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Jingkai Di,1,2,* Liying Song,2,3,* Yaru Liu,2,4,* Zhibo Zhang,1,2 Yawen Wu,2 Tingting Chen,2,5 Chuan Xiang1 1The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Medical University, Taiyuan, People’s Republic of China; 3The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4The Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 5The Fifth Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuan Xiang, The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Tel +86 15903410351, Email chuanxiang@sxmu.edu.cnPurpose: Despite the association between peripheral blood inflammatory biomarkers and a range of inflammatory diseases, the role of these biomarkers in osteoarthritis (OA) progression remains unclear. Additionally, whether alterations in these inflammatory markers impact the prognosis of OA patients remains an understudied area. The aim of our study was to investigate the specific associations between peripheral blood inflammatory markers and OA progression and OA-related mortality.Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database from 1999 through 2018. The primary outcomes were all-cause mortality, cardiac mortality, and renal disease mortality, with information on the corresponding mortality rates for each participant obtained through association with the National Death Index (NDI). Multivariate logistic regression models were used to examine the relationship between peripheral blood lymphocyte counts and OA, and restricted cubic spline (RCS) analysis was utilized to assess whether there was a nonlinear relationship with OA and mortality of OA patients. Interaction and stratified analyses were employed to explore the association between peripheral blood leukocyte counts and OA.Results: This study included 1077 OA patients and 21,612 non-OA participants. In model 3 fully adjusted for covariates, eosinophil-to-lymphocyte ratio (ELR) and eosinophil (EOS) were positive risk factors promoting the development of OA (OR = 3.26, 95% CI: 1.49– 7.14; OR = 1.79, 95% CI: 1.12– 2.88). In stratified models for age, sex, BMI, smoking status, and alcohol consumption, the associations of ELR and EOS with OA were significantly different. RCS curves showed a J-shaped relationship between ELR and EOS and all-cause mortality in patients with OA. ELR was also found to significantly up-regulate cardiac mortality and renal mortality in patients with OA (OR = 3.92, 95% CI: 1.68– 9.14; OR = 22.55, 95% CI: 6.55– 77.70), while EOS was only significantly positively correlation (OR = 3.68, 95% CI: 1.94– 7.01).Conclusion: A significant relationship was found between ELR, EOS and OA. In addition, ELR and EOS were identified as potential predictors of mortality from different causes in patients with OA.Keywords: eosinophil to lymphocyte ratio, osteoarthritis, eosinophil, all-cause mortality

Sihong Li, Xuerong Luo, Lintong Song, Xueping Gao, Yanmei Shen Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaCorrespondence: Yanmei Shen; Xueping Gao, Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of China, Email ymshen@csu.edu.cn; xuepinggao@csu.edu.cnBackground: Childhood maltreatment contributes to an increased risk of eating disorders in adolescents. However, less is known regarding the underlying mechanism between childhood maltreatment and eating disorders’ symptoms. This study tested the mediation effect of social anxiety in the association between childhood maltreatment and eating disorders’ symptoms and whether this mediation was moderated by physical activity.Methods: A longitudinal study was conducted among 848 students in grades 7– 8 from a middle school in Changsha, China. The students completed measurements on childhood maltreatment (Childhood Trauma Questionnaire) at the baseline and measurements on social anxiety (The Social Anxiety Scale-Adolescents), physical activity, and eating disorders’ symptoms (The Eating Attitudes Test) after six months. Mediation and moderation analyses were carried out in SPSS macro-PROCESS.Results: Emotional abuse was significantly related to eating disorders’symptoms, and the association was mediated by social anxiety (indirect effect: β = 0.03, 95% CI: 0.01 to 0.05, p< 0.05). Furthermore, physical activities moderated the path of emotional abuse to social anxiety (β = 0.32, 95% CI: 0.25 to 0.39, p< 0.01) and social anxiety to eating disorders’symptoms (β = 0.18, 95% CI: 0.10 to 0.26, p< 0.01).Conclusion: This research emphasizes the importance of social anxiety in the relationship between childhood maltreatment and eating disorders’ symptoms. Additionally, these associations are weaker for adolescents with more physical activities, addressing the importance of physical activity in the prevention and management of eating disorders’ symptoms.Keywords: childhood maltreatment, social anxiety, eating disorders, adolescent, physical activity, moderated mediation model

Maoye Shen,1 Wenxue Jiang,1 Ping Qian,1 Gaorui Cai,1 Xiaona Wu,1 Jinghua Wang,2 Xianjia Ning,2 Lixia Song1 1Department of Orthopedics, Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 2Center of Clinical Epidemiology, Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Lixia Song, Department of Orthopedics, Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, 29 Bulan Road, Longgang District, Shenzhen, Guangdong Province, 518112, People’s Republic of China, Tel + 86-755-61222333, Fax + 86-755-61238928, Email songlixia525529@163.com Xianjia Ning, Center of Clinical Epidemiology, Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, 29 Bulan Road, Longgang District, Shenzhen, Guangdong Province, 518112, People’s Republic of China, Tel +86-755-61222333, Fax +86-755-61238928, Email xjn0906@163.comBackground: Bilateral hip arthroplasty is a common surgical intervention for patients with bilateral hip disease. The decision between simultaneous versus staged procedures remains debated, primarily due to concerns over cost, postoperative recovery, and complication rates. This study aimed to evaluate the economic burden and clinical outcomes of simultaneous versus staged bilateral hip arthroplasty.Methods: In this single-center, prospective study, patients who underwent bilateral hip replacement at XXX between 2021 and 2022 were included. Participants were divided into groups based on the surgical approach: simultaneous bilateral hip arthroplasty or staged bilateral hip arthroplasty. Data on costs, operation times, hospital stay lengths, and postoperative outcomes were collected and analyzed.Results: A total of 57 patients were studied, with 45 undergoing simultaneous and 12 staged surgeries. The total cost for staged procedures was significantly higher, with a mean difference of 63,967.54 yuan compared to simultaneous procedures. No significant difference was found in prosthesis costs between the groups. Operation times and hospital stays did not significantly differ, with averages closely aligned between the simultaneous (operation time: 3.2 hours, hospital stay: 5 days) and staged groups (operation time: 3.4 hours, hospital stay: 5.2 days). The obesity rate was higher in the simultaneous group (P < 0.05).Conclusion: Simultaneous bilateral hip arthroplasty appears to be an economically favorable option, with comparable perioperative and immediate postoperative outcomes to staged procedures. These insights have significant implications for clinical practice and policy-making, suggesting that simultaneous procedures can be safely implemented for appropriate patients, potentially optimizing healthcare resources.Keywords: Bilateral Hip Arthroplasty, Simultaneous, Staged, Economic Burden, Clinical Outcomes

Lin Song,&ast; Xiaosu Yuan,&ast; Zhonghao Zhao, Peiyan Wang, Weiwei Wu, Jianxun Wang School of Basic Medicine, Qingdao University, Qingdao, 266071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianxun Wang, School of Basic Medicine, Qingdao University, Qingdao, People’s Republic of China, Tel +86 532 82991791, Email wangjx@qdu.edu.cnBackground: Myocardial infarction (MI) is characterized by irreversible cardiomyocyte death resulting from an inadequate supply of oxygenated blood to the myocardium. Recent studies have indicated that ferroptosis, a form of regulated cell death, exacerbates myocardial injury during MI. Concurrently, the upregulation of CD47 on the surface of damaged myocardium following MI impairs the clearance of dead cells by macrophages, thereby hindering efferocytosis. In this context, simultaneously inhibiting ferroptosis and enhancing efferocytosis may represent a promising strategy to mitigate myocardial damage post-MI.Methods: In this study, we engineered platelet membrane-coated hollow mesoporous silicon nanoparticles (HMSN) to serve as a drug delivery system, encapsulating ferroptosis inhibitor, Ferrostatin-1, along with an anti-CD47 antibody. We aimed to assess the potential of these nanoparticles (designated as Fer-aCD47@PHMSN) to specifically target the site of MI and evaluate their efficacy in reducing cardiomyocyte death and inflammation.Results: The platelet membrane coating on the nanoparticles significantly enhanced their ability to successfully target the site of myocardial infarction (MI). Our findings demonstrate that treatment with Fer-aCD47@PHMSN resulted in a 38.5% reduction in cardiomyocyte ferroptosis under hypoxia, indicated by decreased lipid peroxidation and increased in vitro. Additionally, Fer-aCD47@PHMSN improved cardiomyocyte efferocytosis by approximately 15% in vitro. In MI mice treated with Fer-aCD47@PHMSN, we observed a substantial reduction in cardiomyocyte death (nearly 30%), decreased inflammation, and significant improvement in cardiac function.Conclusion: Our results demonstrated that the cooperation between the two agents induced anti-ferroptosis effects and enhanced dead cardiomyocyte clearance by macrophage as well as anti-inflammation effects. Thus, our nanoparticle Fer-aCD47@PHMSN provides a new therapeutic strategy for targeted therapy of MI. Keywords: myocardial infarction, ferroptosis, efferocytosis, HMSN

Lina Du,1 Dezhi Yang,2 Lan Wu,1 Li Mei,1 Sarula Wu,1 Yasula Ba,1 Yongchang Bao,1 Rigugaqiqige Su,1 Lin Song1 1College of Mongolian Medical, Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China; 2Innovative Mongolian Medical Engineering Research Center, Inner Mongolia International Mongolian Hospital, Hohhot, Inner Mongolia, People’s Republic of ChinaCorrespondence: Lin Song, Inner Mongolia Medical University, Tel +15849163188, Email songlinwpsword@163.comObjective: To explored the potential molecular mechanism of Sugemule-4 decoction (MMS-4D) in treating insomnia.Methods: DL-4-chlorophenylalanine (PCPA) + chronic unpredictable mild stress stimulation (CUMS) was used to induce an insomnia model in rats. After the model was successfully established, MMS-4D was intervened at low, medium, and high doses for 7 days. The open-field test (OFT) was used to preliminarily evaluate the efficacy. The potential mechanism of MMS-4D in treating insomnia was investigated using gut microbiota, serum metabolomics, and network pharmacology (NP). Experimental validation of the main components of the key pathways was carried out using ELISA and Western blot.Results: The weights of the insomnia-model rats were significantly raised (p ≤ 0.05), the total exercise distance in the OFT increased (p ≤ 0.05), the rest time shortened, and the number of standing times increased (p ≤ 0.05), after treatment with MMS-4D. Moreover, there was a substantial recovery in the 5-HT, DA, GABA, and Glu levels in the hypothalamus tissue and the 5-HT and GABA levels in the colon tissue of rats. The expression of DAT and DRD1 proteins in the hippocampus of insomnia rats reduced after drug treatment. MMS-4D may treat insomnia by regulating different crucial pathways including 5-HT -, DA -, GABA -, and Glu-mediated neuroactive light receiver interaction, cAMP signaling pathway, serotonergic, glutamatergic, dopaminergic, and GABAergic synapses.Conclusion: This study revealed that MMS-4D can improve the general state and behavioral changes of insomnia model rats. Its mechanism may be related to the reversal of abnormal pathways mediated by 5-HT, DA, GABA, and Glu, such as Serotonergic synapse, Dopaminergic synapse, Glutamatergic synapse, and GABAergic synapse. Keywords: Mongolian medicine sugemule-4 decoction, insomnia, metabolomics, gut microbiota, network pharmacology, molecular mechanism

Lin Song, Kangwei Jia, Fuqing Yang, Jianxun Wang School of Basic Medicine, Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Jianxun Wang, School of Basic Medicine, Qingdao University, Qingdao, People’s Republic of China, Tel +86 (532) 82991791, Email wangjx@qdu.edu.cnAbstract: Myocardial infarction, usually caused by the rupture of atherosclerotic plaque, leads to irreversible ischemic cardiomyocyte death within hours followed by impaired cardiac performance or even heart failure. Current interventional reperfusion strategies for myocardial infarction still face high mortality with the development of heart failure. Nanomaterial-based therapy has made great progress in reducing infarct size and promoting cardiac repair after MI, although most studies are preclinical trials. This review focuses primarily on recent progress (2016–now) in the development of various nanomedicines in the treatment of myocardial infarction. We summarize these applications with the strategy of mechanism including anti-cardiomyocyte death strategy, activation of neovascularization, antioxidants strategy, immunomodulation, anti-cardiac remodeling, and cardiac repair.Keywords: myocardial infarction, nanomaterials, nanomedicine delivery system

Wei Zhang,1,&ast; Yufei Wang,1,&ast; Kaiying Wang,2,&ast; Jinhui Li,2 Jia Liu,1 Shulei Li,1 Lijie Song,1 Chunchen Liao,2 Xiaoli Yang,1 Peng Li,2 Xiong Liu2 1Department of Clinical Laboratory, The Third Medical Center, PLA General Hospital, Beijing, 100039, China; 2Chinese PLA Center for Disease Control and Prevention, Beijing, 100071, China&ast;These authors contribute equally to this workCorrespondence: Peng Li; Xiong Liu, Chinese PLA Center for Disease Control and Prevention, Beijing, 100071, China, Email jiekenlee@126.com; liuxiong714@163.comBackground: Urinary tract infection (UTI) associated with Klebsiella pneumoniae poses a serious threat for inpatients. This study aimed to describe the genomic characteristics of K. pneumoniae causing UTI in a tertiary-care hospital in Beijing, China.Methods: A total of 20 K. pneumoniae strains collected from 2020 to 2021 were performed whole-genome sequencing. The Antibiotic susceptibility of 19 common antimicrobial agents was tested against all strains. The multi-locus sequence types (MLSTs) and serotypes were determined from the WGS data. De novo assemblies were used to identify resistance and virulence genes. The presence and characteristics of the plasmids were detected using hybrid assembly of long and short-read data.Results: These K. pneumoniae strains were clustered into nine sequence types (STs) and twelve K-serotypes. All the carbapenem-resistant K. pneumoniae (CRKP) strains acquired carbapenemase blaKPC-2 (n=7). Two CRKP strains exhibited increased resistance to Polymyxin B with MIC ≥ 4 mg/L due to insertion of an IS5-like sequence in the mgrB gene, and they were also involved in a transmission event in Intensive Care Unit. Long-read assemblies identified many plasmids co-carrying multiple replicons. Acquisition of a new IncM2_1 type blaCTX-M-3 positive plasmid was observed after transfer from ICU to neurovascular surgery by comparing the two strains collected from the same patient.Conclusion: K. pneumoniae is a significant pathogen responsible for urinary tract infections. The ST11-KL47 strain, prevalent at our hospital, exhibits a combination of high drug resistance and hypervirulence. It is imperative to enhance ongoing genomic surveillance of urinary tract infection-causing pathogens.Keywords: Antimicrobial resistance, Klebsiella pneumoniae, urinary tract infections

Xiaoxiao Zhao,1 Hanjun Zhao,1 Runzhen Chen,1 Jiannan Li,1 Jinying Zhou,1 Nan Li,1 Shaodi Yan,2 Chen Liu,1 Peng Zhou,1 Yi Chen,1 Li Song,1 Hongbing Yan2 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, ShenZhen, People’s Republic of ChinaCorrespondence: Hanjun Zhao, Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167, Beijing, 100037, People’s Republic of China, Tel +86-15210020808, Email 15210020808@163.com Hongbing Yan, Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Shenzhen, 518000, People’s Republic of China, Tel +86-1301339287, Email hbyanfuwai2018@163.comBackground and Aim: An elevated triglyceride-glucose (TyG) level is associated with increased risk of mortality in patients with CAD. Trimethylamine N-oxide (TMAO) has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is correlated with adverse outcomes. However, the incremental prognostic value of TMAO and TyG in the cohort of optical coherence tomography (OCT)-defined high-risk ST-segment elevation myocardial infarction (STEMI) patients is unknown.Methods: We studied 274 consecutive aged ≥ 18 years patients with evidence of STEMI and detected on pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019.Outcomes: There were 22 (22.68%), 27 (27.84%), 26 (26.80%), and 22 (22.68%) patients in groups A-D, respectively. The baseline characteristics according to the level of TMAO and TyG showed that patients with higher level in both indicators were more likely to have higher triglycerides (p < 0.001), fasting glucose (p < 0.001) and higher incidence of diabetes (p = 0.008). The group with TMAO > median and TyG ≤ median was associated with higher rates of MACEs significantly (p = 0.009) in fully adjusted analyses. During a median follow-up of 2.027 years, 20 (20.6%) patients experienced MACEs. To evaluate the diagnostic value of the TyG index combined with TMAO, the area under the receiver operating characteristic curve for predicting MACEs after full adjustment was 0.815 (95% confidence interval, 0.723– 0.887; sensitivity, 85.00%; specificity, 72.73%; cut-off level, 0.577). Among the group of patients with TMAO > median and TyG ≤ median, there was a significantly higher incidence of MACEs (p= 0.033). A similar tendency was found in the cohort with hyperlipidemia (p= 0.016) and diabetes mellitus (p= 0.036).Conclusion: This study demonstrated the usefulness of combined measures of the TyG index and TMAO in enhancing risk stratification in STEMI patients with OCT-defined high-risk plaque characteristics.Trial Registration: This study was registered at ClinicalTrials.gov as NCT03593928.Keywords: optical coherence tomography, triglyceride glucose index, trimethylamine N-oxide, high risk plaque feature, major adverse cardiovascular events, prospective study

Jing Wang,1,&ast; Yanxiang Sang,2,&ast; Weijian Chen,3 Liang Cheng,2 Wenxiang Du,2 Hongjie Zhang,2 Benyan Zheng,2 Lei Song,2 Yuan Hu,2 Xiaopeng Ma1 1Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China; 2State Key Laboratory of Fire Science, University of Science and Technology of China, Hefei, Anhui, 230006, People’s Republic of China; 3Technology Center, China Tobacco Anhui Industrial Co, Ltd, Hefei, Anhui, 230088, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuan Hu; Xiaopeng Ma, Email yuanhu@ustc.edu.cn; XiaopengMa@fsyy.ustc.edu.cnIntroduction: As an effective alternative choice to traditional mono-therapy, multifunctional nanoplatforms hold great promise for cancer therapy. Based on the strategies of Fenton-like reactions and reactive oxygen species (ROS)-mediated therapy, black phosphorus (BP) nanoplatform BP@Cu2O@L-Arg (BCL) co-assembly of cuprous oxide (Cu2O) and L-Arginine (L-Arg) nanoparticles was developed and evaluated for synergistic cascade breast cancer therapy.Methods: Cu2O particles were generated in situ on the surface of the BP nanosheets, followed by L-Arg incorporation through electrostatic interactions. In vitro ROS/nitric oxide (NO) generation and glutathione (GSH) depletion were evaluated. In vitro and in vivo anti-cancer activity were also assessed. Finally, immune response of BCL under ultrasound was investigated.Results: Cu2O was incorporated into BP to exhaust the overexpressed intracellular GSH in cancer cells via the Fenton reaction, thereby decreasing ROS consumption. Apart from being used as biocompatible carriers, BP nanoparticles served as sonosensitizers to produce excessive ROS under ultrasound irradiation. The enhanced ROS accumulation accelerated the oxidation of L-Arg, which further promoted NO generation for gas therapy. In vitro experiments revealed the outstanding therapeutic killing effects of BCL under ultrasound via mechanisms involving GSH deletion and excessive ROS and NO generation. In vivo studies have illustrated that the nanocomplex modified the immune response by promoting macrophage and CD8+ cell infiltration and inhibiting MDSC infiltration.Discussion: BCL nanoparticles exhibited multifunctional characteristics for GSH depletion-induced ROS/NO generation, making a new multitherapy strategy for cascade breast cancer therapy.Keywords: black phosphorus, combination cancer therapy, sonodynamic therapy, chemodynamic therapy, nitric oxide gas therapy

Jiawei Lu,1 Lebin Song,1 Jiaochen Luan,2 Yifei Feng,1 Yidan Wang,1 Xuechen Cao,1 Yan Lu1 1Department of Dermatology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Urology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yan Lu, Department of Dermatology, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +86 13913967126, Email luyan6289@163.comBackground: Vitiligo and Hashimoto’s thyroiditis (HT) are concomitant autoimmune diseases characterized by the destruction of melanocytes or thyrocytes. We aimed to explore the immunological mechanism of this comorbidity and screen their potential biomarkers.Methods: We downloaded the microarray datasets from the GEO database. Differentially expressed genes (DEGs) and immune-related genes (IRGs) were selected. The immune-related differentially expressed genes (IRDEGs) were obtained by taking the intersection. Candidate biomarkers were elected by Cytoscape software. CIBERSORT was used to depict immune cell infiltration prospects. Correlation analysis was conducted between infiltrating cells and several indicators. The results were validated by real-time quantitative PCR (RT-qPCR).Results: Three datasets and 60 IRDEGs were obtained in total. Pathway enrichment analysis showed that the T cell receptor signaling pathway, IL-17 signaling pathway, receptor-ligand activity, and signaling receptor activator activity were significantly enriched. We screened out four hub genes, including IFNG, STAT1, IL1B, and CXCL10. The ROC curve indicated the highest diagnostic value of CXCL10 in both vitiligo and HT. Immuno-infiltration analysis revealed significant changes in T cell subsets and macrophage subtypes, which were correlated with four hub genes, melanocyte markers, and thyroid-specific antigens. qPCR validated the hub genes in peripheral blood mononuclear cells from patients with comorbidity.Conclusion: IFNG, STAT1, IL1B, and CXCL10, were the key IRDEGs to vitiligo and HT. These genes may participate in the comorbidity by remodeling the immune cell infiltration pattern, and cross-expressed antigens may mediate the common damage of melanocytes and thyroid tissues.Keywords: depigmenting skin disorder, autoimmune thyroiditis, immune cell infiltration, bioinformatics analysis

Lei Song, Ying-Min Lu, Jin-Chun Zhang, Yu-Min Yuan, Gui-Ru Li Department of Cardiology, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 202150, People’s Republic of ChinaCorrespondence: Ying-Min Lu, Department of Cardiology, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, No. 25 of Nanmen Street, Chengqiao Town, Chongming District, Shanghai, 202150, People’s Republic of China, Tel +86-18939929687, Email Lu_yingmin_2023@163.comObjective: To investigate the association of S100A12 protein and C-reactive protein (CRP) with the onset of malignant ventricular arrhythmias (MVA) after acute myocardial infarction (AMI) in the elderly.Methods: A total of 159 elderly AMI patients admitted to Chongming Hospital affiliated to Shanghai University of Medicine & Health Sciences from January 2018 to January 2023 were enrolled in the study. CRP levels were determined using an automatic biochemical analyzer, and S100A12 levels were measured using enzyme-linked immunosorbent assay (ELISA). Patients were categorized based on the Lown classification into groups without MVA and with MVA. Univariate analysis was initially performed to identify independent variables, followed by multivariate logistic regression to determine the risk factors for malignant ventricular arrhythmias post-AMI. The predictive value of S100A12 protein and CRP for malignant ventricular arrhythmias after acute myocardial infarction in the elderly was analyzed using the receiver operating characteristic (ROC) curve.Results: Among the 159 patients with AMI, 27 (17%) had MVA. Multivariate logistic regression analysis indicated that both S100A12 protein and CRP could be independent risk factors for malignant ventricular arrhythmias following acute myocardial infarction in the elderly (p

Shu Fang,1 Wenhao Shi,2,&ast; Lihua Song1,&ast; 1Department of Breast Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihua Song, Department of Breast Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China, Tel +86-13665312188, Email slh9999@vip.163.com Wenhao Shi, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China, Tel +86-15105411910, Email 86156534@qq.com

Runzhen Chen,1,2,&ast; Jiannan Li,1,3,&ast; Zhaoxue Sheng,4 Jinying Zhou,1,3 Ying Wang,1 Xiaoxiao Zhao,1,3 Nan Li,1 Weida Liu,5 Chen Liu,1,3 Peng Zhou,1,3 Yi Chen,1,3 Shaodi Yan,2 Li Song,1– 3 Hongbing Yan,2,3 Hanjun Zhao1,3 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, People’s Republic of China; 3Coronary Heart Disease Center, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Cardiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 5Medical Research Center, Peking Union Medical College Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbing Yan, Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Nanshan District, Shenzhen, 510000, People’s Republic of China, Email hbyanfuwai2018@163.com; hbyanfuwai@aliyun.com Hanjun Zhao, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, 167 North Lishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Email 15210020808@163.comBackground: As a specialized pro-resolving lipid mediator, resolvin D1 (RvD1) inhibits atherosclerosis progression in vivo by reducing regional oxidative stress and chronic inflammation. However, it is unclear how RvD1 is involved in human coronary artery disease. This study aims to investigate the association between plasma levels of RvD1 and culprit-plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI).Methods: A total of 240 STEMI patients undergoing optical coherence tomography (OCT) examination were analyzed. RvD1 levels were measured in patient plasma samples using an enzyme-linked immunosorbent assay. Logistic regression was performed to assess the association between RvD1 levels and various culprit plaque morphologies, and the receiver operating curve was used to search for an optimal cutoff threshold to predict certain pathological features.Results: The median RvD1 level was 129.7 (56.6– 297.8) pg/mL. According to multivariable logistic regression, high RvD1 was associated with plaque rupture (≥ 111.5 pg/mL, odds ratio [OR]: 2.09, 95% confidence interval [CI]: 1.20– 3.66, P = 0.010), healed plaques (≥ 246.4 pg/mL, OR: 2.17, 95% CI: 1.11– 4.24, P = 0.023), and calcification (≥ 293.38 pg/mL, OR: 2.10, 95% CI: 1.21– 3.66, P = 0.008) at culprit lesions.Conclusion: Increased levels of RvD1 were associated with higher instability of coronary atherosclerotic plaques in STEMI patients.Keywords: resolvin D1, specialized pro-resolving lipid mediator, myocardial infarction, optical coherence tomography, atherosclerosis, inflammation

Tengfei Chen,1,&ast; Sihan Li,1,&ast; Dongyin Lian,1 Qin Hu,2 Hongping Hou,1 Delian Niu,1 Han Li,1 Ling Song,1 Yunhang Gao,1 Ying Chen,1 Xiaoru Hu,3 Jianrong Li,1 Zuguang Ye,1 Bo Peng,1 Guangping Zhang1 1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2College of Life Sciences and Bio-Engineering, Beijing University of Technology, Beijing, People’s Republic of China; 3National Institute for Food and Drug Control, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Peng; Guangping Zhang, Tel +8610 64056575, Email bpeng@icmm.ac.cn; gpzhang@icmm.ac.cnPurpose: This study aimed to investigate the main pharmacological action and underlying mechanisms of Jin Gu Lian Capsule (JGL) against rheumatoid arthritis (RA) based on network pharmacology and experimental verification.Methods: Network pharmacology approaches were performed to explore the core active compounds of JGL, key therapeutic targets, and signaling pathways. Molecular docking was used to predict the binding affinity of compounds with targets. In vivo experiments were undertaken to validate the findings from network analysis.Results: A total of 52 targets were identified as candidate JGL targets for RA. Sixteen ingredients were identified as the core active compounds, including, quercetin, myricetin, salidroside, etc. Interleukin-1 beta (IL1B), transcription factor AP-1 (JUN), growth-regulated alpha protein (CXCL1), C-X-C motif chemokine (CXCL)3, CXCL2, signal transducer and activator of transcription 1 (STAT1), prostaglandin G/H synthase 2 (PTGS2), matrix metalloproteinase (MMP)1, inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) and transcription factor p65 (RELA) were obtained as the key therapeutic targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the efficacy of JGL was functionally involved in regulating immune-mediated inflammation, in which IL-17/NF-κB signaling was recommended as one of the main pathways. Molecular docking suggested that the core active compounds bound strongly to their respective targets. Experimentally, JGL treatment mitigated inflammation, showed analgesic activity, and ameliorated collagen-induced arthritis. Enzyme-linked immunosorbent assay showed that JGL effectively reduced the serum levels of cytokines, chemokines, and MMPs. Immunohistochemistry staining showed that JGL markedly reduced the expression of the targets in IL-17/NF-κB pathway including IL-17A, IL-17RA, NF-κB p65, C-X-C motif ligand 2, MMP1 and MMP13.Conclusion: This investigation provided evidence that JGL may alleviate RA symptoms by partially inhibiting the immune-mediated inflammation via IL-17/NF-κB pathway. Keywords: rheumatoid arthritis, Jin Gu Lian capsules, network pharmacology, experimental validation, immune-mediated inflammation

Wan-Ling Liu,1– 4,&ast; Yong-Qu Zhang,1– 5,&ast; Xiang-Jie Luo,6 Yuan-Yuan Zhu,1– 4 Liang Song,7 Zi-He Ming,1– 4 Li-Xin Zhang,1– 4 Meng-Jun Li,1– 4 Rui-Chan Lv,8 Guo-Jun Zhang,1– 4,9,&ast; Min Chen2– 4,&ast; 1Department of Breast-Thyroid-Surgery and Cancer Center, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer, Xiang’an Hospital of Xiamen University, Xiamen, People’s Republic of China; 3Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, Xiamen, People’s Republic of China; 4Xiamen Research Center of Clinical Medicine in Breast & Thyroid Cancers, Xiamen, People’s Republic of China; 5Department of Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 6College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, People’s Republic of China; 7Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences and Technology University, Xiamen, People’s Republic of China; 8Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi’an, Shanxi, People’s Republic of China; 9Cancer Research Center, School of Medicine, Xiamen University, Xiamen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Chen; Guo-Jun Zhang, Email mchen@xah.xmu.edu.cn; gjzhang@xah.xmu.edu.cnBackground: Durable responses to immune-checkpoint blocking therapy (ICT) targeting programmed cell death protein-1/ligand-1 (PD-1/PD-L1) have improved outcomes for patients with triple negative breast cancer (TNBC). Unfortunately, only 19– 23% of patients benefit from ICT. Hence, non-invasive strategies evaluating responses to therapy and selecting patients who will benefit from ICT are critical issues for TNBC immunotherapy.Methods: We developed a novel nanoparticle-Atezolizumab (NPs-Ate) consisting of indocyanine green (ICG), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), human serum albumin (HSA), and Atezolizumab. The efficiency of Gd-DTPA linking was verified using mass spectrometry, and the size of NPs-Ate was characterized using Nano-flow cytometry. The synthesized NPs-Ate were evaluated for fluorescence stability, penetration depth, and target specificity. TNBC cell lines and tumor-bearing mice models were used to identify the feasibility of this dual-modal second near-infrared/magnetic resonance imaging (NIR-II/MRI) system. Additionally, ICT combination with chemotherapy or radiotherapy in TNBC tumor-bearing mice models were used to assess dynamic changes of PD-L1 and predicted therapeutic responses with NPs-Ate.Results: Atezolizumab, a monoclonal antibody, was successfully labeled with ICG and Gd-DTPA to generate NPs-Ate. This demonstrated strong fluorescence signals in our NIR-II imaging system, and relaxivity (γ 1) of 9.77 mM− 1 s− 1. In tumor-bearing mice, the NIR-II imaging signal background ratio (SBR) reached its peak of 11.51 at 36 hours, while the MRI imaging SBR reached its highest as 1.95 after 12 hours of tracer injection. NPs-Ate specifically targets cells and tumors expressing PD-L1, enabling monitoring of PD-L1 status during immunotherapy. Combining therapies led to inhibited tumor growth, prolonged survival, and increased PD-L1 expression, effectively monitored using the non-invasive NPs-Ate imaging system.Conclusion: The NIR-II/MRI NPs-Ate effectively reflected PD-L1 status during immunotherapy. Real-time and non-invasive immunotherapy and response/prognosis monitoring under NIR-II/MRI imaging guidance in TNBC is a promising and innovative technology with potential for extensive clinical applications in the future.Keywords: dual-modal imaging, triple-negative breast cancer, immune-checkpoint blocking therapy, programmed cell death protein ligand-1, monitoring therapeutic response

Yipengchen Yin,1,&ast; Jiaxin Sun,2,&ast; Tiaoyan Jiang,1 Li Zhu,3 Wenchao Gu,4 Sheng Wang,5 Le Song,6 Changchun Wang,2 Qin Zhang1 1Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People’s Republic of China; 2State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, and Laboratory of Advanced Materials, Fudan University, Shanghai, 200438, People’s Republic of China; 3Department of Radiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People’s Republic of China; 4Department of Diagnostic and Interventional Radiology, University of Tsukuba, Ibaraki, 305-8575, Japan; 5Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China; 6Department of Gerontology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Zhang; Le Song, Email zhangqin@shsmu.edu.cn; song.le@zs-hospital.sh.cnIntroduction: Sentinel lymph node (SLN) is the first regional lymph node where tumor cells metastasize, and its identification and treatment are of great significance for the prevention of tumor metastasis. However, the current clinical modalities for identification and treatment of SLN are still far from satisfactory owing to their high cost, invasiveness and low accuracy. We aim to design a novel nanomedicine system for SLN imaging and treatment with high efficacy.Methods: We designed and prepared hollow mesoporous carbon spheres (HMCS) and loaded with the chemotherapeutic drug doxorubicin (DOX), which is then modified with polyvinyl pyrrolidone (PVP) to obtain nanomedicine: HMCS-PVP-DOX.Results: HMCS-PVP with a size of about 150 nm could retain in the lymph nodes for a long time and stain the lymph nodes, which could be easily observed by the naked eye. At the same time, HMCS-PVP exhibited excellent photoacoustic and photothermal imaging capabilities, realizing multimodal imaging to locate lymph nodes precisely. Due to its high specific surface area, HMCS could be largely loaded with the chemotherapeutic drug doxorubicin (DOX). HMCS-PVP-DOX displayed highly efficient synergistic chemotherapy-photothermal therapy for lymphatic metastases in both cellular and animal experiments due to its significant photothermal effect under 1064 nm laser irradiation. HMCS-PVP-DOX also displayed great stability and biosafety.Discussion: Multifunctional nanomedicine HMCS-PVP-DOX is expected to provide a novel paradigm for designing nanomedicine to the diagnosis and treatment of lymphatic metastases because of its good stability and safety.Graphical Abstract: Keywords: tumor lymphatic metastasis theranostics, hollow mesoporous carbon nanospheres, sentinel lymph node, tri-modal imaging, chemo-photothermal therapy

Peng An,1,2,&ast; Lina Song,1,&ast; Ping Song,3,&ast; Junyan Zhang,1,3 Yong Lin,1,3 Guoyan Feng,1 Junjie Liu3 1Department of Radiology, Xiangyang No.1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000, People’s Republic of China; 2Hubei Provincial Clinical Research Center for Accurate Fetus Malformation Diagnosis, Hubei University of Medicine, Xiangyang, Hubei Province, 441000, People’s Republic of China; 3Department of Obstetrics and Gynecology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junjie Liu; Guoyan Feng, Xiangyang NO.1 People’s Hospital, No. 15 Jiefang Road, Fancheng District, Xiangyang City, Hubei Province, People’s Republic of China, Email liujj2023@yeah.net; fengguoyan2022@yeah.netObjective: The present study aimed to explore the role of modified vascular anatomical molding (MVAM) in prenatal diagnosis teaching and prognosis prediction of fetal complex congenital heart disease (CCHD).Methods: Step 1, MVAM method was used to cast the micro-blood vessels and trachea of 52 CCHD specimens. Subsequently, 52 MVAMs were analyzed and compared with the prenatal ultrasound to summarize their characteristics, misdiagnosis and MVAM’s teaching role. Step 2, the surgical and follow-up data of 206 CCHD cases were retrospectively analyzed. Cases that evolved into critical illnesses or died within 1– 3 years after surgery (poor prognosis) were classified into the study group (n = 77) and those with good prognosis into the control group (n = 129), which were split into the training set and the test set in the ratio 7:3 based on the time cut-off. In the training set, the prognosis of CCHD was predicted using the MVAM anatomical soft markers (distortion and narrowing of aorta/pulmonary artery, right ventricular infundibulum, etc.) and the decision curve analysis (DCA) performed. The model was validated using the test set, and a nomogram was finally established.Results: It was observed that all 52 CCHD cases were confirmed using MVAM. A total of 91 cardiac malformations were recorded, among which 41 malformations were misdiagnosed, and 29 malformations were missed by the prenatal echocardiography. The MVAM method has a good teaching/feedback effect on prenatal diagnosis. The combined model exhibited a higher predictive performance in the training- and test-set. Its high clinical net benefit was proved by DCA. Additionally, the nomogram established using the combined model received a favorable response in clinical practice.Conclusion: The research results indicated that MVAM improved the prenatal diagnosis teaching and training performance. The combined model established based on MVAM anatomical soft markers can offer a high clinical significance for prognosis prediction of CCHD.Keywords: modified vascular anatomical molding, MVAM, complex cardiovascular malformation, CCHD, combined model, CM, interrupted aortic arch, IAA, coarctation of the aorta, COA, pulmonary valve stenosis, PVS, right aortic arch, RAA, transposition of the great arteries, TGA, right aortic arch with mirror-image branching, RAMI, double-outlet right ventricle, DORV

Ya Wang,1 Jianhua Li,2 Fang Wang,1 Yunhua Cui,1 Li Song,1 Biao Ruan,1 Yongmei Yu1 1Department of Otolaryngology, the First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Department of Otolaryngology, the Sixth Affiliated Hospital of Kunming Medical University, Yuxi, People’s Republic of ChinaCorrespondence: Yongmei Yu, Email yuyongmei@kmmu.edu.cnBackground: Rape pollen allergy is a common allergic reaction disorder that affects the health and life of patients seriously. The research on ceRNA regulatory network in rape pollen allergy is poor.Methods: High throughput whole-transcriptome sequencing was conducted on rape pollen allergic samples and non-allergic samples. Differentially expressed microRNAs (DEmiRNAs), circRNAs (DEcircRNAs), long non-coding RNA (DElncRNAs), mRNA (DEmRNAs) were identified and a ceRNA regulatory network was constructed by Cytoscape. Functional enrichment analyses were performed on DEmRNAs in the ceRNA network. Then, the least absolute shrinkage and selection operator (LASSO) regression model was used to identify characteristic genes for rape pollen allergy. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic ability of characteristic genes.Results: A total of 25 DEmiRNAs, 258 DEcircRNAs, 304 DElncRNAs, and 383 DEmRNAs in the allergic group compared with the non-allergic group were uncovered, respectively. A ceRNA network containing 21 miRNAs, 57 circRNAs, 28 lncRNAs, and 33 mRNAs was generated with 139 nodes and 160 edges. The signal transduction-related processes, immune-related processes, the ion, inorganic substance, and hormone regulation processes were associated with mRNAs in the ceRNA network. The results of pathway enrichment illustrated that mRNAs in the ceRNA were significantly linked to IL-17 signaling pathway, inflammatory mediator regulation of trp channels, GMP-PKG signaling pathway, signaling by GPCR, and GPCR downstream signaling pathway. Then, five characteristic genes (KCNQ3, CCR5, FOSB, CFAP43, and PRKG1) were defined by the LASSO algorithm. The AUC values of these genes indicated that these genes had a powerful discrimination ability in discriminating allergic samples from non-allergic samples.Conclusion: Taken together, we revealed the ceRNA regulatory network in rape pollen allergy and excavated five characteristic genes (KCNQ3, CCR5, FOSB, CFAP43, and PRKG1) with the diagnostic value that may be a potential target in diagnosis and treatment.Keywords: rape pollen allergy, ceRNA, characteristic genes, GO, KEGG, IPA

Jianwei Liu,1,&ast; Minmin Sun,2,&ast; Kunpeng Fang,3,&ast; Jie Wang,1 Bowen Ma,1 Li Song,1 Ting Liu,1 Ming Tang,4 Kui Wang,1 Yong Xia4 1Department of Hepatic Surgery II, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 2Department of Hepatic Surgery I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 3Department of Special Treatment I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 4Department of Hepatic Surgery IV, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Xia, Department of Hepatic Surgery (IV), Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), &num;225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel +86-2181875005, Fax +86-2165562400, Email xia.yong@126.com Kui Wang, Department of Hepatic Surgery (II), Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), &num;225 Changhai Road, Shanghai, 200438, People’s Republic of China, Email wangkuiykl@163.comPurpose: To investigate the effect of different liver resection modalities on the prognosis of left lateral lobe hepatocellular carcinoma (HCC) patients.Methods: 315 patients with HCC on left lateral lobe were divided into open left lateral lobectomy (LLL) group (n=249) and open left hepatectomy (LH) group (n=66). The differences in long-term prognosis between two groups were compared.Results: The results showed that narrow resection margin (Hazard Ratio (HR):1.457, 95% Confidential Interval (CI): 1.038– 2.047; HR:1.415, 95% CI: 1.061– 1.887), tumor diameter > 5 cm (1.645, 1.161– 2.330; 1.488, 1.123– 1.971), multiple tumors (2.021, 1.330– 3.073; 1.987, 1.380– 2.861), and microvascular invasion (MVI) (1.753, 1.253– 2.452; 1.438, 1.087– 1.902) are independent risk factors for overall survival (OS) and tumor recurrence (TR), while liver resection modality is not. After propensity score matching, liver resection modality is not an independent risk factor for OS and TR. Further analysis revealed that wide resection margins were achieved in all patients in the LH group but only 59.0% patients in the LLL group. The OS and TR rates were not significantly different between wide patients with resection margins in LLL group and LH group (P=0.766 and 0.919, respectively), but significantly different between patients with narrow resection margins in LLL group and LH group (P=0.012 and 0.017, respectively).Conclusion: Liver resection modality is not an independent risk factor for the prognosis of patients with HCC on the left lateral lobe as long as wide margins are obtained. Nevertheless, with narrow margins, patients who underwent LH rather than LLL did better.Keywords: hepatocellular carcinoma, left lateral hepatic lobe, left lateral lobectomy, left hepatectomy, prognosis

Jing Wang,1,&ast; Weijian Chen,1,2,&ast; Wenxiang Du,2 Hongjie Zhang,2 Matthias Ilmer,3 Lei Song,2 Yuan Hu,2 Xiaopeng Ma1 1Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China; 2State Key Laboratory of Fire Science, University of Science and Technology of China, Hefei, Anhui, 230026, People’s Republic of China; 3Department of General, Visceral, and Transplantation Surgery, Ludwig-Maximilians-University (LMU), Campus Grosshadern, Munich, 81377, Germany&ast;These authors contributed equally to this workCorrespondence: Yuan Hu; Xiaopeng Ma, Email yuanhu@ustc.edu.cn; XiaopengMa@fsyy.ustc.edu.cnIntroduction: Tamoxifen (TAM) has proven to be a therapeutic breakthrough to reduce mortality and recurrence in estrogen receptor-positive (ER+) breast cancer patients. However, the application of TAM exhibits low bioavailability, off-target toxicity, instinct and acquired TAM resistance.Methods: We utilized black phosphorus (BP) as a drug carrier and sonosensitizer, integrated with TAM and tumor-targeting ligand folic acid (FA) to construct TAM@BP-FA for synergistic endocrine and sonodynamic therapy (SDT) of breast cancer. The exfoliated BP nanosheets were modified through in situ polymerization of dopamine, followed by electrostatic adsorption of TAM and FA. The anticancer effect of TAM@BP-FA was evaluated through in vitro cytotoxicity and in vivo antitumor model. RNA-sequencing (RNA-seq), quantitative real-time PCR, Western blot analysis, flow cytometry analysis and peripheral blood mononuclear cells (PBMCs) analysis were performed for mechanism investigation.Results: TAM@BP-FA had satisfactory drug loading capacity, the TAM release behavior can be controlled through pH microenvironment and ultrasonic stimulation. An amount of hydroxyl radical (∙OH) and singlet oxygen (1O2) were as expected generated under ultrasound stimulation. TAM@BP-FA nanoplatform showed excellent internalization in both TAM-sensitive MCF7 and TAM-resistant (TMR) cells. Using TMR cells, TAM@BP-FA displayed significantly enhanced antitumor ability in comparison with TAM (7.7% vs 69.6% viability at 5μg/mL), the additional SDT further caused 15% more cell death. RNA-seq unraveled the TAM@BP-FA antitumor mechanisms including effects on cell cycle, apoptosis and cell proliferation. Further analysis showed additional SDT successfully triggering reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) reduction. Moreover, PBMCs exposed to TAM@BP-FA induced an antitumor immune response by natural killer (NK) cell upregulation and immunosuppression macrophage reduction.Conclusion: The novel BP-based strategy not only delivers TAM specifically to tumor cells but also exhibits satisfactory antitumor effects through targeted therapy, SDT, and immune cell modulation. The nanoplatform may provide a superior synergistic strategy for breast cancer therapy.Keywords: black phosphorus, breast cancer, sonodynamic therapy, tamoxifen, PBMC, combination therapy

Jianwei Liu,1,&ast; Minmin Sun,2,&ast; Kunpeng Fang,3,&ast; Jie Wang,1,&ast; Bowen Ma,1 Li Song,1 Ting Liu,1 Ming Tang,4 Kui Wang,1 Yong Xia4 1Department of Hepatic Surgery II, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 2Department of Hepatic Surgery I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 3Department of Special Treatment I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 4Department of Hepatic Surgery IV, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Xia, Department of Hepatic Surgery (IV), Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), &num;225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel +86-2181875005, Fax +86-2165562400, Email xia.yong@126.com Kui Wang, Department of Hepatic Surgery (II), Eastern Hepatobiliary Surgery Hospital, Navy Medical University, &num;225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel\Fax +86-2181875514, Email wangkuiykl@163.com

Yuan Huang,1 Lu Liang,2 Yong-Xiang Zhao,3 Bi-Hui Yao,2 Rui-Min Zhang,3 Lei Song,2 Zhong-Tao Zhang1 1Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 2Department of General Surgery, Baotou Central Hospital, Baotou, 014000, People’s Republic of Chin; 3Department of Pediatrics and Urology Surgery, Baotou No.4 Hospital, Baotou, 014000, People’s Republic of ChinaCorrespondence: Zhong-Tao Zhang, Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Xicheng District, Beijing, 100050, People’s Republic of China, Tel +8613801060364, Email zhangzht@ccmu.edu.cnObjective: Gastric cancer is one of the most common malignancies worldwide; however, its overall mortality has not improved significantly over the last decade. Chemoresistance plays a critical role in this issue. This study aimed to clarify the role and mechanism of runt-related transcription factor 2 (RUNX2) in platinum-based chemotherapy resistance.Methods: First, a drug-resistant model of gastric cancer cells was established to evaluate the relative expression level of the RUNX2 as a potential biomarker of chemotherapy resistance. Next, exogenous silencing was conducted to study whether RUNX2 could reverse drug resistance and understand the underlying mechanisms. Simultaneously, the correlation between the clinical outcomes of 40 patients after chemotherapy and the RUNX2 expression levels in tumor samples was analyzed.Results: We discovered that RUNX2 was significantly expressed in drug-resistant gastric cancer cells and tissues; it was also reversibly resistant to transformation treatment by exogenous RUNX2 silencing. It is confirmed that RUNX2 negatively regulates the apoptosis pathway of the p53 to reduce the chemotherapeutic effects of gastric cancer.Conclusion: RUNX2 is a possible target for platinum-based chemotherapy resistance.Keywords: gastric cancer, RUNX2, platinum, chemotherapy resistance

Lan Zhong,1,2 Rutie Yin,1,2 Liang Song1,2 1Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Liang Song, Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, No. 20 The Third Section of South Renmin Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-19828966121, Email dr_songliang@163.comAbstract: PARP inhibitors (PARPi) are the maintenance therapy after first line platinum-based chemotherapy for patients with advanced epithelial ovarian cancer (EOC) with germline and pathogenic somatic BRCA1/2 mutations. However, as with chemotherapy, patients can develop resistance to PARPi. The selective pressure generated by heterogeneous somatic BRCA mutations may give rise to chemotherapy or PARPi resistant tumors. Here, we present the case of a patient harboring a pathogenic p.Glu143&ast; (c.427G>T) somatic BRCA1 mutation conferring resistance to olaparib following cytoreductive surgery and platinum-based chemotherapy. We ordered a plasma ctDNA analysis (tissue biopsy of recurrent lesions was contraindicated due to their anatomical location) to figure out the possible resistance mechanism. Analysis of ctDNA did not detect the pathogenic somatic BRCA1 p.Glu143&ast; (c.427G>T) mutation seen before. The tumor cells harboring the pathogenic BRCA1 mutation were probably eliminated by the platinum-based chemotherapy, leaving only those without BRCA mutations to proliferate.Keywords: PARPi resistance, BRCA1 mutation, ovarian carcinoma, circulating tumor DNA, sequencing

Xincong Li,1,&ast; Shuangshuang Ren,1,&ast; Lutong Song,1 Deao Gu,2 Haoran Peng,1 Yue Zhao,1 Chao Liu,2 Jie Yang,3 Leiying Miao1 1Department of Cariology and Endodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210008, People’s Republic of China; 2Department of Orthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210008, People’s Republic of China; 3Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leiying Miao; Jie Yang, Email miaoleiying80@163.com; dorothy0314@sina.comIntroduction: Antibacterial photodynamic treatment (aPDT) has indispensable significance as a means of treating periodontal disorders because of its extraordinary potential for killing pathogenic bacteria by generating an overpowering amount of reactive oxygen species (ROS). The elevated ROS that may result from the antibacterial treatment procedure, however, could exert oxidative pressure inside periodontal pockets, causing irreparable damage to surrounding tissue, an issue that has severely restricted its medicinal applications. Accordingly, herein, we report the use of black phosphorus nanosheets (BPNSs) that can eliminate the side effects of ROS-based aPDT as well as scavenge ROS to produce an antibacterial effect.Methods: The antibacterial effect of ICG/aPDT was observed by direct microscopic colony counting. A microplate reader and confocal microscope enabled measurements of cell viability and the quantification of ROS fluorescence. BPNS administration regulated the oxidative environment. IL-1β, IL-6, TNF-α, IL-10, TGF-β, and Arg-1 mRNA expression levels were used to assess the inflammatory response after BPNS treatment. In vivo, the efficacy of the combination of BPNSs and ICG/aPDT was evaluated in rats with periodontal disease by histomorphometric and immunohistochemical analyses.Results: The CFU assay results verified the antibacterial effect of ICG/aPDT treatment, and ROS fluorescence quantification by CLSM indicated the antioxidative ability of the BPNSs. IL-1β, IL-6, TNF-α, IL-10, TGF-β, and Arg-1 mRNA expression levels were significantly decreased after BPNS treatment, confirming the in vitro anti-inflammatory effect of this nanomaterial. The histomorphometric and immunohistochemical analyses showed that the levels of proinflammatory factors decreased, suggesting that the BPNSs had anti-inflammatory effects in vivo.Conclusion: Treatment with antioxidative BPNSs gives new insights into future anti-inflammatory therapies for periodontal disease and other infection-related inflammatory illnesses and provides an approach to combat the flaws of aPDT.Graphical Abstract: Keywords: periodontitis, black phosphorus nanosheets, reactive oxygen species, antibacterial photodynamic therapy, macrophage polarization

Jing Peng,1,* Jiaming Su,2,* Lei Song,1 Qiuyi Lv,1 Ying Gao,1 Jingling Chang,1 Hua Zhang,1 Yihuai Zou,1 Xing Chen3 1Department of Encephalopathy, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Nephrology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Brain Function Examination, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing Chen, Department of brain function examination, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, No. 05 Haiyuncang Road, Beijing, People’s Republic of China, Tel +86 18610044016, Email yeahchency@sina.comObjective: Limb numbness is a frequent symptom of post-stroke somatosensory dysfunction, which may be alleviated by non-invasive therapy such as acupuncture. However, the precise mechanism via acupuncture remains unknown. The goal of this study was to investigate how the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) changed between stroke patients with limb numbness and healthy people, as well as how acupuncture might work.Methods: 24 stroke sequelae patients with unilateral limb numbness and 14 matched healthy controls were enrolled in the study. The patients with limb numbness received acupuncture therapy three days a week for four weeks. We mainly assessed the clinical outcomes via the visual analogue scale (VAS). In addition, fMRI data from patients with unilateral limb numbness at baseline and after treatment (4th week) were collected, as well as data from healthy controls at baseline.Results: Compared with the healthy subjects, the patient group demonstrated significantly decreased ALFF in several brain regions, mainly associated with the sensorimotor network (SMN) and default mode network (DMN), including left superior frontal gyrus (SFG), right temporal fusiform cortex (TFC), right middle frontal gyrus (MFG), bilateral middle temporal gyrus (MTG), right putamen (PUT), right precentral gyrus (preCG), right planum polare (PP), and left supplementary motor area (SMA). These regions were chosen as the seeds for investigating the FC alteration induced by acupuncture. Several sensorimotor-related brain regions were activated by acupuncture, and the FC of the left supramarginal gyrus (SMG) with right MTG, as well as brain-stem, cerebellum vermis 9 with right MFG showed enhancement following acupuncture in the patient group, which had a significant correlation with clinical outcomes.Conclusion: Acupuncture treatment may be used to stimulate brain areas associated with somatosensory processing and to strengthen the FC of sensorimotor and cognitive brain networks in order to achieve therapeutic effect.Keywords: acupuncture, stroke, somatosensory dysfunction, functional magnetic resonance imaging, amplitude of low-frequency fluctuation, functional connectivity

Xiaoxiao Zhao,1,&ast; Li Song,1,&ast; Jiannan Li,1 Jinying Zhou,1 Nan Li,1 Shaodi Yan,2 Runzhen Chen,1 Ying Wang,1 Chen Liu,1 Peng Zhou,1 Zhaoxue Sheng,1 Yi Chen,1 Hanjun Zhao,1 Hongbing Yan2 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbing Yan, Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Shenzhen, 518000, People’s Republic of China, Tel +86-13701339287, Email hbyanfuwai2018@163.com Hanjun Zhao, Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167, Beijing, 100037, People’s Republic of China, Tel +86-15210020808, Email 15210020808@163.comBackground and Aims: This study aimed to determine whether convertase subtilisin/kexin type 9 (PCSK9)-associated cardiovascular risk is modulated by triglyceride-glucose (TyG) in ST-segment elevation myocardial infarction (STEMI) patients with primary percutaneous coronary disease (PCI).Methods: A total of 1541 patients with STEMI (aged ≥ 18 years) undergoing primary PCI were consecutively enrolled between March 2017 and March 2019.Outcomes: When stratifying the overall population according to TyG indices less than or greater than the median (TyG median = 9.07) as well as according to quartiles of PCSK9 levels, higher TyG index levels were significantly associated with all-cause mortality only when TyG levels were 9.07 or higher (ie, relative to quartile 1 [Q1], the adjusted HR for all-cause mortality was 3.20 [95% CI, 0.54– 18.80] for Q2, p = 0.199; 7.89 [95% CI, 1.56– 40.89] for Q3, p = 0.013; and 5.61 [95% CI, 1.04– 30.30] for Q4, p = 0.045. During a median follow-up period of 1.96 years, the HR for all-cause mortality was higher in the subset of patients with TyG ≥median and PCSK9 ≥median (p for trend = 0.023) among those with type 2 diabetes mellitus (T2DM). However, there were no statistically significant differences among the subgroups. Among T2DM patients with a TyG index greater than the median, the Kaplan-Meier curve showed that patients with the highest PCSK9 levels had an increased risk of all-cause mortality (log-rank p = 0.017) and cardiac-cause mortality (log-rank p = 0.037) compared with lower PCSK9 quartile levels.Conclusion: Elevated PCSK9 levels are related to all-cause mortality and cardiac-related mortality when TyG levels are greater than the median, but not when levels are less than the median. This suggests a potential benefit of lowering circulating PCSK9 levels in STEMI patients with insulin resistance.Keywords: triglyceride glucose index, proprotein convertase subtilisin/kexin type 9, mortality, type 2 diabetes, ST-segment elevation myocardial infarction, primary percutaneous coronary intervention

Jonas Alexander Leppig,1 Lan Song,2 Dorothea C Voigt,1 Felix W Feldhaus,1 Christoph Ruwwe-Gloesenkamp,3 Jacopo Saccomanno,3 Bianca C Lassen-Schmidt,4 Konrad Neumann,5 Katja Leitner,6 Ralf H Hubner,3 Felix Doellinger1 1Department of Radiology, Charité Universitätsmedizin Berlin, Berlin, Germany; 2Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany; 4Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany; 5Institute of Biometrics and Clinical Epidemiology, Charité Universitätsmedizin Berlin, Berlin, Germany; 6Department of Internal Medicine, Kantonsspital Aarau AG, Aarau, SwitzerlandCorrespondence: Jonas Alexander Leppig, Department of Radiology, Charité Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum, Augustenburger Platz 1, Berlin, 13353, Germany, Tel + 49 30 450 627 283, Fax + 49 30 450 527 911, Email Jonas-Alexander.Leppig@charite.dePurpose: To investigate changes in quantitative CT analysis (QCT) and pulmonary function tests (PFT) in pulmonary emphysema patients who required premature removal of endobronchial valves (EBV).Patients and Methods: Our hospital’s medical records listed 274 patients with high-grade COPD (GOLD stages 3 and 4) and pulmonary emphysema who were treated with EBV to reduce lung volume. Prior to intervention, a complete evaluation was performed that included quantitative computed tomography analysis (QCT) of scans acquired at full inspiration and full expiration, pulmonary function tests (PFT), and paraclinical findings (6-minute walking distance test (6MWDT) and quality of life questionnaires). In 41 of these 274 patients, EBV treatment was unsuccessful and the valves had to be removed for various reasons. A total of 10 of these 41 patients ventured a second attempt at EBV therapy and underwent complete reevaluation. In our retrospective study, results from three time points were compared: Before EBV implantation (BL), after EBV implantation (TP2), and after EBV explantation (TP3). QCT parameters included lung volume, total emphysema score (TES, ie, the emphysema index) and the 15th percentile of lung attenuation (P15) for the whole lung and each lobe separately. Differences in these parameters between inspiration and expiration were calculated (Vol. Diff (%), TES Diff (%), P15 Diff (%)). The results of PFT and further clinical tests were taken from the patient’s records.Results: We found persistent therapy effect in the target lobe even after valve explantation together with a compensatory hyperinflation of the rest of the lung. As a result of these two divergent effects, the volume of the total lung remained rather constant. Furthermore, there was a slight deterioration of the emphysema score for the whole lung, whereas the TES of the target lobe persistently improved.Conclusion: Interestingly, we found evidence that, contrary to our expectations, unsuccessful EBV therapy can have a persistent positive effect on target lobe QCT scores.Keywords: chronic obstructive pulmonary disease, pulmonary emphysema, endobronchial valves, lung volume reduction, computed tomography, pulmonary function test

Hongzhi Lu,1 Li Ma,1 Hong Zhang,1 Li Feng,1 Ying Yu,1 Yihan Zhao,1 Li Li,1 Yujiao Zhou,1 Li Song,2,3 Wushuang Li,2,3 Jiangman Zhao,2,3 Lanxiang Liu4 1Department of Infectious Diseases, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of China; 2Shanghai Biotecan Pharmaceuticals Co., Ltd, Shanghai, 201204, People’s Republic of China; 3Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, 201204, People’s Republic of China; 4Medical Imaging Center, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of ChinaCorrespondence: Lanxiang Liu, Department of Medical Imaging Center, First Hospital of Qinhuangdao, 258 Wenhua Road, Qinhuangdao, 066000, Hebei, People’s Republic of China, Email 155354189@qq.comBackground: Metagenomic next-generation sequencing (mNGS) has been widely studied, due to its ability of detecting all the microbial genetic information unbiasedly in a sample at one time and not relying on traditional culture. However, the application of mNGS in the diagnosis of clinical pathogens remains challenging.Methods: From December 2019 to March 2021, 134 specimens including Broncho alveolar lavage fluid (BAFL), blood, sputum, cerebrospinal fluid (CSF), bile, pleural fluid, pus, were continuously collected in The First Hospital of Qinhuangdao, and their retrospective diagnoses were classified into infectious disease (128, 95.5%) and noninfectious disease (6, 4.5%). The pathogen-detection performance of mNGS was compared with conventional microbiological tests (CMT) and culture method. In addition, the antibiotic resistance genes (ARGs) and evolutionary relationship of common drug-resistant A. baumannii were also analyzed.Results: Compared with CMT and culture methods, mNGS showed higher sensitivity in pathogen detection (74.2% vs 57.8%; P < 0.001 and 66.3% vs 31.7%; P < 0.001, respectively). Importantly, for cases that mNGS-positive only, 18 (35%) cases result in diagnosis modification, and 7 (23%) cases confirmed the clinical diagnosis. In 17 cases that A. baumannii were both detected in mNGS and culture, ade genes were the most frequently detected ARGs (from 13 cases), followed by sul2 and APH(3”)-Ib (both from 12 cases). High consistency was observed among these ARGs and the related phenotype (100% for ade genes, 91.6% for sul2 and APH(3”)-Ib). A. baumannii strains were classified into three groups, and most were well-clustered. It suggested those strains may be the epidemic strains.Conclusion: In our study, mNGS had a higher sensitivity than CMT and culture method. And the result of ARGs frequency and cluster analysis of A. baumannii was of great significance to the anti-infective therapy.Keywords: metagenomic next-generation sequencing, sensitivity, antibiotic resistance genes, infection, conventional microbiological tests

Xiaoxiao Zhao,1 Chen Liu,1 Peng Zhou,1 Zhaoxue Sheng,1 Jiannan Li,1 Jinying Zhou,1 Runzhen Chen,1 Ying Wang,1 Yi Chen,1 Li Song,1 Hanjun Zhao,1 Hongbing Yan2 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People’s Republic of China; 2Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, People’s Republic of ChinaCorrespondence: Hongbing Yan, Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Shenzhen, 518000, People’s Republic of China, Tel +86-13701339287, Email hbyanfuwai2018@163.com Hanjun Zhao, Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167, Beijing, 100037, People’s Republic of China, Tel +86-15210020808, Email 15210020808@163.comBackground and Aims: We aimed to develop a clinical prediction tool to improve the prognosis of major adverse cardiac and cerebrovascular events (MACCE) among high-risk myocardial infarction (MI) patients undergoing primary percutaneous coronary intervention (PCI).Methods: The present study was a prospective and observational study. A total of 4151 consecutive MI patients who underwent primary PCI at Fuwai Hospital in Beijing, China (January 2010 and June 2017) were enrolled. Forty-eight patients without follow-up data were excluded from the study. The pre-specified criteria (Supplementary Information 1) were chosen to enroll MI patients at high risk for MACCE complications after PCI.Results: The full model included seven variables, with a risk score of 160 points. Derivation and validation cohort models predicting MACCE had C-statistics of 0.695 and 0.673. The area under the curve (AUC) of the survival receiver operating characteristic curve (ROC) for predicting MACCE was 0.991 and 0.883 in the derivation and validation cohorts, respectively.Conclusion: The predicted model was internally validated and calibrated in large cohorts of patients with high-risk MI receiving primary PCI to predict MACCE and showed modest accuracy in the derivation and validation cohorts.Keywords: primary percutaneous coronary intervention, high-risk, follow-up, risk prediction score

Maoying Wang,1,&ast; Qianrong Ding,2,&ast; Ling Sang,1 Li Song1 1Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Intensive Care Unit Management, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Song, Department of Pain Management, West China Hospital, Sichuan University, West China Hospital, Sichuan University, #37, Guo Xue Xiang, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel +8618980601501, Fax +8602885423593, Email song_li76@163.comBackground: Although pain is commonly observed among medical staff, studies on pain among intensive care unit personnel are uncommon, especially intensive care unit (ICU) doctors and workers. Moreover, few studies have focused on the prevalence of pain and the associated factors.Purpose: The aim of this study was to estimate the prevalence of pain among ICU personnel (including doctors, nurses and workers) and explore the risk factors for their pain.Methods: We conducted an online survey that included sociodemographic and work-related items and questions about pain, ergonomics, and psychological factors. We used the short version of the validated Depression–Anxiety–Stress Scale (DASS-21) to assess the relationship between pain and mental disorders. All ICU personnel at West China Hospital of Sichuan University participated in this study.Results: A total of 356 ICU personnel were included in the final analysis. The prevalence of pain was 72.2% among ICU nurses, 64.4% among ICU doctors and 52.9% among ICU workers. The most frequent location of pain was the lower back among nurses (65.9%) and workers (47.1%) and the neck among doctors (49.1%). The factors contributing to pain among ICU personnel were bending or twisting the neck, high levels of psychological fatigue, low self-perceived health status, female sex and high body mass index (BMI). Moreover, participants with pain indicated significantly higher depression (p ≤ 0.001), anxiety (p ≤ 0.001), and stress levels (p = 0.002) than those without pain.Conclusion: This study indicates that ICU personnel exhibit a high prevalence of pain. Many factors, especially psychosocial and ergonomic factors, contribute to pain levels among ICU personnel and the poorer mental health levels observed in those experiencing pain. Therefore, disease prevention and health promotion measures are needed to protect the health of ICU personnel.Keywords: occupational health, intensive care unit, cross-sectional studies, mental health

Lei Dong,1,&ast; Nana Li,1,&ast; Xixi Wei,2 Yongling Wang,2 Liansheng Chang,3 Hongwei Wu,4 Liujiang Song,5 Kang Guo,6 Yuqiao Chang,1 Yaling Yin,2 Min Pan,7 Yuanyuan Shen,8 Feng Wang1 1Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 2Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 3Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 4Department of Chemistry, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 5Department of Ophthalmology, Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27517, USA; 6Department of Oncology, The Third affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 7Department of Ultrasound, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, 518034, People’s Republic of China; 8National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Wang, Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453002, People’s Republic of China, Email wfeng100@126.com Min Pan, Department of Ultrasound, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, No. 6001 Beihuan Avenue, Shenzhen, 518034, People’s Republic of China, Email min.pan@siat.ac.cnBackground: The blood–brain barrier (BBB) inhibits the delivery of macromolecular chemotherapeutic drugs to brain tumors, leading to low utilization rates and toxic side effects to surrounding tissues and organs. Ultrasonic targeted microbubble destruction (UTMD) technology can open the BBB, leading to a new type of drug delivery system with particular utility in glioma.Purpose: We have developed a new type of drug-loaded microbubble complex based on poly(lactic-co-glycolic acid) (PLGA) that targets gambogic acid (GA) to the area of brain tumors through UTMD.Methods: GA/PLGA nanoparticles were prepared by the double emulsification method, and cationic microbubbles (CMBs) were prepared by a thin film hydration method. The GA/PLGA-CMB microbubble complex was assembled through electrostatic attractions and was characterized chemically. The anti-glioblastoma effect of GA/PLGA-CMB combined with focused ultrasound (FUS) was evaluated by biochemical and imaging assays in cultured cells and model mice.Results: GA/PLGA-CMB combined with FUS demonstrated a significant inhibitory effect on glioblastoma cell lines U87 and U251 as compared with controls (P< 0.05). Tumor access and imaging analyses demonstrated that administration of GA/PLGA-CMBs combined with FUS can open the BBB and target the treatment of glioblastoma in a mouse model, as compared with control groups (P< 0.05).Conclusion: The combination of PLGA-CMB with FUS provides an effective and biocompatible drug delivery system, and its application to the delivery of GA in a mouse glioblastoma model was successful.Keywords: microbubbles, cavitation effect, glioblastoma, focused ultrasound

Zhuang Ma,1 Linpei Song,2 Jun Huang3 1International Business School, Chongqing Technology and Business University, Chongqing, People’s Republic of China; 2School of Business Administration, Gachon University, Seongnam-si, South Korea; 3School of Economics and Management, Southwest University, Chongqing, People’s Republic of ChinaCorrespondence: Linpei Song, School of Business Administration, Gachon University, Seongnam-si, South Korea, Tel +86 13840033660, Email songlinpei@gachon.ac.krPurpose: This study aims to examine the impacts of peer abusive supervision, perceived rivalry and schadenfreude over the abused peers on sales employees’ customer knowledge hiding.Methods: We conducted multiple regression analyses of 283 sales employees’ responses from two Chinese and two South Korean electronic device companies to test the hypotheses, which constitute a theoretical framework.Results: Our empirical results confirmed the positive impact of peer abusive supervision on sales employees’ customer knowledge hiding, with the relationship moderated by rivalry and schadenfreude; moreover, rivalry and schadenfreude jointly exert the greatest impacts on the main effect.Conclusion: This study sheds light on the knowledge hiding literature, with theoretical implications for the research regarding the spillover effect of abusive supervision, rivalry, schadenfreude, customer knowledge sharing, and managerial practices about the management of customer knowledge among sales employees.Keywords: peer abusive supervision, customer knowledge hiding, rivalry, schadenfreude, sales employees

Runzhen Chen,1,2 Chen Liu,1– 3 Peng Zhou,1,3 Jiannan Li,1 Jinying Zhou,1 Ruoqi Song,4 Weida Liu,4 Yi Chen,1 Li Song,1,3 Hanjun Zhao,1,3 Hongbing Yan2,3 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, People’s Republic of China; 3Coronary Heart Disease Center, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Hanjun Zhao; Hongbing Yan, Email 15210020808@163.com; hbyanfuwai2018@163.com; hbyanfuwai@aliyun.comBackground: Associations between D-dimer and outcomes of patients with acute coronary syndrome (ACS) remain controversial. Using age-adjusted D-dimer cutoff thresholds improve the diagnostic accuracy for thrombotic diseases. This study aimed to investigate the prognostic value of age-adjusted D-dimer in ACS patients treated by percutaneous coronary intervention (PCI).Methods: A total of 3972 consecutive patients with ACS treated by PCI were retrospectively recruited. The basal age-adjusted D-dimer threshold was 500 ng/mL and was calculated as age × 10 in patients older than 50 years. Cox regression was used for outcome analysis. C-index, net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to assess the additional prognostic value of age-adjusted D-dimer when combined with established clinical risk factors. The primary outcome was all-cause death.Results: During a median follow-up of 720 days, a total of 225 deaths occurred. High D-dimer level, as defined by age-adjusted thresholds, was an independent predictor for all-cause death (hazard ratio [HR]: 1.75, 95% confidence interval [CI]: 1.32– 2.31, P < 0.001), cardiac death (HR: 1.84, 95% CI: 1.30– 2.60, P = 0.001), and MACE (HR: 1.48, 95% CI: 1.19– 1.83, P < 0.001). Sensitivity and subgroup analysis showed that high D-dimer levels were constantly associated with worse outcomes across common risk factors and comorbidities. Besides, age-adjusted elevation of D-dimer significantly improved the risk predictions for all-cause death when added to the model of established risk factors (C-index: 0.846 vs 0.838, Δ C-index: 0.008, 95% CI: 0.001– 0.015, Pdifference = 0.027; NRI: 0.645, 95% CI: 0.464– 0.826, P < 0.001; IDI: 0.008, 95% CI: 0.001– 0.017, P = 0.048).Conclusion: In ACS patients treated by PCI, age-adjusted elevation of D-dimer was an independent predictor for adverse outcomes and improved the risk predictions for long-term mortality.Keywords: D-dimer, aging, acute coronary syndrome, percutaneous coronary intervention, PCI, ACS

Shaohua Guo,1,2,&ast; Yumeng Ye,3,&ast; Xinyi Liu,4 Yuan Gong,5 Mingyan Xu,4 Lele Song,4,6 Hongyi Liu1 1Department of General Surgery, The First Medical Center of the Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of General Surgery, The Eighth Medical Center of the Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China; 4Department of Medical Division, HaploX Biotechnology, Shenzhen, People’s Republic of China; 5Department of Gastroenterology, The Second Medical Center of the Chinese PLA General Hospital, Beijing, People’s Republic of China; 6Department of Radiotherapy, The Eighth Medical Center of the Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongyi LiuDepartment of General Surgery, The First Medical Center of the Chinese PLA General Hospital, Beijing, People’s Republic of ChinaTel +86-10-66937533Email liushitou2003@163.comLele SongDepartment of Radiotherapy, The Eighth Medical Center of the Chinese PLA General Hospital, Beijing, People’s Republic of ChinaTel +86-13240149188Email songlele@sina.comBackground: The panorama and details of quantitative intratumor heterogeneity have not been fully investigated in colorectal cancer (CRC) patients with solitary lesion without distal metastasis, and its influences on sequencing interpretation and therapeutic strategies have not been explored.Methods: Cancer tissues and matched blood from 70 sporadic CRC patients were collected and were divided into two cohorts. Four individual tissue biopsies were obtained from each of the 47 patients (multi-sample cohort). One random cancer tissue biopsy was obtained from each of the rest 23 patients (single-sample cohort). A 10 mL of blood was collected from all patients and the circulating cell-free DNA (cfDNA) was extracted. A 605-gene panel was used for targeted sequencing with tissue and paired blood.Results: Mutational landscape revealed significantly higher mutational frequency in APC, CARD11 and CSMD3 in multi-sample cohort than single-sample cohort (P< 0.05). The number of mutations and the ratio of trunk, shared and branch mutations showed extensive heterogeneity in multi-sample cohort, and the percentage of trunk mutations in major driver genes, including APC, TP53 and KRAS, was higher than 70%. A total of 929 mutations were detected in tissue/blood in multi-sample group, with 921(99.1%) from tissue and 472(50.8%) from blood (464 common mutations,49.9%). In contrast, 394 mutations were detected in tissue/blood in single-sample group, with 231 (58.6%) from tissue and 219 (55.6%) from blood (56 common mutations, 11.9%). The number of mutations of major driver genes detected in tissue was higher than that in blood in the multi-sample cohort, while it was similar in the single-sample group. Quantification analysis revealed differential correlation between tissue and blood VAF in trunk, shared and branch mutations. Meanwhile, VAF of trunk mutations was significantly higher than shared mutations and branch mutations. VAF exhibited significant differences among distinct stages, locations, differentiation and sex status.Conclusion: Characteristic extensive heterogeneity was revealed for solitary CRC without distal metastasis. Multi-regional biopsy was necessary for comprehensive mutation detection in CRC.Keywords: colorectal cancer, multi-region sequencing, intra-tumor heterogeneity, circulating tumor DNA, ctDNA, APC, KRAS, TP53

Liang Li,1 Xue Yu,2 Guanqiang Ma,1 Zhiqi Ji,1 Shihao Bao,1 Xiaopeng He,1,3 Liang Song,1,3 Yang Yu,1,3 Mo Shi,1,3 Xiangyan Liu1,3 1Department of Thoracic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Pediatrics, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 420100, People’s Republic of China; 3Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Mo Shi; Xiangyan LiuDepartment of Thoracic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People’s Republic of ChinaEmail legendsm01@163.com; liuxiangyan1@163.comBackground: Early-stage lung squamous cell carcinoma (LUSC) progression is accompanied by changes in immune microenvironments and the expression of immune-related genes (IRGs). Identifying innate IRGs associated with prognosis may improve treatment and reveal new immunotherapeutic targets.Methods: Gene expression profiles and clinical data of early-stage LUSC patients were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases and IRGs from the InnateDB database. Univariate and multivariate Cox regression and LASSO regression analyses were performed to identify an innate IRG signature model prognostic in patients with early-stage LUSC. The predictive ability of this model was assessed by time-dependent receiver operator characteristic curve analysis, with the independence of the model-determined risk score assessed by univariate and multivariate Cox regression analyses. Overall survival (OS) in early-stage LUSC patients was assessed using a nomogram and decision curve analysis (DCA). Functional and biological pathways were determined by gene set enrichment analysis, and differences in biological functions and immune microenvironments between the high- and low-risk groups were assessed by ESTIMATE and the CIBERSORT algorithm.Results: A signature involving six IRGs (SREBF2, GP2, BMX, NR1H4, DDX41, and GOPC) was prognostic of OS. Samples were divided into high- and low-risk groups based on median risk scores. OS was significantly shorter in the high-risk than in the low-risk group in the training (P < 0.001), GEO validation (P = 0.00021) and TCGA validation (P = 0.034) cohorts. Multivariate Cox regression analysis showed that risk score was an independent risk factor for OS, with the combination of risk score and T stage being optimally predictive of clinical benefit. GSEA, ESTIMATE, and the CIBERSORT algorithm showed that immune cell infiltration was higher and immune-related pathways were more strongly expressed in the low-risk group.Conclusion: A signature that includes these six innate IRGs may predict prognosis in patients with early-stage LUSC.Keywords: early-stage lung squamous cell carcinoma, prognosis, risk score, gene signature, innate immune-related genes, immune cell infiltration

Shuai Ren, Lina Song, Ying Tian, Li Zhu, Kai Guo, Huifeng Zhang, Zhongqiu Wang Department of Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, 210029, People’s Republic of ChinaCorrespondence: Shuai Ren; Zhongqiu WangDepartment of Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing, Jiangsu Province, 210029, People’s Republic of ChinaEmail sren001@163.com; zhongqiuwang0815@163.comBackground: Pancreatic cancer (PC) remains a difficult tumor to diagnose and treat. It is often diagnosed as advanced by reason of the anatomical structure of the deep retroperitoneal layer of the pancreas, lack of typical symptoms and effective screening methods to detect this malignancy, resulting in a low survival rate. Emodin (EMO) is an economical natural product with effective treatment and few side effects of cancer treatment. Magnetic nanoparticles (MNPs) can achieve multiplexed imaging and targeted therapy by loading a wide range of functional materials such as fluorescent dyes and therapeutic agents.Purpose: The purpose of this study was to design and evaluate a multifunctional theranostic nanoplatform for PC diagnosis and treatment.Methods: In this study, we successfully developed EMO-loaded, Cy7-functionalized, PEG-coated Fe3O4 (Fe3O4-PEG-Cy7-EMO). Characteristics including morphology, hydrodynamic size, zeta potentials, stability, and magnetic properties of Fe3O4-PEG-Cy7-EMO were evaluated. Fluorescence imaging (FI)/magnetic resonance imaging (MRI) and therapeutic treatment were examined in vitro and in vivo.Results: Fe3O4-PEG-Cy7-EMO nanoparticles had a core size of 9.9 ± 1.2 nm, which showed long-time stability and FI/MRI properties. Bio-transmission electron microscopy (bio-TEM) results showed that Fe3O4-PEG-Cy7-EMO nanoparticles were endocytosed into BxPC-3 cells, while few were observed in hTERT-HPNE cells. Prussian blue staining also confirmed that BxPC-3 cells have a stronger phagocytic ability as compared to hTERT-HPNE cells. Additionally, Fe3O4-PEG-Cy7-EMO had a stronger inhibition effect on BxPC-3 cells than Fe3O4-PEG and EMO. The hemolysis experiment proved that Fe3O4-PEG-Cy7-EMO can be used in vivo experiments. In vivo analysis demonstrated that Fe3O4-PEG-Cy7-EMO enabled FI/MRI dual-modal imaging and targeted therapy in pancreatic tumor xenografted mice.Conclusion: Fe3O4-PEG-Cy7-EMO may serve as a potential theranostic nanoplatform for PC.Keywords: pancreatic cancer, emodin, magnetic nanoparticles, passive targeting

Yiran Yan,1,&ast; Yan Chen,2,&ast; Zhongxun Liu,1 Feiyan Cai,3 Wanting Niu,4,5 Liming Song,1 Haifeng Liang,1 Zhiwen Su,1 Bo Yu,1 Fei Yan6 1Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People’s Republic of China; 2Department of Ultrasonic Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People’s Republic of China; 3Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, People’s Republic of China; 4VA Boston Healthcare System, Boston, MA, 02130, USA; 5Department of Orthopedics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA; 6CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei YanShenzhen Institutes of Advance Technology, Chinese Academy of Science, 1068 Xueyuan Avenue, Shenzhen University Town, Shenzhen, Guangdong, 518055, People’s Republic of ChinaTel +86 755 86392284Fax +86 755 96382299Email fei.yan@siat.ac.cnBo YuDepartment of Orthopedics, Zhujiang Hospital, Southern Medical University, 253 Gongye Avenue, Haizhu District, Guangzhou, Guangdong, 510280, People’s Republic of ChinaTel +86 20 67282573Fax +86 20 61643010Email gzyubo@163.comBackground: Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Owing to the presence of blood–brain barrier (BBB), conventional pharmaceutical agents are difficult to the diseased nuclei and exert their action to inhibit or delay the progress of PD. Recent literatures have demonstrated that curcumin shows the great potential to treat PD. However, its applications are still difficult in vivo due to its poor druggability and low bioavailability through the BBB.Methods: Melt-crystallization methods were used to improve the solubility of curcumin, and curcumin-loaded lipid-PLGA nanobubbles (Cur-NBs) were fabricated through encapsulating the curcumin into the cavity of lipid-PLGA nanobubbles. The bubble size, zeta potentials, ultrasound imaging capability and drug encapsulation efficiency of the Cur-NBs were characterized by a series of analytical methods. Low-intensity focused ultrasound (LIFU) combined with Cur-NB was used to open the BBB to facilitate curcumin delivery into the deep brain of PD mice, followed by behavioral evaluation for the treatment efficacy.Results: The solubility of curcumin was improved by melt-crystallization methods, with 2627-fold higher than pure curcumin. The resulting Cur-NBs have a nanoscale size about 400 nm and show excellent contrast imaging performance. Curcumin drugs encapsulated into Cur-NBs could be effectively released when Cur-NBs were irradiated by LIFU at the optimized acoustic pressure, achieving 30% cumulative release rate within 6 h. Importantly, Cur-NBs combined with LIFU can open the BBB and locally deliver the curcumin into the deep-seated brain nuclei, significantly enhancing efficacy of curcumin in the Parkinson C57BL/6J mice model in comparison with only Cur-NBs and LIFU groups.Conclusion: In this work, we greatly improved the solubility of curcumin and developed Cur-NBs for brain delivery of curcumin against PD through combining with LIFU-mediating BBB. Cur-NBs provide a platform for these potential drugs which are difficult to cross the BBB to treat PD disease or other central nervous system (CNS) diseases.Keywords: nanobubbles, blood–brain barrier, low-intensity focus ultrasound, curcumin, Parkinson’s disease

Lulu Song,1 Xiaomu Kong,2 Zhaojun Yang,1 Jinping Zhang,1 Wenying Yang,1 Bo Zhang,1 Xiaoping Chen,1 Xin Wang1 1Department of Endocrinology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Clinical Laboratory, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xin WangDepartment of Endocrinology, China-Japan Friendship Hospital, 2 Yinghua East Road, Beijing, 100029, People’s Republic of ChinaTel +86 1084205254Email xiangpian11@163.comPurpose: To assess the effect of acarbose in lowering low-grade albuminuria compared to metformin in newly diagnosed Chinese type 2 diabetes (T2DM) patients.Patients and Methods: The Metformin and AcaRbose Clinical Trial was a randomized, open-label trial in newly diagnosed T2DM patients. Participants received 48 weeks of monotherapy with acarbose (100 mg three times a day) or metformin (1500 mg once a day). As the hypoglycemic effect of acarbose and metformin has been evaluated in previous reports. This analysis studied the effect of the two antidiabetic drugs on reducing urinary albumin. The percent change in the urinary albumin/creatinine ratio (uACR) from baseline to week 48 was analyzed, and ANCOVA was employed to establish whether the effect in decreasing uACR was mediated by metabolic improvement.Results: Acarbose reduced the adjusted mean percent uACR by − 31.5% (95% confidence interval [CI] − 48.4 to − 7.5) compared with metformin. When adjusting for changes in glycated hemoglobin, body weight, systolic blood pressure and triglycerides or changes in area under the curve of glucagon-like peptide 1 (AUCGLP-1) in the standard meal test, the uACR-lowering effect was not attenuated. If stratified by eGFR, blood glucose level, sex or uACR level, the effect of acarbose versus metformin was consistent across subgroups. The proportion of patients with a reduction in uACR of at least 70% was 48.6% in the acarbose group and 34.1% in the metformin group.Conclusion: Acarbose lowered the uACR compared to metformin in newly diagnosed T2DM patients independent of improvements in hyperglycemia, blood pressure, body weight and triglycerides.Keywords: diabetes mellitus, type 2, diabetic nephropathies, hypoglycemic agents

Li Song,1 Yan Ge,2 Xuyang Zhang3 1Institute of Arts and Humanities, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 2Institute of Psychological and Behavioral Science, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 3School of Humanities, Shanghai Institute of Technology, Shanghai, 201418, People’s Republic of ChinaCorrespondence: Li SongInstitute of Arts and Humanities, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of ChinaTel +86-18585059965Fax +86-21-62932801Email rediscovering@163.comPurpose: WeChat is China’ biggest social media platform. In addition to instant messaging, it has a great many useful functions that can help Chinese citizens adapt to an increasingly digitized society. This study aimed to examine the effect of WeChat use on the subjective well-being (SWB) of Chinese older adults living alone, and how the effect could occur.Participants and Methods: A total of 415 Chinese older adults living alone participated in the survey. Participants filled out questionnaires (scales) measuring their SWB, proficiency in WeChat use, social activity levels and self-esteem respectively. Mean scores of SWB were used to determine the difference in SWB between the users and non-users, and correlation test was performed to find out the association between proficiency in WeChat use and SWB among the users.Results: The mean score of WeChat users was 34.68 (SD = 7.301), significantly higher than that of the non-users, which was 32.73 (SD = 7.168) (t = 2.741, p = 0.006). Among the users, the more proficient in WeChat use one was, the higher their SWB score (r = 0.458, p < 0.01). The results combined to demonstrate that WeChat use has a positive effect on the SWB of Chinese older adults living alone. The findings also showed that the increase in SWB was obtained through the mediation of intergenerational support and social activities.Conclusion: This study suggests that WeChat use by Chinese older adults living alone could increase their intergenerational support and social activities; the increased intergenerational support and social activities then enhance the SWB of Chinese older adults living alone.Keywords: WeChat, older adults, subjective well-being, intergenerational support, social activity, self-esteem

Jiamin Cheng,1,&ast; Yinyin Li,1,&ast; Xiaohui Wang,2,&ast; Zheng Dong,1 Yan Chen,1 Rui Zhang,1 Jiagan Huang,1 Xueyuan Jin,1 Jianfei Yao,2 Aifang Ge,2 Lele Song,2,3,&ast; Yinying Lu,1 Zhen Zeng1 1Comprehensive Liver Cancer Department, The Fifth Medical Center of the Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 2HaploX Biotechnology, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Radiotherapy, The Eighth Medical Center of the Chinese PLA General Hospital, Beijing, 100091, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinying Lu; Zhen ZengComprehensive Liver Cancer Department, The Fifth Medical Center of the Chinese PLA General Hospital, Beijing, 100039, People’s Republic of ChinaEmail luyinying1973@163.com; zengzhen1970@sina.comBackground: Immunotherapy combined with VEGF inhibitor has become the new first-line therapy for advanced or metastatic hepatocellular carcinoma (HCC). However, the biomarkers for response and prognosis stratification of HCC first-line combined immunotherapy have not been clarified.Methods: Here, we obtained the genomic alteration data from pre-therapeutic samples of 103 HCC patients using a 605-gene NGS test, and obtained the transcriptional and T cell receptor (TCR) diversity data from 18 patients who underwent the first-line combined immunotherapy using RNAseq and TCR sequencing, respectively. Patients received sorafenib/sintilimab or lenvatinib/sintilimab combined first-line therapy and the response was assessed at 3– 6 cycles of therapy.Results: No stratification of response was found in high-frequency key driver gene mutations, including TP53 and TERT. However, significantly higher ratio of progression (PD) was found in patients carrying MDM4 amplification. Similarly, FGF/3/4/19 amplifications could also result in high ratio of PD. The mRNA and lncRNA levels of eight genes related to hepatic metabolism and immune microenvironment exhibited significant differences between PR/SD and PD group, including DGKI, TNFSF14, CHST4, ACTIN1, PFKP, SLC51B, LCK and ERN1, suggesting stratification of response. Furthermore, moderate correlation was identified between the stratification genes (CHST4, SLC51B and ERN1) and immune factors (TIGIT, CD34, ICAM1, CCL5, CXCL9 and CXCL10), suggesting potential roles of these factors in immunoregulation. Strong linear correlation was found between any two of the three indexes for TCR CDR3 diversity, including Shannon–Wiener Index, Simpson index and evenness. However, no significant difference was found in the three indexes between the PR/SD and PD group, suggesting no stratification of response by these indexes.Conclusion: We identified several potential biomarkers for response stratification in the first-line combined immunotherapy. MDM4 was capable of predicting disease progression, and a panel mRNA and lncRNA of eight genes may also predict the response. Further validation is needed to verify these biomarkers.Keywords: hepatocellular carcinoma, HCC, immunotherapy, mRNA, lncRNA, TCR, sintilimab, sorafenib, lenvatinib

Xiaoxiao Zhao,1,&ast; Li Song,1,&ast; Ying Wang,1,&ast; Jiannan Li,1 Jinying Zhou,1 Runzhen Chen,1 Chen Liu,1 Peng Zhou,1 Zhaoxue Sheng,1 Yi Chen,1 Hanjun Zhao,1 Hongbing Yan2 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, ShenZhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbing YanFuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Shenzhen, 518000, People’s Republic of ChinaTel +86-13701339287Email hbyanfuwai2018@163.comHanjun ZhaoDepartment of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167, Beijing, 100037, People’s Republic of ChinaTel +86-15210020808Email 15210020808@163.comBackground and Aim: The aim of prospective study was to determine the prognostic value of combined measures of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and pentraxin 3 (PTX3) according to the culprit-plaque morphology (plaque rupture versus plaque erosion) in relation to the in patients with acute ST-elevated myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention.Methods: A total of 434 patients with STEMI aged ≥ 18 years who underwent pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019 were enrolled. Finally, 235 patients who meet the inclusion criteria were enrolled and the cohort was divided into 3 groups according to PCSK9 and PTX3 levels: group A: PCSK9 < median and Pentraxin 3 (N = 72/30.6%); group B: PCSK9 ≥ median or Pentraxin 3≥ median (N = 91/38.7%); group C: PCSK9 ≥ median and Pentraxin 3≥ median (N = 72/30.6%). MACEs were defined as a composite of all-cause death, myocardial infarction (MI) recurrence, and ischemic stroke, revascularization and heart failure.Outcomes: During a median follow-up of 2.01 years, 50 patients has occurred MACE. Two-year MACE was higher in group C (23/31.9%) than in group B (16/17.6%) and group A (11/15.3%) (p = 0.028). There was a correlation between PCSK9 and PTX3 (r = 0.302, p < 0.003). In multivariable analysis adjusted for age, gender, risk factors, and serum indexes, being in group C remained independently associated with an increased risk of MACE (hazard ratio [HR]: 2.90; p = 0.010), and group B tended to have higher MACE (HR: 1.76; p = 0.172) compared with group A. Among patients with plaque erosion by OCT, group C was independently associated with an increased risk of MACE (HR: 9.04; p = 0.048) after fully adjustment. However, the significant association was absence among patients with plaque rupture.Conclusion and Relevance: This study demonstrated the usefulness of combined measures of PCSK9 and PTX3 to enhance risk stratification in patients with STEMI especially among patients with plaque erosion. Patients with elevation of both PCSK9 and PTX3 had a markedly increased risk of MACE.Keywords: pentraxin-3, PCSK9, plaque morphology characteristics, optical coherence tomography, major adverse cardiovascular events, ST-segment elevation myocardial infarction

Ying Wang,1 Xiaoxiao Zhao,1 Peng Zhou,1 Chen Liu,1 Zhaoxue Sheng,1,2 Jiannan Li,1 Jinying Zhou,1 Runzhen Chen,1 Yi Chen,1 Li Song,1 Hanjun Zhao1 &ast;, Hongbing Yan3 &#x002A1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Cardiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, People’s Republic of China&ast; These authors contributed equally to this workCorrespondence: Hongbing YanDepartment of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 12, Langshan Road, Xili Street, Nanshan District, Shenzhen, 518000, People’s Republic of ChinaTel +86-10-88322285Email hbyanfuwai2018@163.comHanjun ZhaoDepartment of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People’s Republic of ChinaTel +86-15210020808Email 15210020808@163.comBackground: Culprit‑plaque morphology [plaque rupture (PR) and plaque erosion (PE) identified by optical coherence tomography (OCT)] and biomarker of vascular inflammation, pentraxin-3 (PTX3), have been reported to influence clinical outcomes in coronary diseases. We aimed to investigate the prognostic implication of culprit-plaque morphology and plasma PTX3 for major adverse cardiovascular events (MACE) in patients with ST-segment elevation myocardial infarction (STEMI).Methods: A total of 236 patients were enrolled and divided into four groups: PE/low-PTX3 (n = 57), PE/high-PTX3 (n = 47), PR/low-PTX3 (n = 78) and PR/high-PTX3 (n = 54). MACE was defined as the composite of all-cause death, recurrence of myocardial infarction, stroke and unplanned revascularization of any coronary artery.Results: During the follow-up of 1.9 years, a total of 40 (16.9%) MACE were observed: 5.3% (3 patients) among patients with PE/low-PTX3, 21.3% (10 patients) among patients with PE/high-PTX3, 17.9% (14 patients) among patients with PR/low-PTX3 and 24.1% (13 patients) among patients with PR/high-PTX3 (Log rank P = 0.013). In fully adjusted analyses, patients with high-PTX3 were associated with higher MACE risk (HR: 2.40, 95% CI: 1.26– 4.57, P = 0.008). Patients with PR/high-PTX3 (HR: 5.63, 95% CI: 1.57– 20.16, P = 0.008) and PE/high-PTX3 (HR: 5.44, 95% CI: 1.46– 20.29, P = 0.012) presented higher MACE risk than those with PE/low-PTX3. Adding plasma PTX3 levels and PR to the risk prediction model increased the area under curves to 76.1% (95% CI: 67.6– 84.5%) and the NRI (28.1%, 95% CI: 0.3– 48.3%, P=0.040) and IDI (2.4%, 95% CI: 0.1– 12.9%, P = 0.040).Conclusion: Patients with PR/high-PTX3 and PE/high-PTX3 presented a poorer prognosis than those with PE/low-PTX3. Combining the culprit-plaque morphology with PTX3 enhanced the predictive ability for MACE and contributed to better identification of high-risk patients.Trial Registration Number: This study is registered at clinical trials.gov as NCT03593928.Keywords: pentraxin-3, plaque rupture, optical coherence tomography, cardiovascular risk, ST-segment elevation myocardial infarction

Peng Huang, Shaomi Zhu, Xin Liang, Qinxiu Zhang, Xiaohong Luo, Chi Liu, Linjiang Song Reproductive & Women-Children Hospital, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People’s Republic of ChinaCorrespondence: Linjiang Song; Chi LiuReproductive & Women-Children Hospital, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People’s Republic of ChinaEmail linjsong_scu@163.com; liuchi1985@163.comAbstract: Cancer cells exhibit distinct metabolic characteristics that employ glycolysis to provide energy and intermediary metabolites. This aberrant metabolic phenotype favors cancer progression. LncRNAs are transcripts longer than 200 nucleotides that do not encode proteins. LncRNAs contribute to cancer progression and therapeutic resistance and affect aerobic glycolysis via multiple mechanisms, including modulating glycolytic transporters and enzymes. Further, dysregulated signaling pathways are vital for glycolysis. In this review, we highlight regulatory mechanisms for lncRNAs in aerobic glycolysis that provide novel insights into cancer development. Moreover, a comprehensive understanding of the regulatory mechanisms of lncRNAs in aerobic glycolysis can provide new strategies for clinical cancer management.Keywords: lncRNA, cancer progression, glycolysis, signaling pathway

Ning Wang,1,* Yanqi Peng,1,* Lu Wang,1 Lin Song,2 Bo Sun,2 Junxiang Wei,3 Ting Wang,4 Yang Mi,3 Wei Cui1 1Department of Endocrinology and Second Department of Geriatrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, People’s Republic of China; 3The Second Department of Obstetrics, Northwest Women and Children’s Hospital, Xi’an, People’s Republic of China; 4Department of Respiratory Medicine, Xi’an No.4 Hospital, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang MiThe Second Department of Obstetrics, Northwest Women and Children’s Hospital, 1616 Yanxiang Road, Xi’an, Shaanxi, 710065, People’s Republic of ChinaTel +86-13700222172Email miyangmm@163.comWei CuiDepartment of Endocrinology and Second Department of Geriatrics, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, Shaanxi, 710061, People’s Republic of ChinaTel +86-13609281695Email doctorweiweixjtu@126.comPurpose: To study the risk factors of gestational diabetes mellitus (GDM) heterogeneity, and to evaluate the correlation between the risk factors and obesity.Methods: We performed a case–control study of 452 women with GDM and 516 women with normal glucose tolerance (NGT) at the first and second trimester. We defined GDM women as GDM-resistance subtype, GDM-dysfunction subtype, and GDM-mixed subtype, according to their simultaneous insulin-release test with predominant insulin-sensitivity defect, insulin-secretion defect, or both defects.Results: We found that higher maternal age, family history of diabetes, the elevated level of fasting blood glucose in the first trimester (≥ 5.1 mmol/L) were risk factors of all GDM subtypes. Pre-pregnancy overweight/obesity and the increased gestational weight gain (GWG) in the first-trimester are risk factors of the GDM-resistance subtype. Indicators including younger age at first menstruation, the elevated levels of alanine aminotransferase (ALT), total bile acid (TBA), triglyceride (TG), and the decreased level of high-density lipoprotein cholesterol (HDL-C) are risk factors of the GDM-resistance subtype. However, the associations between those risk factors and GDM-resistance subtype attenuated after adjusted by pre-pregnancy body mass index (pre-BMI) and gestational weight gain (GWG) in the first trimester. Nonalcoholic fatty liver disease (NAFLD) and the improved level of TG are independent risk factors for the GDM-resistance subtype and the GDM-mixed subtype, respectively.Conclusion: Women with GDM exhibited heterogeneity based on glycemic physiology and their risk factors are not all the same. Some obesity-related risk factors are specific to the GDM-resistance subtype, which are mediated by pre-pregnancy overweight/obesity and the elevated GWG the first-trimester.Keywords: pregnancy, pre-pregnancy BMI, gestational weight gain, obesity, insulin resistance, insulin secretion

Li Song,1,* Yuanjing Lyu,1,* Ling Ding,1 Xiaoxue Li,1 Wen Gao,1 Ming Wang,1 Min Hao,2 Zhilian Wang,2 Jintao Wang1 1Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030000, People’s Republic of China; 2Department of Obstetrics and Gynecology, Second Hospital of Shanxi Medical University, Taiyuan 030000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jintao WangDepartment of Epidemiology, School of Public Health, Shanxi Medical University, 56 Xinjian Nan Road, Taiyuan 030000, People’s Republic of ChinaTel +86 0351-413-5245Email wangjt59@163.comPurpose: High-risk human papillomavirus (HR-HPV) infection is widely known as the major cause of cervical cancer and there are notable differences in HR-HPV prevalence and genotype distribution in different populations. Women with abnormal cervical cytology are at increased risk of cervical cancer; however, the genotype distribution of HR-HPV in women with abnormal cervical cytology remains unclear.Methods: A total of 2,300 women with abnormal cervical cytology (from 39,988 women completing a baseline survey in a cohort established during June 2014 to December 2014) were enrolled in this study. All participants gave informed consent and completed a questionnaire about characteristics related to HPV infection. HPV genotypes were identified using flow-through hybridization, and cytology was assessed by the ThinPrep cytological test. Data were analyzed using SPSS 22.0 for Windows.Results: The overall prevalence of HR-HPV in the 2,300 women with abnormal cervical cytology was 32%, with single and multiple HR-HPV infections making up 70.2% and 29.8%, respectively. The top-five HR-HPV genotypes were HPV16 (13.5%), HPV58 (5.7%), HPV52 (4.9%), HPV53 (2.5%), and HPV51 (2.3%). The prevalence of HR-HPV in atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions or higher was 30.8%, 36.5%, and 54.9%, respectively, showing an increasing trend with severity of cervical cytology (χ2trend=13.952, p< 0.001). The prevalence of HPV16 and HPV33 increased significantly with the degree of cytological abnormality. HR-HPV infection risk was statistically higher in women aged 35– 45 years, with low education, infrequent bathing, multiple gravidity, multiple parity, history of gynecological diseases, and premenopause.Conclusion: HR-HPV infection in women with abnormal cervical cytology was 32%, and the top-five HR-HPV genotypes were HPV16, HPV58, HPV52, HPV53, and HPV51 in Shanxi Province, China. These results shed light on demographic and behavioral characteristics related to HR-HPV infection in women with abnormal cervical cytology and provide an insight for the development of HPV vaccines.Keywords: cervical cancer, high-risk human papillomavirus, genotype distribution, abnormal cervical cytology

Lei Song,1,2 Yi Luo,1 Shaoling Li,2 Ming Hong,1 Qi Wang,1 Xiaoling Chi,2 Cong Yang1 1Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, People’s Republic of China; 2The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, People’s Republic of ChinaCorrespondence: Cong Yang; Xiaoling ChiScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, People’s Republic of ChinaTel +86 15625016580Email yangcong303@163.com; chixiaolingqh@163.comAims: Isoliquiritigenin (ISL), a flavonoid from Glycyrrhiza glabra, has previously been reported to have anti-tumor effects in vivo and in vitro. However, the mechanisms whereby ISL exerts its anticancer effects remain poorly understood in hepatocellular carcinoma (HCC).Purpose: In the present study, we investigated the anticancer efficacy and associated mechanisms of ISL in HCC MHCC97-H and SMMC7721 cells.Results: We found that ISL inhibited cell viability and proliferation and induced apoptosis in a dose- and time-dependent manner in liver cancer lines. Furthermore, ISL could activate autophagy in HCC cells, and the autophagy inhibitor HCQ enhances ISL-induced apoptosis in HCC cells. Additionally, ISL induced apoptosis and autophagy through inhibition of the PI3K/Akt/mTOR pathway. Most importantly, in a xenograft tumor model in nude mice, data showed that the administration of ISL decreased tumor growth and concurrently promoted the expression of LC3-II and cleaved-caspase-3. Interestingly, we found that ISL inhibits mTOR by docking onto the ATP-binding pocket of mTOR (ie, it competes with ATP). We thus suggest that mTOR is a potential target for ISL inhibition of hepatocellular carcinoma development, which could be of interest for future investigations.Conclusion: Taken together, the results reveal that ISL effectively inhibited proliferation and induced apoptosis in HCC through autophagy induction in vivo and in vitro, probably via the PI3K/Akt/mTOR pathway. ISL may be a potential therapeutic agent for hepatocellular carcinoma.Keywords: isoliquiritigenin, hepatocellular carcinoma, apoptosis, autophagy, mTOR

Jinmei Zhang,1 Liwen Song,2 Yanjuan Ma,3 Yan Yin,1 Xinqi Liu,1 Xinyu Luo,1 Jiali Sun,1 Liqin Wang1 1Department of Endocrinology, Weifang Hospital of Traditional Chinese Medicine, Weifang, Shandong Province 261000, People’s Republic of China; 2Department of Endocrinology, Weifang People’s Hospital, Weifang, Shandong Province 261000, People’s Republic of China; 3Department of Endocrinology, Sunshine Fusion Hospital, Sunshine, Shandong Province 261061, People’s Republic of ChinaCorrespondence: Liwen SongDepartment of Endocrinology, Weifang People’s Hospital, Weifang City, Shandong Province 261000, People’s Republic of ChinaTel +86 536-963360Email zjmmjmdr@126.comBackground: It has been reported that lncRNA MEG8 can be induced by glucose in mice model of kidney injury, indicating its role in diabetic nephropathy (DN). This study was carried out to explore the role of MEG8 in DN.Materials and Methods: The expression of MEG8 and miR-770-5p in plasma samples from DN patients (n = 66), diabetic patients (DM patients with no complications, n = 66) and healthy controls (n = 66) was detected by RT-qPCR. The interaction between MEG8 and miR-770-5p in podocyte cells was evaluated by transient transfections. Cell apoptosis under high-glucose treatment was detected by cell apoptosis assay.Results: MEG8 and miR-770-5p were upregulated in plasma of DM patients and were further upregulated in DN patients. MEG8 was positively correlated with miR-770-5p. In podocyte cells, high-glucose treatment resulted in increased expression levels of MEG8 and miR-770-5p. In podocyte cells, overexpression of MEG8 resulted in upregulated expression of miR-770-5p and decreased methylation of the miR-770-5p gene. Cell apoptosis analysis showed that overexpression of MEG8 and miR-770-5p resulted in increased cell apoptotic rate under glucose treatment. In addition, combined overexpression of MEG8 and miR-770-5p showed stronger effects.Conclusion: MEG8 may upregulate miR-770-5p through methylation to promote DN by promoting cell apoptosis.Keywords: diabetic nephropathy, MEG8, miR-770-5p, apoptosis