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Se Chen,1 Zhonglei Wan2 1School of International Education, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi, People’s Republic of China; 2Department of General Education, Jiangxi Youth Vocational College, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Se Chen, Jiangxi Science and Technology Normal University, 589 Xuefu Avenue, Nanchang, Jiangxi Province, 330038, People’s Republic of China, Tel +0086 – 18679059130, Email chense063@foxmail.comBackground: The rapid growth of the global aging population highlights the need to address ageism and promote social inclusiveness. While considerable research has explored the impact of perceived ageism on older adults’ mental health, limited attention has been given to how negative mental health factors—such as depression, anxiety, and stress (DAS)—influence ageist attitudes among younger populations, along with the psychological mechanisms underlying this relationship.Purpose: This study first investigates the prevalence of ageism among undergraduates and its variation across certain socio-demographic factors at the research site. It then examines the predictive effects of depression, anxiety, and stress (DAS) on ageism, accounting for these socio-demographic factors. Finally, the study explores how DAS influences ageism both directly and indirectly through life satisfaction, gratitude, and prosociality.Design and Settings: A cross-sectional study conducted at 11 higher education institutions in Jiangxi, China.Participants: A total of 1,213 undergraduates participated in the study between July and August 2024. Following data cleaning, 1174 responses were included for analysis.Methods: Data were collected using online questionnaires. T-tests and ANOVA assessed socio-demographic differences in ageism, and regression analysis examined DAS’s predictive effects. Structural Equation Modeling (SEM) explored the pathways linking DAS to ageism via mediators.Results: A moderate level of ageism was observed, with significant variations across socio-demographic factors like academic year, physical health, and contact with older adults. Depression and stress directly predicted ageism, while anxiety had indirect effects via depression and stress. DAS—as a composite construct—indirectly affected ageism via life satisfaction, gratitude, and prosociality.Conclusion: Educational interventions should not only target the reduction of ageist attitudes but also address the underlying mental health conditions that fuel these biases. Promoting life satisfaction, gratitude, and prosociality, along with fostering meaningful intergenerational interactions, will be crucial for developing more effective strategies to combat ageism.Plain Language Summary: Our study investigated how psychological factors like depression, anxiety, and stress (DAS) affect undergraduates’ attitudes toward older adults, particularly ageism—a form of prejudice against older individuals. While previous research has often focused on how ageism negatively impacts older adults’ mental health, few studies have looked at whether the mental health of young people plays a role in shaping these attitudes.To investigate this, we surveyed undergraduate students from 11 higher education institutions in Jiangxi Province, China. We examined how DAS is related to ageist attitudes and whether positive traits, such as life satisfaction, gratitude, and prosociality (the tendency to help others), could lessen the negative influence of DAS on ageism.Our findings show that students with higher levels of depression, anxiety, or stress are more likely to hold negative views about older adults. However, positive traits like gratitude, life satisfaction, and prosociality—as well as meaningful interactions with older adults—appear to soften or reduce the harmful effects of DAS on ageism.These results suggest that improving mental health, fostering positive traits, and facilitating quality interactions between young and older generations could be effective strategies for reducing ageism. This research has important implications for educational programs aimed at promoting respect and empathy across generations.Keywords: mental health, ageism, life satisfaction, gratitude, prosociality, undergraduates

Xiaofei Zhang,1,* Yonghong Xiong,2,* Huilan Liu,3 Qian Liu,4 Shubin Chen5 1Department of Gerontology, China Aerospace Science & Industry Corporation 731 hospital, Beijing, People’s Republic of China; 2Department of Cardiology, Beijing Feng Tai Hospital, Beijing, People’s Republic of China; 3Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 4Department of Cardiology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People’s Republic of China; 5Department of Intensive Care Unit, China Aerospace Science & Industry Corporation 731 hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian Liu, Department of Cardiology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, No. 100 of Xianggang Road, Jiangan District, Wuhan, 430015, People’s Republic of China, Tel +86027-82433350, Email qian_liu1124@126.com Shubin Chen, Department of Intensive Care Unit, China Aerospace Science & Industry Corporation 731 hospital, No. 3 Zhen Gang Nan Li, Yun Gang Town, Feng Tai District, Beijing, 100074, People’s Republic of China, Tel +86010-68374065, Email 18610074016@163.comBackground: The aim of this study was to use five machine learning approaches and logistic regression to design and validate the acute kidney injury (AKI) prediction model for critically ill individuals with cardiogenic shock (CS).Methods: All patients who diagnosed with CS from the MIMIC-IV database, the eICU database, and Zhongnan hospital of Wuhan university were included in this study. Clinical information, including demographics, comorbidities, vital signs, critical illness scores and laboratory tests was retrospectively collected. Five machine learning algorithms (LightGBM, decision tree, XGBoost, random forest, and ensemble model) and one conventional logistic regression were applied for the prediction of AKI in critically ill individuals with CS. ROC curves were generated via python software to assess the overall performance of machine learning algorithms and the SHAP analysis was adopted to reveal the impact of prediction for each feature.Results: The ensemble model exhibited the best predictive ability (AUC:0.91, 95% CI, 0.88– 0.94), followed by random forest (AUC:0.90, 95% CI, 0.86– 0.94) and XGBoost (AUC:0.89, 95% CI, 0.84– 0.92). While the logistic regression model obtained the worst predictive performance (AUC:0.62, 95% CI, 0.56– 0.68). When validated the prediction models with eICU database, the ensemble model exhibited the best predictive ability (AUC:0.92, 95% CI, 0.89– 0.96), while the logistic model obtained the worst predictive performance (AUC:0.61, 95% CI, 0.56– 0.67). Finally, we verified the prediction models using the data from our hospital and ensemble model still exhibited the best predictive ability (AUC:0.74, 95% CI, 0.62– 0.86), while the decision tree model obtained the worst predictive performance (AUC:0.52, 95% CI 0.35– 0.70).Conclusion: Machine learning algorithms could be utilized for the AKI prediction among critically ill CS patients, and exhibit superior predictive performance compared to the conventional logistic regression analysis.Keywords: cardiogenic shock, acute kidney injury, MIMIC database, prediction model, machine learning

Hairong Zhao,1,2,* Shuangyan Bao,2,* Shuanglong Chen,1,* Qingmo Yang,1,* Kangliang Lou,3 Yating Gai,4 Jinyan Lin,5 Chaojie Liu,2 Heng Liu,2 Chenggui Zhang,2 Ruiqin Yang1 1Department of Breast Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, People’s Republic of China; 3School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 4Xiamen Research Institute of Food and Drug Quality Inspection, Xiamen, People’s Republic of China; 5School of Public Health, Xi’an Jiaotong University, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruiqin Yang, Department of Breast Surgery, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China, Email yrqxm0822@163.com Chenggui Zhang, Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, People’s Republic of China, Email chenggui_zcg@163.comPurpose: Mastoparan-M (Mast-M) has cytotoxic effects on various tumor cells in vitro, including liver cancer and colorectal cancer. However, the anti-tumor mechanism of Mast-M remains unclear and its potential for anti-tumor therapy has not been investigated. Herein, we aimed to develop a novel phytosome formulation loaded with Mast-M and evaluate its efficacy against breast cancer both in vitro and in vivo. Furthermore, we investigated the underlying anti-tumor mechanisms of Mast-M.Methods: The synthesis of Phy-Mast-M involved a co-solvent technique, followed by solvent evaporation. Its anti-tumor mechanism was investigated using CCK-8, clone formation, and apoptosis assays. Subsequently, the biodistribution and anti-tumor efficacy of Phy-Mast-M were assessed in vivo using the 4T1 tumor-bearing mouse model. Finally, the safety of Phy-Mast-M was evaluated in vivo.Results: The prepared Phy-Mast-M demonstrated an exceptional monodisperse size distribution (125.67 ± 45.79 nm), and exhibited excellent stability under different physiological conditions. Phy-Mast-M could inhibit 4T1 cells growth through multiple channels, including arresting cell growth cycle and disturbing mitochondrial membrane integrity. Phy-Mast-M proved significantly higher accumulation at tumor sites in a tumor-bearing mouse model as compared to free Mast-M. Moreover, in vivo anti-tumor studies demonstrated that Phy-Mast-M exhibited superior curative inhibitory effects on tumor growth and favorable biocompatibility.Conclusion: Phy-Mast-M demonstrates significant anti-tumor activity both in vitro and in vivo. Moreover, its potential for clinical translation suggests promising prospects for cancer therapy, offering more drug options for breast cancer patients. Keywords: breast cancer, Mast-M, phytosomes, cancer therapy, small molecule peptide

Yuwu Luo,* Weifeng Chen,* Duanni Xu, Shuting Chen, Shaoyin Ma Guangzhou Dermatology Hospital, Guangzhou, Guangdong, 510095, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaoyin Ma, Guangzhou Dermatology Hospital, 56 hengfu Road, Guangzhou, 510095, People’s Republic of China, Email msymsb315@163.comAbstract: Acquired vulvar lymphangioma (AVL) is a rare condition characterized by abnormal lymphatic vessels in the vulva. We describe a 10-year-old female patient who presented with vulvar swelling for 23 days. She has no history of sexual assault and irradiation. Two months ago, the patient underwent CO2 laser surgery for a sebaceous gland nevus on the left labia majora, resulting in delayed healing and residual scar tissue. Twenty-three days ago, swelling appeared in the external genitalia, accompanied by mild pain that worsened after activity and lessened when lying down. Treatment with anti-infection and anti-allergy medications at the previous hospital did not show significant improvement. Histopathological examination and genetic testing confirmed Our diagnosis of acquired vulvar lymphangioma with lymphedema.Keywords: acquired vulvar lymphangiectasia, lymphangioma, lymphedema

Xing Qiang, Qin Wen, Jia Li, Siyu Chen, Tinglu Tao, Hongyang Zhang, Ping Wang, Xiangui Peng, Yimei Feng, Xi Zhang Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Xiangui Peng; Yimei Feng, Email P13983190510@163.com; yimeifeng@163.comAbstract: The chronic myeloid leukemia (CML) is easily diagnosed by laboratory examination, however, rare BCR-ABL1 mRNA transcripts variants, such as e1a3 present diagnosis and therapeutic challenges. This case report details the diagnosis and management of a CML patient with the e1a3 transcript by FISH and RT-PCR. Following initial diagnosis, the patient was treated with the tyrosine kinase inhibitor (TKI) Flumatinib. During the treatment, although the FCM-MRD of the bone marrow kept negative, the e1a3 expression detected by PCR always remained positive. After eighteen months, the patient experienced headaches, vomiting, and blurred vision. Subsequent bone marrow analysis and flow cytometry detection of cerebrospinal fluid indicated that the patient had entered the blast phase, progressing to acute myeloid leukemia (AML). Treatment was switched to the third-generation TKI olverembatinib, combined with chemotherapy, followed by allogeneic hematopoietic stem cell transplantation. The patient remains disease-free following olverembatinib maintenance therapy. This case underscores the importance of comprehensive diagnostic apporsches and the potential efficacy of third-generation TKIs and allo-HSCT in the treatment of e1a3-type CML.Keywords: CML-BC, e1a3 transcript, CNS, HSCT, olverembatinib

Zhaogui Wu,1,&ast; Dan Wu,2,3,&ast; Shuohua Chen,4 Sichi Xu,5,6 Shunming Zhang,7 Shouling Wu4 1Department of Cardiology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, Hubei, 441000, People’s Republic of China; 2Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 3Centre for Precision Health, Edith Cowan University School of Medical and Health Sciences, Joondalup, WA, Australia; 4Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei, 063001, People’s Republic of China; 5Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, People’s Republic of China; 6Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, People’s Republic of China; 7School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shouling Wu, Department of Cardiology, Kailuan General Hospital, No. 57, Xinhuadong Street, Lubei District, Tangshan, Hebei, 063001, People’s Republic of China, Tel +86 13363283666, Email drwusl@163.com Shunming Zhang, School of Public Health, Xi’an Jiaotong University Health Science Center, No. 76, Yanta West Road, Xi’an, Shaanxi, 710061, People’s Republic of China, Tel +86 19502920539, Email zhangshunming@xjtu.edu.cnObjective: This study aimed to longitudinally investigate the association between circulating neutrophil count and the progression of arterial stiffness and to ascertain whether resting heart rate (RHR) mediates this association.Methods: The current study included 56,760 participants with brachial-ankle pulse wave velocity (baPWV) measurements from a real-life, prospective cohort in China. The associations of circulating neutrophil (exposure) with baseline baPWV, baPWV progression, and arterial stiffness (outcomes), as well as RHR (mediator) were assessed using multivariable linear and Cox regression models and mediation analysis.Results: After adjusting for cardiometabolic risk factors, for each 1-SD increase in neutrophil count, the corresponding increase was 13.5 cm/s (95% CI, 11.1 to 15.9 cm/s, P< 0.001) for the baseline baPWV and 3.10 cm/s (95% CI, 1.51 to 4.69, P< 0.001) for the annual change in baPWV. Over a median follow-up period of 4.08 (IQR: 2.37 to 6.21) years, there were 3,376 incident cases of arterial stiffness among the 23,263 participants. Each 1-SD increase in neutrophil count was associated with a 7% increase in the risk of developing arterial stiffness (HR: 1.07; 95% CI: 1.04 to 1.10, P< 0.001) in the multivariable-adjusted model. In the mediation analyses, 20.0% (95% CI: 16.8% to 24.2%), 12.6% (95% CI: 8.16% to 26.4%), and 16.7% (95% CI: 9.94% to 51.0%) of the observed associations of neutrophil counts with baPWV at baseline, baPWV progression and developing arterial stiffness, respectively, were mediated by RHR.Conclusion: The present study underlines that circulating neutrophil count is significantly associated with arterial stiffness progression and that the RHR is, in part, a mediator of this association.Keywords: arterial stiffness, inflammation, neutrophil count, resting heart rate, mediator, cohort study

Linlin Ye,1 Shujuan Chen,2 Qing-Wei Chen,3– 5 Xue Luo6 1Mental Health Education Center, Guangzhou Railway Polytechnic, Guangzhou, 511370, People’s Republic of China; 2Department of Psychology, School of Education, Ningxia University, Yinchuan, 750021, People’s Republic of China; 3Lab of Light and Physio-Psychological Health, National Center for International Research on Green Optoelectronics, South China Normal University, Guangzhou, 510006, People’s Republic of China; 4School of Psychology, South China Normal University, Guangzhou, 510631, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Optical Information Materials and Technology & Institute of Electronic Paper Displays, South China Academy of Advanced Optoelectronics, South China Normal University, Guangzhou, 510006, People’s Republic of China; 6Department of Psychiatry, Sleep Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of ChinaCorrespondence: Qing-Wei Chen, National Center for International Research on Green Optoelectronics, South China Normal University, No. 55 West Zhongshan Road, Guangzhou, Guangdong, People’s Republic of China, Email qingwei.chen@m.scnu.edu.cn Xue Luo, Department of Psychiatry, Nanfang Hospital Southern Medical University, No. 1838 North Guangzhou Avenue, Guangzhou, Guangdong, People’s Republic of China, Email nfyy8866@i.smu.edu.cnPurpose: Network analysis is a statistical method that explores the complex interrelationships among variables by representing them as nodes and edges in a network structure. This study aimed to examine the interconnections between family functioning, anxiety, and depression among vocational school students through network analysis approach.Participants and Methods: A sample of 2728 higher vocational school students participated in a survey utilizing the Family APGAR Index Questionnaire (APGAR), Generalized Anxiety Disorder Scale (GAD-7), and Patient Health Questionnaire (PHQ-9). Meanwhile, a network analysis was conducted to investigate the interrelationships between family functioning, anxiety, and depression symptoms among the higher vocational school students.Results: The network analysis revealed that node APGAR2 (“Partnership”) exhibited the highest strength, followed by node GAD5 (“Restlessness”); node GAD7 (“Negative future anticipation”), PHQ9 (“Suicidal ideation”), and PHQ6 (“Guilty”) were bridge nodes linking family functioning, anxiety and depressive symptoms in the sample. The results of the Network comparisons test between male and female indicated that the edge weights and global strength did not exhibit a statistically significant difference.Conclusion: These results emphasized that certain anxiety symptoms and family functioning nodes are more central than others, and thus play a more critical role in the family functioning-anxiety-depression network, which highlight potential targeting symptoms to be considered in future interventions.Keywords: network analysis, family functioning, anxiety, depression, higher vocational college students

Shan Chen,1,&ast; Wan-Hua Chang,2,&ast; Jie Zhang,1,&ast; Xiao-Yuan Liu,3,&ast; Ting Gao,1 Xiao-Wei Qi,4 Dong-Yan Cai,1 Yong Mao,1 Ting-Xun Lu1 1Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, People’s Republic of China; 2Department of Gastroenterology, Huaian Hospital of Huaian City, Huai’an, Jiangsu Province, People’s Republic of China; 3Department of Clinical Pharmacy, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, People’s Republic of China; 4Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ting-Xun Lu, Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, People’s Republic of China, Email lutingxun@163.comPurpose: This study assessed lymphocyte-to-monocyte ratio (LMR) changes to predict postoperative recurrence in Fusobacterium nucleatum-positive (Fn-positive) CRC patients.Patients and Methods: Clinical information and paraffin tissue specimens were collected from a retrospective cohort of 332 patients. The abundance of Fn in tumor tissue was measured using a quantitative polymerase chain reaction. We evaluated the prognostic value and diagnostic performance of the dynamic changes of LMR from pre-operative to post-treatment (pr-LMR-po) and the dynamic alterations of LMR from pre-operative to post-treatment to pre-end of follow-up (pr-LMR-f) in predicting recurrence in Fn-positive CRC.Results: In the total cohort and adjuvant therapy group cohort, pr-LMR-po independently predicted recurrence-free survival in Fn-positive CRC patients. In the adjuvant therapy group, pr-LMR-po (High-High vs Low-Low: HR: 3.896, 95% CI: 1.503– 10.095, p=0.005) was particularly significant. Meanwhile, pr-LMR-f can serve as a predictive biomarker for Fn-positive CRC recurrence, especially in the adjuvant therapy group cohort where the c-statistic for pr-LMR-f was 0.825 (95% CI: 0.804– 0.8251), with a sensitivity of 83.6% and a specificity of 79.3%. Compared to the overall adjuvant therapy group cohort, the prognostic performance of pr-LMR-f was superior in the Fn-positive CRC adjuvant therapy group cohort (AUC: 0.825 VS 0.711). Finally, we constructed a prediction model combining pr-LMR-f and CEA. After internal validation using the bootstrap resampling, the model had an AUC of 0.9295, a sensitivity of 94%, and a specificity of 72.7% in the Fn-positive CRC adjuvant therapy group cohort.Conclusion: This study found that pr-LMR-po predicts Fn-positive CRC prognosis, and pr-LMR-f may predict Fn-positive CRC recurrence.Keywords: longitudinal dynamic changes in LMR, Fusobacterium nucleatum, colorectal cancer, recurrence

Zhenqi Lou, Kanling Jiang, Sanqiang Xia, Sihui Chen, Yi Jiang, Jinyu Zhu, Jieyang Zhu Department of Orthopedics, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of ChinaCorrespondence: Jinyu Zhu; Jieyang Zhu, Department of Orthopedics, Affiliated Hospital of Jiaxing University, 1882 Zhonghuan South Road, Jiaxing, Zhejiang, People’s Republic of China, Email zhujinyu@hotmail.com; zjyzjy970612@163.comPurpose: To evaluate the efficacy and safety of intravenous tranexamic acid (TXA) in patients undergoing percutaneous kyphoplasty (PKP), and identify the factors influencing hidden blood loss (HBL).Methods: This randomized, placebo-controlled trial included 146 patients undergoing PKP surgery from September 2023 to July 2024. Patients were randomly assigned into the TXA group (75 patients received 1.0 g/100mL TXA intravenously) and the placebo group (71 patients received 100mL of normal saline intravenously). Demographic and clinical characteristics were comparable between groups. HBL was calculated and compared on postoperative days 1 (POD1) and 3 (POD3). Visual analog scale (VAS) scores were also recorded preoperatively and during the follow-up. Multivariate logical regression analysis identified independent risk factors for HBL.Results: The HBL in the TXA group was 183.78± 115.48mL on POD 1 and 240.65± 114.73mL on POD 3, which was significantly lower than the placebo group at 251.30± 235.58mL on POD1 (P=0.032) and 384.94± 223.18mL on POD3 (P< 0.001). The drop in hemoglobin in the TXA group was generally lower than that of the placebo group on POD1 (4.72± 3.54 vs 7.62± 8.38 g/L, P=0.007), but showed no significant difference on POD 3. The drop in hematocrit in the TXA group was significantly lower than that in the placebo group on POD1 (1.91± 1.21% vs 2.65± 2.42%, P=0.023) and POD3 (2.49± 1.23% vs 3.92± 2.09%, P< 0.001). Additionally, the VAS scores on POD1 (2.28± 0.88 vs 2.82± 0.98, P< 0.001) and POD3 (1.95± 0.75 vs 2.25± 0.69, P=0.011) were lower in the TXA group than in the placebo group. Multivariate logical regression analysis revealed that the use of TXA (P< 0.001), injury time (P< 0.001), number of punctures (P=0.004), cement leakage (P=0.001), and restoration of vertebral height (P=0.002) were significantly correlated with HBL.Conclusion: A single of 1g dose of intravenous TXA reduces HBL and early postoperative pain in PKP patients without increasing the complication rate. The use of TXA, injury time, number of punctures, cement leakage, and restoration of vertebral height were risk factors for HBL in PKP surgery. (ChiCTR2300075428).Keywords: hidden blood loss, osteoporotic vertebral compression fractures, Percutaneous kyphoplasty, tranexamic acid, multiple regression analysis

Yu Qi,1,&ast; Bo Xu,2,3,&ast; Jinrong He,4,&ast; Bo Jiang,1 Le Yan,1 Haiyan Zhou,5 Saili Chen6– 9 1Traditional Chinese Medicine Classics Laboratory, Hubei University of Chinese Medicine, Wuhan, People’s Republic of China; 2Postdoctoral Mobile Workstation, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 3Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Key Laboratory for Molecular Diagnosis of Hubei Province, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5Foreign Languages College, Hubei University of Science and Technology, Xianning, People’s Republic of China; 6Clinical Medical College, Hubei University of Science and Technology, Xianning, People’s Republic of China; 7National Demonstration Center for Experimental (General Practice) Education (Hubei University of Science and Technology), Xianning, People’s Republic of China; 8Xianning Heji Hospital of Integrated Chinese and Western Medicine, Xianning, People’s Republic of China; 9Xianning Traditional Chinese Medicine Chronic Disease Conditioning and Cancer Rehabilitation Joint Innovation Center, Xianning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Saili Chen, Clinical Medical College, Hubei University of Science and Technology, Xianning, People’s Republic of China, Email sallychen@hbust.edu.cnPurpose: Triple-negative breast cancer (TNBC) is a disease associated with high incidence and high mortality, which is a major problem threatening women’s health. Xiaoyao Sanjie Decoction (XYSJD) exhibits remarkable therapeutic efficacy on TNBC; however, the underlying mechanism is unclear. This study verified the efficacy of XYSJD and its active component in the treatment of TNBC and explored its potential mechanism.Methods: Ultra-high performance liquid chromatography-hybrid quadrupole orbitrap mass spectrometry (UHPLC-Q Exactive HFX-MS) was applied to explore the main chemical constituents of XYSJD. The key targets and potential mechanisms of XYSJD in the treatment of TNBC were predicted through network pharmacology, bioinformatics analysis and molecular docking. The effects of XYSJD against TNBC cells were evaluated by CCK-8 assay, EdU assay, wound healing assay, transwell assay, Hoechst-PI staining and flow cytometry. The mechanism of action was validated by Western blot analysis. Finally, the effect and mechanism of XYSJD and Que on TNBC were further verified by the tumor formation model.Results: UHPLC-Q Exactive HFX-MS identified a total of 9 compounds in XYSJD. Network pharmacological methods identified 206 targets for anti-TNBC. Bioinformatics analysis suggests that the EZH2/AKT1 signaling pathway might play an important role in the effects of XYSJD against TNBC. Gene Ontology enrichment analysis showed that the biological process of XYSJD in TNBC treatment mainly involved apoptosis. XYSJD and Que were observed to have a good anticancer effect in vivo and in vitro. In addition, quercetin could induce the apoptosis of TNBC cells by decreased the expression levels of EZH2/AKT1 signaling pathway. Furthermore, AKT1 overexpression, treatment with the AKT activator (SC79) and EZH2 overexpression could reverse apoptosis induced by quercetin in TNBC cells.Conclusion: This study revealed the anti-TNBC efficacy of XYSJD. Quercetin, the effective component of XYSJD, promoted apoptosis of TNBC cells via blockade of the EZH2/AKT1 signaling pathway. These findings aim to provide a more reliable basis for the clinical application of XYSJD in the treatment of TNBC.Keywords: Xiaoyao Sanjie Decoction, triple-negative breast cancer, network pharmacology, quercetin, EZH2/AKT1 signaling pathway

Cong Zhang, Teding Chang, Deng Chen, Jialiu Luo, Shunyao Chen, Peidong Zhang, Zhiqiang Lin, Hui Li Department of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Hui Li, Email lihuibc@hotmail.comBackground: Deep venous thrombosis (DVT), known to be a major factor in poor outcomes and death rates, is common after polytrauma with traumatic brain injury (TBI). In this study, a nomogram will be developed to predict the risk of DVT in polytrauma patients with TBI, since there is currently no specific and convenient diagnostic method.Methods: A retrospective and observational trial was conducted between November 2021 and May 2023. The predictive model was created using a group of 349 polytrauma patients with TBI in a training set, with data collected between November 2021 and August 2022. A nomogram was presented after using multivariable logistic regression analysis to create the predictive model. Validation of the model was conducted internally. A separate group for validation included 298 patients seen consecutively between August 2022 and May 2023.Results: A total of 647 trauma patients were included in the study. Out of these, 349 individuals were part of the training group, while 298 were part of the validation group. Training cohorts reported 32.1% and validation cohorts reported 31.9% DVT. Age, Smoking, Injury Severity Score (ISS), Glasgow Coma Scale (GCS), D-dimer, Mechanical ventilation (MV) and Application of Vasoactive Drugs (AVD) comprised the individualized prediction nomogram. The model exhibited strong discrimination, achieving a C-index of 0.783 and a statistically insignificant result (P=0.216) following the Hosmer–Lemeshow test. Nomogram calibration plots and decision curve analysis showed the nomogram’s utility in predicting DVT.Conclusion: Our study characterized the incidence of DVT in polytrauma patients with TBI and further emphasized that it represented a substantial health concern, as evidenced by its frequency. Using this nomogram, it is possible to predict DVT in polytrauma patients with TBI based on demographics and clinical risk factors.Keywords: polytrauma, traumatic brain injury, deep venous thrombosis, nomogram

Shimeng Chen,1 Miriam Kessi,1 Fang He,1– 3 Fei Yin,1– 3 Jing Peng,1– 3 Lifen Yang1– 3 1Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Hunan Intellectual and Developmental Disabilities Research Center, Pediatrics, Changsha, People’s Republic of China; 3Clinical Research Center for Children Neurodevelopmental Disabilities of Hunan Province, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Lifen Yang, Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China, Tel +86 − 1367435745, Fax +86-731-84327332, Email yanglifen7@126.comBackground: Anti-glutamate kainate receptor subunit 2 (anti-GluK2) antibodies mediated encephalitis is very rare in both children and adults. This study aimed to describe the second report of the anti-GluK2 encephalitis worldwide, the first youngest patient worldwide, and the first case ever in Asia. Besides, this study provides a summary of the clinical manifestations of all previous reported cases.Methods: The patient was attended at the Department of Pediatrics, Xiangya Hospital, Central South University. Anti-GluK2 antibodies were tested in the serum and cerebrospinal fluid (CSF) by the indirect immunofluorescence on cell-based assays. The clinical information of the patient was collected. In addition, a literature search was carried out in the PubMed.Results: Our patient was a male who presented with lethargy, recurrent dizziness and vomiting, headache and cerebellar ataxia at the age of 13 years. Prodromal illnesses included Herpes Zoster infection and Mycoplasma pneumonia. The anti-GluK2 antibodies and elevated IL-6 levels were detected in serum while high oligoclonal bands levels were found in the CSF. The intravenous methylprednisolone, immunoglobulin, antibiotics and other symptomatic treatments helped the patient to recover full. We could only find one previous report in the literature (from Barcelona). The literature review plus our report unveiled eight patients with pure anti-GluK2 antibodies related encephalitis. The median age of onset was 28.50 years and majority were males (75.00%). Most of the cases (87.50%) presented with acute cerebellitis symptoms and signs. Preceding or concurrent infection was observed in two patients, while paraneoplastic tumors were observed in two patients. Patients had non-parenchymal brain lesions; the commonest anomalies were those localized in the cerebellum (62.50%).Conclusion: Our report provides more evidence that anti-GluK2 antibodies may be pathogenic for the autoimmune encephalitis (cerebellitis). Immunotherapy can be used to treat it with good outcome.Keywords: anti-glutamate kainate receptor subunit 2 (anti-GluK2) antibodies, encephalitis, cerebellitis, immunotherapy

Xiaowen Han,1 Ruiling Xu,1 Yang Xia,2 Ying Liu,3 Shan Chen,3 Mingsong Shi,1 Zhiyan Zou,1 Yuanyuan Liang,1 Tingting Chen,1 Yufeng Tang,4 Wei Tang,3 Xiaoan Li,1,5 Liangxue Zhou2,6,7 1NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 2Department of Neurosurgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 3Institute of Materials, China Academy of Engineering Physics, Jiangyou, 621907, People’s Republic of China; 4Department of Neurology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 5Department of Gastroenterology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 6Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 7Department of Neurosurgery, the Fifth People’s Hospital of Ningxia, Shizuishan, Ningxia, 753000, People’s Republic of ChinaCorrespondence: Xiaoan Li; Liangxue Zhou, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China, Email lixiaoan@sc-mch.cn; liangxue_zhou@126.comPurpose: Skin radiation damage is a prevalent form of tissue injury encountered during radiotherapy, radiation accidents, and occupational exposure. The only clinically approved radioprotective agent, amifostine, is associated with numerous side effects, underscoring the urgent need for the development of safe and effective radioprotective agents. Natural products with reductive properties possess high antioxidant activity and biocompatibility, but their low bioavailability limits their radioprotective efficacy and clinical application. To address this, we utilized epigallocatechin gallate (EGCG) as a model compound and employed nanotechnology to enhance cellular uptake of natural compounds, thereby improving their free radical scavenging capabilities.Methods: EGCG nanoparticles (EGCG NPs) with robust intracellular reactive oxygen species (ROS) scavenging ability were prepared via self-assembly. The morphology, size distribution, and antioxidant capacity of EGCG NPs were characterized. Cytocompatibility, intracellular ROS levels and DNA damage, cell migration and immune response of EGCG NPs to macrophages were tested in vitro. The in vivo radiation protection and biocompatibility of EGCG NPs were assessed in murine model.Results: The EGCG NPs was successfully prepared and compared to free EGCG, EGCG NPs demonstrated better cellular uptake, significantly enhancing their biocompatibility, intracellular ROS scavenging capacity, and ability to mitigate DNA damage. Furthermore, EGCG NPs facilitated fibroblast proliferation and migration, while inhibiting the polarization of macrophages towards the M1 phenotype in vitro. In animal levels, EGCG NPs exhibited markedly improved radioprotective efficacy over free EGCG, effectively reducing skin edema and ulceration, alleviating pathological conditions such as interstitial edema, dermal fluid accumulation, and inflammatory infiltration, decreasing the duration of skin injury, and promoting wound healing.Conclusion: This work offers novel insights into the therapeutic application of EGCG NPs as a potential alternative for skin radioprotection and provides a powerful approach for developing radioprotective agents derived from natural products. Keywords: radiation-induced skin injury, nanoparticles, free radicals scavenging, radioprotection

Xinyi Shao,&ast; Xingyu Pan,&ast; Yangmei Chen, Yan Zhu, Shuang Chen, Jin Chen Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuang Chen; Jin Chen, Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +8617726638759 ; +8615023188592, Email 179409599@qq.com; chenjin7791@163.comAbstract: Atopic dermatitis (AD) may sometimes be comorbid with vitiligo. However, these therapeutic agents are often slow acting and lead to various adverse effects, resulting in poor patient compliance. This report describes a 65-year-old male patient with refractory moderate-to-severe atopic dermatitis (AD) and generalized vitiligo. The patient was treated with repeated antihistamine and dupilumab injections; however, erythema and pruritus did not improve. Consequently, oral abrocitinib was administered to treat AD and vitiligo, and the patient’s generalized erythema, papules, and pruritus ameliorated with the repigmentation of vitiligo lesions. This case provided evidence of the efficacy and safety of oral abrocitinib for patients with concurrent refractory AD and vitiligo.Keywords: atopic dermatitis, vitiligo, abrocitinib, JAK inhibitors

Lin Yang,1,2 Xiaoyu Pan,2 Zhenyu Pan,3 Haina Gao,4 Jiangli Ban,4 Shuchun Chen2,5,6 1Department of Internal Medicine, Hebei North University, Zhangjiakou, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Internal Medicine, Shandong Medical College, Linyi, Shandong, People’s Republic of China; 4Department of Endocrinology, The Second Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of China; 5Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 6Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Internal Medicine, Hebei Medical University, People’s Republic of China, Tel +86 31185988406, Email chenshuc2014@163.comIntroduction: Obesity-induced inflammation and oxidative stress can cause damage to cardiomyocytes. Semaglutide has the potential to reduce glucose levels and weight, while hydroxysteroid dehydrogenase-like protein 2 (HSDL2) also plays a role in regulating lipid metabolism. This study aimed to investigate the expression of oxidative stress markers and HSDL2 in myocardium and serum under high-fat conditions, in order to elucidate the mechanism of obesity-induced myocardial injury and evaluate the impact of semaglutide on myocardial injury through HSDL2.Methods: Mouse models of obesity were established with semaglutide treatment. Palmitic acid-cultured mouse cardiomyocytes with HSDL2 knockout were used, as well as palmitic acid-induced high-fat environment models followed by semaglutide treatment. The levels of inflammatory and oxidative stress markers in serum and cardiomyocytes were measured. Additionally, the expression of HSDL2 and autophagy levels in different cell groups were assessed to evaluate the effect of semaglutide on high-fat diet-induced cardiomyocyte injury mediated by HSDL2.Results: Obesity increased oxidative stress, which was alleviated by intervention with semaglutide. Furthermore, semaglutide down-regulated HSDL2 expression in obese individuals. Moreover, palmitic acid-induced oxidative stress and autophagy were reduced when using cells with knocked out HSDL2 gene.Conclusion: These findings suggest that semaglutide may mitigate cardiomyocyte injury caused by a high-fat diet through regulation of HDLSDSLEP-1 expression. These discoveries are expected to unveil novel molecular mechanisms and provide new targets for clinical treatment.Keywords: obesity, inflammation, oxidative stress, semaglutide, HSDL2

Yi Zheng,1,2 Xinyu Wang,1 Yang He,1 Shuo Chen,1 Linhai He,1,3,&ast; Yi Zhang1,&ast; 1Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, 100081, People’s Republic of China; 2Department of Stomatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 3First Clinical Division, Peking University School and Hospital of Stomatology, Beijing, 100081, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linhai He; Yi Zhang, Email helinhai07@126.com; zhangyi2000@263.netPurpose: Exosomes from mesenchymal stromal cells (MSCs) can prevent the development of medication-related osteonecrosis of the jaw (MRONJ) by promoting tooth socket wound healing; however, the exact mechanism remains to be clarified. In this study, our aim was to explore the mechanisms of exosomes derived from adipose-derived mesenchymal stromal cells (ADSCs) in preventing MRONJ by focusing on macrophage M1 polarization and pyroptosis.Methods: The MRONJ model was established by the administration of zoledronate and tooth extraction. Exosomes isolated from the supernatant of ADSCs were mixed with hydrogel and locally injected into the extraction site after tooth extraction. Stereoscope observations, micro computed tomography (microCT), and histological analysis were used to assess tooth socket wound healing.Results: The results showed that exosomes could effectively avoid MRONJ via accelerating gingival wound healing and tooth socket bone regeneration. Mechanistically, zoledronate triggered the NF-κB signaling pathway and promoted p65 transferring into the nucleus in macrophages, resulting in macrophage M1 polarization and pyroptosis-mediated tissue inflammation, while exosomes could reduce macrophage pyroptosis and pro-inflammation cytokines release by suppressing the NF-κB/NLRP3/IL-1β axis. Additionally, IL-1RA derived from exosomes plays a key role in preventing MRONJ. Pyroptosis-related and inflammatory-related processes were upregulated in MRONJ patients further confirmed by assessing MRONJ gingival samples and healthy gingival tissues.Conclusion: ADSCs-derived exosomes could effectively promote tooth socket healing and prevent MRONJ by inhibiting M1 macrophage activation and pyroptosis by blocking the NF-κB/NLRP3/IL-1β axis.Keywords: Medication-related osteonecrosis of the jaw, exosomes, macrophage M1 polarization and pyroptosis, primary wound healing, NF-κB/NLRP3/IL-1β axis

Haiyan Sun,1,&ast; Siyao Chen,1,&ast; Ayano Nagai,2 Xi Chen,3 Yang Qin,1 Zhiming Wei1 1School of Nursing, Jiangsu Medical College, Yancheng, Jiangsu, People’s Republic of China; 2Social Welfare Corporation Keiseikai Group, Osaka, Japan; 3Department of Nursing, Yancheng NO.1 People’s Hospital, Yancheng, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiming Wei, School of Nursing, Jiangsu Medical College, NO. 283 South Jiefang Road, Yancheng, Jiangsu, 224005, People’s Republic of China, Tel +8613805104291, Email 4826537@qq.comBackground: In China, spouses of patients with advanced cancer have reported experiencing psychological distress. However, little attention has been paid to the positive psychological health trajectories of these caregivers, particularly regarding their resilience and the factors influencing its development over time.Purpose: To examine the trajectories of resilience in Chinese spousal caregivers over a nine-month post-treatment period and to identify the basic characteristics associated with these trajectory patterns.Methods: This was a longitudinal, observational study conducted in mainland Chinese between January 2022 and May 2024. A total of 306 spouses of patients receiving cancer treatment were recruited from five local hospitals. Data was collected in four waves: within one month of initial treatment, and then at three-, six-, and nine-month intervals post-treatment. Socio-demographic questionnaires, the Connor-Davidson Resilience Scale, and the Beliefs in Chinese Familism Scale were used to collect data. Growth mixture modeling was employed to determine the various trajectories of resilience, followed by logistic regression analysis to examine the associated factors to predict types of trajectories.Results: Growth mixture modeling showed two distinct trajectories of resilience were identified: an increased group (N = 78, 25.5%) and a stable group (N = 228, 74.5%). The increased group began with a low baseline level (intercept = 46.713) and showed a slight increase over time (slope = 7.505, p < 0.001), while the stable group had a moderate baseline level (intercept = 56.565) and remained stable over time (slope = 0.068, p > 0.05). Those in the stable group were more likely to be female, and to have achieved a middle school level of education, a lower family income, and greater Chinese familism at baseline than those in the increased group.Conclusion: Our findings underscore the importance of tracking the trajectories of resilience and predictors of trajectory patterns among spouses caring for patients with advanced cancer within a specific cultural context. Healthcare providers should provide tailored interventions to enhance resilience in spousal caregivers, considering the trajectory patterns of mental health change.Keywords: resilience, spouse, advanced cancer, caregivers, trajectories

Lijuan Xia,1,2,&ast; Fanxing Yang,3,&ast; Naoko Hayashi,2,&ast; Yuan Ma,4 Bin Yan,4 Yingxin Du,5 Sujuan Chen,1 Yuke Xia,4 Fang Feng,6 Zhifang Ma1 1Department of Radiotherapy, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Department of Oncology Nursing and Palliative Care/ Chronic Illness and Conditions Nursing, St. Luke’s International University, Tokyo, Japan; 3Department of Labor Delivery Recovery Postpartum, People’s Hospital of Zhengzhou, Zhengzhou, Henan, People’s Republic of China; 4Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 5Department of Clinical Nutrition, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 6Department of Rheumatology and Immunology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lijuan Xia, Department of Radiotherapy, General Hospital of Ningxia Medical University, 804 Shengli South Street, Xingqing District, Yinchuan City, Ningxia, 750004, People’s Republic of China, Email 24DN009@slcn.ac.jp; 974286683@qq.com, Fang Feng, Email 13995409352@163.comIntroduction: Nutritional status is a critical indicator of overall health and immune function, significantly influencing treatment outcomes. Despite its importance, the nutritional status of patients with systemic lupus erythematosus (SLE) often receives insufficient attention. This study aims to evaluate the nutritional status of patients with SLE, identify factors associated with malnutrition, and develop a risk prediction model for malnutrition in this population.Methods: We collected clinical data from a convenience sample of SLE patients at a general hospital in Ningxia Province, China, between January and December 2022. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for malnutrition. A risk prediction model was constructed and evaluated using the receiver operating characteristic (ROC) curve.Results: This study included 420 patients with SLE (mean age: 41.43 years, 91.7% women), of whom 46.2% were malnourished based on their serum albumin levels. Multivariate logistic regression analysis identified monthly income (OR=0.192, P< 0.05), sleep quality (OR=2.559, P< 0.05), kidney involvement (OR=4.269, P< 0.05), disease activity (OR=2.743, P< 0.05), leukocyte count (OR=1.576, P< 0.05), lymphocyte count (OR=0.393, P< 0.05), hemoglobin (OR=0.972, P< 0.05), complement C3 (OR=0.802, P< 0.05), and complement C4 (OR=0.493, P< 0.05) as independent risk factors for malnutrition. The prediction model showed good predictive value with an area under the ROC curve of 0.895 (95% CI: 0.823– 0.840), sensitivity of 0.907, and specificity of 0.827. The Hosmer-Lemeshow test indicated a good model fit (χ²=10.779, P=0.215).Discussion: Malnutrition is a significant concern among SLE patients, influenced by a range of socioeconomic and clinical factors. Our risk prediction model, with its high sensitivity and specificity, provides a robust tool for early identification of malnutrition in this population. Implementing this model in clinical practice can guide healthcare providers in prioritizing at-risk patients, enabling proactive nutritional interventions that could potentially improve clinical outcomes, enhance quality of life, and reduce healthcare costs associated with SLE.Keywords: systemic lupus erythematosus, nutritional status, associated factors, malnutrition, risk prediction model, nomogram

Chengran Wang,&ast; Xiaoqing Zhao,&ast; Keyan Wang, Huixin Liang, Shuhan Chen, Yajie Liu, Hua Yao, Jinlan Jiang Department of Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Yao; Jinlan Jiang, Department of Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China, Tel\Fax +86-13596102816, Email yao_hua@jlu.edu.cn; jiangjinlan@jlu.edu.cnAbstract: Disseminated intravascular coagulation (DIC) is an acquired disorder characterized by systemic activation of blood coagulation, which can arise from various causes. Owing to its abrupt onset, rapid progression, and high mortality rate, DIC presents a major clinical challenge. Anticoagulant drugs, such as heparin or low-molecular-weight heparin, are the current gold standard of treatment; however, these interventions pose considerable bleeding risks. Thus, safer and more effective therapeutic strategies are urgently required. Owing to their strong anti-inflammatory and tissue repair capabilities, mesenchymal stem cell-derived exosomes (MSC-Exos) have gained considerable attention as novel therapeutic options for numerous disorders, including DIC. Their stability in diverse pathological states highlights their potential as promising candidates for DIC therapy. This review presents the latest insights on the pathogenesis of DIC and anti-inflammatory and anticoagulant properties of MSC-Exos. We aimed to elucidate the potential mechanisms by which MSC-Exos influence DIC pathogenesis. We speculate that MSC-Exos offer a multifaceted approach to DIC treatment by attenuating neutrophil extracellular trap formation, modulating M1/M2 macrophage polarization, altering Nrf2/NF-κB signalling pathway to downregulate pro-inflammatory factors, and correcting imbalances in the coagulation-fibrinolysis system through anticoagulant routes. This suggests that MSC-Exos are a potential paradigm in DIC therapy, offering novel targets and treatment modalities for DIC management. Keywords: disseminated intravascular coagulation, mesenchymal stem cell-derived exosomes, anticoagulant therapy, neutrophil extracellular traps, macrophage polarization

Haoxiang Wen,1,2,&ast; Ruiming Liang,3,&ast; Xiaofei Liu,4 Yang Yu,1 Shuirong Lin,1 Zimin Song,1 Yihao Huang,1 Xi Yu,1 Shuling Chen,5 Lili Chen,6 Baifeng Qian,1 Jingxian Shen,7 Han Xiao,8 Shunli Shen1 1Center of Hepato-Pancreatico-Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Medical Statistics, Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 4Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-senUniversity, Guangzhou, Guangdong Province, People’s Republic of China; 5Precision Medicine Institute, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 6Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 7Department of Radiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 8Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shunli Shen, Center of Hepato-Pancreatico-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhong-Shan Road2, Guangzhou, Guangdong Province, People’s Republic of China, Email Shenshli@mail.sysu.edu.cn Han Xiao, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road2, Guangzhou, Guang- Dong Province, People’s Republic of China, Email xiaoh69@mail.sysu.edu.cnPurpose: Predicting the pathological response after neoadjuvant conversion therapy for initially unresectable hepatocellular carcinoma (HCC) is essential for surgical decision-making and survival outcomes but remains a challenge. We aimed to develop a radiomics model to predict pathological responses.Methods: We included 203 patients with HCC who underwent hepatectomy after neoadjuvant conversion therapy between 2015 and 2023 and separated them into a training set (100 patients from Center A) and a validation set (103 patients from Center B). Pathological complete response (pCR)-related radiomic features were extracted from the largest tumor layer in the arterial and portal vein phases of the CT. A synthetic minority oversampling technique (SMOTE) was used to balance the minority groups in the training set. The SMOTE radiomics model was constructed using a logistic regression model in the SMOTE training set and its performance was verified in the validation set.Results: The AUC of the preoperative modified response evaluation criteria in solid tumors (mRECIST) assessment for pCR was 0.656 and 0.589 in the training and validation sets, respectively. The SMOTE radiomics model was established based on ten radiomic features and showed good pCR-predictive performance in the SMOTE training set (AUC, 0.889; accuracy, 87.7%) and the validation set (AUC: 0.843, accuracy: 86.4%). The RFS of the radiomics-predicted-pCR group was significantly better than that of the predicted-non-pCR group in the training cohort (P = 0.001, 2-year RFS: 69.5% and 30.1% respectively) and the validation cohort (P = 0.012, 2-year RFS: 65.9% and 38.0% respectively).Conclusion: The SMOTE radiomics model has great potential for predicting pathological response and evaluating RFS in patients with unresectable HCC after neoadjuvant conversion therapy.Keywords: hepatocellular carcinoma, radiomics, pathological complete response, neoadjuvant conversion therapy

Yihe Ma,1– 3,&ast; Xiaojun Xiao,2,&ast; Yutao Wang,3,&ast; Jie Sun,4 Ping Tang,5 Jing Li,3 Xizhuo Sun,5 Damo Xu,1,2 Zifeng Yang,3 Shiguo Chen,4 Xiaoyu Liu2 1Department of Respiratory and Allergy, Third Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 2State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, School of Medicine, Shenzhen University, Shenzhen, People’s Republic of China; 3State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Nanshan District Key Laboratory for Biopolymers and Safety Evaluation, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, People’s Republic of China; 5Department of General Practice, Third Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyu Liu, State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, School of Medicine, Shenzhen University, Shenzhen, People’s Republic of China, Email lxy0901@szu.edu.cnPurpose: Synthesis and characterization of silver (Ag)/titanium dioxide (TiO2) nanocomposite (ATA) to investigate its antiviral activity against the H1N1 influenza virus and antiviral mechanisms.Materials and Methods: A water-dispersible ATA was prepared by a photocatalytic reduction process from AgNO3 and TiO2. The characterization of ATA was performed by ultraviolet-visible spectroscopy, X-ray diffraction, high-resolution transmission electron microscopy and energy-dispersive X-ray spectroscopy. The antiviral activities and the antiviral mechanism of ATA were investigated in detail by light microscopy, transmission electron microscopy and biological techniques such as cell cytotoxicity, 50% tissue culture infectious dose detection, western blot and reverse transcription-polymerase chain reaction.Results: These results showed the successful synthesis of ATA nanocomposite with uniform particle size and distribution. It demonstrated the highly efficient antiviral activity of ATA in a dose- and time-dependent manner, as indicated by the reduction of viral titer and the reduction of cytopathic effects caused by viral infection. In the presence of ATA, the structure of the H1N1 influenza virus is directly destroyed and even disintegrated, with the damaged surface membrane proteins and fuzzy contour. It reduces the infection efficiency of influenza by suppressing the activity and expression of hemagglutinin and neuraminidase. The results of mechanistic studies suggested that ATA nanocomposite primarily interferes with virus attachment to viral receptors on the cell surface.Conclusion: Our study suggests that ATA may be a good antiviral candidate against the influenza virus. Compared with AgNPs alone, our synthesized ATA nanocomposites can achieve similar viral inactivation rates using only a much smaller concentration of AgNPs, greatly reducing the amount of AgNPs and their potential side effects. It has great practical value for attaching ATA to the high-efficiency particulate air network in the air purifier, which can kill the virus attached to it and limit its spread.Keywords: silver, titanium dioxide, nanocomposites, antivirus, H1N1 influenza virus

Jing Hu, Yang Song, Yuxing Zhang, Peng Yang, Siyu Chen, Zhaoyan Wu, Jun Zhang Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Jun Zhang, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 13953109816, Fax +86 53188382923, Email zhangj@sdu.edu.cnPurpose: This study examines the effects and mechanisms of catalpol (CAT) on the proliferation and osteogenic differentiation of cultured human periodontal ligament stem cells (hPDLSCs) in vitro and assesses the impact of CAT on periodontal remodeling in vivo using an orthodontic tooth movement (OTM) model in rats.Methods: hPDLSCs were cultured in a laboratory setting, and their proliferation and osteogenic differentiation were assessed using the Cell-counting Kit-8 (CCK-8), Alizarin Red Staining (ARS), quantitative calcium assay, alkaline phosphatase (ALP) staining and activity assay, and immunofluorescence assay. Additionally, the expression of collagen type 1 (COL-1), ALP, and runt-related transcription factor-2 (RUNX-2) was evaluated through qRT-PCR and Western blot analysis. To verify the function of the estrogen receptor-α (ER-α)-mediated phosphatidylinositol-3-kinase-protein kinase B (PI3K/AKT) pathway in this mechanism, LY294002 (a PI3K signaling pathway inhibitor) and the ER-α specific inhibitor methyl-piperidine-pyrazole (MPP) were used. The osteogenic markers ER-α, AKT, and p-AKT (phosphoprotein kinase B) were identified through Western blot analysis. Eighteen male Sprague-Dawley rats were assigned to two groups randomly: a CAT group receiving CAT and a control group receiving an equivalent volume of saline. Micro-computed tomography (micro-CT) analysis was employed to evaluate tooth movement and changes in alveolar bone structure. Morphological changes in the periodontal tissues between the roots were investigated using hematoxylin and eosin (HE) staining and tartaric-resistant acid phosphatase (TRAP) staining. The expression of COL-1, RUNX-2, and nuclear factor-κB (NF-κB) ligand (RANKL) was assessed through immunohistochemical staining (IHC) to evaluate periodontal tissue remodeling. Tests were analyzed using GraphPad Prism 8 software. Differences among more than two groups were analyzed by one-way or two-way analysis of variance (ANOVA) followed by the Tukey’s test. Values of p

Liying Lu,1,2 Mengdan Pang,1,2 Tingting Chen,1,2 Yingying Hu,1,2 Likai Chen,3 Xiaoyue Tao,1,2 Shangqin Chen,1,2 Jianghu Zhu,1,2 Mingchu Fang,1,2 XiaoLing Guo,1,4 Zhenlang Lin1,2,4 1Department of Pediatrics, The Second School of Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Key Laboratory of Perinatal Medicine of Wenzhou, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Elson S. Floyd College of Medicine at Washington State University, Spokane, WA, USA; 4Basic Medical Research Center, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: XiaoLing Guo; Zhenlang Lin, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, People’s Republic of China, Tel +00-86-138-0668-9800, Fax +86-0577-88002198, Email guoxling@hotmail.com; linzhenlang@hotmail.comIntroduction: Neonatal hypoxic-ischemic encephalopathy (HIE), caused by perinatal asphyxia, is characterized by high morbidity and mortality, but there are still no effective therapeutic drugs. Mitochondrial biogenesis and apoptosis play key roles in the pathogenesis of HIE. Protopine (Pro), an isoquinoline alkaloid, has anti-apoptotic and neuro-protective effects. However, the protective roles of Pro on neonatal hypoxic-ischemic brain injury remain unclear.Methods: In this study, we established a CoCl2-induced PC12 cell model in vitro and a neonatal rat hypoxic-ischemic (HI) brain damage model in vivo to explore the neuro-protective effects of Pro and try to elucidate the potential mechanisms.Results: Our results showed that Pro significantly reduced cerebral infarct volume, alleviated brain edema, inhibited glia activation, improved mitochondrial biogenesis, relieved neuron cell loss, decreased cell apoptosis and reactive oxygen species (ROS) after HI damage. In addition, Pro intervention upregulated the levels of p-AMPK/AMPK and PGC1α as well as the downstream mitochondrial biogenesis related factors, such as nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), but the AMPK inhibitor compound c (CC) could significantly reverse these effects of Pro.Discussion: Pro may exert neuroprotective effects on neonatal hypoxic-ischemic brain damage via activation of the AMPK/PGC1α pathway, suggesting that Pro may be a promising therapeutic candidate for HIE, and our study firstly demonstrate the neuro-protective roles of Pro in HIE models.Keywords: neonatal hypoxic-ischemic brain damage, protopine, reactive oxygen species, apoptosis, mitochondrial biogenesis

Fengshan Ouyang,1,2 Sheng Chen,1 Shuhuan Li,3 Lanyuan Liu,4 Senhong Guan,1 Zhaohan Yan,1 Shumin Wu,5 Yunying Zeng,1 Jiemei Liu,2 Jiankai Zhong1 1Department of Cardiology, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, People’s Republic of China; 2Department of Rehabilitation Medicine, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, People’s Republic of China; 3Department of Pediatrics, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, People’s Republic of China; 4Department of Ultrasound Medicine, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, People’s Republic of China; 5Department of Clinical Pharmacy, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, People’s Republic of ChinaCorrespondence: Jiankai Zhong, Department of Cardiology, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), No. 1 Jiazi Road, Lunjiao Street, Shunde District, Foshan City, Guangdong Province, 528308, People’s Republic of China, Tel +86 13824530303, Email doctor-zh@smu.edu.cn Jiemei Liu, Department of Rehabilitation Medicine, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, People’s Republic of China, Email liujiemei90@hotmail.comObjective: This study aimed to examine the correlation and prognostic value of serum irisin levels in acute ischaemic stroke (AIS) and the subsequent development of hemiplegia.Methods: This study recruited participants from the Department of Neurology and Rehabilitation Medicine at Shunde Hospital, Southern Medical University. The Fugl–Meyer Assessment was used to assess functional impairment. Serum irisin levels were measured using the enzyme-linked immunosorbent assay method. Multivariate logistic regression was employed to explore the factors related to serum irisin levels and AIS.Results: Serum irisin levels in the AIS group were significantly lower than those in the control group. However, no significant association was observed between serum irisin and stroke severity within the AIS cohort. Multivariate logistic regression analysis revealed an inverse correlation between serum irisin levels and AIS risk, indicating that it serves as a protective factor against AIS. The increase in serum irisin levels (adjusted odds ratio (OR) 0.938, 95% confidence interval [CI]: 0.899– 0.977 per 100 pg/mL increment) was associated with a decreased risk of AIS. Analysis of the receiver operating characteristic curve confirmed the diagnostic value of serum irisin for AIS, with the area under the curve being 0.591 (95% CI: 0.522– 0.659, p = 0.012).Conclusion: Serum irisin levels were significantly lower in AIS and were identified as a protective factor, suggesting that serum irisin may have diagnostic value for AIS.Keywords: irisin, acute ischaemic stroke, hemiplegia, risk factors, predictive value

Haiming Yan,1– 3,&ast; Suling Chen,1,2,&ast; Xinrui Gao,1,2,&ast; Yuanhui Jiang,1,2 Guangyu Liang,1,2 Jie Peng,1,2 Shaohang Cai1,2 1Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Guangdong Provincial Key Laboratory of Viral Hepatitis Research; Guangdong Provincial Clinical Research Center for Viral Hepatitis; Guangdong Institute of Hepatology, Guangzhou, People’s Republic of China; 3Department of Infectious Diseases, The First People’s Hospital of Foshan, Foshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Peng; Shaohang Cai, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email pjie138@163.com; shaohangcai@foxmail.comBackground: Metabolic disorders and immunosenescence increase the risk of complications in people living with HIV (PLWH), affecting mortality and quality of life. However, their relationship remains unclear.Methods: Participants were grouped by median TyG index, and logistic regression identified baseline independent factors of a high TyG index at Week 24. The association of the TyG index for hepatic steatosis was determined using ROC curves. We also explored correlations between the TyG index and aging markers, including CD4/CD8 ratio and CD8+ T cells and evaluated health-related quality of life (HRQoL).Results: A total of 203 PLWH were included in the study. We observed that PLWH in high TyG group tended to be older (P< 0.001), have greater body weight (P< 0.001), higher ALT levels (P=0.021), and increased low-density lipoprotein levels (P=0.001). ROC analysis revealed that TyG index was closely associated with hepatic steatosis at Week 52 (AUC=0.743) and Week 104 (AUC=0.728). Moreover, a higher TyG index was positively correlated with CD8+ T cell counts, while patients in the high TyG group had lower CD4/CD8 ratios at Week 52 and Week 104. Poorer mental health was observed in patients with CD8+ T cell counts ≥ 1000 and a high TyG index. Multivariate analysis further identified baseline older age (OR=1.108, P=0.002), elevated cholesterol (OR=3.407, P< 0.001), and low HDL (OR=0.003, P< 0.001) as factors associated with a high TyG index at Week 24.Conclusion: The TyG index is closely linked to metabolic disorders and immunosenescence in PLWH. It offers a basis for personalized treatment strategies, improving physical and mental health and reducing complication risks.Keywords: HIV/AIDS, triglyceride-glucose index, metabolic disorders, immunosenescence, hepatic steatosis

Gengyu Cen,1,&ast; Jun Wang,1,&ast; Xue Wang,1 Yiting Song,1 Shijian Chen,1 Jing Li,2 Qiuhui Huang,1 Zhijian Liang1 1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Neurology, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Liang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email lzj200415@126.comObjective: To investigate the pathogenesis of cancer-related ischemic stroke (CRIS) and to search for reliable biomarkers of CRIS.Methods: Patients with CRIS, only-cancer and only-ischemic stroke who were hospitalized in the First Affiliated Hospital of Guangxi Medical University from May 2022 to January 2024 were recruited, and laboratory and clinical data of the three groups were collected. Peripheral venous blood was collected and enzyme-linked immunosorbent assay (ELISA) was used to detect markers of coagulation (D-dimer) and endothelial integrity (intercellular adhesion molecule-1 (ICAM-1)).Results: The study included 16 patients with CRIS, as well as 16 patients with only-cancer and 16 patients with only-ischemic stroke. Among patients with CRIS, the most common cancer was lung cancer, and the most common pathological type was adenocarcinoma. It was found that compared with patients with only-cancer and only-ischemic stroke, the hemoglobin and lymphocyte percentage in patients with CRIS were decreased (P< 0.05), while the neutrophil percentage and neutrophil to lymphocyte ratio (NLR) were increased (P< 0.05). Compared with only-ischemic stroke group, the lymphocyte absolute value in patients with CRIS was decreased (P< 0.05), and platelet to lymphocyte ratio (PLR), globulin, prothrombin time (PT), international normalized ratio (INR) and ICAM-1 were increased (P< 0.05). D-dimer level was higher in patients with CRIS than in only-cancer group (P< 0.05).Conclusions: In the present study, the increased NLR, PLR, ICAM-1 and D-dimer were expected to be biomarkers of CRIS, indicating that hypercoagulability mediated by cancer inflammation and endothelial damage may be the pathogenesis of CRIS. The novel findings in the present study will facilitate clinicians to identify the patients at high risk of CRIS. Because of the small sample size, the findings need to be validated by prospective large-sample studies in the future.Keywords: cancer-related ischemic stroke, hypercoagulability, pathogenesis, biomarkers

Shupeng Chen,1 Jie Liu,1 Guilian He,1 Nana Tang,2 Yingjian Zeng2 1School of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, 330004, People’s Republic of China; 2Hematology Department, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330006, People’s Republic of ChinaCorrespondence: Yingjian Zeng, Jiangxi University of Traditional Chinese Medicine Affiliated Hospital, Hematology Department, Nanchang, 330006, People’s Republic of China, Email tcmdrc2023@outlook.comBackground: Cancer poses a major global health challenge, and immunotherapy, known as the third revolution in cancer treatment, has brought new hope to patients. The emerging field of immunometabolism has further enhanced the safety and efficacy of immunotherapy. Over the past two decades, this field has rapidly evolved in oncology, leading to numerous significant findings. This review systematically examines the literature on immunometabolism in cancer, visualizing research trends and identifying future directions.Methods: A comprehensive literature search was conducted in the Web of Science, PubMed, and Scopus databases, covering publications from January 2000 to December 2023. We employed tools like Citespace, VOSviewer, and RStudio for visual analysis of publication trends, regional contributions, institutions, authors, journals, and keywords.Results: A total of 3320 articles were published by 8090 authors across 1738 institutions, involving 71 countries. Leading contributors were China (n=469), the United States (n=361), and Germany (n=82). Harvard University was the most influential institution, while Frontiers in Immunology had the highest number of publications. The top research areas included glucose, lipid, and amino acid metabolism, the tumor microenvironment, and immune cell regulation.Conclusion: International collaboration and interdisciplinary efforts are advancing the field of cancer immunometabolism. Future research will likely focus on the interplay between metabolism and immunity, metabolic markers, immune cell reprogramming, and tumor-immune metabolic competition.Keywords: immunity, metabolism, tumor, metabolic reprogramming, immune evasion, bibliometrics

Yongcheng Yao,1,2 Jie Tang,3 Zhenzhen Li,1 Shuyan Chen,1 Haixia Du,1 Lingeng Lu4 1School of Mathematics and Statistics, Zhengzhou Normal University, Zhengzhou, Henan, People’s Republic of China; 2WorldPop, School of Geography and Environmental Science, University of Southampton, Southampton, UK; 3Library, Zhengzhou University of Technology, Zhengzhou, Henan, People’s Republic of China; 4Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale University, New Haven, CT, USACorrespondence: Yongcheng Yao, School of Mathematics and Statistics, Zhengzhou Normal University, Zhengzhou, Henan, 450044, People’s Republic of China, Email 806306944@qq.comObjective: COVID-19-related lockdown can lead to mental health problem, which displays heterogeneous between individuals. The aim of this study was to explore the association between mental health, social support and psychological capital state of professional staff with different personalities during the COVID-19 pandemic in China.Methods: A cross-section study was conducted via online survey using the questionnaires of General Health Questionnaire (GHQ-12), Multidimensional Scale of Perceived Social Support (MSPSS), Psychological Capital Questionnaire (PCQ), Eysenck Personality Questionnaire-Revision Short Scale of China (EPQ-RSC). A total of 626 employees were included. Multiple regression analysis was performed to investigate the association of psychological capital, perceived social support, EPQ-N and EPQ-E and their interactions in general mental health.Results: About 2.7% of professionals had mental health. The married had a higher mental health score than the single (P

Sumei Chen,1,&ast; Lingrong Yang,2,&ast; Bing Xia,3 Haitao Zhu,4 Zhenghao Piao,5 Youssef Jounaidi6 1Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, 310002, People’s Republic of China; 2Department of Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, 310002, People’s Republic of China; 3Department of Thoracic Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, 310002, People’s Republic of China; 4Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550001, People’s Republic of China; 5Department of Basic Medical Science, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, People’s Republic of China; 6Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA&ast;These authors contributed equally to this workCorrespondence: Youssef Jounaidi, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA, Email yjounaidi@mgh.harvard.eduBackground: Enhancing NK cells’ antitumor activity requires sustained cytokine signaling. Interleukin-15 (IL-15) is a potent immunostimulatory cytokine used to armor CAR-NK and CAR-T cell immunotherapies. However, strategies to increase IL-15 expression and antitumor effect may trigger systemic toxicity with the potential to promote oncogenesis and autoimmune diseases.Methods: To overcome these limitations, we developed a new platform (IL15RB) whereby IL-15 with IL-2 signal peptide is tethered to its receptor, IL2Rβ.Results: NK92-expressing IL15RB (NK92IL15RB) cells expand indefinitely without exogenous cytokines and have significantly higher anticancer activity than NK-92 stimulated by IL-15, IL-2, or expressing tethered IL-2. NK92IL5RB showed resistance to irradiation and IL-4. However, TGFβ 1 substantially reduced NK92IL5RB killing, suggesting the need to inhibit TGFβ 1 in IL-15-mediated immunotherapies. IL15RB induced strong STAT3 but weaker STAT5 and STAT1 activation compared to IL-2. Chronic exposure of NK92IL15RB cells to cancer cells reduced STAT3 and STAT1 activation irreversibly, suggesting a role in exhaustion. Combination with CAR-CD19 enhanced NK92IL15RB antitumor activity against leukemia and increased its STAT5 activation. NK92IL15RB anti-tumors activity was further enhanced by combination with anti-PD1.Conclusion: Our data suggest that the tethering of IL-15 to its receptor IL2Rβ empowers NK cell cytolytic activity. Additionally, the tethering of IL-15 will prevent any systemic risk of toxicity.Keywords: IL-15, IL2RB receptor, natural killer cells, cancer immunotherapy, IL15RB

Lili Wang,1 Le Cheng,1 Chenhui Lv,1 Jie Kou,1 Wenjuan Feng,1 Haoran Xie,1 Ruolin Yan,1 Xi Wang,1 Shuangzhi Chen,1 Xin Song,1 Lushan Xue,1 Cheng Zhang,1 Xuemin Li,2 Haifeng Zhao1,3 1Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Center for Disease Control and Prevention in Shanxi Province, Taiyuan, People’s Republic of China; 3MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, Taiyuan, People’s Republic of ChinaCorrespondence: Haifeng Zhao, Department of Nutrition & Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China, Tel/Fax +86-351-4135046, Email haifengzao75@163.comBackground: The present study aimed to explore the association between the inflammatory potential of diet, assessed by energy-adjusted dietary inflammatory index (E-DII) and reduced rank regression (RRR)-derived inflammatory dietary pattern, and the risk for cognitive impairment (CI) in community-dwelling older adults, especially in older adults with chronic diseases and multimorbidity.Methods: A total of 549 older adults from Taiyuan city were included in the present cross-sectional study. The Chinese Version of the Mini-Mental State Examination (CMMSE) was used for the evaluation of cognitive function. E-DII score was calculated based on semi-quantitative food frequency questionnaire (FFQ). Blood samples, including interleukin (IL)-1β, interleukin (IL)-18, tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP), were tested for calculating RRR-derived inflammatory dietary pattern. Logistic regression was used to assess the association between inflammatory dietary pattern and risk of CI. In addition, patients with diabetes, hypertension, hyperlipidemia and multimorbidity were screened for further analysis among 549 older adults.Results: In those 549 older adults, adjusting for demographic characteristics and chronic disease status, there was no association between E-DII score tertile (ORT3VST1: 1.357, 95%CI:0.813~2.265, Ptrend = 0.267), RRR-derived inflammatory dietary pattern score tertile (ORT3VST1: 1.092, 95%CI:0.679~ 1.758, Ptrend = 0.737) and risk of CI. However, in older adults with diabetes and multimorbidity, the score tertile of E-DII and RRR-derived inflammatory dietary pattern were positively correlated with risk of CI in a dose-responsive manner (All Ptrend < 0.05). There is insufficient evidence to reach similar conclusion in patients with hypertension and hyperlipidemia (All Ptrend > 0.05).Conclusion: In the present study, pro-inflammatory diet contributed to the increased risk of CI in older adults with diabetes and multimorbidity. These results supplemented vital evidence for the prevention and treatment of CI in older adults with chronic diseases.Keywords: chronic diseases, multimorbidity, cognitive impairment, inflammatory dietary pattern, dietary inflammatory index, reduced rank regression

Quirui Nie,1 Hui Qian,2,3 Shenjian Chen,3 Wenwen Xiang,3 Yu Shen3,4 1Department of Gerontology, Nanchang First Hospital, Nanchang, People’s Republic of China; 2Department of Neurology, Fengxin County People’s Hospital, Fengxin, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Yu Shen, Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China, Email shenyu19950712@sina.comObjective: To compare the differences in risk factors and etiological classification between cerebral infarction in young patients and elderly patients, and explore the correlation between cerebral infarction in young patients and white matter lesions (WMLs).Methods: Sixty young patients with cerebral infarction and 142 elderly patients with cerebral infarction were included. The distributions of risk factors such as hypertension, diabetes, heart disease, smoking status, alcohol consumption status, migraine status, and WMLs in the two groups were carefully investigated and statistically analyzed.Results: According to the univariate analysis, the proportions of males, obese patients, patients with migraine, and patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) in the young group were significantly greater than those in the elderly group. Hypertension, heart disease, and hyperhomocysteinemia were significantly more common in the elderly group than in the young group. According to the TOAST classification, the incidence of stroke of undetermined etiology in the young group was greater than that in the elderly group, whereas the incidence of large-artery atherosclerosis (LAA) in the elderly group was greater than that in the young group. Binary logistic regression analysis revealed that male sex, migraine status, and obstructive sleep apnea-hypopnea syndrome were independently associated with cerebral infarction in young adults, whereas hypertension, heart disease, and hyperhomocysteinemia were independently related to cerebral infarction in elderly individuals. In addition, the incidence of WMLs in the migraine group of young cerebral infarction patients was significantly greater than that in the nonmigraine group.Conclusion: Compared with those in elderly patients with cerebral infarction, the risk factors for cerebral infarction in young patients are relatively controllable. Furthermore, more methods are needed to determine the etiology of unexplained cerebral infarction in young patients. WMLs are thought to have a relatively high incidence in young patients with cerebral infarction and are significantly associated with migraine.Keywords: cerebral infarction, white matter lesions, young people, risk factors, migraine

Weiqian Zhang,1,&ast; Shuiying Chen,1,&ast; Zhongyu Bai,1 Menglai Gan,2 Mingwei Chen,2 Ying Zhang,1 Sai Liu,2 Dongjuan Liu1 1Department of Emergency and Oral Medicine, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning, People’s Republic of China; 2Department of Dental Materials, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongjuan Liu, Department of Emergency and Oral Medicine, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, No. 117 Nanjing North Street, Heping District, Shenyang, Liaoning, 110002, People’s Republic of China, Email dongjuanliu@cmu.edu.cn Sai Liu, Department of Dental Materials, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, No. 117 Nanjing North Street, Heping District, Shenyang, Liaoning, 110002, People’s Republic of China, Email liusai@cmu.edu.cnAbstract: Oral squamous cell carcinoma (OSCC) is the most prevalent and deadly malignancy of the head and neck. The standard treatments for OSCC are surgery, radiotherapy, and chemoradiotherapy, which can cause severe cosmetic and functional damage to the oral cavity and impair the patients’ quality of life. Photodynamic therapy (PDT) is a promising alternative that uses light-activated photosensitizers to induce selective phototoxicity and necrosis in the target tissues. PDT has several advantages over conventional treatments, such as minimal invasion, low side effects, high selectivity and preservation of the oral function and appearance. This review explores the principles, mechanisms, and current applications of PDT for OSCC. We address the challenges, such as the depth of light penetration and tissue hypoxia, and underscore the progressive innovations in photosensitizer enhancement, nanotechnological integration, and precision therapy. The exploration of biomarkers for refining patient selection and tailoring individualized treatment regimens is also undertaken. PDT holds promise as a secure and efficacious modality for OSCC management. Nonetheless, additional investigation is imperative to refine treatment protocols and validate sustained therapeutic success. Keywords: oral squamous cell carcinoma, photodynamic therapy, photosensitizers, nanotechnology, biomarkers

Sining Zeng,1,2,&ast; Min Wu,1,&ast; Ling Xu,1 Zining Guo,1 Shufan Chen,1 Keyu Ling,1 Haihan Li,1 Xiaoli Yu,1 Xiaoping Zhu1 1Department of Nursing, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 2School of Nursing, Soochow University, Suzhou, 215031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Zhu, Department of Nursing, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China, Tel +86-021-66300588, Fax +86-021-66307542, Email xiaopingzhu0424@163.comBackground and Objectives: While extensive research has examined the rehabilitation challenges faced by stroke survivors, there is limited literature addressing the difficulties encountered by older adult stroke survivors and their caregivers in accessing rehabilitation and long-term care within the Chinese community. This study aimed to investigate the specific challenges related to access, quality, and coordination of rehabilitation and long-term care experienced by older adult stroke survivors and their caregivers within the Chinese community.Methods: A qualitative phenomenological design was employed to explore the lived experiences of stroke survivors and their caregivers within the Chinese community. A purposive sampling method was used to recruit participants from June to August 2023. Participants engaged in face-to-face semi-structured interviews. The data were analyzed using an inductive thematic analysis approach to identify and understand key themes and sub-themes.Results: The study involved 38 participants, consisting of 21 older adult stroke survivors (13 males, 8 females) and 17 family caregivers (7 males, 10 females), recruited from five Chinese community health service stations. The analysis identified four distinct themes and 11 sub-themes that encapsulated the challenges faced by participants. These themes include (1) Difficulties in accessing medical services (insufficient medical resources, lack of rehabilitation resources, and time-consuming processes), (2) Challenges in daily life (inconvenience in daily mobility, inadequate financial support, and difficulties in applying for home care services), (3) Psychosocial stress (loneliness, powerlessness, and worry about burdening others), (4) Insufficient information (lack of awareness of available community services, and limited public health education activities).Conclusion: Older adult stroke survivors and their caregivers in Chinese communities face significant challenges. To improve their well-being and quality of life, it is crucial to address these challenges through enhanced access to healthcare, better support for daily living, and more effective information dissemination. Meeting these needs requires a coordinated effort from healthcare providers, community stakeholders, and policymakers to develop and implement effective, long-term care solutions.Keywords: stroke, survivors, caregivers, community, qualitative research

Yanling Liao,1,&ast; Siyu Xie,2,&ast; Yifen Zhuo,3,&ast; Sisi Chen,1 Yuxin Luo,1 Ying Wei,4 Yusheng Yao1 1Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 2Department of Anesthesiology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, People’s Republic of China; 3Department of Anesthesiology, Xiamen Haicang Hospital, Xiamen, People’s Republic of China; 4Department of Anesthesiology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Wei, Department of Anesthesiology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, 350025, People’s Republic of China, Email whm444@fjmu.edu.cn Yusheng Yao, Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, 134 Dongjie Street, Fuzhou, 350001, People’s Republic of China, Email fjslyys@126.comPurpose: Emergence delirium and postoperative negative behavioral changes (PNBC) are common complications in pediatric anesthesia. This study evaluated whether intranasal premedication combining dexmedetomidine and esketamine more effectively reduces these complications compared to either drug alone in children undergoing tonsillectomy and/or adenoidectomy with sevoflurane anesthesia.Patients and Methods: This randomized, double-blind trial involved 198 children aged 2− 5 years undergoing tonsillectomy and/or adenoidectomy. Participants received intranasal premedication with either dexmedetomidine (2 μg/kg), esketamine (1 mg/kg), or their combination (dexmedetomidine 1 μg/kg plus esketamine 0.5 mg/kg). The primary outcome was the incidence of emergence delirium, defined as a Pediatric Anesthesia Emergence Delirium (PAED) scale score ≥ 10. Secondary outcomes included the incidence of PNBC, sedation depth, easiness of separation from parents, acceptance of the mask for induction, emergence time, postoperative pain score, parental satisfaction, and adverse events.Results: The combination premedication significantly reduced emergence delirium incidence (9.4%) compared to esketamine alone (38.1%; relative risk [RR] 0.25, 95% confidence interval [CI] 0.11– 0.57, p < 0.001), but not compared to dexmedetomidine alone (17.2%; RR 0.55, 95% CI 0.21– 1.39, p = 0.193). PNBC incidence at day 7 was lower with the combination (28.1%) versus dexmedetomidine (48.4%; RR 0.58, 95% CI 0.36– 0.93, p = 0.018), but not significantly different from esketamine alone (20.6%; RR 1.38, 95% CI 0.74– 2.58, p = 0.326). The combination also provided significantly superior sedation, improved ease of separation from parents, better acceptance of the mask for induction, shorter emergence time, and higher parental satisfaction than both monotherapies.Conclusion: In children undergoing tonsillectomy and/or adenoidectomy with sevoflurane anesthesia, intranasal dexmedetomidine-esketamine premedication more effectively reduces emergence delirium compared to esketamine alone and PNBC compared to dexmedetomidine alone. This combination also improves sedation, shortens emergence times, and enhances parental satisfaction compared to monotherapy without significant adverse effects.Trial Registration: The Chinese Clinical Trial Registry, ChiCTR2300076709. Keywords: adenoidectomy, dexmedetomidine, emergence delirium, esketamine, intranasal administration, pediatric anesthesia, postoperative complications, tonsillectomy

Dan Luo,1– 3,* Yonghui Hou,1– 3,* Jiheng Zhan,1,2,* Yu Hou,1– 3 Zenglu Wang,4 Xing Li,1,2 Lili Sui,5 Shudong Chen,1,2 Dingkun Lin1,2 1Research Laboratory of Spine Degenerative Disease, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Spinal Minimally Invasive Department, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 3Laboratory of Osteology and Traumatology of Traditional Chinese Medicine, Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4ICU Critical Care Medicine Department, Guangdong Second Provincial Traditional Chinese Medicine Hospital, Guangzhou, People’s Republic of China; 5The First College of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dingkun Lin; Shudong Chen, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, 510120, People’s Republic of China, Tel +86-020-81887233, Email lindingkuntcm@126.com; chenshudong_med@163.comPurpose: Spinal cord injury (SCI) is an irreversible neurological disease that can result in severe neurological dysfunction. The Bu Shen Huo Xue Formula (BSHXF) has been clinically shown to assist in the recovery of limb function in patients with SCI. However, the underlying mechanisms of BSHXF’s therapeutic effects remain unclear. This study aimed to evaluate the effects of BSHXF in a mouse model of SCI and to identify potential therapeutic targets.Methods: The composition of BSHXF was analyzed using high-performance liquid chromatography (HPLC). In vivo, SCI was induced in mice following established protocols, followed by administration of BSHXF. Motor function was assessed using the Basso-Beattie-Bresnahan (BBB) and footprint tests. Levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were quantified with specific assay kits. Protein expression analysis was performed using Western blot and immunofluorescence. Additionally, reactive oxygen species (ROS) levels and apoptosis rates were evaluated with dedicated staining kits. In vitro, neurons were exposed to lipopolysaccharide (LPS) to investigate the effects of BSHXF on neuronal oxidative stress. The protective effects of BSHXF against LPS-induced neuronal injury were examined through RT-PCR, Western blot, and immunofluorescence.Results: The eight primary bioactive constituents of BSHXF were identified using HPLC. BSHXF significantly reduced tissue damage and enhanced functional recovery following SCI. Meanwhile, BSHXF treatment led to significant reductions in oxidative stress and apoptosis rates. It also reversed neuronal loss and reduced glial scarring after SCI. LPS exposure induced neuronal apoptosis and axonal degeneration; however, after intervention with BSHXF, neuronal damage was reduced, and the protective effects of BSHXF were mediated by the activation of the Nrf2 pathway.Conclusion: BSHXF decreased tissue damage and enhanced functional recovery after SCI by protecting neurons against oxidative stress and apoptosis. The effects of BSHXF on SCI may be related to the activation of the Nrf2 pathway.Keywords: Bu Shen Huo Xue formula, BSHXF, spinal cord injury, SCI, oxidative stress, neuroprotection, Nrf2 signaling pathway

Yu Yang,1,2 Shuqi Wang,1,3 Boying Jia,1,3 Shuchun Chen1,3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel/Fax +86 311 85988406, Email chenshuc2014@163.comPurpose: To investigate the relationship between the triglyceride-glucose (TyG) index and pulmonary function metrics among the general population undergoing health examinations.Materials and Methods: The enrollment totaled 696 participants. Fasting triglycerides and glucose levels were used to calculate the TyG index. Participants were divided into two categories according to their median TyG: one with high TyG and the other with low TyG. A portable spirometer was used to assess lung function. Fundamental clinical features and lung function indicators were compared between the two groups, and the relationship between the TyG index and lung function parameters was explored.Results: Compared with the low TyG group, the high TyG group exhibited significantly reduced levels of FEV1/FVC, FVC% pred, FEV1% pred, FEV3% pred, FEV3/FVC, FEF75, FEF75% pred, FEF25-75% pred, and MVV% pred, suggesting poor pulmonary function. The TyG index was significantly inversely correlated with multiple pulmonary function metrics, including FVC% pred, FEV1% pred, FEV3% pred, FEV1/FVC, FEV3/FVC, FEF75, FEF75% pred and FEF25-75% pred, which persisted even after accounting for confounding variables.Conclusion: In summary, the present study establishes a correlation between the TyG index and some lung function indicators, offering a new indicator of metabolic abnormalities related to lung functionality.Keywords: triglyceride-glucose index, lung function, insulin resistance, FEV1, FVC

Shutong Ren,1,&ast; Siyu Chen,2,&ast; Jingru Huang,3 Rong Yu,1 Yunli Wu,4 Xian-E Peng1,4 1Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 2State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, School of Public Health, Xiamen University, Xiamen, 361104, People’s Republic of China; 3Department of Clinical Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China; 4Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian-E Peng; Yunli Wu, Email fmuxe@163.com; wuyunli422@163.comObjective: This study aimed to explore the association between serum uric acid (sUA) levels and metabolic-associated fatty liver disease (MAFLD) in Southeast China.Methods: We performed a cross-sectional study of 2605 subjects who underwent physical examination between 2015 and 2017 in Southeast China. To explore the association between sUA levels and the risk of MAFLD, we employed logistic regression, restricted cubic spline (RCS), subgroups and multiplicative interaction analysis.Results: Logistic regression analysis showed a positive association between sUA and MAFLD [aOR total population (95% CI)= 1.90 (1.49 ~ 2.42)], [aOR male (95% CI)= 2.01 (1.54 ~ 2.62)], [aOR female (95% CI)= 1.15 (0.62 ~ 2.11)], respectively. The RCS plot presented a significant nonlinear dose–response relationship between sUA levels and MAFLD risk, and the risk of MAFLD increased significantly when sUA> 5.56 mg/dL (Pnonlinear< 0.001). Subgroups analysis revealed that the positive association between sUA and MAFLD was consistent across strata of gender, age, BMI, drinking status, smoking status and tea drinking status. Significant associations between sUA and MAFLD were not only found in males but also existed in subjects whose age ≤ 60, BMI ≥ 24 kg/m2, drinkers, smokers and tea-drinkers. Adjusted ORs were estimated to be 2.01, 1.95, 2.11, 2.29, 2.64 and 2.20, respectively. Multiplicative interactions were not observed between gender, age, drinking status, smoking status, tea drinking status and sUA (all P interaction> 0.05).Conclusion: According to our study, sUA was positively associated with the risk of MAFLD. Additionally, the risk of MAFLD increased significantly when sUA levels exceeded 5.56 mg/dL. Our study may help clarify whether sUA plays a diagnostic role in MAFLD.Keywords: metabolic-associated fatty liver disease, serum uric acid, risk, cross-sectional study

Shanshan Chen,1,2 Youjia Duan,2 Yongchao Zhang,2 Long Cheng,2 Liang Cai,2 Xiaopu Hou,2 Xiaojun Wang,3 Wei Li1,2 1Cancer Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Integrated Traditional Chinese and Western Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Wei Li, Cancer Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China, Email weili8989@ccmu.edu.cn Xiaojun Wang, Department of Integrated Traditional Chinese and Western Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email w_xiaojun@ccmu.edu.cnPurpose: To determine the effect of aspirin on hepatocellular carcinoma (HCC) recurrence and survival after thermal ablation.Methods: A retrospective analysis was performed to evaluate the efficacy and safety of aspirin in combination with thermal ablation. The clinical data were collected for the enrolled patients. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed.Results: A total of 174 patients with HCC were enrolled. The median PFS was 11.1 (95% confidence interval [CI]: 8.1− 14.0) months for patients who took aspirin and 8.6 (95% CI: 5.5− 11.8) months for patients who did not take aspirin. The median OS of patients in the aspirin group was 76.7 (95% CI: 58.1− 95.3) months and that in the non-aspirin group was 53.5 (95% CI: 42.7− 64.3) months. In patients with non-viral HCC, OS was significantly better for the aspirin group (P = 0.03) after ablation. The PFS of patients who underwent ablation alone in the aspirin group was obviously superior to that of patients in the non-aspirin group (P = 0.002). Stratified Cox regression analysis demonstrated that aspirin use after ablation might be a protective factor in specific HCC patient subgroups. The incidence of major adverse events did not significantly differ between the two groups.Conclusion: Low-dose aspirin use was associated with better OS in patients with non-viral HCC after thermal ablation. In patients who received thermal ablation alone, the administration of low-dose aspirin could improve PFS. Aspirin use might be a protective factor in some patients after ablation.Keywords: thermal ablation, aspirin, hepatocellular carcinoma, survival analysis, retrospective study

Nan Huang,1– 3,&ast; Bing Lu,4,&ast; Zhuan-Zhuan Zhu,5,&ast; Xiang-Yun Zhu,1,3 Sheng Chen,1– 3 Zhi-Yi Shu,1– 3 Gai-Fang Liu,6 You-Fan Peng,7,&ast; Ling Li1– 3,&ast; 1Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China; 2Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China; 3Pancreatic Research Institute, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China; 4Department of Endocrinology, Kunshan Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, 215343, People’s Republic of China; 5Department of Endocrinology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, People’s Republic of China; 6Division of Gastroenterology, Hebei General Hospital, Shijiazhuang, Hebei, 050000, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Li, Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao, Nanjing, Jiangsu, 210009, People’s Republic of China, Email lingli@seu.edu.cn You-Fan Peng, Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan 2nd Road, Baise, Guangxi, 533000, People’s Republic of China, Email youfanpeng@hotmail.comPurpose: Insulin resistance is associated with kidney impairment in patients with type 2 diabetes mellitus (T2DM). The triglyceride glucose-body mass index (TyG-BMI), which combines the TyG index with body mass index (BMI), has received significant attention as a tool for evaluating insulin resistance. Thus, the aim of this study was to explore the association between TyG-BMI and kidney impairment in patients with type 2 diabetes mellitus (T2DM).Patients and Methods: The cross-sectional analysis included 1080 patients with T2DM, and data were collected retrospectively. TyG-BMI was calculated by fasting blood glucose, triglyceride, and body mass index.Results: TyG-BMI was significantly higher in T2DM patients with albuminuria than those without albuminuria (232.16 [206.52– 268.02] vs 229.83 [206.11– 255.64], p =0.023). T2DM patients with chronic kidney disease (CKD) showed a significantly higher value of TyG-BMI compared with those without CKD (232.23 [206.46– 268.28] vs 229.73 [206.11– 255.49], p=0.014). Correlation analysis showed a significantly positive association between TyG-BMI and metabolic parameters including BMI (r = 0.866, p < 0.001), TG (r = 0.630, p < 0.001), TC (r = 0.119, p < 0.001), HDL-C (r = − 0.374, p < 0.001), FBG (r = 0.297, p < 0.001), and HbA1c (r = 0.116, p < 0.001) in patients with T2DM. The binary logistic regression analysis found that TyG-BMI was an independent factor for albuminuria (OR = 1.004, 95% CI: 1.001– 1.008, p = 0.010) and CKD (OR = 1.005, 95% CI: 1.001– 1.008, p = 0.005) in patients with T2DM respectively.Conclusion: The study suggests that TyG-BMI is associated with kidney impairment in patients with T2DM. Given that TyG-BMI is a novel parameter of insulin resistance, the study results indicates that clinicians should pay close attention to screening for kidney impairment in T2DM patients with insulin resistance.Keywords: type 2 diabetes mellitus, TyG-BMI, insulin resistance, kidney impairment

Yuan Zhang,1,2,&ast; Jingjing Zhang,3,&ast; Sirui Chen,1 Mianxin Li,1,4 Jin Yang,1,2 Jingsi Tan,1 Binsheng He,1,&ast; Lemei Zhu1,4,&ast; 1Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha 410219, People’s Republic of China; 2School of Stomatology, Changsha Medical University, Changsha 410219, People’s Republic of China; 3Department of Gynaecology and Obstetrics, Hunan Provincial Maternal and Child Health Hospital, Changsha 410219, People’s Republic of China; 4School of Public Health, Changsha Medical University, Changsha 410219, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Binsheng He; Lemei Zhu, Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Leifeng Road 1501, Wangcheng District, Changsha, 410219, Chnia, Tel +86 731– 88602602, Email hbscsmu@163.com; zhulemei1228@163.comAbstract: Non-coding RNAs (ncRNAs) are transcripts originating from the genome that do not serve as templates for protein synthesis. They function as epigenetic and translational regulators in various pathophysiological mechanisms, including cell proliferation and apoptosis. The ferroptosis signaling pathway, a novel mode of cell death, participates in numerous pathophysiological processes. Its signaling transmission is both complex and precise, featuring interconnected and interdependent pathways. Recent studies suggest that ncRNAs can finely regulate key genes in the ferroptosis pathway, thus modulating cellular functions, reducing oxidative stress, and maintaining maternal-fetal interface homeostasis. Future strategies targeting the ncRNA/ferroptosis axis may provide new perspectives and potential intervention points for treating preeclampsia. This article clarifies how the ncRNA/ferroptosis axis impacts preeclampsia, revealing how ncRNAs interact with ferroptosis, and pinpointing new molecular targets for the treatment of preeclampsia, thereby providing theoretical support for clinical strategies.Keywords: preeclampsia, non-coding RNAs, ferroptosis, network regulation, treatment strategies

Dongzhu Lu,1,&ast; Huapeng Yu,2,&ast; Lichang Chen,3 Jinlan Lin,1 Shijie Chen,1 Yunjian Huang1 1Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 2Department of Respiratory Medicine, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunjian Huang, Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, People’s Republic of China, Tel +86 13805099580, Email yunjian13@126.comPurpose: We compared pulmonary function indices and quantitative CT parameters of airway remodeling, air trapping, and emphysema in asthmatic patients and patients with COPD and asthma–COPD overlap (ACO) and explored their relationships with airflow limitation.Patients and Methods: Patients with asthma (n=48), COPD (n=52), and ACO (n=30) and controls (n=54) who completed pulmonary function tests and HRCT scans were retrospectively enrolled in our study. Quantitative CT analysis software was used to assess emphysema (LAA%), airway wall dimensions (wall area (WA), luminal area (LA), and wall area percentage (WA%)), and air trapping ((relative volume change of − 860 HU to − 950 HU (RVC− 860 to-950) and the expiration-to-inspiration ratio of the mean lung density (MLDE/I))). Differences in pulmonary function and HRCT parameters were compared among the groups. Spearman correlation analysis and regression analysis were utilized to explore structure‒function relationships.Results: The LAA% in COPD and ACO patients was significantly greater than that in asthmatic patients and controls. The WA% and WA in COPD and ACO patients were greater than those in controls, whereas the WA% and LA between asthmatic patients and controls reached statistical significance. The RVC− 860 to − 950 levels decreased in the following order: ACO, COPD, and asthma. RVC− 860 to − 950 independently predicted FEV1% in asthmatic patients; LAA% and MLDE/I in COPD patients; and LAA%, WA% and RVC− 860 to − 950 in ACO patients.Conclusion: Comparable emphysema was observed in patients with COPD and ACO but not in asthmatic patients. All patients exhibited proximal airway remodeling. The bronchi were thickened outward in COPD and ACO patients but are thickened inward in asthmatic patients. Furthermore, air trapping in ACO patients was the most severe among all the groups. Indirect lung densitometry measurements might be more predictive of the degree of airflow limitation than direct airway measurements in obstructive airway diseases.Keywords: asthma, COPD, asthma-COPD overlap, quantitative HRCT, structure-function relationship

Wenguang Lai,1,&ast; Xiaoli Zhao,2,&ast; Zhiyong Gao,1 Haozhang Huang,3,4 Donghui Huang,1 Yang Zhou,3,4 Guoxiao Liang,3,4 Shiqun Chen,3,4 Jin Liu,3 Yong Liu3 1Department of Pharmacy, Heyuan People’s Hospital; Guangdong Provincial People’s Hospital, Heyuan Hospital, Heyuan, 517001, People’s Republic of China; 2Department of Cardiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 3Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Liu; Jin Liu, Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China, Tel +86 02083827812-10528, Fax +86 02083851483, Email liuyong@gdph.org.cn; ljaw397017568@163.comPurpose: Heart failure with preserved ejection fraction (HFpEF) is inherently a complex inflammatory syndrome, and heightened inflammation is strongly associated with an increased risk of death. However, the association of systemic inflammation levels with total and cardiovascular death among patients with HFpEF remains unknown. We aimed to investigate the prognostic impact of systemic inflammation on all-cause and cardiovascular death among patients with HFpEF.Patients and Methods: Patients with HFpEF were included in this study. Systemic inflammation response index (SIRI) is defined as the multiplication of neutrophil and monocyte divided by lymphocyte count, and patients were divided into four groups based on SIRI quartiles. Cox regression models and competing risk models were used to examine the relationships between SIRI and total and cardiovascular‑specific mortality, respectively.Results: 9,986 patients with HFpEF were included in five tertiary hospitals. During a median follow-up period of 4.4 years, a total of 2004 patients died, of which 965 were cardiovascular deaths. After fully adjusting for confounders, elevated SIRI level was significantly related to the increased risk of all-cause death (Q2, Q3, Q4: adjusted hazard ratio (aHR) [95 confidence interval (CI)%] =1.17[1.01– 1.35], 1.31[1.13– 1.52], 1.51[1.30– 1.76], respectively; P for trend < 0.001). The elevated quartile of SIRI showed higher risks of cardiovascular death, but there was no statistically significant increased risk of cardiovascular death across the lower SIRI quartile (model 3: Q2, Q3, Q4: aHR [95CI%] =1.22[0.99– 1.51], 1.50[1.20– 1.86], 1.73[1.37– 2.18], respectively; P for trend < 0.001).Conclusion: Elevated systemic inflammation level on admission was correlated with an increased risk of all-cause and cardiovascular death among patients with HFpEF. The SIRI may serve as a promising marker of risk stratification for patients with HFpEF.Keywords: heart failure with preserved ejection fraction, systemic inflammatory response index, all-cause death, cardiovascular death

Chengran Wang,1,&ast; Yihong Zhang,1,&ast; Weihui Kong,2 Xin’ao Rong,1 Ziming Zhong,1 Lei Jiang,3 Shuhan Chen,1 Chuang Li,1 Fuqiang Zhang,1 Jinlan Jiang1 1Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Department of Stomatology, the First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 3Department of Geriatric Medicine, Changchun Central Hospital, Changchun, Jilin Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fuqiang Zhang; Jinlan Jiang, Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China, Email zfqzhang@jlu.edu.cn; jiangjinlan@jlu.edu.cnAbstract: Osteosarcoma is the predominant primary malignant bone tumor that poses a significant global health challenge. MicroRNAs (miRNAs) that regulate gene expression are associated with osteosarcoma pathogenesis. Thus, miRNAs are potential therapeutic targets for osteosarcoma. Nanoparticles, widely used for targeted drug delivery, facilitate miRNA-based osteosarcoma treatment. Numerous studies have focused on miRNA delivery using nanoparticles to inhibit the progress of osteosarcoma. Polymer-based, lipid-based, inorganic-based nanoparticles and extracellular vesicles were used to deliver miRNAs for the treatment of osteosarcoma. They can be modified to enhance drug loading and delivery capabilities. Also, miRNA delivery was combined with traditional therapies, for example chemotherapy, to treat osteosarcoma. Consequently, miRNA delivery offers promising therapeutic avenues for osteosarcoma, providing renewed hope for patients. This review emphasizes the studies utilizing nanoparticles for miRNA delivery in osteosarcoma treatment, then introduced and summarized the nanoparticles in detail. And it also discusses the prospects for clinical applications. Keywords: osteosarcoma, MicroRNAs, nanoparticle delivery, molecular targeted therapy

Siyuan Chen,1,2 Jia Liu,1,2 Zhili Feng,1,2 Liubo Zhou,1,2 Yuexiang Cai,1,2 Qiancheng Jing1,2 1Department of Otolaryngology Head and Neck Surgery, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of China; 2Institute of Otolaryngology Head and Neck Surgery, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Qiancheng Jing, Department of Otolaryngology Head and Neck Surgery, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of China, Email 2022050001@usc.edu.cnBackground: Exosomes carry various types of transcripts and serve as promising biomarkers for inflammatory diseases. However, the role of serum exosomal microRNAs (miRNAs) in chronic rhinosinusitis with nasal polyps (CRSwNP) is poorly clarified.Methods: A prospective exploratory cohort of 10 CRSwNP patients was conducted, and the serum exosome samples were subjected to miRNA sequencing. Two independent prospective cohorts, consisting of 40 and 54 patients respectively, were recruited from different medical centers for validation. These cohorts were monitored for over two years, with postoperative recurrence serving as the primary outcome measure. The top 3 differentially exosomal miRNAs were validated in the serum samples, and their predictive values for recurrence were assessed.Results: Eight CRSwNP patients completed the follow-up, comprising 4 non-recurrent cases and 4 recurrent cases. Distinctive profiles of serum exosomal miRNAs were identified between the two groups. In the first validation cohort, reverse transcription-polymerase chain reaction results indicated elevated serum exosomal miR-3174 and miR-6750-5p expressions, along with reduced miR-192-3p levels in the recurrence group compared to the non-recurrence group. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival analysis demonstrated significant correlations between expressions of exosomal miR-3174 and miR-192-3p and the risk of postoperative recurrence. These findings were further validated in the second cohort, confirming the elevation of both miRNAs in the recurrence group and their associations with recurrence risk. Additionally, serum exosomal miR-3174 levels increased in recurrent cases compared to their baseline levels.Conclusion: Circulating exosomal microRNA signatures may influence the risk of postoperative recurrence in CRSwNP patients. Serum exosomal elevated exosomal miR-3174 and decreased miR-192-3p were correlated with CRSwNP recurrence risk.Keywords: exosome, chronic rhinosinusitis with nasal polyps, biomarker, recurrence

Huanhuan Wang,1,&ast; Dan Xiao,2,&ast; Hua Zhou,3,&ast; Shu Chen,4 Guangjun Xiao,4 Juan Hu,4 Hui Quan,2 Miao Luo,5 Shaocheng Zhang2,6 1School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 2Department of Laboratory Medicine, the Second Affiliated Hospital of Chengdu Medical College (Nuclear Industry 416 Hospital), Chengdu, Sichuan, People’s Republic of China; 3Department of Laboratory Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Laboratory Medicine, Suining Central Hospital, Suining, Sichuan, People’s Republic of China; 5Department of Laboratory Medicine, the People’s Hospital of Yubei District of Chongqing, Chongqing, People’s Republic of China; 6School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaocheng Zhang; Miao Luo, Email 102024001@cmc.edu.cn; 536513878@qq.comPurpose: Visceral adiposity is a significant risk factor for severe COVID-19. However, the impact of the Chinese visceral adiposity index (CVAI) on the efficacy of SARS-CoV-2 vaccines remains poorly understood. This study aims to explore the impact of CVAI on the production of neutralizing antibodies (NAb) in inactivated SARS-CoV-2 vaccines and the potential mechanism, thereby optimizing vaccination guidance.Methods: In this cross-sectional study, 206 health workers (completed two SARS-CoV-2 vaccination on February 8th and March 10th, 2021, respectively) were recruited. All baseline anthropometric parameters of the participants were collected, and venous blood samples were obtained 6 weeks later to measure peripheral innate immune cells, inflammatory cytokines, and NAb titers against SARS-CoV-2. CVAI were calculated according to the formula and divided participants into two groups depending on CVAI median.Results: The median NAb titer among healthcare workers was 12.94 AU/mL, with an efficacy of 87.86% for the SARS-CoV-2 vaccine. NAb titers were lower in the CVAI dysfunction group than in the CVAI reference group (median: 11.40 AU/mL vs 15.57 AU/mL), the hsCRP levels (median: 0.50 mg/L vs 0.30 mg/L) and peripheral monocyte count (mean: 0.47 × 109/L vs 0.42 × 109/L) in the CVAI dysfunction group were higher than in the CVAI reference group. Additionally, CVAI showed positive correlations with hsCRP, monocytes, lymphocytes, and B-lymphocytes, and a negative correlation with NAb titers.Conclusion: CVAI may inhibit SARS-CoV-2 neutralizing antibody expression through inducing immune dysfunction and chronic inflammation. Thus, more attention should be paid to the vaccination for high CVAI population to improve the effectiveness of vaccination, which could provide more robust support for COVID-19 epidemic prevention and control.Keywords: Chinese visceral adiposity index, immune function, chronic inflammation, SARS-CoV-2 vaccine, neutralizing antibody

Xiaoming Fu,1 Fuhai Zeng,2 Linling Li,1 Guoquan Liu,1 Qing Zhong,3 Shouwan Chen1 1Department of Burn and Plastic Surgery, The People’s Hospital of Jianyang City, Jianyang, Sichuan, People’s Republic of China; 2Department of Plastic and Maxillofacial Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Science and Technology, The People’s Hospital of Jianyang City, Jianyang, Sichuan, People’s Republic of ChinaCorrespondence: Shouwan Chen, Department of Burn and Plastic Surgery, The People’s Hospital of Jianyang City, No. 180 Hospital Road, Jianyang, Sichuan, 641400, People’s Republic of China, Email drshouwang@163.comBackground: The existing observational research on the relationship between physical activity (PA) and skin cancer (SC) is contentious, which points to the intricate nature of their association and underscores the imperative for more nuanced research to untangle the causal dynamics at play. The aim of this article is to delve deeper into this complex relationship, seeking to clarify whether PA serves as a protective factor against SC, or contributes to its risk.Methods: We utilized data from the genome-wide association study (GWAS) of PA from GWAS Catalog (include self-reported moderate to vigorous PA (MVPA), self-reported vigorous PA (VPA), and accelerometer-based average-accelerated PA). The data of SC is from FinnGen. All of the participants are of European ancestry. We used two-sample Mendelian Randomization (TSMR) to analyze the causal relationship between PA and SC.The research was conducted using inverse variance weighted (IVW) method as the primary approach, and MR Egger regression as supplementary analytical method. To ensure the robustness of the results, Cochran’s Q-test and MR pleiotropy residual sum and outlier (MR-PRESSO) global tests were used to measure sensitivity.Results: Our analysis indicated that average-accelerated PA was associated with an increased risk of SC (ORIVW = 0.94, 95% CI 0.93– 0.96, P

Xuanwen Luo, Suqin Chen,&ast; Weiliang Luo,&ast; Qingyun Li, Yening Zhu, Jiming Li Department of Neurology, Huizhou Central People’s Hospital, Huizhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiliang Luo; Suqin Chen, Department of Neurology, Huizhou Central People’s Hospital, No. 41, Eling North Road, Huizhou, Guangdong Province, 516001, People’s Republic of China, Tel +8613631986803, Fax +867522288160, Email lwl306@126.com; csq621@139.comPurpose: To investigate the benefit (90-day mRS score) and rate of major complications (early symptomatic intracranial hemorrhage-SICH) after reperfusion therapy (RT) (including intravenous thrombolysis -IVT and mechanical thrombectomy -MT) in patients over 80 years with acute ischemic stroke (AIS).Patients and Methods: AIS patients aged over 80 admitted to Huizhou Central People’s Hospital from September 2018 to 2023 were included in this study. Data on SICH, NIHSS, and mRS were analyzed. A good prognosis was defined as a mRS ≤ 2 or recovery to pre-stroke status at 90 days.Results: Of 209 patients, 80 received non-RT, 100 received IVT and 29 underwent MT. The non-RT group had the lowest baseline NIHSS while the MT group had the highest (non-RT 6.0 vs IVT 12.0 vs MT 18.0, P < 0.001). Higher NIHSS was associated with increased SICH risk (OR 1.083, P=0.032), while RT was not (OR 5.194, P=0.129). The overall SICH rate in the RT group was higher but not significantly different after stratification by stroke severity. Poor prognosis was associated with higher admission NIHSS, stroke due to large artery atherosclerosis (LAA) combined with cardioembolism (CE), and stroke-associated pneumonia (SAP) (OR 0.902, P< 0.001; OR 0.297, P=0.029; OR 0.103, P< 0.001, respectively). The RT group showed a greater reduction in NIHSS (delta NIHSS) than the non-RT group (non-RT 2.0 vs IVT 4.0 vs MT 6.0, P< 0.005). For severe AIS, the IVT group had a better prognosis at 90 days (non-RT 0% vs IVT 38.2%, P=0.039). No 90-day mortality difference was found between groups after stratification.Conclusion: Stroke severity, rather than RT, is an independent risk factor for SICH in AIS patients over 80. RT in severe stroke patients improves NIHSS at 90 days, suggesting RT is safe and effective in this demographic. Further studies with larger samples are required to confirm these findings.Keywords: acute ischemic stroke, elderly, intravenous thrombolysis, mechanical thrombectomy, symptomatic intracranial hemorrhage, therapeutic efficacy

Shuqi Wang,1,2 Boying Jia,1,2 Sifan Niu,2,3 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Department of Internal Medicine, North China University of Science and Technology, Tangshan, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comPurpose: To explore the correlation between hemoglobin, albumin, lymphocyte count, platelet count (HALP) score and type 2 diabetic retinopathy (DR).Methods: The study was conducted on 674 patients with type 2 diabetes (T2DM). According to the results of the fundus examination, they were divided into non-diabetic retinopathy group (NDR, n=388) and diabetic retinopathy group (DR, n=286). Collected patients baseline data, calculated HALP score, analyzed the correlation between HALP score and DR.Results: In all patients, male patients and female patients, the HALP score of the DR group was lower than that of the NDR group (P< 0.001), and the HALP score was negatively correlated with the incidence of DR (P< 0.05). HALP score was independent risk factors for DR, regardless of gender. In male patients, HALP score and DR had a linear relationship, but in female patients, HALP score and DR showed a nonlinear relationship, and HALP score was more sensitive to the onset of DR in male patients. The combined diagnostic model of HALP score, course of disease, SBP and BUN was used to diagnose DR, and it was found that the diagnostic value was the highest among male patients, with AUC of 0.761, sensitivity of 58.3% and specificity of 80.3%.Conclusion: HALP score was an independent risk factor for DR, attention should be paid to monitoring HALP score, especially in male T2DM patients. The accuracy of HALP score, disease course, SBP and BUN combined model diagnosis of DR was high, which can become a biological indicator for early screening of DR.Keywords: HALP score, type 2 diabetes, diabetic retinopathy

Huiqian Guo,1,2,&ast; Jing Luo,1,3,&ast; Suming Chen,1 Ting Yu,4 Xiaofei Mu,4 Fangzhou Chen,4 Xiuhui Lu,4 Jiaqi He,4 Yali Zheng,4 Chunmei Bao,2 Peng Wang,4 Zhe Yin,4 Boan Li1– 3 1Department of Clinical Laboratory, the Fifth Medical Center of PLA General Hospital, Beijing, 100039, People’s Republic of China; 2School of Medical Laboratory, Weifang Medical University, Weifang, 261053, People’s Republic of China; 3Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 4State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Boan Li, Department of Clinical Laboratory, the Fifth Medical Center of PLA General Hospital, Beijing, 100039, People’s Republic of China, Email lba@263.net Zhe Yin, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China, Email jerry9yin@163.comPurpose: To investigate the genetic diversity of IncG plasmids, we have proposed a typing scheme based on replicon repA and performed comparative genomic analysis of five IncG plasmids from China.Methods: p30860-KPC, p116965-KPC, pA1705-KPC, pA1706-KPC and pNY5520-KPC total in five IncG plasmids from clinical isolates of Pseudomonas and Enterobacteriaceae, respectively, were fully sequenced and were compared with the previously collected reference plasmid p10265-KPC.Results: Based on phylogeny, IncG-type plasmids are divided into IncG-I to IncG-VIII, the five plasmids belong to IncG-VIII. A detailed sequence comparison was then presented that the IncG plasmid involved accessory region I (Tn 5563a/b/c/d/e), accessory region II (ISpa19), and accessory region III (blaKPC-2-region). Expect for the pNY5520-KPC, the rest of the plasmids had the same backbone structure as the reference one. Within the plasmids, insertion sequences Tn 5563d and Tn 5563e were identified, a novel unknown insertion region was found in Tn 5563b/c/d/e. In addition, Tn 6376b and Tn 6376c were newly designated in the study.Conclusion: The data presented here including a typing scheme and detailed genetic comparison which provide an insight into the diversification and evolution history of IncG plasmids.Keywords: IncG plasmids, blaKPC-2, phylogenetic tree, multidrug resistance, mobile elements

Qi-Feng Chen,1,&ast; Xiong-Ying Jiang,1,2,&ast; Yue Hu,1,&ast; Song Chen,1 Jun-Zhe Yi,1 Sui-Xing Zhong,1 Jiong-Liang Wang,1 Ning Lyu,1 Ming Zhao1 1Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Interventional Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510210, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Zhao, Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +862087343272, Email zhaoming@mail.sysu.edu.cnPurpose: The combination of sorafenib and hepatic arterial infusion chemotherapy (SoHAIC) has shown to enhance overall survival rates in patients with advanced hepatocellular carcinoma and major portal vein tumor thrombosis (HCC-Vp3-4) compared to sorafenib alone. Our objective was to evaluate the cost-effectiveness of SoHAIC versus sorafenib for the treatment of HCC-Vp3-4, taking into account the viewpoint of Chinese healthcare payers.Methods: This pharmacoeconomic study employed a Markov model to assess the cost-effectiveness of treating HCC-Vp3-4 with SoHAIC in comparison to sorafenib. The patient characteristics were drawn from individuals from the trial conducted between June 2017 and November 2019, with cost and health value data sourced from published literature. The primary outcome measure in this research was the incremental cost-effectiveness ratio (ICER), which indicates the additional cost per quality-adjusted life year (QALY). The willingness-to-pay (WTP) threshold per QALY was set at &dollar;30,492.00. Furthermore, 1-way sensitivity and probabilistic sensitivity analyses were carried out to validate the consistency of the results.Results: In the baseline scenario, sorafenib resulted in 0.42 QALY at a cost of &dollar;10,507.89, while SoHAIC generated 1.66 QALY at a cost of &dollar;32,971.56. When comparing SoHAIC to sorafenib, the ICER was &dollar;18,237.20 per QALY, which was below the WTP threshold per QALY. Furthermore, the 1-way sensitivity analysis demonstrated that the ICER remained within the WTP threshold despite fluctuations in variables. In the probabilistic sensitivity analysis, SoHAIC had a 98.8% probability of being cost-effective at the WTP threshold, considering a wide range of parameters.Conclusion: In this cost-effectiveness evaluation, SoHAIC demonstrated cost-effectiveness over sorafenib for HCC with major portal vein tumor thrombosis, as observed from the perspective of a Chinese payer.Keywords: HCC, portal vein tumor thrombosis, sorafenib, HAIC, Cost-effectiveness