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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

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

A transonic natural laminar flow (NLF) nacelle, which is a streamlined fairing used to contain a turbofan engine and mounted under the wing of civil aircraft, can reduce friction drag. Because the fluid mechanism of the interaction between an NLF nacelle and a wingbody is not clear, laminar flow at high Reynolds numbers in the transonic regime is maintained difficultly. In this work, such interaction on a civil aircraft is investigated. Three NLF nacelles with different pressure distribution characteristics and a baseline nacelle with the turbulent flow are examined. These are installed under the wing of a widebody aircraft to investigate the fluid mechanism between a natural laminar flow nacelle and wingbody. The results show that the influence of the wingbody on the fluid characteristics of the nacelle should be considered in the NLF nacelle design. A well-designed isolated NLF nacelle is different from the one that considers the effect of the wingbody. A favorable pressure gradient in the front part of the nacelle is a key factor in drag reduction. An installed NLF nacelle owning a large pressure peak with a weak favorable pressure gradient and a strong shock wave in front of the nacelle is recommended to be applied in civil aircraft. [ABSTRACT FROM AUTHOR]