparticles with excellent anticancer and delivery properties have emerged for cancer therapy. However, potential toxicity, high production cost and complex preparation procedures have been obstacles to their use in biomedicine. Here, we obtained cucumber-derived nanovesicles (CDNVs) at high yield and low cost by simple juicing and ultracentrifugation. The anticancer effects of CDNVs were evaluated in vitro and in vivo.Methods: Transmission electron microscope, nanoparticle tracking analysis and laser particle size analysis were used to characterize the morphology, diameter and zeta potential of CDNVs, respectively. The anticancer effects of CDNVs in vitro were evaluated by MTT and apoptosis assays. The mechanism was further explored by measuring the protein levels of signal transducer and activator of transcription 3 pathway, reactive oxygen species, cell cycle distribution and caspase activity. In-vivo anticancer efficacy was evaluated by measuring tumor volume and weight of mice in three different treatment groups (CDNVs, cucurbitacin B and PBS).Results: CDNVs inhibited proliferation of human non-small cell lung cancer cells by suppressing signal transducer and activator of transcription 3 activation, generating reactive oxygen species, promoting cell cycle arrest, and activating the caspase pathway. These CDNVs exhibited strong anticancer effects both in vitro and in vivo, and reduced the rate of tumor growth without obvious toxicity to mouse visceral organs. Compared with an equivalent dose of cucurbitacin B, CDNVs exerted stronger anticancer effects in vitro and in vivo.Conclusion: These results demonstrate that CDNVs suppress tumor growth. This study addresses the development of cancer therapeutic drugs using plant-derived nanovesicles that are cost-efficient, simple to produce in high yields, and provide an alternative approach to drug isolation that may help advance sustainability of medicinal plants.Keywords: ROS, STAT3, cucurbitacin B, anticancer

Xingyue Zeng,1,&ast; Songsong Lu,1,&ast; Meng Li,1 Mohan Zheng,2 Tianci Liu,1 Rui Kang,1 Lijuan Xu,3 Qinzhu Xu,1 Ying Song,1 Chen Liu1 1Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of China; 2School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, People’s Republic of China; 3Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chen Liu, Department of Clinical Laboratory, Peking University People’s Hospital, 11# Xizhimen South Street, Beijing, 100044, People’s Republic of China, Tel +86 10 88326203, Fax +86 10 88326300, Email liuchen-best@pku.edu.cnBackground: Follicular T helper (TFH) and follicular regulatory T (TFR) cells play important roles in humoral immunity. Nevertheless, their significance in rheumatoid arthritis (RA) pathogenesis has not been fully elucidated. As an important treatment strategy, the effect of inflammatory factor-neutralizing antibodies on TFH and TFR in RA remains unclear.Methods: We used the collagen-induced arthritis (CIA) mouse model to illustrate the quantity and functional changes in TFH and TFR cells. The changes of plasmablast, TFH and TFR cells in the spleen and peripheral blood of CIA mice were analyzed by flow cytometry. The levels of TFH and TFR and their functional subsets in the spleen after anti-inflammatory antibody treatment were analyzed and compared. The functional changes of TFH and TFR in CIA mice before and after treatment were detected by in vitro culture experiments.Results: Plasmablast levels were increased in CIA spleen and peripheral blood and both TFH and TFR cell levels were upregulated. TFH and TFR cells were decreased significantly after the anti-inflammatory antibody treatment. TIGIT+ and TIGIT+CD226− TFH cells in CIA mouse spleen were elevated and PD-1 and ICOS expression on spleen TFH and TFR cells was increased. Both the ability of TFH cells to secrete IL-21 and aid B cells and the ability of TFR cells to secrete IL-10 and inhibit TFH cells were enhanced in the CIA mice. After antibody treatment, the cell subsets and functions were recovered.Conclusion: Germinal center TFH and TFR cells were increased and their functions were enhanced. With inflammatory factor-neutralizing antibody treatment, TFH and TFR subsets and their functions returned to normal. These findings provide important information on the dynamics of humoral immune-related cell subsets in RA and the effects of treatment on them.Keywords: TFH, TFR, collagen-induced arthritis, rheumatoid arthritis, inflammatory cytokines

Lu Yang,1,&ast; Li Sun,1 Yalan Cao,1 Qi Wang,1,2 Anni Song,1 Ru Zhu,1 Wenqi Liu,1 Shengjun Lu1,&ast; 1Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Histology and Embryology, School of Basic Medicine, Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengjun Lu; Wenqi Liu, Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Tel +86 15307159688 ; +86 13886014791, Fax +86-27-83692608, Email Lushengjun@hust.edu.cn; liu_wq2002cn@hotmail.comPurpose: In schistosomiasis-associated hepatic fibrosis, the role of murine UL16-binding protein-like transcript 1 (MULT1), the strongest ligand of natural killer group 2-member D receptor (NKG2D), remains unclear. Here, Schistosoma japonicum-infected mice administered with MULT1-encoding DNA were used to test MULT1 as a potential therapy for schistosomiasis-associated hepatic fibrosis and explore relevant mechanisms.Materials and Methods: A recombinant plasmid encoding MULT1 (p-rMULT1) was constructed and administered to Schistosoma japonicum-infected BALB/c mice via hydrodynamic tail vein injection. Egg granulomas in liver, hepatic fibrosis biomarkers and levels of cytokines were investigated. Comparisons of CD4+ T, CD8+ T, NK and NKT proportions as well as their phenotype were performed not only between Schistosoma infected, p-rMULT1 treated group and Schistosoma infected, backbone plasmid pEGFP-N1 treated group but also between infected, nontreated group and health control group.Results: Reduced area of granuloma formation and fibrosis around single eggs, downregulated expression of collagen I, α-smooth muscle actin, TGF-β and IL-10, and upregulated expression of IFN-γ, were observed in the livers of p-rMULT1 treated mice. p-rMULT1 treatment improved Schistosoma infection impacted immune microenvironment by modulating proportion of CD4+ T CD8+ T, natural killer (NK) and NKT cells, enhancing expression of NKG2D, in lymphocytes, and augmenting IFN-γ secretion by CD4+ T, CD8+ T, NK and NKT cells, as well as partially reversing some other phenotype changes of lymphocytes.Conclusion: To the best of our knowledge, we provided the first in vivo evidence that MULT1 is a favorable anti-fibrosis factor in the context of schistosomiasis. The inhibitory effect of MULT1 overexpression on schistosomiasis associated with hepatic fibrosis may result from augmenting the proportion and function of NKG2D-expressing immune cells, and from enhancing NK- and T-cell activation, as well as regulating the helper T (Th)1/Th2 balance.Keywords: schistosomiasis, NKG2D, liver fibrosis, IFN-γ, natural killer cells, T lymphocytes

Xiaohong Yu,1,&ast; Jing Wang,1,&ast; Qianqian Han,1,&ast; Wen Chu,1 Shaowen Lu,1 Yu Liu,2 Yi Peng,1 Jie Xu,1 Yanqing Shui1 1Department of Periodontology, School and Hospital of Stomatology, Kunming Medical University, Yunnan, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Kunming Medical University, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanqing Shui, Department of Periodontology, Affiliated Stomatology Hospital of Kunming Medical University, Block C, Hecheng International, No. 1088 Haiyuan Middle Road, Wuhua District, Kunming, 650106, Yunnan, People’s Republic of China, Tel +86 15987150210, Email amy.shui@163.comBackground: Yunnan Baiyao, as a traditional Chinese herbal remedy with definite curative effect, has recently been proven can promote the proliferation of osteoblasts and differentiation of human periodontal ligament fibroblasts. Bio-Oss® scaffold is a porous bone graft material of natural and antigen-free bovine bone origin.Methods: To observe the effect of Yunnan Baiyao on the differentiation of HPDLFs on the Bio-Oss® collagen scaffold in vivo, the HPDLFs-Bio-Oss® collagen complex was constructed in vitro, and Yunnan Baiyao aqueous solution was added, respectively. The complex was divided into Yunnan Baiyao group I (50 μg/mL), Yunnan Baiyao group II (100 μg/mL), positive control (rhBMP-2) group and sham group. HPDLFs were identified by immunocytochemistry and immunofluorescence. The compatibility of HPDLFs with Bio-Oss® collagen was observed by fluorescence microscope and scanning electron microscope. The specimens were taken for HE staining after 8 weeks since the complex was implanted into nude mice, and the expressions of osteocalcin (OC), bone sialoprotein (BSP), osteopontin (OPN), and collagen I (CON-I) were detected by immunohistochemistry and qRT-PCR.Results: The number of capillaries and osteoblasts increased significantly after Yunnan Baiyao stimulation, and the expressions of BSP, OC, OPN and CON-I were increased after Yunnan Baiyao stimulation in a dose-dependent manner.Conclusion: Yunnan Baiyao solution can promote the differentiation of HPDLFs and the generation of capillaries on Bio-Oss® collagen scaffold in a dose-dependent manner.Keywords: Yunnan Baiyao, human periodontal ligament fibroblasts, Bio-Oss® collagen, differentiation

Fen Xu,1,* Juping Tang,1,* Zhiping Zhu,2 Yan Chen,3 Wen Hu,4 Sha Lu,5 Yunxian Zhou,6 Ding Lin7 1Department of Nursing, Hangzhou Third Hospital, Hangzhou, People’s Republic of China; 2Department of Vascular Surgery, Hangzhou Third Hospital, Hangzhou, People’s Republic of China; 3Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Department of Obstetrics and Gynecology, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, People’s Republic of China; 6School of Nursing, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 7Department of Cardiovascular Medicine, Hangzhou Third Hospital, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunxian Zhou, School of Nursing, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou, Zhejiang, 310053, People’s Republic of China, Tel +860571-86633121, Email yunxianzhou@hotmail.com Ding Lin, Department of Cardiovascular Medicine, Hangzhou Third Hospital, No. 38 Xihu Road, Hangzhou, Zhejiang Province, 310009, People’s Republic of China, Tel +860571-87827512, Email linting11222021@163.comPurpose: To investigate the current state of medication adherence among patients with inflammatory bowel disease (IBD) in China and analyze the influencing factors.Patients and Methods: We recruited as many eligible subjects as possible and a total of 105 patients with IBD finished this cross-sectional survey. The General Information Questionnaire and Morisky Medication Adherence Scale were used as measurement instruments. The factors influencing the Morisky score were studied by multiple linear regression analysis.Results: The average Morisky score was 6.11 ± 1.93. Univariate analysis showed that there were statistically significant differences in Morisky scores among patients with different ages, education levels, disease types, medication administration methods, medication frequencies, disease understanding and knowledge learning frequencies (P < 0.05). Multiple stepwise linear regression analyses showed that medication frequency, medication administration method and disease understanding were important factors influencing the Morisky score (P < 0.001).Conclusion: Our data confirmed that the medication adherence of IBD patients was poor, especially among patients taking oral medication, those taking medications with a high frequency and those with a low understanding of the disease. To reduce symptom recurrence and control the disease, medical staff should pay attention to the individual patient factors, simplify the medication regimens, formulate effective coping strategies for drug management support.Keywords: Crohn’s disease, inflammatory bowel disease, medication adherence, ulcerative colitis

Cheng-Tao Yu,1,&ast; Tongqing Chen,1,&ast; Sicheng Lu,1,&ast; Wenlong Hu,1 Qinchang Zhang,1 Jiani Tan,1 Dongdong Sun,1 Liu Li,1 Xin Sun,1 Changliang Xu,1 Yueyang Lai,1 Minmin Fan,1 Zhengjie Shen,2 Weixing Shen,1 Haibo Cheng1 1The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Medical Oncology Department, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weixing Shen; Haibo Cheng, The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China, Tel +86 13815857118, Fax +86 2585811006, Email haibocheng@njucm.edu.cn; weixingshen@njucm.edu.cnPurpose: Colorectal cancer (CRC) remains the third most common tumor worldwide. Ulcerative colitis (UC) could cause chronic inflammation and ulcers in the colon and rectum. UC is a risk factor for a high incidence of CRC, and the incidence of UC-associated CRC (UC-CRC) is still increasing. Chinese medicine prescription, Xian-Lian-Jie-Du decoction (XLJDD), has been proven its efficacy in some UC-CRC patients. However, the mechanism of XLJDD in treating UC-CRC remains unknown. This study aimed to investigate the mechanism of XLJDD in treating UC-CRC.Methods: We constructed an AOM/DSS mouse model that could simulate the various stages of UC-CRC in humans. XLJDD and its 5 main components are used to treat the AOM/DSS model, respectively. With the power of high-throughput sequencing technology, we described the mechanism of XLJDD from transcriptomics, proteomics, and single-cell transcriptomics.Results: Our results showed that XLJDD could effectively suppress the occurrence and development of colorectal tumors. Using the weighted correlation network analysis (WGCNA), several mRNA and protein modules that respond to XLJDD have been identified. Moreover, two essential genes, Mfsd2a and Ccdc85c, were caught our attention. They were prognostic markers in CRC patients, and their expression could be significantly modulated by XLJDD, showing their potential as effective targets of XLJDD. In addition, we also discovered that XLJDD could affect the cell composition of the colorectal tumor environment, especially in the infiltration of B cells.Conclusion: We demonstrated that XLJDD could prevent the initiation and development of colorectal tumors by modulating the expression of Mfsd2a and Ccdc85c and reducing the infiltration of B cells in the tumor microenvironment of colorectal tumor.Keywords: colorectal tumor, Mfsd2a, Ccdc85c, inflammation pathway, B cell infiltration

Siliang Lu,1,2 Ke Li,1,2 Yinxiang Yang,2 Qian Wang,2 Yu Yu,1,2 Zhaoyan Wang,2 Zuo Luan1 1The First Clinical Medical College, Guangxi Medical University, Nanning, 530021, Guangxi, People’s Republic of China; 2Laboratory of Pediatrics, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, People’s Republic of ChinaCorrespondence: Zhaoyan Wang, Laboratory of Pediatrics, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, People’s Republic of China, Tel +86-13581827961, Email wangzhaoyan999@126.com Zuo Luan, The First Clinical Medical College, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-18600310270, Fax +86-1066958303, Email luanzuo@aliyun.comObjective: Stem cell administration via the intranasal route has shown promise as a new therapy for hypoxic-ischemic encephalopathy (HIE). In this study, we aimed to improve the intranasal delivery of stem cells to the brain.Methods: Human neural stem cells (hNSCs) were identified using immunofluorescence, morphological, and flow cytometry assays before transplantation, and cell migration capacity was examined using the transwell assay. Cerebral hypoxia-ischemia (HI) was induced in 7-day-old rats, followed by the intranasal transplantation of CM-Dil-labeled hNSCs. We examined various experimental conditions, including preconditioning hNSCs with hypoxia, catheter method, multiple low-dose transplantation, head position, cell appropriate concentration, and volume. Rats were sacrificed 1 or 3 days after the final intranasal administration, and parts of the nasal tissue and whole brain sections were analyzed under a fluorescence microscope.Results: The isolated hNSCs met the characteristics of neural stem cells. Hypoxia (5% O2, 24 h) enhanced the surface expression of CXC chemokine receptor 4 (CXCR4) (9.21 ± 1.9% ∼ 24.76 ± 2.24%, P < 0.01) on hNSCs and improved migration (toward stromal cell-derived factor 1 [SDF-1], 0.54 ± 0.11% ∼ 8.65 ± 1.76%, P < 0.001; toward fetal bovine serum, 8.36 ± 0.81% ∼ 21.74 ± 0.85%, P < 0.0001). Further improvement increased the number of surviving cell distribution with increased uniformity on the olfactory epithelium and allowed the cells to stay in the nasal cavity for at least 72 h, but they did not survive for longer than 48 h. Optimization of pre-transplantation conditions augmented the success rate of intranasally delivered cells to the brain (0– 41.6%). We also tentatively identified that hNSCs crossed the olfactory epithelium into the tissue space below the lamina propria, with cerebrospinal fluid entering the cribriform plate into the subarachnoid space, and then migrated toward injured areas along the brain blood vessels.Conclusion: This study offers some helpful advice and reference for addressing the problem of repeatability in the intranasal delivery of stem cells.Keywords: neural stem cell, intranasal, optimization, transplantation, hypoxic-ischemic brain injury

Zhenpeng Yang,1,2,&ast; Shuai Lu,1,2,&ast; Yuying Wang,1,2 Huazhen Tang,1,2 Bing Wang,1,2 Xibo Sun,1,3 Jinxiu Qu,1,2 Benqiang Rao1,2 1Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Key Laboratory of Cancer FSMP for State Market Regulation, Beijing Shijitan Hospital, Beijing, People’s Republic of China; 3Department of Breast Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Benqiang Rao Tel +86 13521237767Email raobenqiang@bjsjth.cnObjective: This study aims at exploring the relationship between necroptosis-related miRNAs and colon cancer prognosis.Methods: We downloaded the miRNA sequencing data from the TCGA, and eight differentially expressed necroptosis-related miRNAs were screened. Then, we used Cox regression analysis to establish a prediction model of necroptosis-related miRNA. Finally, the prognosis related miRNAs were used to predict the target genes, and functional analysis was used to explore the potential mechanism of these target genes.Results: The miRNA-seq data of 444 COAD cases were downloaded from TCGA. We identified 8 differentially expressed miRNAs (has-miR-16-5p, has-miR-141-3p, has-miR-148a-3p, has-miR-425-5p, has-miR-7-5p, has-miR-223-3p, has-miR-200a-5p, and has-miR-500a-3p), then Cox analysis was performed for determining eight-miRNA signature prognostic biomarkers with obviously different OS. The area under the curve (AUC) of receiver operating characteristic (ROC) curve for predicting 1-, 3-, and 5-year survival were 0.663, 0.653 and 0.639, respectively. The multivariate analysis also implied that the risk score was an independent prognostic factor considering other confounding factors (HR = 1.847, 95% CI = 1.197– 2.848, P = 0.006). According to the Kaplan–Meier analysis, the expression of hsa-miR-500a-3p (P = 0.003), hsa-miR-16-5p (P = 0.004) and hsa-miR-148a-3p (P = 0.035) significantly affected OS outcomes. We predicted the target genes of these three miRNAs and then screened 10 hub genes (CCND1, SMAD3, SMAD2, CDK1, TGFB2, CDC25A, CHEK1, VEGFA, CCNE1, WEE1). In addition, CHEK1 was associated with the survival prognosis.Conclusion: Our study demonstrated that necroptosis is closely associated with colon cancer, and the model of eight necroptosis-related miRNAs are potentially useful prognostic biomarkers and therapeutic targets for colon cancer.Keywords: necroptosis, colon cancer, prognosis

Fenghai Liu, Meng Zhao, Shan Lu, Liqing Kang Department of Magnetic Resonance Imaging, Cangzhou Central Hospital, Cangzhou, Hebei Province, 061001, People’s Republic of ChinaCorrespondence: Liqing KangDepartment of Magnetic Resonance Imaging, Cangzhou Central Hospital, No. 16 of Xinhua West Road, Cangzhou, 061001, Hebei Province, People’s Republic of ChinaTel +86 13333367921Email 13333367921@163.comObjective: DCE-MRI is an imaging technique that reflects the blood perfusion status of the tissue’s microcirculation. The purpose of this article is to explore the clinical value of dynamic contrast-enhanced (DCE)-MRI in distinguishing benign and malignant tongue lesions and the internal heterogeneity of a tumour.Methods: The patients were divided into a tongue cancer group (22 patients) and a glossitis group (7 patients) based on the pathology results. All of the patients underwent DCE-MRI examination.Results: The results of this study showed that the volume transfer constant (Ktrans), rate constant (Kep), contrast enhancement ratio (CER) and initial area under the gadolinium contrast agent concentration time curve (IAUGG) values of the tongue cancer group were significantly higher than those of the glossitis group, and the difference was statistically significant (P < 0.05). However, the extravascular extracellular volume fraction (Ve), fractional plasma volume (fPV), maximum slope (MaxSlope), and bolus arrival time (BAT) values measured by DCE-MRI in the tongue cancer group were not significantly different from those in the glossitis group (P > 0.05). The results of this study showed that the Ktrans, Kep, and IAUGG values measured by DCE-MRI had a good ability to distinguish tongue inflammation from tumours and Ktrans threshold of 0.484 has the best discriminative ability among them. The mean Ktrans values of stage I–II lesions were significantly higher than that of stage III–IV lesion (p = 0.045).Conclusion: DCE-MRI is effective in distinguishing between benign and malignant tongue lesions and the internal heterogeneity of the tumour; it is worth following up in a larger study.Clinical Registration Number: Research registry 6393.Keywords: DCE-MRI, tongue cancer, tumour heterogeneity, tumour microenvironment, tumour precision diagnosis and treatment

Yanan Xu,1,&ast; Zihao Li,1,&ast; Shounan Lu,2 Chaoqun Wang,2 Shanjia Ke,2 Xinglong Li,2 Bing Yin,2 Hongjun Yu,2 Menghua Zhou,1 Shangha Pan,3 Hongchi Jiang,1 Yong Ma2 1Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Hepatic Minimal Invasive Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 3Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongchi Jiang; Yong MaKey Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150001, People’s Republic of ChinaTel +86-451-85553886; +86-451-85555376Email jianghc2013@163.com; mayong@ems.hrbmu.edu.cnPurpose: Itaconate is well known for its strong anti-inflammatory and antioxidant effect, but little is known about the potential role of long non-coding RNAs (lncRNAs) in the underlying mechanisms of hepatic ischemia-reperfusion (IR) injury. The aim of our study is to identify lncRNAs related to IR injury and itaconate-mediated protection and to demonstrate the mechanism by which itaconate acts in liver IR injury from the new perspective of lncRNAs.Methods: 4-Octyl itaconate (OI), a membrane-permeable derivative of itaconate, was used as a substitute for itaconate in our study. By using a mouse model of hepatic IR injury, serum and liver samples were collected to measure indexes of liver injury. Then, the liver samples of the mice were subjected to RNA sequencing (RNA-seq) and subsequent bioinformatics analysis.Results: Itaconate attenuated liver IR injury. A total of 138 lncRNAs and 156 messenger RNAs (mRNAs) were markedly differentially expressed in the IR-damaged liver tissues pretreated with OI compared with the matched liver tissues treated with vehicle. Functional analysis indicated that lncRNAs may indirectly participate in the effects of itaconate. Furthermore, 41 mRNAs were examined for the protein–protein interaction (PPI) network analysis, and a key gene cluster was defined. Then, combined the coexpression analysis and the cis and trans regulatory function prediction of lncRNAs, some “candidate” lncRNA-mRNA pairs which might relate to itaconate-mediated liver protection were identified, while the relationship requires future validation.Conclusion: Our study revealed that itaconate could protect the liver against IR injury and that lncRNAs might play a role in this process. Our study provides a novel way to investigate the mechanism by which itaconate affects hepatic IR injury and exerts its anti-inflammatory and antioxidative stress effects.Keywords: itaconate, ischemia-reperfusion injury, liver, lncRNA

Siyao Deng,1 Wenjing Ye,1 Shichuan Zhang,2,3 Guiquan Zhu,4 Peng Zhang,2 Yanqiong Song,2 Fanglei Duan,3 Jinyi Lang,2,3 Shun Lu2,3 1School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, People’s Republic of China; 4State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Shun LuDepartment of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Renmin South Road 55#, Chengdu, 610041, People’s Republic of ChinaTel +86 28 85420897Fax +86 28 85420110Email lushun1982@live.cnPurpose: Fanconi anemia (FA) is a rare genetic disorder characterized by congenital anomalies, progressive bone marrow failure and high susceptibility to solid tumors, especially head and neck squamous cell carcinoma (HNSCC). Management of FA patients with head and neck cancer is a challenge due to increased risk of surgery, poor tolerance of chemotherapy, and severe myelotoxicity of radiotherapy.Patients and Methods: We present a case of a 33-year-old man with carcinoma of oral tongue (T1N2M0), who experienced prolonged and profound bone marrow failure as a consequence of concurrent cisplatin/radiation. The young patient who developed HNSCC without risk factors, the myelotoxicity after exposure to platinum-based agent cisplatin and the further evaluation of phenotypic characteristics raised suspicion of FA. Whole exome sequencing performed for the patient and parents ultimately established the diagnosis of FA.Results: Genetic testing in 23 FANC genes revealed two novel heterozygous mutations, c.367C>T and c.3971_3972delCGinsTT in FANCA gene of the patient, which were inherited from his father and mother, respectively. Radiotherapy with reduced dose has successfully alleviated the symptoms of tumor invasion and progression, and the radiation-related side effects were acceptable. Unfortunately, the patient eventually died of locoregional disease progression.Conclusion: This case highlights the importance of considering the diagnosis of FA in young patients who develop HNSCC in the absence of risk factors, thus permitting more effective oncological treatment strategies and improved outcomes. In conclusion, any decision on different modalities of management in such patients should be based on a balance between locoregional control and therapeutic toxicity.Keywords: fanconi anemia, radiotherapy, cisplatin, head and neck squamous cell carcinoma, toxicity

Peng Xu,1 Shuo Wang,1 Yukun Luo,1 Jun Yin,1 Yazid Belkacemi,2 Shun Lu,1 Mei Feng,1 Jinyi Lang1 1Department of Radiation Oncology, Sichuan Cancer Hospital and Research Institute, Chengdu, People’s Republic of China; 2Department of Radiation Oncology, APHP – University Hospital of Henri Mondor, Creteil, FranceCorrespondence: Jinyi LangDepartment of Radiation Oncology, Sichuan Cancer Hospital and Research Institute, Chengdu, 610041, People’s Republic of ChinaTel +862885420152Email langjy610@163.comObjective: This study was retrospectively evaluated the outcome of postoperative intensity modulation radiotherapy (IMRT) for patients with adenoid cystic carcinoma of head and neck (ACCHN), and identified the unfavorable prognostic factors.Methods: Fifty-five ACCHN patients treated in Sichuan Cancer Hospital between January 2007 and December 2016 were retrospectively evaluated. Median age of patient was 47 years (range, 21– 73 years). Thirty-five patients were male and 20 were female. In 30 patients, tumors were located in major salivary glands (54.5%), and 25 patients in minor salivary glands (45.5%). The numbers of R0, R1, and R2 surgical resection classification patients were 22 (40.0%), 20 (36.4%), and 13 (23.6%). The median total RT dose was 62 Gy (range, 46– 72 Gy), and 54.5% of patients were treated with adjuvant chemotherapy. Statistical analyses were performed using the Log rank test for univariate analysis and the Cox proportional hazard model for multivariate analysis.Results: Median follow-up period was 68.5 months (12– 132 months). The 5-year local-regional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 93.9%, 75.3% and 82.5%. In univariate analysis, T stages (p=0.025) and AJCC stages (p=0.036) were the prognostic factors for OS; Age (p=0.042), T stages (p=0.025), N stages (p=0.021), AJCC stages (p=0.021) and adjuvant chemotherapy (p=0.010) were the prognostic factors for DMFS; T stage (p=0.049) was the prognostic factor for LRRFS. In multivariate factors analyses, T stages (p=0.026), AJCC stages (p=0.028) and RT dose (p=0.025) were the significant prognosticators for OS. The most common acute toxicities over three degrees were myelosuppression (5.5%), mucositis (9.1%) and dermatitis (1.8%).Conclusion: Postoperative IMRT seems to achieve reasonable local-regional control and OS in patients with adenoid cystic carcinoma of head and neck, with acceptable treatment relative toxicities.Keywords: ACCHN, postoperative radiotherapy, IMRT, clinical efficacy, prognostic analysis

Xiaoqin Zhu,1,2,* Jia Zhu,1,2,* Feifei Sun,1,2,* Zijun Zhen,1,2 Dalei Zhou,1,3 Suying Lu,1,2 Junting Huang,1,2 Yi Que,1,2 Lian Zhang,1,2 Ruiqing Cai,1,2 Juan Wang,1,2 Yizhuo Zhang1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Pediatric Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yizhuo Zhang; Juan Wang Email zhangyzh@sysucc.org.cn; wangjuan@sysucc.org.cnObjective: The association between UGT1A1*6/*28 polymorphisms and treatment outcomes of irinotecan in children remains unknown. This retrospective study investigated the influence of UGT1A1*6/*28 polymorphisms on irinotecan toxicity and survival of pediatric patients with relapsed/refractory solid tumors.Methods: The present study enrolled a total of 44 patients aged younger than 18 years at Sun Yat-sen University Cancer Center between 2014 and 2017.Results: There were 26 boys and 18 girls; the median age at first VIT course was six years (range: 1– 18 years). The tumor types included neuroblastoma (n = 25), rhabdomyosarcoma (n = 11), Wilm’s tumor (n = 4), medulloblastoma (n = 2), and desmoplastic small round cell tumor (n = 2). Overall, 203 courses of VIT regimens were prescribed. Neither UGT1A1*6 nor *28 polymorphisms were associated with the incidence rates of severe (grade III–IV) irinotecan-related toxicities, but tended to reduce the patient overall survival (UGT1A1*6, P = 0.146; UGT1A1*28, P = 0.195). Moreover, patients with mutant UGT1A1*6 genotypes were more likely to develop grade I–IV irinotecan-related diarrhea (P = 0.043) and anemia (P = 0.002). Overall, the UGT1A1*28 polymorphism may play a protective role against irinotecan-related diarrhea and abdominal pain.Conclusion: In relapsed/refractory pediatric solid tumors, the UGT1A1*6 polymorphism was a risk factor of irinotecan-related diarrhea and anemia. The UGT1A1*28 polymorphism may serve a protective role in irinotecan-related abdominal pain and diarrhea. Both mutations had a tendency to be risk factors for survival. Nevertheless, prospective studies are required to verify such conclusions.Keywords: UGT1A1 *6/*28 polymorphism, irinotecan toxicity, pediatric, relapsed/refractory solid tumors

Liqiang Qi,1 Bo Sun,2 Beibei Yang,2 Su Lu2 1Department of Breast Surgical Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 2The 2nd Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People’s Republic of ChinaCorrespondence: Liqiang QiDepartment of Breast Surgical Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People’s Republic of ChinaTel +86 10-87787130Email qiliqiang_bj@tom.comIntroduction: Long intergenic non-protein coding RNA 665 (LINC00665) has been revealed to contribute cancer progression in many cancer types including liver and gastric cancer. However, the roles of LINC00665 in breast cancer (BC) remain to be explored.Methods: We explored LINC00665 expression in BC tissues and normal tissues at GEPIA. Then, its expression in BC cells (HCC-1937, MDA-MB-231, and MCF-7) and normal cells (MCF10A) was analyzed with qRT-PCR. In addition, the mechanisms of LINC00665 in BC were explored using bioinformatic analyses, luciferase activity reporter assay, RNA pull-down assay, and rescue experiments.Results: We showed LINC00665 expression was significantly increased in both BC tissues and cells. The knockdown of LINC00625 significantly inhibits BC cell growth and promotes cell apoptosis in vitro, while the overexpression of LINC00625 has the opposite effects on BC progression. LINC00665 could affect BC progression via regulating miR-551b-5p.Discussion: Taken together, our study showed that the LINC00665/miR-551b-5p axis was involved in the progression of BC.Keywords: LINC00665, miR-551b-5p, breast cancer, progression

Yang Li,1 Yuhan Zhang,1 Shuaibing Wang,2 Su Lu,1 Yixuan Song,1 Hong Liu1 1The Second Surgical Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China; 2Oncology Department, China National Petroleum Corporation Central Hospital, Langfang, Hebei Province, 065000, People’s Republic of ChinaCorrespondence: Hong LiuThe Second Surgical Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Road, Hexi District, Tianjin, 300060, People’s Republic of ChinaTel +86-18622221169Email liuhongzhang0101@163.comPurpose: We aimed to examine the effect of pregnancy on prognosis in young breast cancer (YBC) patients with hormone receptor (HR) positive after surgery and the safety of interrupting endocrine therapy (ET).Methods: A retrospective cohort study was performed in patients who became pregnant after BC surgery under the age of 35 and were matched (1:4) to nonpregnant patients from 2006 to 2014. The primary endpoints were disease-free survival (DFS) and overall survival (OS) in HR-positive BC patients, and the secondary endpoints were DFS and OS in HR-negative BC patients and the whole population. Subgroup analyses included the DFS of patients who became pregnant within 5 years after surgery and DFS according to the ET interval time (≤ 30 months v > 30 months) in the pregnant group.Results: A total of 1323 YBC patients were collected in our study, which included 68 pregnant patients and 264 matched nonpregnant patients. There were no statistically significant differences in DFS and OS among HR-positive patients (P=0.657, P=0.250, respectively) and the whole population (P=0.058, P=0.152, respectively). A BC pregnancy interval ≤ 5 years showed a better DFS (P=0.042), and an ET interval ≤ 30 months had a worse DFS (P = 0.01).Conclusion: This study did not observe a worse prognosis in patients with HR-positive disease who became pregnant after BC surgery, and an ET interval less than 30 months in pregnant patients led to a worse outcome. Patients were able to become pregnant within 5 years after surgery.Keywords: young breast cancer, prognosis, pregnancy, hormone receptor positive, endocrine therapy

Suying Lu,1,2,* Chengtao Sun,3,* Huimou Chen,1,2,* Chao Zhang,1,4,* Wei Li,5 Liuhong Wu,1,2 Jia Zhu,1,2 Feifei Sun,1,2 Junting Huang,1,2 Juan Wang,1,2 Zijun Zhen,1,2 Ruiqing Cai,1,2 Xiaofei Sun,1,2 Yizhuo Zhang,1,2 Xing Zhang1,6 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, People’s Republic of China; 2Department of Pediatric Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China; 3Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of China; 4Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China; 5Department of Cardiology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 6Department of Medical Melanoma and Sarcoma, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing ZhangDepartment of Medical Melanoma and Sarcoma, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Guangzhou, Guangdong 510060, People’s Republic of ChinaTel/Fax +86-020-87343629Email zhangxing@sysucc.org.cnYizhuo Zhang Department of Pediatric OncologySun Yat-sen University Cancer Center, 651 East Dongfeng Road, Guangzhou, Guangdong 510060, People’s Republic of ChinaTel/Fax +86-020-87342458Email zhangyzh@sysucc.org.cnPurpose: The goal of the current study was to identify potential prognostic biomarkers of rhabdomyosarcoma (RMS).Materials and Methods: We screened chip sequencing datasets of RMS through the gene expression omnibus (GEO) database. A total of 74 RMS patient tissues and 39 normal muscle cell tissues were analyzed. Limma R software was used to identify the differentially expressed genes (DEGs) between RMS tissues and normal controls. The GO plot R package was used to visualize the results of the GO analysis. We screened for pathaffy package enrichment of DEGs by the Kyoto Encyclopedia of Genes and Genomes (KEGG). The cutoff criterion was a P-value < 0.05. Immunohistochemistry (IHC) was applied to validate the expression of CDK1 (cyclin-dependent kinases 1) and MAD2L1 (Mitotic Arrest Deficient 2 Like 1) in RMS.Results: We obtained a total of 498 up- and 480 down-regulated DEGs. The hub genes are mainly involved in the cell cycle and P53 singling pathway. CDK1 expression was associated with tumor size and COG-STS (Children’s Oncology Group-soft tissue sarcoma) staging of RMS. For the low CDK1 expression group and high CDK1 expression group, the 5-year overall survival (OS) rate was 83.0% vs 63.5% (P = 0.004), and the 5-year event-free survival (EFS) rate was 47.5% vs 27.5% (P = 0.049) respectively. When compared low MAD2L1 expression group with high MAD2L1 expression group, the 5-year OS rate was 80.0% vs 43.2% (P = 0.001), and the 5-year EFS rate was 45.1% vs 21.8% (P = 0.038), respectively. If patients were divided into three groups: low CDK1 and low MAD2L1 expression group, high CDK1 or high MAD2L1 expression group, and high CDK1 and high MAD2L1 expression group, the 5-year OS rate was 87.1%, 58.6%, 39.6% (P = 0.001), while the 5-year EFS rate of RMS patients was 54.2%, 23.2%, 21.7% (P = 0.028), respectively.Conclusion: This study has identified that CDK1 and MAD2L1 were adverse prognostic factors of RMS.Keywords: rhabdomyosarcoma, GEO, TCGA, CDK1, MAD2L1, prognosis