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Guangzan Yu, Lulu Liu, Qian Ma, Fusheng Han, Hua He Cardiac Division of Emergency Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of ChinaCorrespondence: Hua He, Email hehua430@163.comBackground: A large number of studies have demonstrated links between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVDs). However, the causal relationship between COPD and CVDs and the reverse causality remains divergent.Methods: Exposure and outcome data from the largest available genome-wide association studies were extracted for Mendelian randomization (MR) studies. Univariate MR analysis was performed using IVW as the primary analysis method, and multiple sensitivity analyses were used to enhance the robustness of the results. Furthermore, this was followed by mediation MR analysis of positive results after excluding confounding factors with multivariable MR analysis.Results: The MR estimation based on IVW method indicated a strong association between genetically determined COPD and heart failure (HF) (OR = 1.117, 95% CI: 1.066– 1.170, p < 0.001), coronary heart disease (CHD) (OR = 1.004, 95% CI: 1.002– 1.006, p < 0.001), essential hypertension (EH) (OR = 1.009, 95% CI: 1.005– 1.013, p < 0.001) as well as Stroke (OR = 1.003, 95% CI: 1.001– 1.004, p < 0.001). The results of multivariable MR analysis revealed that COPD is not significantly associated with CHD after adjusting for IL-6, LDL, or total cholesterol (p> 0.05). Our findings indicated that BMI, smoking initiation, smoking status, obesity, and FEV1 played a role in the causal effect of COPD on HF, EH, and Stroke.Conclusion: We found positive causal relationships between COPD and HF, EH, and Stroke essentially unaffected by other confounding factors. The causal relationship exhibited between COPD and CHD was influenced by confounding factors. BMI, obesity, initiation of smoking, smoking status, and FEV1 were the mediators between COPD and CVDs.Keywords: chronic obstructive pulmonary disease, cardiovascular diseases, Mendelian randomization

Mengmeng Wang,1 Huanhuan Wang,1,2 Zhaoyan Feng,1 Shuai Wu,1 Bei Li,1,2 Fang Han,1 Fulong Xiao1 1Division of Sleep Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 2School of Nursing, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Fulong Xiao; Fang Han, Division of Sleep Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China, Email xiaofulong1681@163.com; hanfang1@hotmail.comObjective: Depression is a common psychiatric issue among patients with narcolepsy type 1 (NT1). Effective management requires accurate screening and prediction of depression in NT1 patients. This study aims to identify relevant factors for predicting depression in Chinese NT1 patients using machine learning (ML) approaches.Methods: A total of 203 drug-free NT1 patients (aged 5– 61), diagnosed based on the ICSD-3 criteria, were consecutively recruited from the Sleep Medicine Center at Peking University People’s Hospital between September 2019 and April 2023. Depression, daytime sleepiness, and impulsivity were assessed using the Center for Epidemiologic Studies Depression Scale for Children (CES-DC) or the Self-Rating Depression Scale (SDS), the Epworth Sleepiness Scale for adult or children and adolescents (ESS or ESS-CHAD), and the Barratt Impulse Scale (BIS-11). Demographic characteristics and objective sleep parameters were also analyzed. Three ML models-Logistic Regression (LR), Random Forest (RF), and Support Vector Machine (SVM)-were used to predict depression. Model performance was evaluated using receiver operating curve (AUC), accuracy, precision, recall, F1 score, and decision curve analysis (DCA).Results: The LR model identified hallucinations (OR 2.21, 95% CI 1.01– 4.90, p = 0.048) and motor impulsivity (OR 1.10, 95% CI 1.02– 1.18, p = 0.015) as predictors of depression. Among the ML models, SVM showed the best performance with an AUC of 0.653, accuracy of 0.659, sensitivity of 0.727, and F1 score of 0.696, reflecting its effectiveness in integrating sleep-related and psychosocial factors.Conclusion: This study highlights the potential of ML models for predicting depression in NT1 patients. The SVM model shows promise in identifying patients at high risk of depression, offering a foundation for developing a data-driven, personalized decision-making tool. Further research should validate these findings in diverse populations and include additional psychological variables to enhance model accuracy.Keywords: narcolepsy type 1, depression, machine learning, support vector machine

Lin Shen,1,&ast; Zixuan Chen,1,&ast; Zhi Zhang,2,&ast; Yunjiang Wu,3 Yue Ren,1 Ying Li,1 Yue Li,1 Xudong Yin,1 Fang Han,1 Yong Chen1 1Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou City, Jiangsu Province, People’s Republic of China; 2Department of Medical Oncology, Baoying Clinical College, Medical College of Yangzhou University, Yangzhou City, Jiangsu Province, People’s Republic of China; 3Department of Thoracic Surgery, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou City, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Chen, Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Hanjiang Middle Road No. 368, Yangzhou, Jiangsu, 225009, People’s Republic of China, Tel +86-18051062926, Email chenyong_jsyz@sina.comPurpose: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line standard treatment for locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). The evidence also demonstrates improved synergistic effects of chemotherapy when combined with delayed administration of ICIs. In this study, we conducted a retrospective investigation into the treatment efficacy of taxol plus platinum (TP) chemotherapy combined with delayed administration of PD-1 inhibitors for ESCC patients.Patients and Methods: Clinical data of ESCC patients who received PD-1 inhibitors 3– 5 days after TP chemotherapy as first-line treatment was retrospectively reviewed between January 2019 and April 2023. Clinical outcomes and treatment safety were analyzed. The potential roles of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) were investigated.Results: A total of 34 locally advanced, recurrent or metastatic ESCC patients received PD-1 inhibitors 3– 5 days following TP chemotherapy were included. The objective response rate (ORR) and disease control rate (DCR) were 85.3% and 97.1% respectively. The median progression-free survival (PFS) and overall survival (OS) were 13.2 and 19.1 month respectively. Seven patients received radical surgery, 1 patient achieved pathologic complete response (pCR) and 3 patients achieved major pathologic response (MPR). Among the 27 patients without surgery, the median PFS and OS were 9.7 and 19.1 month respectively. A more favorable prognosis was correlated with NLR less than 3 at the 3rd and 4th cycle of immunochemotherapy. No significant correlations between other parameters (PLR, MLR and PIV) and prognosis were observed. A total of 22 patients developed grade 3– 4 toxicity events.Conclusion: The optimized sequence of PD-1 inhibitors administered 3– 5 days after TP chemotherapy as the first-line treatment of ESCC demonstrated favorable treatment efficacy. Pretreatment NLR of less than 3 at the 3rd and 4th cycle of immunochemotherapy is associated with a better prognosis.Keywords: immune checkpoint inhibitors, chemotherapy, rational sequence, esophageal squamous cell carcinoma, peripheral blood parameters

Min Yu,1– 3 Zeliang Hao,1– 3 Liyue Xu,4 Long Zhao,4 Yongfei Wen,4 Fang Han,4,&ast; Xuemei Gao1– 3,&ast; 1Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, People’s Republic of China; 2Center for Oral Therapy of Sleep Apnea, Peking University Hospital of Stomatology, Beijing, People’s Republic of China; 3National Center for Stomatology, Beijing, 100081, People’s Republic of China; 4Sleep Division, Peking University People’s Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Han, Sleep Division, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Tel +86-010-88324204, Email hanfang1@hotmail.com Xuemei Gao, Department of Orthodontics, Peking University School and Hospital of Stomatology, No. 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, People’s Republic of China, Tel/Fax +86-010-82195350, Email xmgao@263.netPurpose: Catathrenia is a rare sleeping disorder characterized by repetitive nocturnal groaning during prolonged expirations. Patients with catathrenia had heterogeneous polysomnographic, comorbidity, craniofacial characteristics, and responses to treatment. Identifying phenotypes of catathrenia might benefit the exploration of etiology and personalized therapy.Patients and Methods: Sixty-six patients diagnosed with catathrenia by full-night audio/video polysomnography seeking treatment with mandibular advancement devices (MAD) or continuous positive airway pressure (CPAP) were included in the cohort. Polysomnographic characteristics including sleep architecture, respiratory, groaning, and arousal events were analyzed. Three-dimensional (3D) and 2D craniofacial hard tissue and upper airway structures were evaluated with cone-beam computed tomography and lateral cephalometry. Phenotypes of catathrenia were identified by K-mean cluster analysis, and inter-group comparisons were assessed.Results: Two distinct clusters of catathrenia were identified: cluster 1 (n=17) was characterized to have more males (71%), a longer average duration of groaning events (18.5± 4.8 and 12.8± 5.7s, p=0.005), and broader upper airway (volume 41,386± 10,543 and 26,661± 6700 mm3, p< 0.001); cluster 2 (n=49) was characterized to have more females (73%), higher respiratory disturbance index (RDI) (median 1.0 [0.3, 2.0] and 5.2 [1.2, 13.3]/h, p=0.009), more respiratory effort-related arousals (RERA)(1 [1, 109] and 32 [13, 57)], p=0.005), smaller upper airway (cross-sectional area of velopharynx 512± 87 and 339± 84 mm2, p< 0.001) and better response to treatment (41.2% and 82.6%, p=0.004).Conclusion: Two distinct phenotypes were identified in patients with catathrenia, primary catathrenia, and catathrenia associated with upper airway obstruction, suggesting respiratory events and upper airway structures might be related to the etiology of catathrenia, with implications for its treatment.Keywords: subtype, groaning, upper airway, treatment, OSA, sleep-disordered breathing

Fang Zhai,1 Fulei Han,2 Qiulin Wang1 1College of Physical Education, Yangzhou University, Yangzhou, Jiangsu, 225009, People’s Republic of China; 2Kunshan No. 1 Vocational School in Jiangsu Province, Kunshan, Jiangsu, 215300, People’s Republic of ChinaCorrespondence: Qiulin Wang, Email wangql@yzu.edu.cnPurpose: The continuous spread of the epidemic has inflicted serious harm upon individual’s mental well-being, and effective coping mechanisms are associated with positive mental health outcomes. Prosocial behavior and a sense of meaning in life can enhance individuals’ subjective well-being, which can subsequently positively impact their mental health. Thus, in the context of epidemic prevention and control, this study investigates the relationship between the meaning in life, prosocial behavior, and coping styles of outstanding physical education students and the impact on their mental health.Methods: The study involved a questionnaire survey on 498 outstanding physical education students, consisting of 297 boys (mean age = 13.16) and 201 girls (mean age = 12.87 years). Subsequently, the data was analyzed using the mediating effect and Bootstrap tests.Results: The coping style positively predicted the meaning in life (β=0.294) and prosocial behavior (β=0.293). Conversely, mental health was predicted in a negative direction (β=– 0.494). Mental health negatively predicted prosocial behavior (β=– 0.810), although prosocial behavior positively predicted meaning in life (β=0.644). Finally, prosocial behavior negatively predicted mental health (β=– 0.513). Additionally, the interplay between prosocial behavior and meaning in life is established in terms of both the individual and chain mediating roles.Conclusion: This study demonstrates that coping styles during a normalized epidemic prevention and control situation directly impact the mental health of Shanghai’s outstanding physical education students. Additionally, these coping styles indirectly influence mental health through the mediating effects of meaning in life and prosocial behaviors. Furthermore, meaning in life and prosocial behaviors act as chain mediators in this relationship.Keywords: coping style, mental health, meaning in life, prosocial behavior

Yubo Li,1,2,&ast; Chengming Li,1,2,&ast; Tao Luo,3,&ast; Tian Yue,4 Wenjing Xiao,5 Ling Yang,1,2 Zaiyuan Zhang,6 Fei Han,3,&ast; Pan Long,3 Yonghe Hu6 1School of Clinical Medicine, Chengdu University of TCM, Chengdu, People’s Republic of China; 2Basic Medical Laboratory, The General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 3Department of Ophthalmology, The General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 4School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, People’s Republic of China; 5Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 6College of Medicine, Southwest Jiaotong University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pan Long, Department of Ophthalmology, The General Hospital of Western Theater Command, Rongdu Avenue &num;270, Chengdu, People’s Republic of China, Tel +86-181-9125-6132, Email longpan1005@qq.com Yonghe Hu, College of Medicine, Southwest Jiaotong University, No. 111, North First section of the Second Ring Road, Chengdu, People’s Republic of China, Tel +86-138-8059-6789, Email huyonghezyy@163.comAbstract: With the increasing of altitude activities from low-altitude people, the study of high altitude cerebral edema (HACE) has been revived. HACE is a severe acute mountain sickness associated with exposure to hypobaric hypoxia at high altitude, often characterized by disturbance of consciousness and ataxia. As for the pathogenesis of HACE, previous studies suggested that it might be related to the disorder of cerebral blood flow, the destruction of blood-brain barrier and the injury of brain parenchyma cells caused by inflammatory factors. In recent years, studies have confirmed that the imbalance of REDOX homeostasis is also involved in the pathogenesis of HACE, which mainly leads to abnormal activation of microglia and destruction of tight junction of vascular endothelial cells through the excessive production of mitochondrial-related reactive oxygen species. Therefore, this review summarizes the role of REDOX homeostasis and the potential of the treatment of REDOX homeostasis in HACE, which is of great significance to expand the understanding of the pathogenesis of HACE. Moreover, it will also be helpful to further study the possible therapy of HACE related to the key link of REDOX homeostasis.Keywords: high altitude cerebral edema, hypobaric hypoxia, REDOX homeostasis, mitochondria dysfunction, microglia

Jin Yu Gu,1 Fei Han,2 Si-Yu Chen,2 Qing Zhang1 1Department of Orthopaedic, The Hospital of Wang Jing, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Orthopaedic, The Hospital of Guang An Men, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Qing Zhang, Department of Orthopaedic, The Hospital of Wang Jing, China Academy of Chinese Medical Sciences, Huajiadi Street, Chao Yang District, Beijing, 100102, People’s Republic of China, Tel +86-13911570607, Email 3219040781@stu.cpu.edu.cnPurpose: Clinical treatment of knee osteoarthritis has gained great interest, and numerous clinical studies have been reported. Few studies have described the detailed characterizations of clinical trials on knee osteoarthritis. This study is to identify, visualize, and characterize the clinical trials in knee osteoarthritis research.Design and Methods: Articles published in recent two decades were extracted from the Web of Science core collection database using a query based on MeSH terms and topics of knee osteoarthritis and clinical trial. Basic characteristics of publications were analyzed based on the publication year, authors, institutions, counties, and keywords covered in the article. CiteSpace and VOS viewer were used for data visualization. The data were retrieved on May 28, 2022.Results: A total of 1972 trials on knee osteoarthritis were identified. The number of publications has experienced rapid growth in the past two decades. America, England, and China had strong contributions in publication. Osteoarthritis and Cartilage, Annals of the Rheumatic Diseases and American Journal of Sports Medicine were highly cited and bellwether journals. Clustering mapping of the collaborative network, co-citation, and co-occurrence analyses showed that the research hotspots are mainly focused on disease-modifying medications, intra-articular injections, physical therapy for symptom control, lifestyle intervention, Chinese medicine treatment, and knee replacement.Conclusion: Clinical treatments of knee OA are evolving. Pharmacologic therapy, intra-articular therapy, nonpharmacologic therapy including exercise or diet, self-management programs, Chinese medicine treatment, and knee replacement were highly represented in clinical trials of knee OA. Adjustment of combination therapy may be the next study focus in the future.Keywords: knee osteoarthritis, treatment, clinical trial, bibliometric analysis, public health

Hua-Man Wu,1,2,&ast; Zhi-Jun Wang,1,&ast; Chao-Hong Cheng,1 Tong Su,1 Jing Wang,1 Ye-Zhou Li,3 Qiao-Jun Wang,4 Fei Han,4 Rui Chen1,4 1Department of Respiratory, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Zigong First People’s Hospital, Zigong, Sichuan, People’s Republic of China; 3School of Medicine, the University of Manchester, Manchester, UK; 4Department of Sleeping Center, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Chen, Department of Respiratory/Department of Sleeping Center, the Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, People’s Republic of China, Tel +86(0512)67784857, Email chenruigood@126.comPurpose: Obstructive sleep apnea hypopnea syndrome (OSAHS) can lead to cognitive impairment, though few studies have so far examined hypercapnia as its causal mechanism, due to the invasive nature of conventional arterial CO2 measurement. The study aims to investigate the effects of daytime hypercapnia on working memory in young and middle-aged patients with OSAHS.Patients and Methods: This prospective study screened 218 patients and eventually recruited 131 patients (aged 25– 60 years) with polysomnography (PSG)-diagnosed OSAHS. Using a cut-off of 45mmHg daytime transcutaneous partial pressure of carbon dioxide (PtcCO2), 86 patients were assigned into the normocapnic group and 45 patients into the hypercapnic group. Working memory was evaluated using the Digit Span Backward Test (DSB) and the Cambridge Neuropsychological Test Automated Battery.Results: Compared with the normocapnic group, the hypercapnic group performed worse in verbal, visual, and spatial working memory tasks. PtcCO2≥ 45mmHg was an independent predictor for lower DSB scores (OR=4.057), lower accuracy in the immediate Pattern Recognition Memory (OR=2.600), delayed Pattern Recognition Memory (OR=2.766) and Spatial Recognition Memory (OR=2.722) tasks, lower Spatial Span scores (OR=4.795), and more between errors in the Spatial Working Memory task (OR=2.734 and 2.558, respectively). Notably, PSG indicators of hypoxia and sleep fragmentation did not predict task performance.Conclusion: Hypercapnia may be plays an important role in working memory impairment in patients with OSAHS, perhaps more so than hypoxia and sleep fragmentation. Routine CO2 monitoring in these patients could prove of utility in clinical practices.Keywords: hypercapnia, obstructive, sleep apnea, working memory

Beibei Wang,1,&ast; Fei Han,1,&ast; Ran You,1 Chen Chen,2 Haifeng Xie1 1Department of Prosthodontics, Affiliated Stomatology Hospital, Nanjing Medical University; Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, 210029, People’s Republic of China; 2Department of Endodontics, Affiliated Stomatology Hospital, Nanjing Medical University; Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haifeng Xie, Affiliated Stomatology Hospital, Nanjing Medical University, Han-Zhong Road 136th, Nanjing, 210029, People’s Republic of China, Tel +8625 69593081, Fax +8625 86516414, Email xhf-1980@126.comObjective: To investigate the effects of proanthocyanidins (PA), myricetin, resveratrol, and kaempferol on the modification of dentin collagen and the inhibition of matrix metalloproteinase (MMP) activity, and to evaluate their contributions to the biomimetic remineralization and resin-dentin bonding performance.Methods: Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and in situ zymography were applied to verify the collagen modification and MMP activity inhibition induced by these four polyphenols. Scanning electron microscopy/energy dispersive spectrometer (SEM/EDS) analysis, X-ray diffraction (XRD), ATR-FTIR, Vickers hardness numbers (VHN), and micro-computed tomography (micro-CT) were performed to characterize the remineralized dentin. Microtensile bond strength (μTBS) and nanoleakage were investigated to evaluate the effects of the four polyphenols on resin-dentin bonding durability.Results: ATR-FTIR and in situ zymography confirmed that these four polyphenols could modify dentin collagen and inhibit MMP activity, respectively. Chemoanalytic characterization exhibited the efficacies of the four polyphenols in promoting dentin biomimetic remineralization. The surface hardness of PA-pretreated dentin was the greatest. Micro-CT results demonstrated that the PAs group possessed the highest amount of dentin surface minerals and the lowest amount of deep-layer minerals. The surface and deep-layer mineral contents of the Myr group were higher than Res and Kae groups. Treatment with these four polyphenols significantly increased the initial μTBS compared with the control group without primer conditioning. μTBS decreased significantly during aging, and the decrease was more severe in the PAs and Kae groups than in the Myr and Res groups. With or without aging, the polyphenol groups exhibited relatively less fluorescence. However, the Myr and Res groups showed less serious nanoleakage after aging.Conclusion: PA, myricetin, resveratrol, and kaempferol can modify dentin collagen, inhibit MMP activity, promote biomimetic remineralization, and improve resin-dentin bond durability. Compared with PA and kaempferol, myricetin and resveratrol are more effective in improving resin-dentin bonding.Graphical Abstract: Keywords: polyphenols, collagen, amorphous calcium phosphate nanoparticles, remineralization, resin-dentin bonding

Yang Yang,1 Jun Zhang,2 Fang Han,3 Fulong Xiao4 1Department of Neuropsychiatry and Behavioral Neurology and Clinical Psychology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Neurology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China; 3Sleep Medicine Center, Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China; 4Department of General Internal Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaCorrespondence: Fang Han; Fulong Xiao, Peking University People’s Hospital, No. 11, South Avenue, Beijing, People’s Republic of China, Email hanfang1@hotmail.com; xiaofulong1681@163.comObjective: To detect the factors associated with total and subscales impulsivity scores in narcolepsy and further explore the non-linear relationship between these factors and impulsivity score.Methods: One hundred and fifty-eight narcolepsy type 1 (NT1) patients were involved in this cross-sectional study. Patients completed questionnaires evaluating impulsivity symptoms (Barratt impulse scale-11, BIS-11), depression symptoms (Center for Epidemiologic Studies Depression Scale for Children, CES-DC or Self-Rating Depression Scale, SDS) and sleepiness (Epworth Sleepiness Scale, ESS). Parameters from polysomnography and multiple sleep latency test were also collected. Linear regression analysis was performed to detect the factors associated with total and subscales impulsivity scores. Then, generalized additive models and smooth curve fitting were performed to explore the non-linear relationship between chronological age and impulsivity scores.Results: Factors associated with higher total impulsivity score were higher ESS, older onset and adolescents. Factors associated with higher attentional impulsivity score were higher ESS, older onset and adolescents. Factors associated with higher motor impulsivity score were higher ESS, younger onset and depression symptoms. Factors associated with higher non-planning impulsivity score were adolescents, older onset and depression symptoms. A non-linear relationship between age and impulsivity scores (total impulsivity score, attentional impulsivity score and non-planning impulsivity score) was detected in NT1 patients.Conclusion: Not only excessive daytime sleepiness but also onset-age, depression symptoms and chronological age were associated with impulsivity in NT1 patients. The non-linear relationship between age and impulsivity scores suggested brain and mental development alterations in NT1 patients.Keywords: narcolepsy, impulsivity, excessive daytime sleepiness, depression, smooth curve fitting

Yunming Tian,1 Wei-Zeng Huang,2 Lei Zeng,3 Li Bai,1 Fei Han,4,* Yuhong Lan1,* 1Department of Radiation Oncology, Huizhou Central People’s Hospital, Huizhou, Guangdong Province, People’s Republic of China; 2Department of Medical Oncology, Huizhou First Hospital, Huizhou, Guangdong Province, People’s Republic of China; 3Department of Medical Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jixiang Province, People’s Republic of China; 4Department of Radiation Oncology, Sun Yat-Sen University Cancer Centre, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Han, Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, People’s Republic of China, Email hanfeisysucc@126.com Yuhong Lan, Department of Radiation Oncology, Hui Zhou Municipal Central Hostpital, Huizhou, Guangdong Province, People’s Republic of China, Email lanyuhonghzyy@126.comObjective: To investigate the treatment outcomes, failure patterns and surveillance strategy in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT).Methods: A cohort of patients with NPC who had received the full course of IMRT between 2008 and 2012 were retrospectively analyzed. The failure patterns, time to recurrence, and detection methods were recorded. The survival was calculated using the Kaplan–Meier method. Multivariate proportional hazard regression models were used to test the prognostic factors.Results: In total, 2607 patients with NPC treated with IMRT were recruited. After the median follow-up of 112 months, 402 (15.4%) patients experienced distant metastasis, 225 (8.6%) patients had local recurrence, and 77 (3.0%) patients had regional recurrences. The 10-year overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 74.5%, 90.1%, and 79.3%, respectively. The factors of male sex, age > 50 years, lactate dehydrogenase > 245 IU/L, advanced T classification, and advanced N classification were associated with poor OS. The N disease classification was the most important factor in predicting distant metastasis, and advanced T disease classification for high risk of local recurrence. For patients with T1 disease, the incidence of local recurrence was less than 2%, and the incidence of distant metastasis was less than 5% for patients with N0 disease. About 83% of the recurrence occurred in the first 5 years, and 20% of the recurrences showed no symptoms.Conclusion: High rate of local-regional control can be achieved for patients with NPC after IMRT, while distant metastasis remains as the major cause of failures. Patients with advanced N classification has high risk to develop distant metastasis, and most occurred within 5 years. Developing rational and individualized surveillance strategies based on the high risk factors of recurrence is helpful to balance the survival benefit and medical cost.Keywords: failure patterns, intensity-modulated radiotherapy, nasopharyngeal carcinoma, surveillance

Rui Zhao,1 Jianbo Xue,1 Xueli Zhang,1 Maohuan Peng,1 Jing Li,1 Bing Zhou,1 Long Zhao,1 Thomas Penzel,2 Meir Kryger,3 Xiao Song Dong,1 Zhancheng Gao,1 Fang Han1 1Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Sleep Medicine Center, Charité-Universitätsmedizin, Berlin, Germany; 3Division of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USACorrespondence: Xiao Song Dong; Zhancheng Gao, Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, No. 11 Xizhimen Nandajie, Xicheng District, Beijing, 100044, People’s Republic of China, Email dongxiaosong@pkuph.edu.cn; zcgao@bjmu.edu.cnObjective: A novel ring-worn oximeter (Circul) uses reflective photoplethysmography and automated signal processing to calculate oxygen desaturations. We evaluated the ability of Circul to detect obstructive sleep apnea in Chinese adults.Methods: We recruited 207 Chinese Han subjects: 70% males, mean age 48.2± 14.7 years, mean BMI 27.6± 4.8 kg/m2 and mean AHI 28.6± 25.2 events/h. All participants underwent simultaneous polysomnography (PSG) and Circul testing in a sleep laboratory. Oxygen desaturation index (ODI), mean oxygen saturation (MSpO2), cumulative time at SpO2< 90% (CT90), cumulative percentage of sleep time spent with SpO2< 90% (CT90/TST) were derived and compared for the Circul and the PSG.Results: The ODI was 25.3± 24.5 events/h using PSG and 22.2± 24.5 events/h using Circul (P< 0.0001), with an intraclass correlation coefficient (ICC) of 0.884. CT90 and CT90/TST between the two methods were not different; the MSpO2 level calculated by PSG was slightly lower than Circul, 95.0% (93.0– 96.0%) vs 95.3% (93.9– 96.6%), P< 0.0001. Circul-ODI had a good correlation (r=0.91, p< 0.0001) and close agreement with PSG-AHI (Bland-Altman analysis: Mean Difference 6.4, 95% CI − 14.8 to 27.5 events/h). Using a threshold of AHI ≥ 5 events/h, the Circul had 87% sensitivity, 83% specificity, 5.09 positive likelihood ratio (LR+), 86% accuracy, and 0.929 area under the curve (AUC).Conclusion: Circul ring pulse oximetry can detect OSA with reasonable reliability. The Circul system is a reliable and comfortable choice for OSA assessment.Keywords: obstructive sleep apnea, reflective photoplethysmography, pulse oximetry, polysomnography

Brigitte Holzinger,1,2 Franziska Nierwetberg,1 Frances Chung,3 Courtney J Bolstad,4 Bjørn Bjorvatn,5 Ngan Yin Chan,6 Yves Dauvilliers,7 Colin A Espie,8 Fang Han,9 Yuichi Inoue,10 Damien Leger,11 Tainá Macêdo,12 Kentaro Matsui,13,14 Ilona Merikanto,15,16 Charles M Morin,17 Sérgio A Mota-Rolim,18 Markku Partinen,19 Giuseppe Plazzi,20,21 Thomas Penzel,22 Mariusz Sieminski,23 Yun Kwok Wing,6 Serena Scarpelli,24 Michael R Nadorff,4,25 Luigi De Gennaro24,26 1Institute for Consciousness and Dream Research, Vienna, Austria; 2Medical University Vienna, Postgraduate Master ULG Sleep Coaching, Vienna, Austria; 3Department of Anesthesiology and Pain Medicine, University Health Network, University of Toronto, Toronto, ON, Canada; 4Mississippi State University, Mississippi State, MS, USA; 5Department of Global Public Health and Primary Care, University of Bergen and Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway; 6Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region, People’s Republic of China; 7Sleep-Wake Disorders Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, INM, Univ Montpellier, INSERM, Montpellier, France; 8Sir Jules Thorn Sleep & Circadian Neuroscience Institute (SCNi), University of Oxford, Oxford, UK; 9Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 10Tokyo Medical University, Tokyo, Japan; 11Université de Paris, APHP, Hôtel-Dieu, Centre du Sommeil et de la Vigilance, Paris, France; 12Department of Psychology, Federal University of Rio Grande do Norte, Natal, Brazil; 13Department of Laboratory Medicine, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Japan; 14Department of Psychiatry, Tokyo Women’s Medical University, Tokyo, Japan; 15SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 16Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; 17École de Psychologie, Centre d’étude des troubles du sommeil, Centre de recherche CERVO/Brain Research Center, Université Laval, Québec, QC, Canada; 18Brain Institute, Physiology and Behavior Department, and Onofre Lopes University Hospital - Federal University of Rio Grande do Norte, Natal, Brazil; 19Helsinki Sleep Clinic, Terveystalo Healthcare, and Department of Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland; 20IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 21Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 22Sleep Medicine Center, Charité Universitätsmedizin Berlin, Berlin, Germany; 23Department of Emergency Medicine, Medical University of Gdansk, Gdansk, Poland; 24Department of Psychology, Sapienza University of Rome, Rome, Italy; 25Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA; 26IRCCS Fondazione Santa Lucia, Rome, ItalyCorrespondence: Brigitte Holzinger, Tel +43 699 101 99 042, Email brigitte.holzinger@meduniwien.ac.atPurpose: The COVID-19 pandemic affects mental health and sleep, resulting in frequent nightmares. Therefore, identifying factors associated with nightmare frequency is important, as it can indicate mental health issues. The study aimed to investigate increases in nightmare frequency comparing the pre-pandemic and pandemic period, and identify its risk factors. Further, the mediating role of post-traumatic stress disorder symptoms between the pandemic and nightmares is explored.Patients and Methods: For this cross-sectional survey data were obtained via self-rating online survey (ICOSS: details in Partinen et al, 2021), which was open to anyone older than 18 years. The final volunteer sample consisted of 15,292 participants, divided according to their nightmare frequency (high: ≥ 1– 2 nights/week; low: < 1– 2 nights/week). A total of 9100 participants were excluded if answers on variables of interest were missing or receiving rewards for participation. Chi-square tests identified changes of nightmare frequency. Predictors of high nightmare frequency were assessed using logistic regression and presented as Odds Ratios. Post-hoc mediation models were used to investigate the role of post-traumatic stress symptoms (PTSS).Results: The mean age was 41.63 (SD=16.55) with 64.05% females. High nightmare frequency increased significantly from 13.24% to 22.35% during the pandemic. Factors associated with it included self-reported PTSS (OR=2.11), other mental disorders and various sleep disorders or problems. Financial burden due to the pandemic, confinement, having had COVID-19, and work situation during the pandemic were associated with nightmare frequency, those relations were partly mediated through PTSS.Conclusion: Our results display the pandemic influence on nightmare frequency, which in turn connects to multiple mental health and sleep factors. These relations were partly mediated through PTSS. The COVID-19 pandemic appears to have caused traumatization of a substantial proportion of society. Health care workers should consider nightmares in their screening routines, as it might indicate PTSS and/or other mental and sleep disorders.Keywords: COVID-19, nightmares, mental health, sleep, post-traumatic stress disorder, collective trauma

Fen Zhao,1,&ast; Xiaoning Sun,2,&ast; Yingyan Wang,1 Yunqing Zhou,1 Yingzhong He,1 Cuijin Wang,1 Feng Han,1 Jie Liu,1 Shao-Yu Tsai,3 Guanghai Wang,2 Jiwen Wang1 1Department of Pediatric Neurology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Paediatric Translational Medicine Institute, Department of Developmental and Behavioral Pediatrics, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3School of Nursing, College of Medicine, National Taiwan University, Taipei, Taiwan&ast;These authors contributed equally to this workCorrespondence: Guanghai Wang, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dongfang Road, Shanghai, 200127, People’s Republic of China, Email wang-guanghai@163.com Jiwen Wang, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, People’s Republic of China, Email wangjiwen@scmc.com.cnObjective: To investigate the association between sleep disturbances and behavioral problems as well as quality of life (QOL) in Chinese children with epilepsy.Methods: Caregivers of 167 epileptic children aged 3 to 12 years completed the Child Sleep Habits Questionnaire (CSHQ), the Strengths and Difficulties Questionnaire (SDQ), and the Pediatric Quality of Life Inventory (PedsQL™, 4.0 Core).Results: The prevalence of sleep disturbances (CSHQ total score > 41) in epileptic children was 73.7% [95% CI (66.9%.80.4%)]. Epileptic children with sleep disturbances demonstrated more behavioral problems and lower QOL compared to those without sleep disturbances. Sleep disturbances such as sleep anxiety and daytime sleepiness were associated with more behavioral problems and lower QOL (p < 0.05). Linear regression analyses showed that higher disturbance in sleep duration domain were associated with more behavioral problems, while higher sleep disordered breathing domains was associated with lower QOL (p < 0.05). The interaction between sleep disturbances and behavioral problems in predicting QOL was not significant. The sensitivity analysis using 48 as an alternative cutoff for CSHQ total score obtained consistent results.Conclusion: Sleep disturbances occur frequently among Chinese children with epilepsy, and are associated with more behavioral problems and lower QOL. The sleep disturbance-QOL association is unlikely contingent on behavioral problems. This study highlights the necessity of evaluating and treating sleep disturbances multidimensionally among children with epilepsy to promote their whole health and wellbeing.Keywords: sleep disturbances, behavioral problems, quality of life, epilepsy, children

The coexistence of ulnar nerve subluxation and snapping medial head triceps is an uncommon occurrence. There have been few studies and case reports since it was first described in 1970. In this article, we present a case in which the condition occurred after a push-up. We analysed the pathoanatomy of the condition, and reviewed the literature regarding potential causes, typical presentations of the coexistence of both ulnar nerve subluxation and medial snapping triceps and describe our surgical technique in treatment. Elbow pain is very often under evaluated as many physicians may not be aware that elbow pain could be attributed to the coexistence of both ulnar nerve subluxation and medial snapping triceps. A thorough evaluation with physical examination and imaging are recommended. Early surgery with an appropriate rehabilitation programme may hasten recovery and return to sports in patients who continue to remain symptomatic following a trial of conservative therapy.

Jun Hou,1,&ast; Dezhi Zheng,2,&ast; Xudong Wen,3,&ast; Wenjing Xiao,4 Fei Han,5 Hongmei Lang,6 Shiqiang Xiong,1 Wei Jiang,5 Yonghe Hu,4 Mengshan He,7 Pan Long4,5 1Department of Cardiology, Chengdu Third People’s Hospital/Affiliated Hospital of Southwest Jiaotong University, Chengdu, People’s Republic of China; 2Department of Cardiovascular Surgery, the 960th Hospital of the PLA Joint Logistic Support Force, Jinan, People’s Republic of China; 3Department of Gastroenterology and Hepatology, Chengdu First People’s Hospital, Chengdu, People’s Republic of China; 4School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, People’s Republic of China; 5Department of Ophthalmology, the General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 6The Center of Obesity and Metabolic Diseases, Department of General Surgery, Chengdu Third People’s Hospital & the Affiliated Hospital of Southwest Jiaotong University, Chengdu, People’s Republic of China; 7Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pan Long, Department of Ophthalmology, the General Hospital of Western Theater Command, Rongdu Avenue #270, Chengdu, People’s Republic of China, Tel +86-181-9125-6132, Email longpan1005@qq.com Yonghe Hu, School of Materials Science and Engineering, Southwest Jiaotong University, No. 111, North First Section of the Second Ring Road, Chengdu, People’s Republic of China, Tel +86-138-8059-6789, Email huyonghe789@sina.comPurpose: High-altitude environment mainly with hypobaric hypoxia could induce pathological alterations in ocular tissue. Previous studies have mostly focused on sporadic case reports and simulated high-altitude hypoxia experiments. This aim of this study was to explore the proteomic and morphological changes of ocular tissue in mice at real altitude environment.Methods: In this study, mice were flown from Chengdu (elevation: 500 m) to Lhasa (elevation: 3600 m). After exposure for 1day, 3, 6, 10, 20, 30, and 40days, the mice were euthanatized to obtain blood and ocular tissue. Serological tests, ocular pathological examinations, integral ocular proteomics analysis, and Western blot were conducted.Results: We focused on acute phase (1– 3 days) and chronic phase (> 30 days) during high-altitude acclimatization. Serum interleukin-1 was increased at 3 days, while superoxide dismutase, interleukin-6, and tumor necrosis factor-α showed no statistical changes. H&E staining demonstrated that the cornea was edematous at 3 days and exhibited slower proliferation at 30 days. The choroid showed a consistently significant thickening, while there existed no noticeable changes in retinal thickness. Overall, 4073 proteins were identified, among which 71 and 119 proteins were detected to have significant difference at 3 days and 40 days when compared with the control group. Functional enrichment analysis found the differentiated proteins at 3 days exposure functionally related with response to radiation, dephosphorylation, negative regulation of cell adhesion, and erythrocyte homeostasis. Moreover, the differential profiles of the proteins at 40 days exposure exhibited changes of regulation of complement activation, regulation of protein activation cascade, regulation of humoral immune response, second-messenger-mediated signaling, regulation of leukocyte activation, and cellular iron homeostasis. Interestingly, we found the ocular proteins with lactylation modification were increased along high-altitude adaptation.Conclusion: This is the first work reporting the ocular proteomic and morphological changes at real high-altitude environment. We expect it would deep the understanding of ocular response during altitude acclimatization.Keywords: altitude response, ocular proteomics analysis, cornea edema, choroid thickening, post-translational modification

Qing Zhao,1,&ast; Yixue Gao,2,&ast; Xin Jin,1 Fei Han,2 Kai Chen,3 Chen Chen1 1Department of Endodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, 210029, People’s Republic of China; 2Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, 210029, People’s Republic of China; 3Collaborative Innovation Center of Atmospheric Environment and Equipment Technology, Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control, School of Environmental Science and Engineering, Nanjing University of Information Science and Technology, Nanjing, 210044, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chen Chen, Department of Endodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, 210029, People’s Republic of China, Tel +8625 6959 3031, Fax +8625 8651 6414, Email ccchicy@njmu.edu.cnPurpose: This study aimed to investigate the hydrolytic stability of 10-methacryloyloxydecyl dihydrogen phosphate calcium (MDP-Ca) salts with nanolayered and amorphous structures in different pH environments.Methods: The MDP-Ca salts were synthesized from MDP and calcium chloride and characterized by X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and transmission electron microscopy (TEM). Inductively coupled plasma-mass spectrometry (ICP-MS) was used to quantify the release of calcium from the synthesized MDP-Ca salt, MDP-treated hydroxyapatite (MDP-HAp), and untreated HAp after soaking in acidic and neutral solutions for 1, 7, and 30 days. To study the hydrolytic process, we carried out molecular dynamics (MD) simulations of the nanolayered MCS-MD (monocalcium salt of the MDP dimer) and DCS-MD (dicalcium salt of the MDP dimer) structures, as well as of the amorphous-phase MCS-MM (monocalcium salt of the MDP monomer).Results: The TEM images showed that the nanolayered structures were partially degraded by acid attack. Based on the ICP-MS results, the hydrolysis rate of the MDP-Ca salt in acidic and neutral environments followed the order HAp > MDP-HAp > MDP-Ca salt. The MD simulations showed that, in acidic environments, clusters of MDP remained aggregated and all Ca2+ ions separated from the MDP monomer to interact with water molecules in aqueous solution. In neutral environments, Ca2+ ions always interacted with phosphate groups, OH− ions, and water molecules to form clusters centered on Ca2+ ions.Conclusion: MDP-Ca presented higher hydrolysis rates in acidic than neutral environments. Nanolayered MCS-MD possessed the highest resistance to acidic hydrolysis, followed by amorphous MCS-MM and DCS-MD.Graphical Abstract: Keywords: 10-methacryloyloxydecyl dihydrogen phosphate calcium salts, nanolayering, hydrolysis, molecular dynamics simulations, dentin bonding

Gangqiang Guo,1,&ast; Huijing Wang,2,&ast; Xinya Tong,1,&ast; Lele Ye,1 Xinyu Shi,1 Su Fang,1 Ya Hu,3 Fei Han,2 Chaosheng Chen,3 Ning Ding,1 Bofeng Su,3 Xiangyang Xue,1 Huidi Zhang3 1Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research & Precision Medicine, Wenzhou Key Laboratory of Cancer-Related Pathogens & Immunity, Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 2Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China; 3Department of Nephrology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bofeng Su; Huidi ZhangDepartment of Nephrology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China, Email 24449681@qq.com; hd_zhang@163.comObjective: Enhancer RNAs (eRNAs), a class of non-coding RNAs, play indispensable roles in regulating target gene transcription and maintaining cell identity in cooperation with promoters. In this study, we investigated the transcriptional landscape and potential functions of eRNAs in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE).Methods: PBMCs from five patients with stable SLE, five patients with active SLE, and ten healthy individuals (HCs) were subjected to RNA-sequencing. Putative regulators, differential expression, and pathways were analyzed. eRNAs that were significantly upregulated were first validated by RT-qPCR in 12 samples. Then, candidate eRNAs were confirmed in a validation cohort of 45 samples. We conducted comprehensive pathway analyses to explore the correlations between the candidate eRNAs and SLE pathology.Results: By analyzing eRNA transcript data from PBMCs from SLE patients and HCs, we identified various eRNAs and functional super-enhancers potentially related with SLE. The SLE-specificity of eRNAs seemed to be largely driven by SLE-specific transcription factors (TFs). A Venn diagram of eRNAs differentially expressed in stable, active, and total SLE vs HCs revealed that 13 and 23 eRNAs were commonly upregulated and downregulated, respectively, in patients with stable SLE and those with active SLE. The commonly upregulated eRNAs participate in regulating SLE-related pathways. Only eRNA TCONS_00034326 was significantly (P < 0.05) upregulated in PBMCs of patients with SLE when compared with those of HCs as indicated by RT-qPCR. The area under the receiver-operating curve of TCONS_00034326 for distinguishing SLE patients from HCs was 0.691. Through its putative SLE-related master TF, TCONS_00034326 is involved in multiple SLE-relevant signaling pathways, especially tumor necrosis factor signaling.Conclusion: This study unraveled the transcriptional landscape of eRNAs, eRNA-related TFs, and super-enhancers in PBMCs from SLE patients and HCs. We identified a panel of SLE-relevant eRNAs, providing potential targets in SLE pathogenesis.Keywords: enhancer RNA, eRNA, systemic lupus erythematosus, SLE, PBMCs, transcription factors, TFs, super-enhancer

Fei Fan,1 Long Hao,2 Si Zhang,1 Ying Zhang,3 Zhaoxiang Bian,4 Xuan Zhang,4 Qiong Wang,5 Fei Han1 1Department of Paediatrics, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Paediatrics, Beijing Fangshan District Liangxiang Hospital, Beijing, People’s Republic of China; 3Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Chinese EQUATOR Centre, Hong Kong Chinese Medicine Clinical Study Centre, Chinese Clinical Trial Registry (Hong Kong), School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong, People’s Republic of China; 5Clinical Medical School, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Fei HanDepartment of Paediatrics, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, No. 5, Beixiange Road, Xicheng District, Beijing, 100053, People’s Republic of ChinaTel +86 10-8800 1128Email hf4383@126.comBackground: The Jingxin Zhidong formula (JXZDF), a traditional Chinese medicine, has been widely used to treat tic disorder (TD) in China. However, its efficacy has not yet been evaluated in a randomized controlled trial. We aimed to compare the effectiveness and safety of JXZDF and aripiprazole in patients with TD.Methods: In this randomized, double-blind, double-dummy, parallel controlled trial, 120 patients with TD, aged 6– 16 years were randomly assigned to receive either JXZDF (n = 60, 17.6 g/day) or aripiprazole (n = 60, 10 mg/day) for 12 weeks. The primary outcome was measured using the Yale Global Tic Severity Scale (YGTSS). Adverse events were assessed using the Treatment Emergent Symptom Scale.Results: JXZDF produced greater improvements than aripiprazole in the following YGTSS subscale scores at the endpoint: total tic scores (P = 0.004, 95% CI: 1.085– 3.494) and total motor scores (P = 0.004, 95% CI: 0.313– 1.739). The difference in rate between the groups was no significant (χ2 = 0.702, degrees of freedom = 1, P = 0.402). The overall incidence of adverse events was significantly lower in the JXZDF group than in the aripiprazole group (0% vs 6.67%, P < 0.001).Conclusion: JXZDF had a better safety profile than aripiprazole, and it was not inferior in terms of clinical efficacy. JXZDF warrants consideration as a potential treatment option for TD.Trial Registration: CHiCTR, ChiCTR2000039601 (Registered November 2, 2020).Keywords: tic disorder, Tourette syndrome, Chinese herbal Medicine formula, randomized controlled trial, Jingxin Zhidong formula

Chenyang Li,1 Liang Xie,2 Shaomei Shang,1 Xiaosong Dong,3 Xiaoling Wang,4 Long Zhao,3 Chi Zhang,3 Fang Han3 1Peking University School of Nursing, Beijing, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Sleep Medicine Center, Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 4PKU-UPenn Sleep Center, Peking University International Hospital, Beijing, People’s Republic of ChinaCorrespondence: Fang HanSleep Medicine Center, Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaEmail hanfang1@hotmail.comObjective: This study aimed to translate and validate the narcolepsy quality-of-life instrument with 21 questions (NARQoL-21) in Chinese pediatrics with narcolepsy.Methods: NARQoL-21 was translated following the 10 steps of scale translation. The translated version was tested by exploratory factor analysis (EFA), confirmatory factor analysis (CFA), known-group validity, criterion validity, Cronbach’s α and test-rest reliability.Results: The Chinese version of NARQoL-21 consisted of two factors: (psychosocial factors and future outlook factor), including 20 items. EFA yielded 3 domains for psychosocial factors and 1 domain for future outlook factor. The Chinese version had a negative correlation with the overall Modified Epworth Sleepiness Scale (r = − 0.518, p< 0.001) and meaningful difference in score between drug naïve and treated group (p< 0.05). The Cronbach’s α coefficient was higher than 0.7 and intraclass correlation coefficient (ICC) ranged from 0.75 to 0.905, indicating that it had good reliability.Conclusion: The Chinese version of the NARQoL-21 is available and can be used to evaluate the health-related quality of life (HRQoL) of pediatric narcoleptics, despite that there is a shift in factors compared to the English version due to cultural differences. Future studies are recommended to further validate the scale in Chinese pediatrics with narcolepsy.Keywords: narcolepsy, pediatrics, quality of life, validation study

Fuqiang Liu,1– 4 Feng Han,4,5 Xiaoli Liu,4,5 Lina Yang,4,5 Caixia Jiang,4,5 Chen Cui,1– 4 Fang Yuan,1– 4 Xin Zhang,1– 4 Lei Gong,1– 4 Xinguo Hou,1– 4 Yuan Liu,1– 4 Li Chen1– 4 1Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong, 250012, People’s Republic of China; 4Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, Shandong, 250012, People’s Republic of China; 5Department of Endocrinology, Zhangqiu District People’s Hospital, Jinan, 250200, People’s Republic of ChinaCorrespondence: Yuan Liu; Li Chen Email liuyuan198735@163.com; chenli3@medmail.com.cnBackground: To investigate the correlation between serum interleukin-17A (IL-17A) levels and diabetic retinopathy (DR) in elderly individuals with type 2 diabetes mellitus (T2DM).Methods: The study included 194 elderly patients (94 males and 100 females) with T2DM. Digital retinal photography as well as fundus fluorescein angiography was employed to distinguish between nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). In addition, multiple logistic regression analysis was conducted to determine the correlation between serum IL-17A levels and DR status.Results: The average age of the study cohort was 69.14 ± 6.33 years, of which 52.08% were male. The study participants with the highest IL-17A (Q4) levels had higher TC, DBP, and low-density lipoprotein cholesterol (LDL-C) values than those the other groups. Analysis using unadjusted and adjusted linear regression revealed that the effect size of 1.09 for DR in the unadjusted model indicates that IL-17A is associated with an increase of 1.09 in DR (mmol/L) (β 1.09, 95% confidence interval (CI) 1.03, 1.16). Using the minimum-adjusted model (the model 2), as IL-17A increased, DR was higher by 1.11 (β 1.11, 95% CI 1.04, 1.18). With the fully adjusted model (the model 3), for each additional IL-17A increase, DR was higher by 1.15 (β 1.15, 95% CI 1.06, 1.24).Conclusion: Serum IL-17A levels are apparently positively correlated to DR in Chinese elderly individuals with T2DM.Keywords: interleukin-17A, diabetic retinopathy, type 2 diabetes mellitus

Yue Zhang, Lianping Ren, Jinyuan Sun, Fengfeng Han, Xuejun Guo Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Xuejun GuoDepartment of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200092, People’s Republic of ChinaTel +86-21-25078999-7373Email guoxuejun@xinhuamed.com.cnBackground: This study aimed to reveal the correlation between serum soluble interleukin-2 receptor (sIL-2R) and prognosis in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods: A total of 315 patients diagnosed with AECOPD between December 2017 and June 2020 were enrolled. The patients were divided into the good and adverse groups based on the outcomes. An adverse outcome in COPD exacerbation was defined by the presence of at least one of the following: (1) death from a respiratory cause during hospitalisation or within 1 month of follow-up; (2) intensive care unit admission; (3) invasive or non-invasive mechanical ventilation; and (4) COPD-related emergency visit or readmission within 1 month of follow-up. A good outcome was considered as the absence of all the aforementioned issues. The patients underwent lung function (spirometry) assessment, and clinical and inflammatory profiles were collected. Univariate and multivariate analyses were performed to identify the correlation between serum sIL-2R concentration and other variables related to adverse outcomes of AECOPD. The receiver operating characteristic curve was used to show the predictive ability of sIL-2R for adverse outcomes of AECOPD.Results: We enrolled 315 patients, of whom 161 and 154 had good and adverse outcomes, respectively. We demonstrated that patients with adverse outcomes of AECOPD had a higher concentration of serum sIL-2R than patients with good outcomes (p < 0.001). The increased serum sIL-2R was positively associated with mMRC scores (p < 0.001), GLOD grades (p < 0.001), frequent exacerbation (p < 0.001), and smoking (p < 0.001) in patients with AECOPD and negatively correlated with pulmonary function (p < 0.001). An elevated sIL-2R level was a predictor for the risk of adverse outcomes in AECOPD with a cut-off value of 860 U/mL.Conclusion: Increased serum sIL-2R concentration correlated with the risk of the adverse outcomes in AECOPD, indicating that it can be a predictive factor contributing to the diagnosis and assessment of adverse outcomes in patients with AECOPD.Keywords: chronic obstructive pulmonary disease, acute exacerbation, soluble interleukin-2 receptor, predictive factor

Jianhua Wang,1,2,&ast; Juan Xu,1– 3,&ast; Shuling Liu,1,2 Fei Han,1,4 Qiaojun Wang,1,4 Hao Gui,1,4 Rui Chen1,2 1Sleep Center, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215004, People’s Republic of China; 2Department of Respiratory Medicine, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, People’s Republic of China; 3Department of Respiratory Medicine, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng City, Yancheng, People’s Republic of China; 4Department of Neurology, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Chen Email chenruigood@126.comPurpose: To investigate the effect of continuous positive airway pressure (CPAP) on sleep electroencephalogram (EEG) activity in patients with obstructive sleep apnea (OSA) and to examine the correlation between quantitative EEG changes and cognitive function.Patients and Methods: A total of 69 men and 11 women were collected with an average age of 39.61 ± 7.67 years old from among middle-aged patients who had first visits with snoring as their main complaint. All of them completed sleep questionnaires, neurocognitive tests and night polysomnography (PSG). The patients in the OSA group also completed the second night of PSG monitoring under CPAP after pressure titration. A power spectrum analysis of EEG was used, and the correlation between the frequency powers of EEG and the scores of the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA) were further analyzed.Results: Compared with the control group, the delta/alpha power ratio (DAR) and the (delta + theta)/(alpha + beta) power ratio (the slowing ratio, TSR) of the OSA group before CPAP were higher (P < 0.05). The DAR and TSR of the OSA patients decreased significantly after CPAP. ESS scores were correlated with parameters such as respiratory-related microarousal index (RRMAI), apnea hypopnea index (AHI), and the average absolute power of delta, DAR and TSR (P < 0.05). The PSQI, MMSE and MoCA scores were not correlated with the average absolute power of each frequency band, DAR or TSR (P > 0.05).Conclusion: Patients with OSA have greater slow frequency EEG activity during sleep than the control group. CPAP treatment reversed the slow frequency EEG activity in patients with OSA.Keywords: obstructive sleep apnea, quantitative electroencephalogram, cognitive function, continuous positive airway pressure

Qi Li,1 Suna Cai,1 Mengjiao Li,1 Kab Ibrahim Salma,1 Xiaojie Zhou,1 Feiyu Han,2 Jinzhao Chen,2 Ting Huyan1,3 1Key Laboratory for Space Biosciences and Biotechnology, Institute of Special Environment Biophysics, School of Life Sciences, Northwestern Polytechnical University, Xi’an, 710072, People’s Republic of China; 2Shanxi Weiqidaguangming Pharmaceutical Co., Ltd, The First Medical Park, Economic & Technology Development Zone, Datong, 037000, People’s Republic of China; 3Institute of Flexible Electronics (IFE), Northwestern Polytechnical University, Xi’an, 710072, People’s Republic of ChinaCorrespondence: Ting HuyanKey Laboratory for Space Biosciences and Biotechnology, Institute of Special Environment Biophysics, School of Life Sciences, Northwestern Polytechnical University, Xi’an, 710072, People’s Republic of ChinaTel/Fax +86 29 8846 0332Email huyanting@nwpu.edu.cnAbstract: Nowadays, tumor has been the serious threat to human health and life. To further explore the mechanism of tumor genesis and development is necessarily for developing the effective treatment strategy. Extracellular vesicles are the vesicles secreted by almost all types of cells, and they play an important part in intercellular communication by transporting their cargoes. Immune cells are the vital components of the human defense system, which defense against infection and tumor through cytotoxicity, immune surveillance, and clearance. However, via release tumor-derived extracellular vesicles, tumor could induce immune cells dysfunction to facilitate its proliferation and metastasis. Studies have shown that tumor-derived extracellular vesicles play dual role on immune cells by their specific cargoes. Here, we reviewed the effects of tumor-derived extracellular vesicles on immune cells in recent years and also summarized their research progress in the tumor immunotherapy and diagnosis.Keywords: tumor-derived extracellular vesicles, immune cell, regulatory effects, drug delivery, immunotherapy

Yang Yang,1,&ast; Chenyang Li,2,&ast; Long Zhao,2 Jing Li,2 Fang Han,2 Fulong Xiao3 1Department of Neuropsychiatry and Behavioral Neurology and Clinical Psychology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 2Sleep Medicine Center, Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China; 3Department of General Internal Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Han; Fulong XiaoPeking University People’s Hospital, No. 11, South Avenue, Beijing, People’s Republic of ChinaEmail hanfang1@hotmail.com; xiaofulong1681@163.comObjective: We evaluate the association between depression symptoms, clinical features (disease onset-age, disease duration, sleep-related hallucination), sleepiness, and polysomnography parameters in adolescent narcolepsy type 1 patients.Methods: Eighty-three adolescent narcolepsy type 1 patients were involved in this cross-sectional study. Patients completed questionnaires evaluating depression symptoms (Center for Epidemiologic Studies Depression Scale) and sleepiness (Epworth Sleepiness Scale). Parameters from polysomnography and multiple sleep latency test were also collected.Results: Patients with depression symptoms (62.7%) have later disease onset-age. Depression symptoms were associated with sleep-related hallucination (OR = 2.75). Six independent variables were associated with sub-dimensional depression symptoms, including sleep latency, sleep efficiency, sleep-related hallucination, Epworth sleepiness scale, disease duration, and disease onset-age.Conclusion: Sleep-related hallucination is associated with total depression symptoms in adolescent narcolepsy. Subjective sleepiness is associated with depressed affect, somatic symptoms, and interpersonal problems. Lower sleep efficiency is associated with a lack of positive affect.Keywords: narcolepsy, adolescents, depression symptoms, hypnagogic/hypnopompic hallucination

Haiyan Ge,1,&ast; Xuanqi Liu,1,&ast; Wenchao Gu,2 Xiumin Feng,3,4 Fengying Zhang,5 Fengfeng Han,6 Yechang Qian,7 Xiaoyan Jin,8 Beilan Gao,9 Li Yu,10 Hong Bao,11 Min Zhou,12 Shengqing Li,13 Zhijun Jie,14 Jian Wang,15 Zhihong Chen,16 Jingqing Hang,5 Jingxi Zhang,3 Huili Zhu1 1Department of Respiratory and Critical Care Medicine, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Respiratory Medicine, Pudong New District People’s Hospital, Shanghai, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Changhai Hospital Affiliated to Navy Military Medical University, Shanghai, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Changji Branch of First Affiliated Hospital of Xinjiang Medical University, Xinjiang, People’s Republic of China; 5Department of Respiratory Medicine, Putuo District People’s Hospital, Shanghai, People’s Republic of China; 6Department of Respiratory Medicine, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 7Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, People’s Republic of China; 8Department of Respiratory Medicine, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 9Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China; 10Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 11Department of Respiratory Medicine Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China; 12Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 13Department of Respiratory and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 14Department of Respiratory Medicine, Shanghai Fifth’s Hospital, Fudan University, Shanghai, People’s Republic of China; 15Department of Respiratory Medicine, Shanghai Ninth’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 16Department of Respiratory and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huili Zhu Email zhuhuili001@126.comJingxi Zhang Email jingxizhang2000@126.comBackground: Chronic obstructive pulmonary disease (COPD) often coexists with multiple comorbidities which may have a significant impact on acute exacerbations of patients. At present, what kind of comorbidities affects acute exacerbations and how comorbidities lead to poor prognosis are still controversial. The purpose of our study is to determine the impact of comorbidities on COPD exacerbation and establish an acute exacerbation risk assessment system related to comorbidities.Methods: A total of 742 COPD patients participated in the Shanghai COPD Investigation on Comorbidity Program (SCICP, ChiCTR2000030911). Finally, the baseline information of 415 participants and one-year follow-up data were involved in the analysis. We collected hemogram indices, pulmonary function tests and acute exacerbation of COPD with regular medical follow-up. Q-type cluster analysis was used to determine the clusters of participants. Receiver operating characteristic (ROC) analysis was constructed to assess the ability of indicators in predicting acute exacerbations.Results: Almost 65% of the population we investigated had at least one comorbidity. The distribution and incidence of comorbidities differed between exacerbation group and non-exacerbation group. Three comorbidity clusters were identified: (1) respiratory, metabolic, immune and psychologic disease (non-severe cases); (2) cardiovascular and neoplastic disease (severe cases); (3) less comorbidity. Different sub-phenotypes of COPD patients showed significant distinction in health status. Anxiety (OR=5.936, P=0.001), angina (OR=10.155, P=0.025) and hypertension (OR=3.142, P=0.001) were found to be independent risk factors of exacerbation in a year. The novel risk score containing BODEx and four diseases showed great prognostic value of COPD exacerbation in developing sample.Conclusion: Our study detailed the major interaction between comorbidities and exacerbation in COPD. Noteworthily, a novel risk score using comprehensive index – BODEx – and comorbidity parameters can identify patients at high risk of acute exacerbation.Keywords: chronic obstructive pulmonary disease, exacerbation, comorbidity, risk score

Yun-Ming Tian,1 Lei Zeng,2 Yu-Hong Lan,1 Xia Yuan,3 Li Bai,1,* Fei Han4,* 1Department of Radiation Oncology, Huizhou Central People’s Hospital, Huizhou, Guangdong, People’s Republic of China; 2Department of Medical Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Medical Oncology, Huizhou Central People’s Hospital, Huizhou, Guangdong, People’s Republic of China; 4Department of Radiation Oncology, Sun Yat-Sen University Cancer Centre; State Key Laboratory of Oncology in South China; Collaborative Innovation Centre for Cancer Medicine, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li BaiDepartment of Radiation Oncology, Hui Zhou Municipal Central Hospital, No. 41 Eling North Road, Huizhou, Guangdong, People’s Republic of ChinaEmail bailihuizhou@126.comFei HanDepartment of Radiation Oncology, Sun Yat-Sen University Cancer Center, No. 651 Dongfeng East Road, Guangzhou, People’s Republic of ChinaEmail hanfeisysucc@126.comObjective: To investigate the prognostic value of cervical node features in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) and build a prognostic nomogram to predict the long-term survival.Methods: In this study, 1752 patients after IMRT from 2008 to 2011 were recruited. The clinical and laboratory characteristics and the nodal features including the nodal number, maximum dimension diameter, extranodal extension (ENE), and cervical node necrosis (CNN) were retrospective analyzed. Univariate Cox and multivariate proportional hazard regression models were used to test the prognostic value of nodal features. Prognostic nomograms were established to predict survival.Results: The 10-year distant metastases-free survival (DMFS) and disease-specific survival (DSS) rates were 86.5% and 80.8%, respectively. Multivariate analysis showed that age, sex, lactate dehydrogenase (LDH), CNN, ENE, T stage, and N stage were independent factors for DSS. Two nomograms—nomogram A (without nodal features) and nomogram B (with nodal features)—were built. The calibration curve for the probability of DSS showed good agreement between prediction by nomogram and the actual observation. The C-index of nomogram B was higher than that for nomogram A in predicting DSS (0.708 vs 0.676, P< 0.01).Conclusion: The nodal features including ENE and CNN were negative prognostic factors for NPC, and the prognostic nomogram incorporating the nodal features was more accurate in predicting survival than the nomogram without nodal features.Keywords: nodal features, extranodal extension, nodal necrosis, nasopharyngeal carcinoma, prognostic value

Cui Ying Wei,1,* Zhong Ming He,2,* Han Yan,3 Jing Li,3 Pei An,3 Long Zhao,3 Li Nong Ji,4 Zhan Cheng Gao,3 Xiao Song Dong,3 Fang Han3 1Department of Endocrinology, First Affiliated Hospital, Baotou Medical College, Baotou, Inner Mongolia, People’s Republic of China; 2Department of Pulmonary Medicine, Karamay Central Hospital, Karamay, Xinjiang, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 4Department of Endocrinology, Peking University People’s Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao Song DongDepartment of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of ChinaTel/Fax +86-10-88324207Email dongxiaosong@pkuph.edu.cnPurpose: The study aimed at assessing glucose control measured with a continuous glucose monitoring system (CGMS) before and after short-term continuous positive airway pressure (CPAP).Materials and Methods: Twenty-four type 2 diabetic patients (T2DM) with Obstructive sleep apnea syndrome (OSAS) (mean age 55.0 ± 9.0 years; BMI 29.5 ± 5.2 kg/m2) were admitted and kept under diet control for 2 days, then underwent 2 overnight polysomnographies: a diagnostic study and one with CPAP titration. Then they were treated by CPAP during sleep for the following three nights. Participants were divided into subgroup D (only diet control) and subgroup M (with DM medication). CGMS was utilized over the last five days. Glucose control was also assessed with plasma insulin and a clinical measure of insulin resistance (HOMA-IR) index.Results: The mean (±SD) apnea-hypopnea index (AHI) at diagnostic polysomnography was 51.2 ± 22.4 (range 10– 88) events/h. CPAP treatment in the subjects with OSAS resulted in the index of oxygenation desaturations being reduced from 33.3 ± 20.1 to 1.1 ± 1.6 (P =0.00). CGMS showed mean 24-hours glucose values significantly lower after CPAP treatment than at baseline in both subgroups (7.97± 1.31 vs 7.52± 0.94, P=0.033 in subgroup D; and 7.72± 1.51 vs 7.17± 1.21, P=0.05 in subgroup M), as the fasting plasma insulin levels and HOMA-IR were also decreased significantly after CPAP treatment (13.0 ± 7.5μU/mL vs 10.8 ± 5.4μU/mL, P=0.044; and 4.2 ± 2.2 vs 3.1± 1.7, P=0.003, respectively). Standard deviation (SD) and mean amplitude of glucose excursions (MAGE) were also decreased in the subgroup D (1.91 ± 1.10 vs 1.61 ± 1.20, P=0.014; 1.26 ± 1.13 vs 1.01 ± 0.98, P=0.008, respectively) only.Conclusion: Short-term CPAP treatment in OSAS with type 2 diabetic patients is accompanied by a decrease in blood glucose level and improved insulin sensitivity. Glucose variability was reduced but only in the patients with diet control.Keywords: type 2 diabetes mellitus, obstructive sleep apnea syndrome, continuous positive airway pressure, continuous glucose monitoring system, glucose variability, HOMA-IR

Xijiang Zhao,1,* Linna You,1,* Tao Wang,1 Xianjun Zhang,1 Zexi Li,2 Luguang Ding,2 Jiaying Li,2 Can Xiao,2 Fengxuan Han,2 Bin Li2 1Department of Orthopedics, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, People’s Republic of China; 2Departments of Orthopaedic Surgery and Stomatology, The First Affiliated Hospital, Orthopaedic Institute, Soochow University, Suzhou, Jiangsu 215006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin LiSoochow University (South Campus), 708 Renmin Road, Rm 308 Bldg 1, Suzhou, Jiangsu 215007, People’s Republic of ChinaTel/Fax (+86) 512-6778-1163Email binli@suda.edu.cnCan XiaoThe First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, People’s Republic of ChinaEmail canxiao0511@163.comIntroduction: Despite great progress made in developing orthopedic implants, the development of titanium (Ti) implants with ideal early osseointegration remains a big challenge. Our pilot study has demonstrated that Si-TiO2 nanotubes on the surface of Ti substrates could enhance their osteogenic activity. Hence, in this study, we aim to comprehensively evaluate the effects of silicon-doped titania (Si-TiO2) nanotubes on the osseointegration property of Ti implants.Materials and Methods: The Ti implants were surface modified with Si-TiO2 nanotubes through in situ anodization and Si plasma immersion ion implantation (PIII) method. Three groups were divided as Ti implants (Ti), Ti modified with TiO2 nanotubes (TiO2-NTs) and Ti modified with Si-TiO2 nanotubes (Si-TiO2-NTs). The morphology of Si-TiO2 nanotubes was observed by scanning electron microscope. The growth and osteogenic differentiation of MC3T3-E1 cells on the Ti implants were evaluated. Further, the pull-out tests and in vivo osseointegration ability evaluation were performed after implanting the screws in the femur of Sprague Dawley rats.Results: The Si-TiO2 nanotubes could be seen on the surface of Ti implants. The MC3T3-E1 cells could grow on the surface of Ti, TiO2-NTs and Si-TiO2-NTs, and showed fast proliferation rate on the Si-TiO2-NTs. Moreover, the production of some osteogenesis-related proteins (ALP and Runx2) at one week and calcium deposition at four week was also enhanced in Si-TiO2-NTs rather than other groups. In vivo osseointegration results showed that Si-TiO2 nanotube-modified Ti screws had higher pullout force at two and four weeks as well as enhanced new bone formation at six weeks compared to bare Ti screws and Ti screws modified with TiO2 nanotubes alone.Discussion: The modification of Si-TiO2-NTs on the Ti substrate could generate a nanostructured and hydrophilic surface, which can promote cell growth. Moreover, the existence of the TiO2 nanotubes and Si element also can improve the in vitro osteogenic differentiation of MC3T3-E1 cells and early bone formation around the implanted screws. Together, findings from this study show that surface modification of Ti implants with Si-TiO2 nanotubes could enhance early osseointegration and therefore has the potential for clinical applications.Keywords: osseointegration, implant, silicon, titanium dioxide, nanotubes

Fang Han,1,2,* Shuang Liu,1,3,* Jingjing Jing,1 Hao Li,1 Yuan Yuan,1 Li-Ping Sun1 1Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, Shenyang 110001, People’s Republic of China; 2Hepatobiliary and Pancreatic Surgery, Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou 310014, People’s Republic of China; 3Department of Oncology, Shanxi Provincial Tumor Hospital, Xi’an 710076, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Ping Sun; Yuan Yuan Email lpsun@cmu.edu.cn; yuanyuan@cmu.edu.cnBackground: Ring finger protein 180 (RNF180) is a tumor suppressor gene regulated by promoter methylation. We previously demonstrated that the RNF180 promoter methylation could be a risk factor for gastric cancer (GC); and eight high-frequency hypermethylated CpG sites were associated with GC. However, it is not clear whether these key sites can affect gene expression and involve in prognosis. The aim of this study was to investigate the effects of above CpG sites on the gene expression and prognosis of GC.Patients and Methods: A total of 164 GC tissues were enrolled and followed up. Tissue samples were used for DNA and RNA isolation. Methylation status of RNF180 was detected using bisulfite sequencing PCR (BSP). Expression levels of RNF180 were detected using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). JASPAR and PROMO databases were used to predict the transcription factors (TFs) binding to the CpG site.Results: The methylation in RNF180 promoter region increased and mRNA expression decreased in GC tissue. Correlation analysis revealed that the average methylation rate (AMR) and four CpG sites methylation rate were negatively related to RNF180 expression, including M3(− 165)(Chr5:64165942), M5(− 148)(Chr5:64,165,959), M7(− 133)(Chr5:64,165,974) and M8(− 130)(Chr5:64,165,977). Furthermore, the methylation rate of M5(− 148)(Chr5:64,165,959) and M27(− 26)(Chr5:64,166,081) above 0.3 indicated poor prognosis (PM5 = 0.008, PM27 = 0.003, HRM5(− 148) = 2.000 (1.201,3.332), HRM27(− 26)=2.389 (1.336,4.271)), which could be independent factors of prognosis.Conclusion: By focusing on the methylation sites in the RNF180 promoter region, we identified two high-frequency methylation sites, M5(− 148)(Chr5:64,165,959) and M27(− 26)(Chr5:64,166,081), which could affect gene expression and predict the prognosis of GC. In the future, the possible molecular mechanism involved needs to be further studied.Keywords: gastric cancer, RNF180, methylated CpG sites, prognosis, methylation

Fei Han,1 Peng Zhang,2 Tianwu Chen,2 Chao Lin,1 Xuejun Wen,1 Peng Zhao1 1Institute for Translational Medicine, Institute for Biomedical Engineering and Nanoscience, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200092, People’s Republic of China; 2Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of ChinaCorrespondence: Peng Zhao; Peng ZhangInstitute for Translational Medicine, Institute for Biomedical Engineering and Nanoscience, Shanghai East Hospital, Tongji University School of Medicine, Tongji University, Room 222, Shixun Building, Shanghai 200092, People’s Republic of ChinaTel +86 21 65988029Fax +86 21 65983708-0Email zp@tongji.edu.cn; zhangpengym@163.comIntroduction: In anterior cruciate ligament (ACL) reconstruction, hamstring tendon autograft is a well-accepted surgical choice as an alternative ACL graft. But the main disadvantage of autograft is its inefficient healing with host bone-tunnel which will leading to surgery failure.Methods: A biomimetic nanofibrous membrane for tendon-bone integration is fabricated in this work, which is composed of polycaprolactone (PCL) electrospinning membrane and chitosan/hyaluronic acid (CS/HA) multilayers film.Results: By using layer-by-layer (LbL) self-assembly this functional CS/HA multilayer films are deposited on the surface of PCL nanofiber to enable the local delivery of stromal cell-derived factor-1 α (SDF-1α) and bone morphogenetic protein-2 (BMP-2) in tendon-bone interface. This membrane can promote cell proliferation and recruitment, as well as inducing the osteogenic differentiation and recruitment of BMSCs.Conclusion: Further in vivo studies demonstrate that to wrap the tendon autograft using the membrane may afford superior tendon-bone integration and inhibit scar tissue formation in a rabbit ACL reconstruction model. More importantly, the biomechanical properties of the tendon-bone interface have been improved. This study shows that this biomimetic nanofibrous membrane is effective for improving tendon-bone healing after ACL reconstruction surgery.Keywords: anterior cruciate ligament reconstruction, tendon-bone healing, layer-by-layer self-assembly, nanofibrous membrane, stromal derived factor-1α

Hong Cui,1 Feng Han,1 Ling Zhang,1 Li Wang,1 Mukesh Kumar2 1Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450008, China; 2Chandra Shekhar Singh College of Pharmacy, Allahabad, India Introduction: Hepatocellular carcinoma (HCC) is one of the known major health problems across the globe, and is sixth ranked among all cancer, due to its high mortality rate. Polyunsaturated fatty acids (PUFAs) play an important role in the formation of a cell membrane, along with the fluidity of the membrane and proteins. Gamma linolenic acid (GLA) is member of the ω-6 family of PUFAs and converts into the arachidonic acid via a series of elongation and desaturation reactions. The aim of the current investigation was to scrutinize the effect of GLA on mitochondrial mediated apoptosis and anti-inflammatory pathway against diethylnitrosamine (DEN) induced HCC.Materials and methods: Chemical carcinogenesis in Wistar rats was introduced by an intraperitoneal dose of DEN (200 mg/kg). The rats received the various doses of GLA for 22 weeks. The progressions of serum biomarkers and histopathology components of hepatic tissue were used to access the prophylactic effects. The antioxidant parameters, cancer preventive agent status, and apoptosis mechanism were reviewed to scrutinize the possible mechanism.Results: Dose-dependent treatment of GLA significantly (P

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Muli Hu,1,2,* Zhiwei He,2,3,* Fengxuan Han,1,2 Chen Shi,4 Pinghui Zhou,2 Feng Ling,1,2 Xuesong Zhu,2 Huilin Yang,2 Bin Li2,5 1Department of Polymer Science, College of Chemistry, Chemical Engineering and Materials Science, Orthopaedic Institute, Soochow University, Suzhou, China; 2Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China; 3Department of Orthopaedics, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China; 4Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore; 5China Orthopaedic Regenerative Medicine Group (CORMed), Hangzhou, China *These authors contributed equally to this work Background: Bone cement plays an important role in the treatment of osteoporotic vertebral compression fractures. Calcium phosphate cement (CPC) is a potential alternative to poly(methyl methacrylate), currently the gold standard of bone cements. However, the poor mechanical properties of CPCs limit their clinical applications. The objective of this study was to develop reinforced CPCs for minimally invasive orthopedic surgeries by compositing silk fibroin (SF) with α-tricalcium phosphate.Methods: SF solution was treated with calcium hydroxide and characterized by Zeta potential analyzer and Fourier transform infrared spectroscopy. The alkaline-treated SF (tSF) was composited with α-tricalcium phosphate to obtain tSF/CPC composite, which was characterized using mechanical tests, scanning electron microscopy, handling property and biocompatibility tests, and sheep vertebral augmentation tests.Results: Upon treatment with calcium hydroxide, larger SF particles and more abundant negative charge appeared in tSF solution. The tSF/CPCs exhibited a compact structure, which consisted of numerous SF -CPC clusters and needle-like hydroxyapatite (HAp) crystals. In addition, high transition rate of HAp in tSF/CPCs was achieved. As a result, the mechanical property of tSF/CPC composite cements was enhanced remarkably, with the compressive strength reaching as high as 56.3±1.1 MPa. Moreover, the tSF/CPC cements showed good injectability, anti-washout property, and decent biocompatibility. The tSF/CPCs could be used to augment defected sheep vertebrae to restore their mechanical strength.Conclusion: tSF/CPC may be a promising composite bone cement for minimally invasive orthopedic surgeries. Keywords: bone cement, silk fibroin, calcium phosphate, calcium hydroxide, reinforcement

Inleiding: Dit onderzoek betreft posttraumatische stressklachten en posttraumatische stressstoornis (PTSS) bij gerontopsychiatrische (GP) patiënten in het verpleeghuis. PTSS bij ouderen is onderbelicht en deze groep ouderen is hier niet eerder op onderzocht. PTSS gaat vaak samen met ernstige psychiatrische problematiek, kan invloed hebben op, of zelfs verklarend zijn voor onbegrepen probleemgedrag. De huidige trend is dat psychiatrische problematiek steeds vaker reden voor opname is. Deze studie onderzoekt in hoeverre traumatische ervaringen en PTSS bij deze populatie aanwezig zijn en in hoeverre regiebehandelaars (specialisten ouderengeneeskunde) dit onderkennen. Methode: Om psychotrauma en PTSS te screenen werd de Trauma Screeningsvragenlijst (TSV) afgenomen. De inschatting van de regiebehandelaars omtrent de aanwezigheid van psychotrauma en PTSS werd geobjectiveerd middels twee vragen. Deelnemers: Alle 52 GP-patiënten in de onderzochte zorginstelling, van wie 16 de TSV-vragen niet hebben beantwoord. Conclusie: Traumatische ervaringen komen bij deze groep zeer frequent voor. Zij worden deels niet herkend door regiebehandelaars. Een advies voor de klinische praktijk is om bij GP-patiënten van een verpleeghuis niet alleen de TSV af te nemen, maar daarbij ook te vragen naar mogelijke vermijding van traumatische herinneringen. De kans op onderdiagnostiek van psychotrauma en PTSS kan hiermee worden verkleind.

Shiqing Feng,1,* Juan Xiao,2,3,* Fabin Han,4 Lin Chen,5 Wenyong Gao,2,3 Gengsheng Mao,2 Hongyun Huang2,3 On behalf of Neurorestoratology Professional Committee of Chinese Medical Doctors Association (Chinese Association of Neurorestoratology) 1International Science and Technology Cooperation Base of Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of China; 2Institute of Neurorestoratology, The General Hospital of Chinese People’s Armed Police Forces, Beijing 100039, People’s Republic of China; 3Cell Therapy Center, Beijing Hongtianji Neuroscience Academy, Beijing 100043, People’s Republic of China; 4The Institute for Tissue Engineering and Regenerative Medicine, Liaocheng University/Liaocheng People’s Hospital, Liaocheng 252000, People’s Republic of China; 5Department of Neurosurgery, Tsinghua University Yuquan Hospital, Beijing 100040, People’s Republic of China *These authors contributed equally to this work Abstract: In order to promote the clinical use of neural progenitor or precursor cells for treating neurological diseases and damage, we need to standardize culture procedures for these cells. The Chinese Association of Neurorestoratology put forward these standards for training operators, standardized use and management of materials and equipment, standardized isolation and culture for neural progenitor/precursor cells, and the standardized management in preservation, transport, and related safe operation procedures of the neural progenitors. These cultures and quality control standards also include the Good Manufacturing Practice environment, routine maintenance as well as the monitoring and reporting of the clinical-grade neural progenitor cells. The aim of these standards is to improve the therapeutic efficacy and minimize the possible side effects from lake of quality control. Keywords: standardization, cell culture, quality control, neural progenitor cells, neural precursor cells, neurorestoratology

Ya-li Lv, Fei-fei Han, Yang-jie Jia, Zi-rui Wan, Li-li Gong, He Liu, Li-hong Liu Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China Background: Human cytomegalovirus (HCMV) infection has been associated with inflammatory bowel disease (IBD). Numerous studies have been conducted to analyze the association between HCMV infection and risk of IBD and steroid-resistant IBD, but no clear consensus had been reached. Objectives: The aim of this study was to confirm this relationship precisely by doing a systematic review and meta-analysis. Study design: We identified relevant studies through a search of PubMed and Embase. Studies were eligible for inclusion if they 1) evaluated the association between HCMV infection and IBD disease; 2) evaluated the association between HCMV infection and steroid-resistant IBD disease; 3) were case–control studies or nested case–control studies; 4) provided the numbers (or percentage) of positivity for HCMV infection in cases and controls, respectively. Data were extracted and analyzed independently by two investigators. Results and conclusion: A total of 18 studies including 1,168 patients and 951 health groups was identified, and HCMV infection was distinctly confirmed as a risk factor for the occurrence and development of IBD. When involving 17 studies including 1,306 IBD patients, a total of 52.9% of patients in the cytomegalovirus (CMV)-positive groups were observed to have steroid resistance, compared with 30.2% of patients in the CMV-negative groups. There was a significant difference in the risk of steroid resistance between people exposed to HCMV infection and those not exposed HCMV infection in IBD patients. This meta-analysis suggested that HCMV infection is associated with an increased risk for IBD and steroid-resistant IBD. Keywords: cytomegalovirus, infection, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, meta-analysis