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Wei Zu,1,* Shaojiong Zhou,2,* Tao Du,1 Chenyanwen Zhu,3 Siyue Nie,4 Hongwei Zhu1 1Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurology & Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders, Beijing, People’s Republic of China; 3 4+4 Medical Doctor Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 4Chinese PLA Medical School; Department of Oncology, Chinese PLA General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongwei Zhu, Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China, Email zhuhongwei@xwh.ccmu.edu.cnIntroduction: This study aims to investigate the potential causal effects of modifiable risk factors on Fibromyalgia (FM).Methods: Genetic variants associated with 34 exposure factors were obtained from Genome-wide association studies (GWAS). Summary statistics for FM were acquired from the FinnGen consortium. Bidirectional Mendelian randomization (MR) analysis was conducted between all exposures and outcomes. The inverse-variance weighted (IVW) method was employed as the primary estimation technique. Heterogeneity and pleiotropy were assessed using MR-PRESSO global test, the weighted median, Cochran’s Q statistic and MR-Egger.Results: Depression (OR=2.087, 95% CI: 1.466– 2.971), alcohol consumption (OR=1.489, 95% CI: 1.094– 2.028), body fat percentage (OR=1.524, 95% CI: 1.153– 2.013) and body mass index (BMI) (OR=1.542, 95% CI: 1.271– 1.872) were associated with an increased risk of FM among genetically susceptible individuals. Conversely, higher education level (OR=0.404, 95% CI: 0.297– 0.549), longer years of education (OR=0.489, 95% CI: 0.290– 0.825) and higher household income (OR=0.328, 95% CI: 0.215– 0.502) were protective against FM. Additionally, rheumatoid arthritis (OR=1.138, 95% CI: 1.061– 1.221) and ankylosing spondylitis (OR=1.079, 95% CI: 1.021– 1.140) were identified as important risk factors for FM.Conclusion: This MR study unveiled a complex causal relationship between modifiable risk factors and FM. Psychosocial factors significantly increase the odds of FM, while obesity and some autoimmune diseases that frequently coexist with FM demonstrate causal associations. Additionally, lifestyle habits such as alcohol consumption are causally related to FM. Further investigation is needed to determine whether risk factors contribute to the pathogenesis of FM through mechanisms involving central sensitization, inflammatory, and hyperalgesia. This study enhances our understanding of the factors that drive FM onset and progression, offering valuable insights for future targeted prevention and treatment strategies.Keywords: fibromyalgia, modifiable risk factors, causal association, Mendelian randomization

Man Zhang,1,2,* Siman Nie,3,* Ziwei Hai,2 Yixin Du,2 Menghan Jiang,4 Chunfeng Cai2 1Department of Oncology, The First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Wuhan University School of Nursing, Wuhan, Hubei, People’s Republic of China; 3Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 4Shandong University of Traditional Chinese Medicine College of Health Sciences, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunfeng Cai, Faculty of Wuhan University School of Nursing, Wuhan, Hubei, People’s Republic of China, Email 1660433132@qq.comAim: Chronic disease self-management is critical to disease prognosis and patient quality of life. Several psychological factors influence this process of self-management. In this background, the present study investigated the impact of illness perceptions and coping style on self-management in people with peritoneal dialysis (PD).Methods: The study is a cross-sectional study. From May 2022 to January 2023, a convenience sampling method was used to recruit 246 peritoneal dialysis patients. General information questionnaire, brief illness perception questionnaire, medical coping style modes questionnaire and the self-management scale for peritoneal dialysis patients were used in this study. We used SPSS 24.0 to analyze the data, and the statistical methods included descriptive analysis, single factor analysis, Pearson correlation analysis and multiple linear regression analysis.Results: A total of 246 patients were included in this study (93.89% response rate). Cognitive representations and emotional representations were 30.40, 14.18, respectively. However, illness comprehensibility was 2.87. Illness perceptions were negative significantly correlated with self-management. With regard to coping style, our patients were more likely to adopt avoidance and resignation coping style. Confrontation and avoidance were positively related to self-management, while acceptance-resignation was negatively related.Conclusion: Self-management of peritoneal dialysis patients needs to be improved. Age, female sex, monthly income, illness perceptions and coping style were independently associated with self-management.Impact: These findings suggest that interventions that improve illness perceptions and coping style should be explored to ultimately improve their self-management. For example, patients can be provided with psychological counseling so that they can face the disease correctly, and we should pay attention to the positive role of social support.Keywords: peritoneal dialysis, illness perception, coping style, self-management

Yanan Huang,1,* Yunfeng Wang,2,* Tianyu Zheng,1,* Shuang Nie,1 Yanli Wang,3 Hui Shen,1 Fengfeng Mo1 1Department of Naval Nutrition and Food Hygiene, Faculty of Navy Medicine, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Gastroenterology, Changhai Hospital, Shanghai, People’s Republic of China; 3International Joint Research Center of Human-Machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province, Hainan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanli Wang; Fengfeng Mo, Email hyyaoxueyuan2022@163.com; mofengfeng@smmu.edu.cnPurpose: Erythrocytes and fibroblasts in the pancreatic cancer tumor microenvironment promote tumor cell growth and invasion by providing nutrients and promoting immunosuppression. Additionally, they form a barrier against the penetration of chemotherapeutic drugs. Therefore, the search for diversified tumor-targeting materials plays an essential role in solving the above problems.Methods: Physicochemical characterization of Graphene fluorescent nanoparticles (GFNPs) and nanomedicines were analyzed by transmission electron microscopy (TEM), elemental analyzers and ultraviolet fluorescence (UV/FL) spectrophotometer. Localization of GFNPs in cell and tissue sections imaged with laser confocal microscope, fluorescence scanner and small animal in vivo imager. Qualitative detection and quantitative detection of GFNPs and GFNPs-GEM were performed using High performance liquid chromatography (HPLC).Results: Based on the 3 nm average dimensions, GFNPs penetrate vascular endothelial cells and smooth muscle cells, achieve up to label 30% tumor cells and 60% cancer-associated fibroblasts (CAFs) cells, and accurately label mature red blood cells in the tumor microenvironment. In orthotopic transplanted pancreatic cancer models, the fluorescence intensity of GFNPs in tumors showed a positive correlation with the cycle size of tumor development. The differential spatial distribution of GFNPs in three typical clinical pancreatic cancer samples demonstrated their diagnostic potential. To mediate the excellent targeting properties of GFNPs, we synthesized a series of nanomedicines using popular chemotherapeutic drugs, in which complex of GFNPs and gemcitabine (GFNPs-GEM) possessed stability in vivo and exhibited effective reduction of tumor volume and fewer side effects.Conclusion: GFNPs with multiple targeting tumor microenvironments in pancreatic cancer possess diagnostic efficiency and therapeutic potential. Keywords: graphene fluorescent nanoparticles, cancer-associated fibroblasts, pancreatic cancer cells, dual-targeting, chemo-target therapy

Chenxi Ouyang,1,2 Changjiang Meng,3 Fei Li,3 Shanshan Nie,3 Liying Gong,4 Yu Cao,5 Hong Yuan,3,5 Zeying Feng6 1School of Pharmacology, University of South China, Hengyang, Hunan, People’s Republic of China; 2The Affiliated Nanhua Hospital, Department of Pharmacy, Hengyang Medical School University of South China, Hengyang, Hunan, People’s Republic of China; 3Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 5Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 6Clinical Trial Institution Office, Liuzhou Hospital of Guangzhou Women and Children’s Medical Center, Liuzhou, Guangxi, People’s Republic of ChinaCorrespondence: Zeying Feng, Clinical Trial Institution Office, Liuzhou Hospital of Guangzhou Women and Children’s Medical Center, No. 50 Boyuan Avenue, Liuzhou, Guangxi, 545000, People’s Republic of China, Email fengzeying@foxmail.comPurpose: Mechanistic studies showed that morphine may impair the antiplatelet effect of P2Y12 inhibitors. However, Several clinical studies with cardiovascular events as an outcome are contradictory, and the broader impact of this drug interaction on additional organ systems remains uncertain. With multisource data, this study sought to determine the effects of morphine interaction with P2Y12 inhibitors on major adverse outcomes comprehensively, and identify the warning indicators.Patients and Methods: Interaction signals were sought in 187,919 safety reports from the FDA Adverse Event Reporting System (FAERS) database, utilizing reporting odds ratios (repOR). In a cohort of 5240 acute coronary syndrome patients, the analyses were validated, and the biological effects of warning indicators were further studied with Mendelian randomization and mediation analysis.Results: Potential risk of renal system adverse events in patients cotreated with morphine is significantly higher in FAERS (repOR 4.83, 95% CI 4.42– 5.28, false discovery rate adjusted-P =3.55*10− 209). The analysis of in-house patient cohorts validated these results with an increased risk of acute kidney injury (adjusted OR: 1.65; 95% CI: 1.20 to 2.26), and we also found a risk of myocardial infarction in patients treated with morphine (adjusted OR: 1.55; 95% CI: 1.14 to 2.11). The Morphine group exhibited diminished Plateletcrit (PCT) levels post-surgery and lower PCT levels were associated with an increased risk of AKI.Conclusion: The administration of morphine in patients treated with P2Y12 receptor inhibitors should be carefully evaluated. PCT may serve as a potential warning indicator for morphine-related renal injury.Keywords: P2Y12 receptor inhibitors, morphine, kidney injury, Mendelian randomization

Zile Chen,&ast; Yiting Li,&ast; Shu Nie, Zhouwei Wu Department of Dermatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhouwei Wu, Department of Dermatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Email zhouwei.wu@shgh.cnPurpose: Vitiligo is an acquired depigmented skin disorder. Though genetic background, autoimmune dysregulation, and oxidative stress were reported involved in the development of vitiligo, the exact pathogenesis remains largely unknown. This study aimed to investigate potential functional proteins, pathways, and serum biomarkers involved in active vitiligo.Patients and Methods: Tandem Mass Tags (TMT) method was used to determine differentially expressed proteins (DEPs) in serum samples between 11 active vitiligo patients and 7 healthy controls of Chinese Han population.Results: A total of 31 DEPs were identified (P < 0.05, fold change > 1.2), with 21 proteins upregulated and 10 proteins downregulated in the vitiligo group. DEPs were enriched in GO terms such as “extracellular exosome” and “immunoglobulin receptor binding”, as well as KEGG pathways including “cysteine and methionine metabolism” and other immune-related pathways. Furthermore, ALDH1A1 and EEF1G achieved areas under receiver-operating characteristic (ROC) curve of 0.9221 and 0.8571, respectively. The expression levels of these 2 proteins were validated in another active vitiligo patient group.Conclusion: Our research provided novel insight into serum proteomic profile for vitiligo patients, detecting ALDH1A1 and EEF1G as potential biomarkers for active vitiligo and therapeutic intervention. Our work also detected several DEPs and associated pathways in the serum of active vitiligo patients, reinforcing the roles of retinoic acid and exosome processes in vitiligo pathogenesis.Keywords: vitiligo, active, proteomic profile, serum, biomarker

Zhongyu Fan,1– 4,&ast; Yunliang Guo,1– 3,&ast; Xunyao Hou,1– 3 Renjun Lv,5 Shanjing Nie,1– 3 Song Xu,1– 3 Jian Chen,1– 3 Yan Hong,1– 3 Shuo Zhao,6 Xueping Liu1– 3 1Department of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 2Department of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Anti-Aging Monitoring Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 4Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 5The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 6Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueping LiuDepartment of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of ChinaEmail Liuxueping1962@163.comBackground: Few reports have implied electrophysiological alterations and neurocognitive abnormalities in patients with cerebral small vessel disease (CSVD), while no investigation is available regarding emotional processing. In the present study, pre-attentive processing of facial expressions was compared between CSVD sufferers and healthy controls using expression-related visual mismatch negativity (EMMN) as the indicator.Methods: A total of 22 CSVD patients (12 males) and 21 age-matched healthy controls (12 males) were recruited for neuropsychological and emotional assessments, as well as electroencephalogram recording and analysis. We employed an expression-related oddball paradigm to investigate automatic emotional processing, and a series of schematic emotional faces (neutral, happy, sad) unrelated to subject’s task were present in the test to avoid low-level processing of facial features.Results: Although the distinctions of neuropsychological (MoCA and MMSE), emotional (GAD-7 and PHQ-9) and behavioral parameters (reaction time to target stimuli and response accuracy) did not reach significant levels, mean amplitudes of sad EMMN in time intervals of 150– 250 ms and 250– 350 ms were remarkably reduced in CSVD patients compared with healthy controls, but not for happy EMMN. Furthermore, in the control group, sad EMMN was demonstrated to be larger (more negative) than happy EMMN, while this interesting phenomenon disappeared in the CSVD group.Conclusion: Our findings confirmed selective impairment of processing expressions which were task-irrelevant in CSVD patients, without the existence of negative bias (sad superiority) effect. The efficacy of EMMN as an electrophysiological evaluation marker of CSVD should be taken into account in future investigations.Keywords: cerebral small vessel disease, expression-related visual mismatch negativity, pre-attentive processing of facial expressions, negative bias effect

Shanjing Nie,1– 3 Chao Shen,1,2 Yunliang Guo,1– 3 Xunyao Hou,1– 3 Yan Hong,1– 3 Song Xu,1– 3 Renjun Lv,4 Xueping Liu1– 3 1Department of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 2Department of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Anti-Aging Monitoring Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 4Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Xueping LiuDepartment of Senile Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, People’s Republic of ChinaEmail Liuxueping1962@163.comBackground: Cerebral small vessel disease is the primary cause of cognitive impairment. Therefore, early recognition is of great significance. Some studies have shown that asymptomatic cerebral small vessel disease (aCSVD) patients have abnormal neurocognitive function, but this is not readily apparent at the initial stage. The objective of this paper was to assess visual spatial attention by event-related potential (ERP) examination and to analyze the relationship between ERP data and clinical characteristics in patients with aCSVD.Methods: We selected 25 aCSVD patients and enrolled 23 age-matched normal subjects as the control group. We measured the latency and amplitude of original/corresponding differential ERP components using the modified visual oddball paradigm, which included a standard stimulus, target stimulus, and new stimulus. Additionally, we selected aberrant ERP components to study the correlations between the ERP data and clinical characteristics of the patients with aCSVD.Results: We found not only lower amplitude but also significantly longer P3 latency in the aCSVD patients. The above results were further verified by analyzing the different components (target minus standard and novel minus standard) of P3. Furthermore, abnormal ERPs in the aCSVD patients were closely related to the changes observed with imaging.Conclusion: It was demonstrated that the speed and capability of processing visual spatial information was impaired in aCSVD patients compared with healthy controls. Thus, ERP examination could detect the presence of attentional deficits and might become a rapid and sensitive method for the early diagnosis of aCSVD. However, its availability needs further investigation.Keywords: asymptomatic cerebral small vessel, event-related potential, cognitive impairment, P3, visual spatial attention impairment

Ziyuan Shen,1,&ast; Fei Wang,2,&ast; Chenlu He,1,&ast; Dashan Li,3 Shanlin Nie,3 Zhenzhen Bian,3 Mingkang Yao,4 Yuhao Xue,5 Ying Wang,6 Weiying Gu,2 Taigang Zhu,7 Yuye Shi,5 Hao Zhang,4 Shuiping Huang,1,8 Yuqing Miao,9 Wei Sang3 On behalf of the Huaihai Lymphoma Working Group1Department of Epidemiology and Biostatistics, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Hematology, The First People’s Hospital of Changzhou, Changzhou, Jiangsu, People’s Republic of China; 3Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 5Department of Hematology, The First People’s Hospital of Huaian, Huaian, Jiangsu, People’s Republic of China; 6Department of Personnel, Suqian First Hospital, Suqian, Jiangsu, People’s Republic of China; 7Department of Hematology, The General Hospital of Wanbei Coal-Electric Group, Suzhou, People’s Republic of China; 8Center for Medical Statistics and Data Analysis, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 9Department of Hematology, Yancheng First People’s Hospital, Yancheng, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei SangDepartment of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of ChinaTel +8613645207648Email xyfylbl515@xzhmu.edu.cnYuqing MiaoDepartment of Hematology, Yancheng First People’s Hospital, Yancheng, Jiangsu, People’s Republic of ChinaTel +8613851342032Email miaomiaomyq@163.comIntroduction: Immunonutritional status is associated with the survival of DLBCL. This multicenter retrospective study aimed to explore the prognostic value of Prognostic Nutrition Index (PNI) in DLBCL patients by using propensity score matched analysis (PSM).Methods: A total of 990 DLBCL cases were recruited from 5 centers of Huaihai Lymphoma Working Group (HHLWG). A 1:1 PSM analysis was performed using the nearest-neighbor method, with a caliper size of 0.02. Cox regression analysis was used to examine factors associated with survival.Results: The median age at diagnosis was 62 years and 52.5% were males, with the 3-y overall survival of 65.1%. According to the MaxStat analysis, 44 was the optimal cut-off point of PNI. After PSM analysis, a total of 282 patients in PNI < 44 group could be propensity matched to PNI ≥ 44 patients, creating a group of 564 patients. Multivariable analysis revealed that PNI, age, central nervous system involvement and International Prognostic Index (IPI) were independent prognostic factors for DLBCL. Kaplan–Meier analysis indicated that patients with low PNI in Ann Arbor Stage (III/VI), ECOG (< 2), IPI (LR+LIR), GCB, and BCL-2 negative groups had a poor prognosis.Discussion: PNI could accurately stratify the prognosis of DLBCL after PSM analysis.Keywords: diffuse large B-cell lymphoma, prognostic nutrition index, propensity score matched, prognosis

Renjun Lv,1– 5 Shanjing Nie,1– 4 Zhenhua Liu,6 Yunliang Guo,1– 4 Yue Zhang,7 Song Xu,1– 4 Xunyao Hou,1– 4 Jian Chen,1– 4 Yingjuan Ma,8 Zhongyu Fan,1– 5 Xueping Liu1– 4 1Department of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, People’s Republic of China; 2Department of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, People’s Republic of China; 3Anti-Aging Monitoring Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, People’s Republic of China; 4Department of Anti-Aging, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, People’s Republic of China; 5Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250021, Shandong, People’s Republic of China; 6Center of Sleep Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, People’s Republic of China; 7Department of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, People’s Republic of China; 8Department of Otolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Xueping Liu Tel +86-53168777165Email Liuxueping1962@163.comAim: Obstructive sleep apnea syndrome (OSAS) is a prevalent chronic disease characterized by sleep fragmentation and intermittent hypoxemia. Several studies suggested that electrophysiological changes and neurocognitive abnormalities occurred in OSAS patients. In this study, we compared automatic processing of emotional facial expressions schematic in OSAS patients and matched healthy controls via assessing expression-related mismatch negativity (EMMN).Methods: Twenty-two OSAS patients (mean age 44.59 years) and twenty-one healthy controls (mean age 42.71 years) were enrolled in this study. All participants underwent Montreal Cognitive Assessment (MoCA) scale test and polysomnographic recording. An expression-related oddball paradigm was used to elicit EMMN and the electroencephalogram was recorded and analyzed. Furthermore, Pearson’s correlations were calculated to discuss the correlation between neuropsychological test scores, clinical variables and electrophysiological data.Results: Compared with healthy controls, OSAS sufferers demonstrated significantly reduced EMMN mean amplitudes within corresponding time intervals, regardless of happy or sad conditions. Meanwhile, we observed that amplitude of sad EMMN was larger (more negative) than happy EMNN in healthy controls, while not in patients. Moderate correlations were found between MoCA test scores, sleep parameters and EMMN amplitudes.Conclusion: Our findings suggested pre-attentive dysfunction of processing emotional facial expressions in patients with OSAS, without the existence of negative bias effect. Moreover, correlation analysis showed that clinical characteristics of OSAS patients could affect EMMN amplitudes. Further studies on the advantages of EMMN as clinical and electrophysiological indicators of OSAS are warranted.Keywords: OSAS, EMMN, facial expressions, pre-attentive processing, negative bias effect

Shaobo Nie,* Ming Li,* Jiantao Li, Yanpeng Zhao, Xiang Cui, Gaoxiang Xu, Licheng Zhang, Wei Zhang, Peifu Tang Department of Orthopedics, The First Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation, Beijing 100853, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Zhang; Peifu TangDepartment of Orthopedics, The First Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation, Beijing 100853, People’s Republic of ChinaTel +86-10-68212342Email bszw@hotmail.com; pftang301@163.comBackground: Anterior cortical impingement is a common phenomenon after intramedullary fixation in Asian patients with intertrochanteric fractures. It may cause thigh pain and even fracture of the femoral shaft, which may seriously affect postoperative rehabilitation and limb function of patients. However, little was known about risk factors for anterior cortical impingement in Chinese elderly after intramedullary nailing. Hence, the aim of this study was to certify the risk factors for anterior cortical impingement treated with intramedullary nails of intertrochanteric fracture, hoping to provide suggestions for surgical treatment.Patients and Methods: A retrospective consecutive series of 94 patients who had been diagnosed as intertrochanteric fracture at our institution was included from January 2019 to November 2019. All patients were treated with intramedullary fixation and followed up for at least 6 months. Demographic, surgical and anesthesiologic information, as well as radiographic data and complications were collected and reviewed.Results: The ratio of anterior cortical impingement is significantly higher in female patients than that of males (80.4% vs 18.6%, P=0.041). Higher incidence of anterior cortical impingement was found in the longer intramedullary nail group, especially in females. Gender (as a female patient) and length of nail were significant risk factors for anterior cortical impingement in intertrochanteric fracture patients treated with intramedullary nail (OR =2.662, 95% CI =1.010– 7.018, P=0.447; OR =1.047, 95% CI =1.016– 1.079, respectively). The length of nail was a risk factor for anterior cortical impingement in female intertrochanteric fracture patients treated with intramedullary nail (OR =1.051, 95% CI =1.015– 1.089).Conclusion: Elderly female patients with intertrochanteric fractures treated with intramedullary nails had a higher incidence of anterior cortical impingement. The length of short intramedullary nail is a risk factor for anterior cortical impingement. Patients with anterior cortical impingement may suffer serious complications.Keywords: anterior cortical impingement, intramedullary nail, risk factors, intertrochanteric fracture

Shu Nie,1 Xiuli Wang,2 Hongwei Wang1 1Department of Dermatology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, People’s Republic of China; 2Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, People’s Republic of ChinaCorrespondence: Hongwei WangDepartment of Dermatology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, People’s Republic of ChinaEmail hongweiwang2017@163.comXiuli WangInstitute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, People’s Republic of ChinaEmail wangxiuli_1400023@tongji.edu.cnBackground: Long-term tumor control following PDT is a result of its direct effect on tumor and vasculature in combination with induction of inflammatory-reactions upregulating the immune system. When PDT induces necrosis of tumors and vascular system, an immune cascade can be initiated to release all kinds of cytokines including IL1β. This further leads to the activation of inflammatory-cells and hence death of tumor cells.Methods: Ultraviolet irradiation was used to induce cSCC mice model, gene chip was used to screen inflammatory cytokines, qPCR, ELISA and implanted tumor mice model were used to verify the changes and important role of interleukin-1β, and WB preliminarily explored the production mechanism of interleukin-1β.Results: Inflammatory cytokines and receptors transcript screening identify IL1r1 as the top4. After ALA-PDT, IL1r1 and IL1β increased in patients’ biopsies, principally in mesenchymal cells. In vivo, the inhibition of ALA-PDT on tumor growth of cutaneous squamous cell carcinoma (cSCC) mice in the group with intralesional injection of anti-IL1β mAb or caspase1-inhibitor was significantly weaker than the control groups. Furthermore, NLRP3-inflammasome and p-p65/p65 were elevated after ALA-PDT mediated IL1β production in cancer-associated-fibroblasts.Discussion: By means of activating NLRP3-inflammasome with IL1β production in CAFs, PDT stimulates local acute-inflammatory-response, which further promotes PDT effect for cSCC.Keywords: cancer-associated fibroblast, photodynamic therapy, interleukin-1β, NLRP3-inflammasome, squamous cell carcinoma

Yao Cheng,1 Jianhua Liu,2 Qing Liao,1 Xuejiao Hu,1 Hongyan Lv,3 Peiyan Ding,3 Shaofa Nie,1 Li Tan4 1Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Infectious Diseases Prevention and Control, Yichang Centers for Diseases Prevention and Control, Yichang, People’s Republic of China; 3Department of Chronic Disease Prevention and Control, Jiang’an District Centers for Disease Preventive and Control, Wuhan, People’s Republic of China; 4Department of Hospital Infection Management, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Shaofa NieDepartment of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, People’s Republic of ChinaTel +86 130 0719 9772Email sf_nie@mails.tjmu.edu.cn Li TanTongji Hospital of Tongji Medical College 1095 Hangkong Road, Wuhan 430030, People’s Republic of ChinaTel +86 159 9745 1097Email tanlidyx@126.comObjective: Incidence and mortality rates of malignant tumors in China are higher than global averages, especially for gastrointestinal (GI) cancers. To advance understanding of the epidemiology of GI cancers and to seek clues for cancer control, this study compared the incidence, mortality, and survival for GI cancers among residents of Wuhan (central China) and Chinese Americans.Methods: A population-based study of cancer epidemiology was carried out on Wuhan residents and Chinese Americans. Data were collected from the Cancer Registry of Jiang’an District in Wuhan and the Surveillance, Epidemiology, and End Results (SEER) program. Joinpoint regression analyses were used to examine trends in the incidence and mortality of GI cancers in Wuhan. Furthermore, we estimated age-specific rates of incidence and mortality and survival rates of GI cancers in both populations.Results: Among male GI cancer patients, mortality rates exhibited a significant increasing trend during 2006–2016 in Wuhan, with an annual percentage change (APC) of 7.4% (95% CI 1.7%–13.3%). Among female patients, the incidence of GI cancers showed a declining trend (APC –2.3%, 95% CI –3.4% to –1.3%) during 2006–2013, then escalated with an APC of 6.2% (95% CI 2.3%–10.2%) during 2013–2016. Both male and female patients with esophageal cancer in Wuhan experienced better survival than Chinese Americans. However, survival rates for the other three GI cancers in Wuhan were relatively lower than Chinese Americans.Conclusion: Escalating trends were observed in incidence among women and mortality among men with GI cancers. In addition, the survival rates of GI cancer patients in Wuhan were lower than Chinese Americans. As such, additional efforts are needed to control GI cancers in Wuhan, central China.Keywords: mortality, incidence, population-based data, gastrointestinal cancer, China

Yao Cheng,1 Yaqiong Yan,2 Jie Gong,2,* Niannian Yang,2,* Shaofa Nie1,* 1Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 2Department of Chronic Disease Prevention and Control, Wuhan Centers for Disease Prevention and Control, Wuhan, China *These authors contributed equally to this work Purpose: Following the implementation of breast cancer (BC) control strategies for years in Central China, the outcome needs to be evaluated and further strategies based on long-term surveillance should be formulated. Therefore, we examined the trends of BC incidence and mortality during 1990–2014 and projected them to 2024 in Wuhan, Central China.Patients and methods: The incidence and mortality data of BC were extracted from the Wuhan Cancer Registry. The average annual percentage changes (AAPCs) of the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were analyzed using Joinpoint regression. The Nordpred R-package was used to project BC incidence and mortality between 2015 and 2024. The age–period–cohort analysis was applied to evaluate the age, period, and cohort effects on the trends of BC incidence and mortality.Results: Overall, the ASIR increased markedly from 20.01 to 44.26 per 100,000 (AAPC=3.3%, 95% CI: 1.7%, 5.0%) during 1990–2014, and it was projected to keep increasing in the next decade (AAPC=3.0%, 95% CI: 2.0%, 4.1%). The ASMR of BC leveled off during the study period (AAPC=0.4%, 95% CI: −0.2%, 0.9%). The BC mortality of the older group (aged 50–79 years) showed significant upward trends in both observed and projected periods. Strong age, period, and cohort effects were observed in BC incidence, and BC mortality was significantly driven by age and cohort effects.Conclusion: The ASIR in Wuhan was approaching those areas with the highest BC risk in China, and the evident increase in BC incidence suggested that prior strategies for BC control should be adopted. In particular, further strategies for reducing BC mortality in older age groups should be reinforced in Wuhan, Central China. Keywords: breast cancer, incidence, mortality, trend, rate projection

Li-Ting Chen,1,* Xiao-Le Fan,2,* Hai-Jun Li,1 Si Nie,1 Hong-Han Gong,1 Wei Zhang,3 Xian-Jun Zeng,1 Ping Long,4 De-Chang Peng1 1Department of Radiology, 2Department of General Surgery, 3Department of Pneumology, 4Department of Otolaryngology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Purpose: Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder that can damage cognitive function. However, the functional network organization remains poorly understood. The aim of this study was to investigate the topological properties of OSA patients using a graph theoretical analysis.Patients and methods: A total of 30 male patients with untreated severe OSA and 25 male education- and age-matched good sleepers (GSs) underwent functional magnetic resonance imaging (MRI) examinations. Clinical and cognitive evaluations were conducted by an experienced psychologist. GRETNA (a toolbox for topological analysis of imaging connectomics) was used to construct the brain functional network and calculate the small-world properties (γ, λ, σ, Eglob, and Eloc). Relationships between these small-world properties and clinical and neuropsychological assessments were investigated in OSA patients.Results: The networks of both OSA patients and GSs exhibited efficient small-world topology over the sparsity range of 0.05–0.40. Compared with GSs, the OSA group had significantly decreased γ, but significantly increased λ and σ. The OSA group’s brain network showed significantly decreased Eglob (P

Ning Wang, Zhihan Wang,* Shihong Nie,* Linjiang Song, Tao He, Suleixin Yang, Xi Yang, Cheng Yi, Qinjie Wu, Changyang Gong State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China *These authors contributed equally to this work Abstract: The combination of chemotherapy drugs attracts more attention in clinical cancer trials. However, the poor water solubility of chemotherapeutic drugs restricts their anticancer application. In order to improve antitumor efficiency and reduce side effects of free drugs, we prepared paclitaxel (PTX) and honokiol (HK) combination methoxy poly(ethylene glycol)–poly(caprolactone) micelles (P–H/M) by solid dispersion method against breast cancer. The particle size of P–H/M was 28.7±2.5 nm, and transmission electron microscope image confirmed that P–H/M were spherical in shape with small particle size. After being encapsulated in micelles, the release of PTX or HK showed a sustained behavior in vitro. In addition, both the cytotoxicity and the cellular uptake of P–H/M were increased in 4T1 cells, and P–H/M induced more apoptosis than PTX-loaded micelles or HK-loaded micelles, as analyzed by flow cytometry assay and Western blot. Furthermore, the antitumor effect of P–H/M was significantly improved compared with PTX-loaded micelles or HK-loaded micelles in vivo. P–H/M were more effective in inhibiting tumor proliferation, inducing tumor apoptosis, and decreasing the density of microvasculature. Moreover, bioimaging analysis showed that drug-loaded polymeric micelles could accumulate more in tumor tissues compared with the free drug. Our results suggested that P–H/M may have potential applications in breast cancer therapy. Keywords: paclitaxel, honokiol, micelles, codelivery, breast cancer

Wenjuan Li,1 Peng Cheng,2 Shangdan Nie,1 Wen Cui1 1School of Forensic and Laboratory Medicine, Jining Medical University, 2Shandong Academy of Medical Sciences, Shandong Institute of Parasitic Diseases, Jining, People’s Republic of China Abstract: Japanese encephalitis (JE) is one of the most severe viral infections of the central nervous system. No effective treatment for JE currently exists, because its pathogenesis remains largely unknown. The present study was designed to screen the potential microRNAs (miRNAs) involved in JE. Glioblastoma cells were collected, after being infected with the Japanese encephalitis virus (JEV). Total miRNAs were extracted and analyzed using an miRNA chip. One of the most severely affected miRNAs was selected, and the role of miR-370 in JEV infection was investigated. Cell viability and apoptosis of the host cells were evaluated. JEV replication was detected via analysis of gene E expression. Real-time polymerase chain reaction was used to determine the levels of endogenous miR-370 and expression of innate immunity-related genes. Following JEV infection, 114 miRNAs were affected, as evidenced by the miRNA chip. Among them, 30 miRNAs were upregulated and 84 were downregulated. The changes observed in five miRNAs were confirmed by real-time polymerase chain reaction. One of the significantly downregulated miRNAs was miR-370. Therefore, miR-370 mimic was transfected into the cells, following which the levels of endogenous miR-370 were significantly elevated. Concurrently, JEV replication was significantly reduced 24 hours after transfection of miR-370 mimic. Functionally, miR-370 mimic mitigated both JEV-induced apoptosis and the inhibition of host cell proliferation. Following JEV infection, interferon-β and nuclear factor-kappa B were upregulated, whereas miR-370 mimic prevented the upregulation of the genes induced by JEV infection. The present study demonstrated that miR-370 expression in host cells is downregulated following JEV infection, which further mediates innate immunity-related gene expression. Taken together, miR-370 mimic might be useful to prevent viral replication and infection-induced host cell injury. Keywords: miR-370, Japanese encephalitis, glioblastoma cells, NF-κB

Hai-Jun Li,1 Xiao Nie,1 Hong-Han Gong,1 Wei Zhang,2 Si Nie,1 De-Chang Peng11Department of Radiology, 2Department of Pneumology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of ChinaBackground and objective: Abnormal resting-state functional connectivity (rs-FC) between the central executive network and the default mode network (DMN) in patients with obstructive sleep apnea (OSA) has been reported. However, the effect of OSA on rs-FC within the DMN subregions remains uncertain. This study was designed to investigate whether the rs-FC within the DMN subregions was disrupted and determine its relationship with clinical symptoms in patients with OSA. Methods: Forty male patients newly diagnosed with severe OSA and 40 male education- and age-matched good sleepers (GSs) underwent functional magnetic resonance imaging (fMRI) examinations and clinical and neuropsychologic assessments. Seed-based region of interest rs-FC method was used to analyze the connectivity between each pair of subregions within the DMN, including the medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), hippocampus formation (HF), inferior parietal cortices (IPC), and medial temporal lobe (MTL). The abnormal rs-FC strength within the DMN subregions was correlated with clinical and neuropsychologic assessments using Pearson correlation analysis in patients with OSA. Results: Compared with GSs, patients with OSA had significantly decreased rs-FC between the right HF and the PCC, MPFC, and left MTL. However, patients with OSA had significantly increased rs-FC between the MPFC and left and right IPC, and between the left IPC and right IPC. The rs-FC between the right HF and left MTL was positively correlated with rapid eye movement (r=0.335, P=0.035). The rs-FC between the PCC and right HF was negatively correlated with delayed memory (r=-0.338, P=0.033).Conclusion: OSA selectively impairs the rs-FC between right HF and PCC, MPFC, and left MTL within the DMN subregions, and provides an imaging indicator for assessment of cognitive dysfunction in OSA patients. Keywords: obstructive sleep apnea, functional connectivity, default mode network, functional MRI, cognitive impairment

Xiao Nie,1,* Yi Shao,2,* Si-yu Liu,3 Hai-jun Li,1 Ai-lan Wan,4 Si Nie,1 De-chang Peng,1 Xi-jian Dai1,5 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nangchang, Jiangxi, People’s Republic of China; 2Department of Ophthalmology,The First Affiliated Hospital of Nanchang University, Nangchang, Jiangxi, People’s Republic of China; 3Medical College of Nanchang University, Nangchang, Jiangxi, People’s Republic of China; 4Department of Psychosomatic Medicine, The First Affiliated Hospital of Nanchang University, Nangchang, Jiangxi, People’s Republic of China; 5Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China *These authors contributed equally to this work Objective: The aim of this study is to explore the resting-state functional connectivity (FC) differences between the paired default mode network (DMN) subregions in patients with primary insomnia (PIs).Methods: Forty-two PIs and forty-two age- and sex-matched good sleepers (GSs) were recruited. All subjects underwent the resting-state functional magnetic resonance imaging scans. The seed-based region-to-region FC method was used to evaluate the abnormal connectivity within the DMN subregions between the PIs and the GSs. Pearson correlation analysis was used to investigate the relationships between the abnormal FC strength within the paired DMN subregions and the clinical features in PIs.Results: Compared with the GSs, the PIs showed higher Pittsburgh Sleep Quality Index score, Hamilton Anxiety Rating Scale score, Hamilton Depression Rating Scale score, Self-Rating Depression Scale score, Self Rating Anxiety Scale score, Self-Rating Scale of Sleep score, and Profile of Mood States score (P

Yang Lei1,2, Yi Lu2, Jianping Qi2, Sufang Nie1, Fuqiang Hu3, Weisan Pan1, Wei Wu21School of Pharmacy, Shenyang Pharmaceutical University, Shenyang; 2School of Pharmacy, Fudan University, Shanghai; 3School of Pharmacy, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of ChinaBackground: The objective of this study was to evaluate fluid-bed coating as a new technique to prepare a pellet-based solid self-nanoemulsifying drug delivery system (SNEDDS) using cyclosporin A as a model of a poorly water-soluble drug.Methods: The rationale of this technique was to entrap a Liquid SNEDDS in the matrix of the coating material, polyvinylpyrrolidone K30, by fluid-bed coating. Pseudoternary phase diagrams were used to screen the liquid SNEDDS formulations. The optimal formulation was composed of Labrafil M® 1944 CS, Transcutol P®, and Cremophor® EL in a ratio of 9:14:7. To prepare solid SNEDDS pellets, liquid SNEDDS was first dispersed in an aqueous solution of polyvinylpyrrolidone and then sprayed onto the surface of non-pareil pellets. Upon evaporation of water, polyvinylpyrrolidone precipitated and formed tight films to entrap the liquid SNEDDS. Visual observation and scanning electron microscopic analysis confirmed good appearance of the solid SNEDDS pellets.Results: Our results indicated that up to 40% of the liquid SNEDDS could be entrapped in the coating layer. Powder x-ray diffraction analysis confirmed nonexistence of crystalline cyclosporin A in the formulation. Solid SNEDDS pellets showed a slower redispersion rate than the liquid SNEDDS. An increase in the total liquid SNEDDS loading led to faster redispersion, whereas increased coating weight (up to 400%) significantly decreased the redispersion rate. Both cyclosporin A loading and protective coating with 5% polyvinylpyrrolidone K30 did not significantly affect the redispersion rate.Conclusion: It is concluded that fluid-bed coating is a new technique with considerable potential for preparation of pellet-based solid SNEDDS formulations.Keywords: solid, self-nanoemulsifying, fluid-bed coating, cyclosporin A, pellets

In thermal fatigue test, the key point is whether the temperature field on the top surface of cylinder head induced by the heat source can well match it in real service. In order to produce the target temperature field in service which is measured by thermocouples, shaped laser beam generated by diffractive optics element (DOE) is chosen as the heat source to irradiate on the top surface of cylinder head. The DOE is designed based on the Gerchberg-Saxton (GS) algorithm and the simulated temperature field is calculated by finite element model (FEM). The results show that the simulated and experimental temperature field can well match the target one which demonstrates that this method is feasible to produce the target temperature field and can be used in thermal fatigue test.

A topological superconductor (TSC) is a new type of superconductor with non-trivial topology in its bulk electronic structure, which has great potential in both fundamental research and application. However, despite the intensive research efforts worldwide, to date only a few intrinsic (non-heterostructures) materials have been proposed as TSC candidates. In this work, following the theoretical prediction, we experimentally studied a newly proposed TSC candidate, TaSe3. The topological non-trivial surface states were directly observed by using angle-resolved photoemission spectroscopy, while the superconductivity of the compound was examined by both transport and scanning tunneling microscopy measurement. Therefore, TaSe3 was proved to be a promising candidate as a TSC, and a promising research platform for the related novel physics phenomena.