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Anan Li,1,2 Yangfan Nie,1,2 Meixuan Chi,1,2 Naijuan Wang,1,2 Siying Ji,1,2 Zhaoying Zhu,1,2 Shan Li,1,2 Yunying Hou1,2 1Department of Nursing, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2School of Nursing, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Yunying Hou, Email houyunying@suda.edu.cnPurpose: Given the importance of adherence to health behaviors in patients with acute coronary syndrome (ACS) and the potential influence of mindfulness, it is important to determine the association between mindfulness and adherence to health behaviors and its potential mechanisms in this population. Perceived health competence is a person’s confidence in his/her ability to achieve health goals successfully and may explain how mindfulness influences adherence to health behaviors. This study aimed to examine the association between mindfulness and adherence to health behaviors and whether this association was mediated by perceived health competence.Methods: A cross-sectional study (N = 555) was conducted at the First Affiliated Hospital of Soochow University from September 2022 to January 2024. Patients’ sociodemographic and clinical data, mindfulness (Mindful Attention Awareness Scale [MAAS]), and perceived health competence (Perceived Health Competence Scale [PHCS]) were assessed one-two days before discharge, and adherence to health behaviors (Medical Outcomes Study Specific Adherence Scale [MOSSAS]) was assessed one month after discharge. Good adherence to health behaviors was defined as achieving a cumulative score of ≥ 80%. A mediating effect model was used to analyze data.Results: The mean score of adherence to health behaviors was 42.58 ± 7.13 and only 27.39% (152/555) of the patients had good adherence. Mindfulness positively predicted adherence to health behaviors (β = 0.13, P < 0.01). Perceived health competence partially mediated the association between mindfulness and adherence to health behaviors, with the mediating effect accounting for 7.00% of the total effect (P = 0.03).Conclusion: The adherence to health behaviors in patients with ACS was very low. Mindfulness positively predicted adherence to health behaviors, and perceived health competence partially mediated the association between mindfulness and adherence to health behaviors. Healthcare providers could intervene patients’ mindfulness or perceived health competence to improve adherence to health behaviors.Keywords: adherence to health behaviors, mindfulness, perceived health competence, mediating effect

Yanyu Zhong,1,&ast; Nan Wang,1,&ast; Sihui Lu,2 Yaqian Lu,2 Xin Pan,3 Ying Zhou1 1Reproductive Medicine Centre, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Zhou, Reproductive Medicine Centre, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Gusu District, Suzhou, Jiangsu Province, 215008, People’s Republic of China, Tel +86-0512-67973182, Email zhouyingzzzyyy@163.com Xin Pan, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Gusu District, Suzhou, Jiangsu Province, 215008, People’s Republic of China, Tel +86-0512-67973182, Email panxinxin9@outlook.comObjective: This study aimed to analyze uterine artery and spiral artery hemodynamics in patients with unexplained recurrent pregnancy loss (URPL) with varying pregnancy outcomes.Methods: 174 pregnant women with URPL and 144 pregnant women without adverse pregnancy histories were enrolled in this retrospective study. Based on pregnancy outcomes, these patients were divided into two groups: normal pregnancy outcomes (URPL-N, n=138) and adverse pregnancy outcomes (URPL-A, n=36). Control group participants were categorized into normal pregnancy outcomes (CON-N, n=129) and adverse pregnancy outcomes (CON-A, n=15). We compared uterine artery and spiral artery hemodynamics during different stages of gestation and the predictive value of these parameters for pregnancy outcomes.Results: URPL-N group had fewer pregnancy losses and lower BMI compared to URPL-A group (P< 0.05). Spiral artery hemodynamics in URPL-N and CON-N groups were lower than those in URPL-A and CON-A groups during the mid-luteal phase, 11– 13 weeks, 15– 17 weeks, and 19– 21 weeks of gestation, respectively. Uterine artery hemodynamics ((Pulsatility index (mPI), resistive index (mRI), and systolic-to-diastolic ratio (mS/D)) in the mid-luteal period were lower in URPL-N group than URPL-A group. Similarly, in CON-N group were lower than CON-A group. The URPL-A and CON-A groups had higher uterine artery and spiral artery hemodynamics when compared to the URPL-N and CON-N groups. Spiral artery hemodynamics exhibited larger areas under the ROC curve compared to uterine artery parameters.Conclusion: Abnormal hemodynamics in these arteries may contribute to URPL and adverse pregnancy outcomes. Spiral artery hemodynamics are more reliable predictors of pregnancy outcomes than uterine artery parameters.Keywords: unexplained recurrent pregnancy loss, spiral artery, uterine artery, blood flow, pregnancy outcome

Xia Zhao,1,&ast; Huimin Guo,2,&ast; Guangxi Shi,3 Bingying Li,1 Ning Wang2 1Department of Radiology, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, 250014, People’s Republic of China; 2Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 3Department of Breast and Thyroid Surgery, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, 250014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Wang, Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 9677 Jingshi Road, Jinan, Shandong, 250021, People’s Republic of China, Email 327242909@qq.comIntroduction: Incidental Enhancement Lesions (IELs) complicate patient management but may be detected through multiparameter MRI including dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) and synthetic magnetic resonance imaging (syMRI). The multiparameter MRI model gave greater objectivity to avoid unnecessary biopsy.Case Presentation: A 60 year-old woman had a history of occasional right breast pain and a mass was identified in the right breast. A thickening in the upper quadrant of the right outer breast was found during physical examination but no mass was palpable. Breast dynamic contrast enhancement MRI and synthetic MRI were performed prior to ultrasound-guided biopsy of the right breast lesion. Resection of the right breast lesion and sentinel lymph node was performed 2 days later. Chronic inflammation, locally invasive ductal carcinoma and high-grade ductal carcinoma in situ were found by pathological examination.Discussion: Differentiation between benign and malignant breast IELs was facilitated by use of a multiparameter MRI model with DCE-MRI and syMRI, giving greater objectivity in differentiating between benign and malignant lesions.Keywords: breast cancer, intraductal carcinoma, magnetic resonance imaging

Zixiang Geng,1,2,&ast; Tiancheng Sun,1,2,&ast; Jie Yu,1,2,&ast; Ning Wang,1,2 Qiang Jiang,1,2 Peige Wang,1,2 Guangyue Yang,1,2 Yifei Li,3 Yue Ding,4 Jiange Zhang,5 Guoqiang Lin,5 Yongfang Zhao1,2 1Shi’s Center of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Institute of Traumatology and Orthopedics, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 4School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 5The Research Center of Chiral Drugs, Innovation Research Institute of Traditional, Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zixiang Geng, Institute of Traumatology and Orthopedics, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Email gengzx@foxmail.com Yongfang Zhao, Shi’s Center of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Email zhaoyongfang@shutcm.edu.cnBackground: Cinobufagin, the primary active compound in toad venom, is commonly used for anti-tumor, anti-inflammatory, and analgesic purposes. However, its specific bone-protective effects remain uncertain. This research aims to ascertain the bone-protective properties of cinobufagin and investigate underlying mechanisms.Methods: Mice were ovariectomized to establish an osteoporosis model, followed by intraperitoneal injections of cinobufagin and cinobufagin-treated RAW.264.7-derived exosomes for therapy. MicroCT, HE staining, and TRAP staining were employed to evaluate bone mass and therapeutic outcomes, while mRNA sequencing and immunoblotting were utilized to assess markers of bone metabolism, inflammation, and lipid peroxidation. Osteoblast and osteoclast precursor cells were differentiated to observe the impact of cinobufagin-treated exosomes derived from RAW264.7 cells on bone metabolism. Exosomes characteristics were studied using transmission electron microscopy and particle size analysis, and miRNA binding targets in exosomes were determined by luciferase reporting.Results: In ovariectomized mice, cinobufagin and cinobufagin-treated exosomes from RAW264.7 cells increased trabecular bone density and mass in the femur, while also decreasing inflammation and lipid peroxidation. The effect was reversed by an exosomes inhibitor. In vitro experiments revealed that cinobufagin-treated exosomes from RAW264.7 cells enhanced osteogenic and suppressed osteoclast differentiation, possibly linked to Upregulated miR-3102-5p in RAW-derived exosomes. MiR-3102-5p targets the 3′UTR region of alox15, thereby suppressing its expression and reducing the lipid peroxidation process in osteoblasts.Conclusion: Overall, this study clarified cinobufagin’s bone-protective effects and revealed that cinobufagin can enhance the delivery of miR-3102-5p targeting alox15 through macrophage-derived exosomes, demonstrating anti-lipid peroxidation and anti-inflammatory effects. Keywords: osteoporosis, cinobufagin, exosomes, miR-3102-5p

Na Wang,1,2 Guofeng Wang,2 Xiuli Feng,2 Teng Yang2 1Department of Endocrinology, Lianyungang Clinical College of Nanjing Medical University, Lianyungang City, Jiangsu Province, 222000, People’s Republic of China; 2Department of Endocrinology, Jinzhou Medical University(The First People’s Hospital of Lianyungang), Lianyungang City, Jiangsu Province, 222000, People’s Republic of ChinaCorrespondence: Guofeng Wang, Department of Endocrinology, Lianyungang Clinical College of Nanjing Medical University (The First People’s hospital of Lianyungang), No. 6 Zhenhua East Road, Haizhou District, Lianyungang City, Jiangsu Province, 222000, People’s Republic of China, Email wangguofengo@21cn.comPurpose: This study aimed to investigate the abnormal infiltration of immune cells in type 1 diabetes mellitus (T1D) and elucidate their regulatory mechanisms.Methods: Public T1D-related gene expression data were obtained from the Gene Expression Omnibus database.The GSE123658 dataset analyzed whole blood RNA-seq data from type 1 diabetic patients and healthy volunteers. The GSE110914 dataset analyzed neutrophils purified from peripheral blood of patients with symptomatic and pre-symptomatic type 1 diabetes (T1D), at risk of T1D, and healthy controls. Immune cell infiltration analysis was performed to identify abnormally infiltrating immune cells. Differentially expressed immune genes (DEIGs) in T1D samples were identified, followed by the construction of an immune gene signature (IGS) using a protein-protein interaction (PPI) network and Least absolute shrinkage and selection operator Cox regression analyses (LASSO Cox regression analyses). The regulatory mechanisms underlying IGS were explored using gene set enrichment analysis. Furthermore, expression validation, diagnostic efficacy evaluation, and upstream miRNA prediction of hub signature genes were performed. We verified the miRNA expression of the key gene colony stimulating factor 1 (CSF1) and microRNA-326 (miR-326) by reverse transcription-quantitative PCR (RT‒qPCR).Results: The proportion of infiltrating T and natural killer (NK) cells differed between the T1D and control samples, and 207 immune genes (IGs) related to these immune cells were extracted. After differential expression, PPI, and LASSO Cox regression analyses, four signature DEIGs were identified for IGS construction: notch receptor 1 (NOTCH1), Janus kinase 3 (JAK3), tumor necrosis factor receptor superfamily member 4(TNFRSF4), and CSF1. Key pathways such as the Toll-like receptor signaling pathway were significantly activated in the high-risk group. Moreover, the upregulation of CSF1 in T1D samples was confirmed using a validation dataset, and CSF1 showed high diagnostic efficacy for T1D. Furthermore, CSF1 was targeted by miR-326.We used validated key genes in T1D patients, several of which were confirmed by RT‒qPCR.Conclusion: In conclusion, the identified key IGs may play an important role in T1D. CSF1 can be developed as a novel diagnostic biomarker for T1D.Keywords: Type 1 diabetes, immune cell infiltration, immune gene signature, diagnosis, CSF1

Ningning Wang, Yuanyuan Xu, Guangde Yang, He Chen, Xia Wang, Juanjuan Fu, Li Li, Xiucheng Pan Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Xiucheng Pan, Email xzpxc68@126.comPurpose: There is limited research on whether Proton Pump Inhibitors (PPIs) will affect the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC).This study aimed to determine whether PPIs affect the survival outcomes of patients with HBV-associated advanced HCC receiving combination therapy based on ICIs.Methods: We retrospectively analyzed patients with hepatitis B virus (HBV)-associated advanced HCC who underwent ICIs combination therapy from January 1, 2020, to December 30, 2022. Patients were stratified into PPI and non-PPI groups based on whether they received PPI treatment within 30 days before or after ICIs therapy. Patients’ survival and the risk of PPI-associated mortality was assessed. Adverse events were also evaluated.Results: A total of 183 patients with HBV-associated HCC treated with ICI combination therapy were included. The median survival time (12.5 months vs 13.7 months, P = 0.285) and incidence of adverse events (P = 0.729) did not significantly differ between the PPI and non-PPI groups. Even after propensity score matching, the difference in median overall survival (OS) between the two groups was not significant (10.7 months vs 11.4 months; P = 0.596) and the patient’s OS is not significantly related to the dosage of PPI application (P > 0.05).However, according to our subgroup analysis, among HCC patients with a serum HBV DNA concentration ≥ 200 IU/mL, the use of PPIs significantly increased the risk of mortality in patients receiving ICI combination therapy (P = 0.024).Conclusion: PPIs do not notably influence the survival prognosis of patients receiving ICI combination therapy for HBV-associated advanced HCC. However, among patients with high levels of HBV DNA, PPIs increase the risk of mortality. Therefore, antiviral therapy should be intensified in the patients with HBVDNA > 200 IU/mL. Additionally, PPIs do not impact the incidence of adverse reactions in these patients.Keywords: hepatocellular carcinoma, immune checkpoint inhibitors, proton pump inhibitors, chronic hepatitis B virus infection

Vivian Andoh,1,&ast; Dickson Kofi Wiredu Ocansey,2,3,&ast; Hassan Naveed,1 Naijian Wang,4 Liang Chen,1 Keping Chen,1 Fei Mao2 1School of Life Sciences, Jiangsu University, Zhenjiang, People’s Republic of China; 2Department of Laboratory Medicine, Lianyungang Clinical College, Jiangsu University, Lianyungang, Jiangsu, People’s Republic of China; 3Directorate of University Health Services, University of Cape Coast, Cape Coast, Central Region, CC0959347, Ghana; 4Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China&ast;The first two authors contributed equally to this workCorrespondence: Fei Mao, Department of Laboratory Medicine, Lianyungang Clinical College, Jiangsu University, Lianyungang, Jiangsu, 222006, People’s Republic of China, Tel/Fax +86 511 8503 8215, Email maofei2003@ujs.edu.cnAbstract: The relentless pursuit of effective cancer diagnosis and treatment strategies has led to the rapidly expanding field of nanotechnology, with a specific focus on nanocomposites. Nanocomposites, a combination of nanomaterials with diverse properties, have emerged as versatile tools in oncology, offering multifunctional platforms for targeted delivery, imaging, and therapeutic interventions. Nanocomposites exhibit great potential for early detection and accurate imaging in cancer diagnosis. Integrating various imaging modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging, into nanocomposites enables the development of contrast agents with enhanced sensitivity and specificity. Moreover, functionalizing nanocomposites with targeting ligands ensures selective accumulation in tumor tissues, facilitating precise imaging and diagnostic accuracy. On the therapeutic front, nanocomposites have revolutionized cancer treatment by overcoming traditional challenges associated with drug delivery. The controlled release of therapeutic agents from nanocomposite carriers enhances drug bioavailability, reduces systemic toxicity, and improves overall treatment efficacy. Additionally, the integration of stimuli-responsive components within nanocomposites enables site-specific drug release triggered by the unique microenvironment of the tumor. Despite the remarkable progress in the field, challenges such as biocompatibility, scalability, and long-term safety profiles remain. This article provides a comprehensive overview of recent developments, challenges, and prospects, emphasizing the transformative potential of nanocomposites in revolutionizing the landscape of cancer diagnostics and therapeutics. In Conclusion, integrating nanocomposites in cancer diagnosis and treatment heralds a new era for precision medicine. Keywords: nanocomposites, cancer, diagnosis, therapy, nanoparticles, theranostic

Ziteng Zhang, Guoting Sun, Yuying Wang, Ningjian Wang, Yingli Lu, Yi Chen, Fangzhen Xia Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Fangzhen Xia; Yi Chen, Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Zhizaoju road No. 639, Shanghai, 200011, People’s Republic of China, Tel +86 21 23271699-5256, Email xiafzh9h@163.com; chenyi9h@126.comObjective: Chronic low-grade inflammation of the pancreatic islets is the characteristic of type 2 diabetes (T2D), and some of the immune checkpoints may play important roles in the pancreatic islet inflammation. Thus, we aim to explore the immune checkpoint genes (ICGs) associated with T2D, thereby revealing the role of ICGs in the pathogenesis of T2D based on bioinformatic analyses.Methods: Differentially expressed genes (DEGs) and immune checkpoint genes (ICGs) of islets between T2D and control group were screened from datasets of the Gene Expression Omnibus (GEO). A risk model was built based on the coefficients of ICGs calculated by ridge regression. Functional enrichment analysis and immune cell infiltration estimation were conducted. Correlations between ICGs and hub genes, T2D-related disease genes, insulin secretion genes, and beta cell function-related genes were analyzed. Finally, we conducted RT-PCR to verify the expression of these ICGs.Results: In total, pancreatic islets from 19 cases of T2D and 84 healthy subjects were included. We identified 458 DEGs. Six significantly upregulated ICGs (CD44, CD47, HAVCR2, SIRPA, TNFSF9, and VTCN1) in T2D were screened out. These ICGs were significantly correlated with several hub genes and T2D-related genes; furthermore, they were correlated with insulin secretion and β cell function-related genes. The analysis of immune infiltration showed that the concentrations of eosinophils, T cells CD4 naive, and T cells regulatory (Tregs) were significantly higher, but CD4 memory resting T cells and monocytes were lower in islets of T2D patients. The infiltrated immune cells in T2D pancreatic islet were associated with these six ICGs. Finally, the expression levels of four ICGs were confirmed by RT-PCR, and three ICGs were validated in another independent dataset.Conclusion: In conclusion, the identified ICGs may play an important role in T2D. Identification of these differential genes may provide new clues for the diagnosis and treatment of T2D.Keywords: type 2 diabetes, immune checkpoint gene, bioinformatics, microenvironment

Zirui Bian,1,&ast; Tianzhe Bao,2,&ast; Xuequan Sun,3,4 Ning Wang,1 Qian Mu,5 Ting Jiang,6 Zhongxiang Yu,6 Junhang Ding,2 Ting Wang,7 Qihui Zhou2 1Department of Bone, Huangdao District Central Hospital, Qingdao, People’s Republic of China; 2Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, People’s Republic of China; 3Weifang Eye Institute, Weifang Eye Hospital, Zhengda Guangming Eye Group, Weifang, People’s Republic of China; 4Zhengda Guangming International Eye Research Center, Qingdao Zhengda Guangming Eye Hospital, Qingdao University, Qingdao, People’s Republic of China; 5Department of Biomaterials, LongScience Biological (Qingdao) Co, LTD, Qingdao, People’s Republic of China; 6Heart Center, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao University, Qingdao, People’s Republic of China; 7Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qihui Zhou; Junhang Ding, Tel +86-17660670299, Email qihuizhou@uor.edu.cn; dingjunhang@uor.edu.cnIntroduction: The emergence and rapid spread of multidrug-resistant bacteria (MRB) caused by the excessive use of antibiotics and the development of biofilms have been a growing threat to global public health. Nanoparticles as substitutes for antibiotics were proven to possess substantial abilities for tackling MRB infections via new antimicrobial mechanisms. Particularly, carbon dots (CDs) with unique (bio)physicochemical characteristics have been receiving considerable attention in combating MRB by damaging the bacterial wall, binding to DNA or enzymes, inducing hyperthermia locally, or forming reactive oxygen species.Methods: Herein, how the physicochemical features of various CDs affect their antimicrobial capacity is investigated with the assistance of machine learning (ML) tools.Results: The synthetic conditions and intrinsic properties of CDs from 121 samples are initially gathered to form the raw dataset, with Minimum inhibitory concentration (MIC) being the output. Four classification algorithms (KNN, SVM, RF, and XGBoost) are trained and validated with the input data. It is found that the ensemble learning methods turn out to be the best on our data. Also, &epsiv;-poly(L-lysine) CDs (PL-CDs) were developed to validate the practical application ability of the well-trained ML models in a laboratory with two ensemble models managing the prediction.Discussion: Thus, our results demonstrate that ML-based high-throughput theoretical calculation could be used to predict and decode the relationship between CD properties and the anti-bacterial effect, accelerating the development of high-performance nanoparticles and potential clinical translation. Keywords: carbon dots, machine learning, antibacterial, minimum inhibitory concentration, classification algorithms

Li Guo,1,&ast; Shi-Cui Hong,1,2,&ast; Xuan Wang,1,3,&ast; Sheng-Qi Wang,1,4 Neng Wang,4,5 Xiao-Qing Wei,1 Hong-Lin Situ,1,3,4 Zhi-Yu Wang1– 5 1Breast Disease Specialist Hospital of Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 2The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 4Guangdong-Hong Kong-Macau Joint Laboratory on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 5The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Yu Wang, Breast Disease Specialist Hospital of Guangdong Provincial Hospital of Chinese Medicine, No. 55, Inner Road West, Higher Education Mega Center(Hospital Branch Address), Guangzhou, 510120, Guangdong, People’s Republic of China, Tel +86-18819480766, Email wangzhiyu@gzucm.edu.cnBackground: Triple-negative breast cancer (TNBC) is the most aggressive malignancy. Psychological distress and elevated CXCL1 level have been reported to be closely associated with the poor prognosis and quality of life of patients with TNBC. In preclinical studies using xenograft mouse models, XIAOPI formula, a nationally approved drug prescribed to patients at high risk for breast cancer, inhibited CXCL1 expression and improved survival. Traditional Chinese medicine has unique advantages in improving patients’ emotional disorders and quality of life. However, the impact of XIAOPI formula on the serum level of CXCL1, psychological distress, and quality of life among patients with TNBC is currently unknown.Methods: In this study, we designed a randomized, double-blind, placebo-controlled trial. Patients with TNBC were randomly assigned to receive either the XIAOPI formula or a placebo for three months. The primary outcomes include serum CXCL1 expression, Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS). Secondary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and the Functional Assessment of Cancer Therapy-Breast (FACT-B).Results: A total of 60 patients with TNBC were enrolled in the investigation. The results showed that the XIAOPI formula significantly decreased CXCL1 expression compared with the control group. Moreover, in comparison to the placebo, the XIAOPI formula increased FACT-B scores while decreasing SDS, SAS, and PSQI scores.Conclusion: In patients with TNBC, XIAOPI formula may be effective in reducing CXCL1 levels, enhancing psychological well-being, and quality of life. While our research offers a natural alternative therapy that may enhance the prognosis of TNBC, future validation of its therapeutic effects will require large-scale, long-term clinical trials.Clinical Registration Number: Registration website: www.chictr.org.cn, Registration date: 2018-1-19, Registration number: ChiCTR1800014535.Keywords: anxiety, CXCL1, depression, quality of life, sleep quality, triple-negative breast cancer, XIAOPI formula

Congyang Xue,1 Xiaopei Lu,2 Guangda Sun,1 Nan Wang,1 Gansheng He,1 Wenqiang Xu,1 Zhipeng Xi,1 Lin Xie1 1Department of Spine Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Traditional Chinese Medicine Surgery, Nanjing Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaCorrespondence: Lin Xie, Department of Spine Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100th. Shizi Street, Nanjing, Jiangsu Province, 210028, People’s Republic of China, Email xielin@njucm.edu.cnPurpose: To explore the validity of the thoracic spine Hounsfield Unit (HU) measured by chest computed tomography (CT) for opportunistic screening of diabetic osteoporosis. The current study attempted to establish a diagnostic threshold for thoracic spine HU in a type 2 diabetes mellitus (T2DM) population with osteoporosis.Patients and Methods: The current study retrospectively included 334 patients with T2DM. They underwent chest CT and Dual-energy X-ray (DXA) between August 2021 and January 2022 in our hospital. HU values were measured on the resulting chest CT images at thoracic spine 11 and 12 to construct regions of interest. All patients were grouped according to the lowest T-value of DXA examination: osteoporosis, osteopenia and normal bone density. HU values were compared with T-values in each group of patients, and receiver operating characteristics curves were plotted to calculate diagnostic thresholds as well as sensitivity and specificity.Results: There was a strong correlation between the HU values of chest CT and the T-values of DXA (p < 0.01). The sensitivity for osteoporosis was 88.7% for T11 attenuation≤ 98 HU and the specificity for osteoporosis was 87.5% for T12 attenuation ≤ 117HU; the specificity for normal BMD was 85.4% for T11 attenuation ≥ 147 HU and 82% for T12 attenuation ≥ 146 HU.Conclusion: Chest CT can be used to screen patients with T2DM for opportunistic osteoporosis and help determine if they need DXA screening. The current study suggests that when the HU threshold of T11 ≤ 98/T12 ≤ 117, patients may need further osteoporosis screening.Keywords: osteoporosis, T2DM, HU, thoracic vertebra, chest CT

Nan Wang,1 Qiqi Hou,2 Shouling Wu,3 Quanle Han,4 Kangbo Li5 1Catheterization Unit, Tangshan Gongren Hospital, Tangshan, People’s Republic of China; 2Hebei Medical University, Shijiazhuang, People’s Republic of China; 3Department of Cardiology, Kailuan General Hospital, Tangshan, People’s Republic of China; 4Department of Cardiology, Tangshan Gongren Hospital, Tangshan, People’s Republic of China; 5School of Clinical Medicine, North China University of Science and Technology, Tangshan, People’s Republic of ChinaCorrespondence: Quanle Han, Email quanle.han@outlook.comBackground: Aspirin (ASA), the mainstay antiplatelet treatment in patients with cardiovascular disease (CVD), has been received by a considerable number of AF patients. This study sought to examine the association between ASA monotherapy and the risk of major adverse cardiac and cerebrovascular events (MACCE) in patients with atrial fibrillation (AF).Methods: A total of 850 patients with AF were identified from a community-based Kailuan study. All patients were assigned to two groups according to their medicine history: an aspirin therapy group (ASA group) (n = 174), and a non-aspirin therapy group (non-ASA group) (n = 676). The clinical endpoints are MACCE, including myocardial infarction (MI), ischemic stroke (IS), and hemorrhagic stroke (HS). Incidence curves for MACCE were plotted using the Kaplan–Meier method, and the Log rank test was used to assess the differences in incidence rates. The hazard ratios (HR) and 95% confidence intervals (CI) for MACCE were analyzed using Cox proportional-hazards analysis regression models.Results: During the 7.2-year follow-up, 30 MACCE occurred in the ASA group, and 101 in the non-ASA group, with a cumulative incidence of 19.88% vs 17.27%, P = 0.511; 3 cases of MI occurred in the ASA group, and 18 cases in the non-ASA group, with a cumulative incidence of 1.78% vs 2.90%, P = 0.305. Twenty-seven cases of IS occurred in the ASA group, and 84 cases in the non-ASA group, with a cumulative incidence of 1.78% vs 2.90%, P = 0.305. Eight cases of HS occurred in the ASA group, and 13 cases in the non-ASA group, with a cumulative incidence of 5.01% vs 2.34%, P = 0.045. Multivariate regression analysis showed that ASA therapy was not associated with MACCE (HR: 1.130, 95% CI: 0.747– 1.710, P = 0.562). In addition, ASA therapy was not associated with IS (HR: 1.309, 95% CI: 0.843– 2.034, P = 0.231). However, ASA therapy was significantly associated with HS (HR: 2.563, 95% CI: 1.024– 6.418, P = 0.044).Conclusion: ASA monotherapy is not associated with a lower risk of ischemic events, while significantly associated with a higher risk of bleeding events. Patients with AF are unlikely to benefit from aspirin monotherapy.Keywords: atrial fibrillation, aspirin monotherapy, major adverse cardiac and cerebrovascular events, myocardial infarction, ischemic stroke, hemorrhagic stroke

Hua Shao,1,&ast; Na Wang,2,&ast; Guoyan Liu3,4,&ast; 1Clinical Psychology Department, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Gynecology and Obstetrics Department, Tianjin Haihe Hospital, Tianjin, People’s Republic of China; 3Gynecology and Obstetrics Department, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 4Gynaecological Oncology Department, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoyan Liu, Tel +86 15510993428, Email liuguoyan2023@163.comPurpose: To investigate the accuracy of intraoperative frozen section (FS) diagnosis for predicting the permanent section (PS) diagnosis of mucinous ovarian tumors and evaluate the factors affecting the diagnostic discordance.Patients and Methods: This retrospective cohort study was performed in Tianjin Medical University General Hospital. All women who underwent ovarian surgery with FS between January 2011 and December 2022 were identified, and those with a diagnosis of mucinous ovarian tumor (MOT) by FS or PS were reviewed. Clinical and pathologic data were extracted.Results: A total of 180 women were included, of which 141 (78.33%) had diagnostic concordance between FS and PS, yielding a sensitivity of 83.43% and a positive predictive value (PPV) of 92.76%. Under- and over-diagnosis occurred in 28 cases (15.56%) and 11 cases (6.11%). Tumor size > 13cm (OR 3.79, 95% CI 1.12– 12.73) was an independent risk factor for under-diagnosis, and tumor size ≤ 13cm (OR 16.78, 95% CI 0.01– 0.49), laparoscopic surgery (OR 0.14, 95% CI 0.02– 0.92), the combination of other tumor components (including serous, Brenner tumor, and chocolate cyst; OR 7.00, 95% CI 1.19– 41.12) were independently associated with over-diagnosis. The Kaplan-Meier survival curves and the Log rank test showed no significant difference between misdiagnosed and accurately diagnosed patients (all P > 0.05).Conclusion: Intraoperative frozen pathology of MOT is problematic for under- and over-diagnosis. The incorrect diagnosis of FS was related to determining the extent of surgery but had no impact on the patients’ long-term recurrence and survival outcomes. In future clinical practice, surgeons need to obtain material accurately and enhance communication with pathologists during the operation to improve the accuracy of FS diagnosis.Keywords: mucinous ovarian tumors, frozen section, diagnosis

Liwen Feng,1 Junbo Liang,1 Naiguo Wang,2 Qingyu Zhang2 1Department of Orthopedics, Weihaiwei People’s Hospital, Weihai, Shandong Province, 264200, People’s Republic of China; 2Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, 250021, People’s Republic of ChinaCorrespondence: Qingyu Zhang, Tel +86-13296402823, Email zqy2008512@163.com; zqy2008512@126.com; zhangqingyu@sdfmu.edu.cn Naiguo Wang, Tel +86-13505319917, Email naiguow@outlook.comPurpose: The purpose of this study is to preliminarily assess the change in perioperative systemic inflammatory markers and clinical outcomes between open TLIF and BE-TLIF procedures.Patients and Methods: In total, 38 patients who underwent single-level lumbar fusion surgery (L4-5 or L5-S1) were retrospectively reviewed. 19 patients were treated by the BE-TLIF technique, while the other patients were managed using open TLIF. The perioperative serum C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR) of the two groups were compared to determine if there was a statistical difference. Meanwhile, clinical evaluations were conducted to assess various factors including operative duration, estimated blood loss (EBL), drainage catheter stay, length of hospitalization, visual analogue scale (VAS), and Oswestry disability index (ODI) scores.Results: The perioperative analysis revealed that BE-TLIF cases experienced a longer operative duration than open TLIF cases (open TLIF: 138.63 ± 31.59 min, BE-TLIF: 204.58 ± 49.37 min, p < 0.001). Meanwhile, the EBL showed an increased trend in the BE-TLIF group (260.7 ± 211.9 mL) in comparison with the open TLIF group (200.9 ± 211.9 mL) (p =0.485). In terms of systemic inflammatory markers, the mean postoperative CRP, NLR, LMR, and PLR were lower in the BE-TLIF group than in the open TLIF group, although these differences were not statistically significant (p > 0.05). The VAS and ODI scores in both groups were significantly improved after surgery (p < 0.05).Conclusion: There was no significant difference found between BE-TLIF and open TLIF in terms of systemic inflammatory markers, and clinical outcomes. Overall, BE-TLIF can be considered a viable choice for lumbar canal decompression and interbody fusion for less invasion. It is worth noting that BE-TLIF does have a longer operation time, indicating that there is still potential for further improvement in this technique.Keywords: transforaminal lumbar interbody fusion, unilateral biportal endoscope, systemic inflammatory markers

Naigeng Wang,1 Fei Li,2 Jing Du,3 Jianhong Hao,1 Xin Wang,2 Yueru Hou,3 Zhenguo Luo1 1Department of Anesthesiology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 3Second Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of ChinaCorrespondence: Zhenguo Luo, Email luozhenguo@stu.xjtu.edu.cnBackground: This study aims to investigate the protective effect of quercetin against global cerebral ischemia‒reperfusion (GCI/R) injury in rats and elucidate the underlying mechanism.Methods: A GCI/R injury rat model was established using a four-vessel occlusion (4-VO) method. An oxygen–glucose deprivation/reoxygenation (OGD/R) injury model was induced in BV2 cells. The extent of injury was assessed by evaluating neurological deficit scores (NDS) and brain water content and conducting behavioral tests. Pathomorphological changes in the prefrontal cortex were examined. Additionally, the study measured the levels of inflammatory cytokines, the degree of microglial activation and polarization, and the protein expression of Toll-like receptor 4 (TLR4) and TIR-domain-containing adaptor inducing interferon-β (TRIF).Results: Quercetin pretreatment significantly ameliorated neurological impairment, improved learning and memory abilities, and reduced anxiety in rats subjected to GCI/R injury. Furthermore, quercetin administration effectively mitigated neuronal injury and brain edema. Notably, it suppressed microglial activation and hindered polarization toward the M1 phenotype. Simultaneously, quercetin downregulated the expression of TLR4 and TRIF proteins and attenuated the release of IL-1β and TNF-α.Conclusion: This study highlights the novel therapeutic potential of quercetin in alleviating GCI/R injury. Quercetin demonstrates its neuroprotective effects by inhibiting neuroinflammation and microglial activation while impeding their transformation into the M1 phenotype through modulation of the TLR4/TRIF pathway.Keywords: quercetin, cerebral ischemia, neuroprotection, neuroinflammation

Hanwen Cheng,1,&ast; Haoyu Wu,1,&ast; Ni Tan,2,&ast; Zhuojie Liu,1 Ning Wang,1 Ningyi Chen,1 Chunhai Li1,3 1Department of Orthopaedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Cellular and Molecular Diagnostics Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 3Teaching and Research Bureau of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunhai Li, Department of Orthopaedics, Sun Yat-sen Memorial Hospital, Sun Yat‐sen University, Guangzhou, Guangdong Province, 510000, People’s Republic of China, Tel +86-18602079796, Fax +86-(20)81332523, Email lichhai@mail.sysu.edu.cnPurpose: Early diagnosis of spinal infections remains challenging, and emerging metagenomic next-generation sequencing (mNGS) technology holds promise in addressing this issue. The aim of this study is to investigate the diagnostic efficacy of mNGS in spinal infections.Patients and Methods: A total of 78 cases with suspected spinal infections were enrolled in this study, all of whom underwent laboratory, histopathological and mNGS examinations upon admission. Lesion samples were obtained by surgical or C-arm-guided puncture. Sensitivity, specificity, positive predictive value and negative predictive value of culture and mNGS were calculated for statistical analysis.Results: With histopathological results as the reference, the included 78 patients were categorized into 50 cases in the spinal infection group and 28 cases in the aseptic group. The sensitivity (84%) and negative predictive value (77.14%) of mNGS were significantly higher than those of culture (32% and 44.26%, respectively), whereas no significant differences were observed in terms of specificity and positive predictive value. In the subgroup analysis for Mycobacterium tuberculosis, the sensitivity of mNGS (90.91%) and T-spot (90.91%) was significantly higher than that of culture (0). Additionally, mNGS demonstrated markedly higher specificity (100%) compared to T-spot (85.07%).Conclusion: This study underscores the substantial advantages of mNGS in terms of diagnostic accuracy and bacterial coverage for spinal infections. The findings provide compelling clinical evidence that supports the enhanced diagnostic efficacy of mNGS.Keywords: culture, diagnosis, sensitivity, specificity, bacteria, clinical evidence

Kun Zhang, Wen Zhang, Fangzhen Xia, Ningjian Wang, Yingli Lu, Chunhua Sui, Bin Wang Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of ChinaCorrespondence: Bin Wang; Chunhua Sui, Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People’s Republic of China, Tel +86-21-23271699 ; +86-21-53315139, Email binwang1126@163.com; chunhsui@icloud.comObjective: Obesity has been identified as a risk factor for chronic kidney disease. However, the impact of obesity, with or without a metabolically healthy condition, on diabetic kidney disease (DKD) remains unclear. We aimed to examine the associations of obesity patterns and metabolic abnormalities with the prevalence of DKD.Methods: This cross-sectional study included 4079 patients with type 2 diabetes from eleven communities in Shanghai, China. General obesity was assessed by body mass index (BMI) and abdominal obesity assessed by waist-to-hip ratio. Metabolic abnormalities were determined according to the Adult Treatment Panel III criteria. DKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urinary albumin-creatinine ratio ≥ 30 mg/g. Poisson regression model with inverse probability of treatment weighting was used to estimate prevalence ratios (PRs) and 95% CIs.Results: Higher BMI and WHR were each associated with a greater prevalence of DKD after mutual adjustment. When considered jointly, patients with both general obesity and abdominal obesity had the highest odds of DKD (PR 1.51, 95% CI 1.29– 1.76). The associations of BMI and WHR with prevalent DKD were mainly observed in patients with use of antidiabetic drugs but not in those without drug use. Compared with normal-weight patients with 0– 1 metabolic abnormality, patients who were overweight or obese with 0– 1 metabolic abnormality showed increased odds of DKD. The PRs (95% CI) of DKD for patients with both overweight/obesity and abdominal obesity who had 0– 1, 2, and 3 metabolic abnormalities were 1.59 (1.20– 2.10), 1.68 (1.29– 2.18), and 2.16 (1.67– 2.78), respectively, relative to those with normal BMI and no abdominal obesity who had 0– 1 metabolic abnormality.Conclusion: BMI and WHR were positively associated with DKD prevalence. Obesity composite and metabolic abnormalities had an additive effect on the odds of DKD. Further longitudinal studies are warranted to elucidate the role of obesity and metabolic abnormalities in the development of DKD.Keywords: abdominal obesity, general obesity, diabetic kidney disease, metabolic abnormality

Ju J, Wang N, Wang J, Wu F, Ge J, Chen F. Drug Des Devel Ther. 2018;12:997-1008. At the request of the authors, the Editor and Publisher of the journal Drug Design, Development and Therapy have retracted the published article. Following publication of the article, the authors raised concerns about the duplication of images from Figure 2 with those from an unrelated article and the duplication of images within Figure 8. Specifically, Images from Figure 2B, MDA-MB-453 and MDA-MB-231, have been duplicated with the same images for Figure 2F and 3I from Dong SR, Ju XL, Yang WZ. STAT5A reprograms fatty acid metabolism and promotes tumorigenesis of gastric cancer cells. Eur Rev Med Pharmacol Sci. 2019;23(19):8360-8370. https://doi.org/10.26355/eurrev_201910_19147. Images for Figure 8, FL-/siRNA+ and FL+/siRNA-, 0 h; FL-/siRNA- and FL-/siRNA+, 12 h; FL-/siRNA-, 24 h and FL-/siRNA+, 48 h; and FL-/siRNA-, 48 h and FL+/siRNA-, 24 h, have been duplicated. The corresponding author was cooperative and responded to our queries but was unable to provide a satisfactory explanation for how the images came to be duplicated or provide satisfactory original data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the authors requested to retract the article and the Publisher and Editor agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Jiawei Zhou,1 Xiaomeng Li,1 Xiang Li,2 Na Wang,3 Xu Cai,4 Lei Zhang,1 Chen Li,1 Wei Wang,1,&ast; Na Yu1,&ast; 1Department of Respiratory and Critical Care Medicine, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Central Hospital Affiliated to Shenyang Medical College, Shenyang, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Tieling County Central Hospital, Tieling, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wang; Na Yu, Email wwbycmu@126.com; yunacmu@163.com

Yuying Zhao,1 Hanxu Tan,2 Juping Zhang,1,3 Bo Pan,1 Neng Wang,2 Tongkai Chen,4 Yafei Shi,1,2 Zhiyu Wang1,3,5 1State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Guangdong-Hong Kong-Macau Joint Laboratory on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 4Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Zhiyu Wang; Yafei Shi, Email wangzhiyu@gzucm.edu.cn; shiyafei@gzucm.edu.cnAbstract: Lipid-structured vesicles have been applied for drug delivery system for over 50 years. Based on their origin, lipid-structured vesicles are divided into two main categories, namely synthetic lipid vesicles (SLNVEs) and vesicles of mammalian origin (MDVEs). Although SLNVEs can stably transport anti-cancer drugs, their biocompatibility is poor and degradation of exogenous substances is a potential risk. Unlike SLNVEs, MDVEs have excellent biocompatibility but are limited by a lack of stability and a risk of contamination by dangerous pathogens from donor cells. Since the first discovery of plant-derived vesicles (PDVEs) in carrot cell supernatants in 1967, emerging evidence has shown that PDVEs integrate the advantages of both SLNVEs and MDVEs. Notably, 55 years of dedicated research has indicated that PDVEs are an ideal candidate vesicle for drug preparation, transport, and disease treatment. The current review systematically focuses on the role of PDVEs in cancer therapy and in particular compares the properties of PDVEs with those of conventional lipid vesicles, summarizes the preparation methods and quality control of PDVEs, and discusses the application of PDVEs in delivering anti-cancer drugs and their underlying molecular mechanisms for cancer therapy. Finally, the challenges and future perspectives of PDVEs for the development of novel therapeutic strategies against cancer are discussed. Keywords: plant-derived vesicles, cancer therapy, drug delivery, liposome nanoparticles, mammalian-derived exosomes

Zhaojun Liang,1,2 Nan Wang,1,2 Chunxue Fan,1,2 Lili Shang,1,2 Yaping Zhang,1,2 Chong Gao,3 Jing Luo1,2 1Division of Rheumatology, Department of Medicine, the Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Key Laboratory for Immunomicroecology, the Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Jing Luo, Email ljty966@hotmail.comIntroduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to disorders of immune function and a decrease in the diversity of intestinal flora. We aimed to explore the changes of circulating immune cell subsets and the plasma level of intestinal short-chain fatty acids (SCFAs) in patients with Coronavirus disease 2019 (COVID-19), further understanding the pathogenesis of COVID-19.Methods: The study included 83 newly diagnosed COVID-19 patients and 39 non-COVID-19 controls. All have completed a full course of vaccination against SARS-CoV-2. The levels of peripheral lymphocyte subsets and plasma cytokines were detected by flow cytometry. Targeted metabolomics was used to explore the level of SCFAs in plasma.Results: Compared with the non-COVID-19 group, COVID-19 patients showed a decrease in CD19+B cells, CD4+T cells, CD8+T cells, NK cells, CD4+CD8+T cells and CD4–CD8–T cells (all p< 0.001) and concomitantly an increase in sIL-2R, IL-6 and IL-10 (all p< 0.005). These alterations were more pronounced in those critical patients. In addition, COVID-19 patients had lower levels of propanoic acid (PA), butyric acid (BA), isobutyric acid (IBA) and isohexanoic acid (ICA) (all p< 0.01). Among them, the level of ICA is positively correlated with the absolute number of immune cells.Conclusion: Our study suggests the immune cell subsets in COVID-19 patients who had completed vaccination were still severely disturbed and concomitantly lower SCFAs, especially in severe patients with poor prognosis. Lower levels of plasma SCFAs may contribute to lymphopenia in COVID-19. The potential relationship between plasma SCFAs and immune cell reduction provides a new direction for the treatment of COVID-19.Keywords: coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, adaptive immunity, short-chain fatty acids

Na Wang,1 Pei Li,1 Dandan Suo,1 Hongyan Wei,1 Huanhuan Wei,2 Run Guo,2 Wen Si2 1Department of Infectious Diseases, Tangdu Hospital, Air Force Medical University, Xi’an, People’s Republic of China; 2Department of General Practice Medicine, Tangdu Hospital, Air Force Medical University, Xi’an, People’s Republic of ChinaCorrespondence: Wen Si, Department of General Practice Medicine, Tangdu Hospital, Air Force Medical University, 569 Xinsi Road, Baqiao District, Xi’an, Shaanxi Province, People’s Republic of China, Tel +86 15829643781, Email 15829643781@163.comPurpose: This study aims to identify the novel risk predictors of low medication adherence of cirrhosis patients in a large cohort and construct an applicable predictive model to provide clinicians with a simple and precise personalized prediction tool.Patients and Methods: Patients with cirrhosis were recruited from the inpatient populations at the Department of Infectious Diseases of Tangdu Hospital. Patients who did not meet the inclusion criteria were excluded. The primary outcome was medication adherence, which was analyzed by the medication possession ratio (MPR). Potential predictive factors, including demographics, the severity of cirrhosis, knowledge of disease and medical treatment, social support, self-care agency and pill burdens, were collected by questionnaires. Predictive factors were selected by univariable and multivariable logistic regression analysis. Then, a nomogram was constructed. The decision curve analysis (DCA), clinical application curve analysis, ROC curve analysis, Brier score and mean squared error (MSE) score were utilized to assess the performance of the model. In addition, the bootstrapping method was used for internal validation.Results: Among the enrolled patients (460), most had good or moderate (344, 74.78%) medical adherence. The main risk factors for non-adherence include young age (≤ 50 years), low education level, low income, short duration of disease (< 10 years), low Child-Plush class, poor knowledge of disease and medical treatment, poor social support, low self-care agency and high pill burden. The nomogram comprised these factors showed good calibration and good discrimination (AUC = 0.938, 95% CI = 0.918– 0.956; Brier score = 0.14). In addition, the MSE value was 0.03, indicating no overfitting.Conclusion: This study identified predictive factors regarding low medication adherence among patients with cirrhosis, and a predictive nomogram was constructed. This model could help clinicians identify patients with a high risk of low medication adherence and intervention measures can be taken in time.Keywords: medication adherence, cirrhosis, nomogram, prediction model

Min Li,1,2,&ast; Shuling Wan,1,&ast; Nanbu Wang,3 Jiahao Chen,4 Jiangang Duan,5 Jian Chen,6 Xuxiang Zhang,7 Ran Meng,1,2 Xunming Ji2,6 1Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute for Brain Disorders, Capital Medical University, Beijing, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China; 5Department of Emergency, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 7Department of Ophthalmology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ran Meng, Department of Neurology, Xuanwu Hospital, Capital Medical University, 45 Changchun Road, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-13693080599, Email ranmeng2011@126.com Xunming Ji, Beijing Institute for Brain Disorders, Capital Medical University, 10 You an Men Wai Road, Fengtai District, Beijing, 100069, People’s Republic of China, Tel +86-13911077166, Email jixm@ccmu.edu.cnIntroduction: Cerebral venous thrombosis (CVT) is a rare subtype of stroke. However, existing scales were insufficient to evaluate the overall severity of CVT. The aim of this study is to develop and validate a CVT severity scale.Methods: Items 1– 11 were directly derived from NIHSS. New items were generated from a literature review and focus group discussion. A total of 170 CVT patients were prospectively recruited from 26 top tertiary hospitals in China Mainland from January 2021 to May 2022 to validate the CVT severity scale. The CVT severity scale, NIHSS, mRS and GCS were rated at admission. The lumbar puncture opening pressure was also recorded. Twenty randomly selected CVT patients were rated with the CVT severity scale again 24 hours later. The clinical outcome of CVT was evaluated by mRS at 6 months after baseline.Results: We successfully established a CVT severity scale with 18 items. Exploratory factor analysis showed that 18 items were attributed to factor 1 (focal neurological deficits), factor 2 (diffuse encephalopathy), factor 3 (intracranial hypertension) and factor 4 (cavernous sinus syndrome). CVT severity scale was positively correlated with ICP, NIHSS and mRS, and negatively correlated with GCS at baseline. CVT severity scale > 3 or factor 3 > 2 indicated intracranial hypertension. CVT severity scale > 10 indicated poor clinical outcome at 6 months of follow-up. Meanwhile, CVT severity scale showed high internal consistency and test–retest reliability.Conclusion: The CVT severity scale included 18 items encompassing 4 domains of focal neurological deficits, diffuse encephalopathy, IH and cavernous sinus syndrome. CVT severity scale correlated well with ICP, NIHSS, mRS and GCS. Patients with CVT severity scale > 10 can be defined as severe CVT. The CVT severity scale may serve as a valid and reliable tool for measuring the overall severity of CVT.Keywords: cerebral venous thrombosis, clinical manifestations, severity scale, reliability, validity

Kexi Zha, Ningjian Wang, Ying Zhou, Rong Ying, Tao Gu, Yan Zhao, Hui Guo, Zengmei An, Yingli Lu Department of Endocrinology and Metabolism, Huangpu Branch of Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Yingli Lu; Zengmei An, Department of Endocrinology and Metabolism, Huangpu Branch of Shanghai Ninth People’s Hospital, Shanghai, 200011, People’s Republic of China, Tel +86-13636352507 ; +86-15921537791, Fax +86-21-63136856, Email luyingli2008@126.com; am327.ok@163.comObjective: Little is known about whether diabetic dyslipidaemia contributes to increased bone fragility in patients with diabetes. This study aimed to explore the potential effects of dyslipidaemia on vitamin D and bone metabolism in elderly subjects with type 2 diabetes (T2D).Methods: A total of 1479 male patients and 1356 female patients 50 years or older with T2D were included in Shanghai, China. Lipid profiles, 25-hydroxyvitamin D (25(OH)D), serum procollagen type I N-terminal propeptide (P1NP), β-C-terminal telopeptide (β-CTX) and other parameters were measured. Principal component regression (PCR) and mediation analysis were used to estimate the associations of lipid profile, 25(OH)D and bone turnover levels.Results: Female patients presented with higher blood lipids, lower 25(OH)D, and higher P1NP and β-CTX levels than male patients with T2D. TC was associated with P1NP in males and females (β=0.056, P< 0.05; β=0.095, P< 0.01, respectively), and 25(OH)D fully mediated the associations in males and mediated approximately 17.89% of the effects in females. LDL-C was associated with P1NP in males and females (β=0.072 and 0.105 respectively, all P< 0.01), and 25(OH)D mediated the relationships approximately 20.83% in males and 14.29% in females. TG was negatively associated with P1NP (in males, β= − 0.063, P< 0.05; in females, β= − 0.100, P< 0.01) and β-CTX (in males, β= − 0.108; in females, β= − 0.128, all P< 0.01) independent of 25(OH)D, while HDL-C was not associated with P1NP or β-CTX in diabetic patients.Conclusion: Hypercholesterolemia and hypertriglyceridaemia might affect bone metabolism by distinguishing pathways in diabetes patients. Ameliorating lipid control in elderly diabetes patients, especially female patients, will benefit both vitamin D and bone metabolism.Plain Language Summary: Diabetic dyslipidaemia may be one of the factors involved in increased bone fragility in diabetes. Currently, there have been few studies regarding the effects of dyslipidaemia on vitamin D and bone metabolism in diabetes. We aimed to explore the potential effects of dyslipidaemia on vitamin D and bone metabolism in elderly subjects with T2D. Thus, we conducted a cross-sectional study of 2835 adult T2D patients 50 years or older in Shanghai, China. Our study revealed that high levels of cholesterol and triglycerides might have detrimental effects on vitamin D metabolism and bone turnover by distinguishing pathways in elderly patients with T2D, and discrepancies exist between male and female patients. Ameliorating lipid control in elderly diabetes patients, especially female patients, will benefit both vitamin D and bone metabolism.Keywords: type 2 diabetes, elderly patients, lipid profile, vitamin D, bone turnover markers

Huang Y, Chen J, Yang S, et al. Drug Des Devel Ther. 2020;14:4625–4637. We, the Editor and Publisher of the journal Drug Design, Development and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 4 and 6. Specifically, Images for Figure 4F, MG63, control and 80 µM, have been duplicated. Images for Figure 4J, MG63, 12H, control and 100 µM, have been duplicated. Images for Figure 6D, Osteosarcoma, Blank (x 200) and 75 mg/kg (x 200) have been duplicated. Images for Figure 6E, p-Akt (Ser473), 50 mg/kg (x 400) and 75 mg/kg (x 400) have been duplicated. The authors responded to our queries but were unable to provide a satisfactory explanation for the duplicated images or provide satisfactory data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Zhixin Liu,1,2,&ast; Huanyu Zhang,1 Nan Wang,1,&ast; Yajie Feng,1,&ast; Junping Liu,1 Lin Wu,1 Zhaoyue Liu,1 Xinru Liu,1 Libo Liang,1 Jie Liu,3 Qunhong Wu,1 Chaojie Liu4 1Department of Social Medicine, School of Health Management, Harbin Medical University, Harbin, People’s Republic of China; 2Department of Health Policy and Management, School of Public Health, Peking University, Beijing, People’s Republic of China; 3Intensive Care Unit, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Public Health, School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia&ast;These authors contributed equally to this workCorrespondence: Libo Liang; Jie Liu, Email llbhit@163.com; liujie21814@126.comBackground: This study aimed to test the mediating role of anxiety and insomnia in the association between fear of infection and fatigue.Methods: A cross-sectional questionnaire survey was conducted on the nurses deployed to Heihe. A serial multiple mediation model was established to determine the role of anxiety and insomnia in the association between fear of infection and fatigue.Findings: Over half (53.0%) of the study participants reported experiencing fear of infection despite stringent personal protection measures. The scores of anxiety (11.87± 5.19), insomnia (16.33± 5.95), and fatigue (45.94± 12.93) were moderately correlated, with a Pearson correlation coefficient ranging from 0.501 to 0.579. Anxiety, either alone or in combination with insomnia, mediated the association between fear of infection and fatigue.Conclusion: The findings suggest that anxiety and insomnia play a mediating role in the relationship between fear of infection and fatigue. These results emphasize the importance of implementing targeted mental health interventions and work arrangements to address the well-being of healthcare professionals.Keywords: fear of infection, anxiety, insomnia, fatigue, COVID-19

Xin Zhao,1,&ast; Pingyuan Ge,1,&ast; Shaohua Lei,1 Siqi Guo,1 Peng Zhou,1 Li Zhao,1 Yiyu Qi,1 Xiaotong Wei,2 Weizhen Wu,2 Ningjing Wang,2 Rui Guo,3 Nianyun Yang,1 Qingqing Xiao,1 Qichun Zhang,1,2 Huaxu Zhu1 1Department of Traditional Chinese Medicine Processing and Preparation, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qichun Zhang; Huaxu Zhu, Email zhangqichun@njucm.edu.cn; zhuhx@njucm.edu.cnIntroduction: Neuroinflammation is one of the major pathogeneses in Alzheimer’s disease (AD) and mainly involves abnormal inflammatory activation of microglia by multiple pathological stimuli. The treatment of AD remains a major challenge due to the multifactorial characterization of AD and the inefficient ability of therapeutic drugs to permeate through the blood‒brain barrier (BBB). Accordingly, drug combination treatment and drug carrier delivery have become important therapeutic tools for the treatment of multifactorial diseases, especially AD.Methods: Inflammatory cytokine levels in microglia, including NO, TNF-α, IL-1β, IL-4, and IL-10, were detected. The Morris water maze and object location task were used to investigate the learning and memory functions of APP/PS1 mice in different treatment groups. The number of neurons and plasticity of synapses were evaluated by immunofluorescence double labelling. Additionally, the ratio of β-amyloid plaques and the number of activated microglia were evaluated by immunofluorescence staining. The concentrations of β-amyloid plaques and inflammatory factors in the hippocampus were determined by ELISA. Microglia-derived exosomes (Exos) were extracted and purified by size exclusion chromatography. The distribution of exosomes and drugs was investigated in vitro and in vivo.Results: Compared to single drug interventions, the combination of Ber and Pal (Ber/Pal) modulated microglial inflammatory cytokine levels. Ber/Pal promoted the recovery of learning and memory impairment in APP/PS1 mice. Immunofluorescence staining indicated that Ber/Pal restored neurons, inhibited Aβ plaque formation and microglial activation, and regulated the secretion of inflammatory factors. Exos promoted the accumulation of drugs in cells and tissues and improved the targeting of drugs across the BBB.Conclusion: Ber/Pal could offer a synergistic and more comprehensive therapeutic effect in AD. Additionally, the microglia-derived Exos-Ber/Pal delivery system promoted the targeting and permeation of drugs into the brain, suggesting a creative strategy for targeting AD therapy by regulating neuroinflammation in microglial cells.Keywords: Alzheimer’s disease, neuroinflammation, phytoconstituents, drug combination, BBB permeability, exosomes

Wenqi Shen,&ast; Lingli Cai,&ast; Bin Wang, Yuying Wang, Ningjian Wang, Yingli Lu Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingli Lu, Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Tel +86 136 3635 2507, Email luyingli2008@126.comPurpose: This study aimed to determine the associations of relative fat mass (RFM), a novel adiposity indicator, with the prevalence of non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) and compared the disease discriminative ability of RFM with other common adiposity indicators in the general Chinese population.Patients and Methods: This cross-sectional study consisted of 11,532 adult participants from the SPECT-China study (2014– 2016). We included RFM and six other adiposity indicators, including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), visceral adiposity index (VAI), and lipid accumulation product (LAP). Binary logistic regression analysis was used to assess the relationship between adiposity indicators and the prevalence of NAFLD and CVD. The receiver operating characteristic (ROC) curve was used to evaluate the ability to screen NAFLD and CVD.Results: After adjusting for confounding variables, RFM showed a strong association with the prevalence of NAFLD and CVD. In men, each 1-SD (standard deviation) increase in RFM was associated with more than 3-fold increased risk of NAFLD (OR: 4.33, 95% CI: 3.79– 4.93) and 66% increased risk of CVD (OR: 1.66, 95% CI: 1.36– 2.02); in women, per 1-SD increase in RFM was associated with about 4-fold increased risk of NAFLD (OR: 5.16, 95% CI: 4.62– 5.77) and 26% increased risk of CVD (OR: 1.26, 95% CI: 1.08– 1.47). ROC analysis showed that RFM and WHtR were the strongest predictors for CVD.Conclusion: RFM was significantly associated with prevalent NAFLD and CVD in Chinese adults and might be considered a simple tool for disease prediction. Further large longitudinal studies are needed to verify our findings.Keywords: relative fat mass, obesity, anthropometric measures, non-alcoholic fatty liver disease, cardiovascular disease

Dong Zhang,1 Yan Qu,2 Changlin Sui,2 Meiling Li,1 Yanmei Yuan,1 Ningning Wang,1 Weiyuan Ma1 1Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Dermatology, Yantai Yuhuangding Hospital, Yantai, Shandong, People’s Republic of ChinaCorrespondence: Weiyuan Ma, Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China, Email fymaweiyuan@wfmc.edu.cnBackground: Condyloma cuminata (CA) is a sexually transmitted disease caused by human papillomavirus (HPV) infection, which is prone to recurrence and difficult to cure in the short term. CD207 is a C-type lectin receptor that is specifically expressed on the surface of Langerhans cells (LCs) and is considered as an LC-specific immunohistochemical marker. The main purpose of this study is to explore the correlation between the expression of CD207 in CA skin lesions and the duration of CA disease course and frequency of recurrence, in order to provide new prognostic markers for CA to clinicians.Materials and Methods: A total of 40 male patients with CA and their skin lesions were collected, as well as 40 healthy male penile tissue samples. The skin lesions of CA were clinically and histologically confirmed by acetic acid test. The expression of CD207 in epidermal tissues was detected using immunohistochemistry. The difference in the number of CD207 positive cells between CA skin lesions and healthy skin controls was compared, and the association between the number of CD207 positive cells in CA skin lesions and the duration of disease course and the frequency of recurrence was determined through Spearman correlation analysis.Conclusion: In CA skin lesions, CD207 positive cells were found to have morphological abnormalities and the number of cells was significantly reduced compared to healthy skin, suggesting that there may be antigen presentation dysfunction in CA skin lesions, which may be the reason for the prolonged and unresolved condition of the disease. The fewer CD207 positive cells in CA skin lesions, the longer the disease course and the more frequent the recurrence, therefore, the expression level of CD207 can be used as a new prognostic marker for predicting the outcome of CA.Keywords: condyloma acuminata, CD207, langerhans cells, prognosis, biomarker

Ruixian Zhang,1 Sha Luo,1 Nan Wang,1 Hongying Zhang,2 Xuping Wu1 1The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210003, People’s Republic of China; 2Nanjing Center for Disease Control and Prevention Affiliated to Nanjing Medical University, Nanjing, Jiangsu, 210008, People’s Republic of ChinaCorrespondence: Xuping Wu, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210003, People’s Republic of China, Email xuping.wu@njucm.edu.cn Hongying Zhang, Email xiao99now@aliyun.comBackground: Nontuberculous mycobacteria (NTM) are easily misdiagnosed as multidrug-resistant tuberculosis (MDR-TB), and treatment drugs are very limited. The main objective of our study was to evaluate the minimal inhibitory concentration (MIC) in vitro of bedaquiline (BDQ), clofazimine (CFZ), linezolid (LZD), delamanid (DLM), and pretomanid (PA-824) for treatment of M. abscessus and M. intracellulare. Furthermore, we determined whether MAB_1448, MAB_4384, MAB_2299c, MAB_1483, MAB_0540, rplD, rplC, and rrl were related to drug resistance to provide an experimental basis for the use of these five drugs in the treatment of NTM.Methods: We identified sample characteristics of epidemics in 550 patients with suspected NTM infection in Nanjing from 2019 to 2021 using the PCR-reverse spot hybrid method. Furthermore, we evaluated the MIC of BDQ, CFZ, DLM, LZD, and PA-824 against 155 clinical isolates of NTM using the microbroth dilution method. The resistant isolates were sequenced using Sanger sequencing.Results: The top three dominant species of NTM distributed in Nanjing were M. intracellulare, M. avium, and M. abscessus. Notably, the proportion of M. abscessus infections increased. The proportion of M. abscessus increased from 12% in 2019 to 18% in 2021. Demographic analysis showed that female infection rates were substantialy greater than male for M. abscessus (P=0.017, < 0.05). Our results demonstrate that NTM are highly sensitive to bedaquiline and clofazimine in vitro. However, delamanid and pretomanid had little effect on M. abscessus and M. intracellulare. In addition, we found 30– 41 nucleotide deletion mutations and some novel point mutations in the MAB_0540 gene of M. abscessus that are resistant to clofazimine.Conclusion: Bedaquiline, clofazimine, and linezolid were more successful in vitro treatments against M. abscessus and M. intracellulare. The MAB_0540 mutation may be associated with resistance of M. abscessus to clofazimine.Keywords: nontuberculous mycobacteria, minimal inhibitory concentration, gene mutations

Shuang Guan,1,&ast; Ya-Nan Yu,1,&ast; Bing Li,2 Hao Gu,1 Lin Chen,1 Nian Wang,1 Bo Wang,1 Xi Liu,1 Jun Liu,1 Zhong Wang1 1Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhong Wang; Jun Liu, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimennei, Beijing, People’s Republic of China, Email zhonw@vip.sina.com; franlj1104@aliyun.comBackground: The Xueyu Zheng (XYZ) phenome is central to coronary heart disease (CHD), but efforts to detect genetic associations in the XYZ phenome have been disappointing.Methods: The phenomic alteration-related genes (PARGs) for the XYZ phenome were screened using |ρ| > 0.4 and p < 0.05 after treatment with Danhong injection at day 14 and day 30. Then, the driver genes for the Protein-Protein Interaction (PPI) networks of the PARGs established using STRING 11.0 were detected using a personalized network control algorithm (PNC). Finally, the molecular correlations of the driver genes with the XYZ phenome were analyzed with the Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways from a holistic viewpoint.Results: A total of 525 and 309 PARGs in the XYZ phenome at day 14 and day 30 were identified. These genes were separately enriched in 48 and 35 pathways. Furthermore, five driver genes were detected. These genes were mainly correlated with endoplasmic reticulum stress-mediated apoptosis and autophagy regulation, which could suppress atherosclerosis progression.Conclusion: Our study detected the drug-responsive PARGs of the XYZ phenome in CHD and provides an exemplary strategy to investigate the genetic associations among this common phenome and its component symptoms in patients with CHD.Trial Registration: ClinicalTrials.gov, NCT01681316; registered on September 7, 2012.Graphical Abstract: Keywords: coronary heart disease, Xueyu Zheng phenome, phenomics strategy, driver gene

Na Wang,1,&ast; Minghua Zhan,2,&ast; Teng Wang,3 Jinlu Liu,1 Caiqing Li,1 Baoliang Li,1 Xuying Han,1 Huiying Li,4 Shuting Liu,5 Jing Cao,1 Xinran Zhong,1 Chunmei Lei,1 Wei Zhang,1 Zhihua Zhang6 1Microbiology Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 2Clinical Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 3Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 4Obstetrics and Gynecology Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 5Hemodialysis Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 6Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Zhang; Zhihua Zhang, Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, No. 14, Changqing Road, Zhangjiakou City, Hebei Province, 075000, People’s Republic of China, Tel +86-03138043503, Fax +86-1088326317, Email 15369318318@163.com; zzh19641229@163.comPurpose: Through long-term and large sample size statistical analysis, we revealed the pattern of Klebsiella pneumoniae (KP) infection and drug resistance and provided epidemiological data for the treatment and prevention and control of multidrug-resistant bacterial infection in our hospital.Patients and Methods: Strains were identified using the BD PhoenixTM 100 system, minimal inhibitory concentration of antibiotics were determined by the broth method, and data were statistically analyzed using WHONET 5.6 and SPSS27.0.Results: The isolation rate of KP from Enterobacteriaceae (26.2%, 4547/17358) in our hospital showed an increasing annual trend, ranking second only to Escherichia coli. Carbapenem-resistant KP (CRKP) accounted for the highest proportion of carbapenem-resistant Enterobacteriaceae (72.2%, 431/597), showing an upward trend. Infected patients had a male-to-female ratio of approximately 2:1 and were mainly > 60 years of age (66.2%), with intensive care units being the most commonly distributed department. Sputum was the most common specimen type (74.0%). Compared with spring and summer, autumn and winter were the main epidemic seasons for KP and extended-spectrum β-lactamase KP (ESBL-KP). The resistance rate of KP to common antibiotics was low, but all showed an increasing trend each year. ESBL-KP was > 90% resistant to piperacillin, amoxicillin/clavulanic acid, and cefotaxime and less resistant to other common antibiotics, but showed an increasing trend in resistance to most antibiotics. CRKP resistance to common antibiotics was high, with resistance rates > 90%, excluding amikacin (64.1%), gentamicin (87.4%), cotrimoxazole (44.3%), chloramphenicol (13.6%), and tetracycline (30.5%).Conclusion: KP in our hospital mainly caused pulmonary infection in older men, which occurred frequently in autumn and winter, and the isolation and drug resistance rates showed an increasing trend. Age over 70 years, admission to intensive care unit, and urinary tract infection were found to be the risk factors for CRKP and ESBL-KP-resistance.Keywords: Klebsiella pneumoniae, antibacterial drugs, resistance trends, carbapenem-resistant, extended-spectrum β-lactamase, antimicrobial susceptibility surveillance

We report on the search results of Fast Radio Bursts (FRBs) from three Gamma- ray Bursts (GRBs) at 2256 MHz using the 40-m radio telescope located at the YunNan Astronomical Observatory (YNAO). The search for signals was triggered by the Burst Alert Telescope (BAT) on- board the Swift satellite. Radio single pulses are searched in the data over a large range of dispersion measure from 0 to 5000 pc/cm3 in step of 50 pc/cm3. No FRB-like emission from the prompt phase of GRBs are detected with significance > 5σ. If there are FRBs related to the GRBs, we set an upper limit on the ux density of radio pulses of 2.5 Jy for GRB140512A and 8.0 Jy for GRBs 140629A and 140703A with the sensitivity of the telescope. A statistical analysis of the GRB data reveals that the events detected above 5σ are consistent with the thermal noise uctuations.

Yan Xuan,1,2 Wen Zhang,1 Yuying Wang,1 Bin Wang,1 Fangzhen Xia,1 Kun Zhang,1 Qing Li,1 Ningjian Wang,1 Yingli Lu1 1Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Endocrinology, Luwan Branch, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200020, People’s Republic of ChinaCorrespondence: Yingli Lu, Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, People’s Republic of China, Tel +86-13636352507, Fax +86-21-63136856, Email luyingli2008@126.comAim: Previous studies have implicated the uric acid to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) was associated with type 2 diabetes. However, the association between UHR and diabetes-related vascular damages is still unclear.Methods: The total of 4551 patients with type 2 diabetes from the cross-sectional Environmental Pollutant Exposure and Metabolic Diseases in Shanghai study (METAL study) were enrolled. UHR was calculated as uric acid to HDL-C ratio. Cardiovascular disease (CVD) was defined as previously diagnosed with stroke, coronary heart disease, or peripheral arterial disease. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2 and/or urinary albumin to creatinine ratio ≥ 30 mg/g. Fundus image was examined by trained individuals and degree of diabetic retinopathy (DR) was evaluated.Results: UHR was positively correlated with CVD (OR = 1.28, 95% CI: 1.02– 1.61) and CKD (OR = 1.78, 95% CI: 1.39– 2.27) after adjusting for all confounders. No association was found between UHR and DR. In stratified analyses, UHR was predominantly correlated with CVD in diabetic patients with age older than 65 (OR = 1.41, 95% CI: 1.08– 1.85), female (OR = 1.43, 95% CI: 1.06– 1.94) and BMI≥ 24kg/m2 (OR = 1.57, 95% CI: 1.17– 2.11). A 1-SD increment of UHR was also positively associated with CVD (OR 1.26, 95% CI 1.03, 1.15) and CKD (OR 1.28, 95% CI 1.20,1.39). UHR was positively associated with CKD in all subgroups analysis. No significant interaction effect was observed between UHR and all subgroup variables in CVD and CKD risk.Conclusion: Our study reported a positive association between the UHR and diabetic-related vascular complications in men and postmenopausal women. The relationship between the UHR and DR seems to be uncertain and requires further investigation. And no significant interaction effect was observed between the UHR and all subgroup variables in CVD and CKD risk.Keywords: type 2 diabetes, uric acid to HDL cholesterol ratio, cardiovascular disease, chronic kidney disease, diabetic retinopathy, inflammation

Xin Zhang,1,&ast; Yang Zhang,2,&ast; Ning Wang,1 Yetong Shen,1 Qing Chen,2 Lu Han,1 Bo Hu1 1Department of Biochemistry and Molecular Biology, School of Life Sciences, China Medical University, Shenyang, 110122, People’s Republic of China; 2School of Pharmacy, Shenyang Medical College, Shenyang, 110034, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Hu, Email bhu@cmu.edu.cn; 86hubo86@163.comIntroduction: To present a safer tumor therapy based on bacteria and identify in detail how the activation and infection behavior of spores can be controlled remotely by near-infrared light (NIR-irradiation) based on nanoheaters’ modification.Methods: Spores bring a better tolerance to surface modification. Transitive gold-nanorods-allied-nanoclusters-modified spores (Spore@NRs/NCs) were constructed by covalent glutaraldehyde crosslink. The photothermal properties of nanoheaters before and after attachment to spores were studied by recording temperature–irradiation time curves. The controlled viability and infection behavior of Spore@NRs/NCs were investigated by NIR-irradiation.Results: In this work, a controllable sterilizing effect to activated vegetative bacteria was obtained obviously. When met with a suitable growth-environment, Spore@NRs/NCs could germinate, activate into vegetative bacteria and continue to reproduce. Without NIR-irradiation, nanoheaters could not affect the activity of both spores and vegetative bacterial cells. However, with NIR-irradiation after incubating in growth medium, nanoheaters on spores could control the spores’ germination and affect the growth curve as well as the viability of the vegetative bacterial cells. For Spore@NRs/NCs (Spore:NCs:NRs=1:1:4, 67.5 μg mL− 1), a ~98% killing rate of vegetative bacterial cells was obtained with NIR-irradiation (2.8 W cm− 2, 20 min) after 2 h-incubation. In addition, these nanoheaters modified on spores could be taken not only to the vegetative bacteria cells, but also to the first-generation bacteria cells with their excellent photothermal and bactericidal performance, as well as synergetic anticancer effect. NIR-irradiation after 2 h-incubation could also trigger Spore@NRs/NCs (1:1:4, 6 μL) to synergistically reduce the viability of HCT116 cells to 15.63± 2.90%.Conclusion: By using NIR-irradiation, the “transitive” nanoheaters can remotely control the activity of both bacteria (germinated from spore) and cancer cells. This discovery provides basis and a feasible plan for controllable safer treatment of bacteria therapy, especially anaerobes with spores in hypoxic areas of the malignant solid tumors.Graphical Abstract: Keywords: transitive nanoheaters, modified spores, NIR-remotely triggered, controlled sterilization, hyperthermia, adjustable activity behavior

Na Wang1 &ast;, Jing-yi Tang2 &ast;, Zi Wang,3 Liu-yao Wang,4 Tian-tian Song,5 Bei-bei Li,5 Lin Wang5 1Department of Pediatrics, Wuhan No. 1 Hospital, Wuhan, People’s Republic of China; 2Department of Pharmacy, Wuhan No. 1 Hospital, Wuhan, People’s Republic of China; 3Department of Dermatology, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, People’s Republic of China; 4Department of Pediatrics, Fuyong People’s Hospital, Shenzhen, People’s Republic of China; 5Department of Neonatology, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Wang, Department of Neonatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email wl1894@yeah.netAbstract: Trichosporon asahii is an uncommon cause of fungal sepsis among neonates, but it is an important life-threatening opportunistic systemic pathogen. We report a case of T. asahii sepsis in a 980-g female baby born at 27 weeks of gestation. The extremely preterm initially presented with recurrent feeding intolerance and bloating; she subsequently developed oxygen saturation fluctuations, apnea, and a decreased heart rate. Blood culture was positive, and the causative agent was identified as T. asahii by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). According to reported minimum inhibitory concentration (MIC) values, the infant received a high dose of fluconazole (FLC, 12 mg/kg, qod) and was successfully treated.Keywords: preterm, Trichosporon asahii, fluconazole, voriconazole, China

Ying Yang,1 Ning Wang,2 XinXin Tian,1 XiaoLi Wang,1 Jing Yang,1 XiGang Leng,1 HaiLing Zhang1 1Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomaterials, Tianjin, People’s Republic of China; 2Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: HaiLing Zhang, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomaterials, Tianjin, People’s Republic of China, Tel +86 22 8789 1191, Fax +86 22 8789 0153, Email zhanghl@bme.pumc.edu.cnBackground: Tumor immunotherapy, a novel type of therapeutic treatment, has a wide range of applications with potentially prolonged benefits. However, current immunotherapy has a low overall response rate in treating a variety of tumors. Combination of immunotherapy with other therapies can improve the therapeutic response rates. The purpose of this work was to explore the potential of anti-angiogenic treatment in combination with tumor cell lysate loaded polydopamine nanoparticle vaccine as a therapeutic strategy for colon tumor.Methods: We grafted tumor cell lysate onto polydopamine nanoparticles as nano-vaccine (TCLN) and fabricated alginate hydrogel loaded with Endostar (EH), then detected characteristics of EH and TCLN. We also estimated the cytotoxicity of EH/TCLN in vitro. In the tumor-bearing mouse model, we evaluated the antitumor effect of EH/TCLN treatment, and developed the animal survival study. After performing the EH/TCLN treatment, we also analyzed T cells and DCs using flow cytometry, and determined T cell responses and tumor microenvironmental cytokines. At last, we assessed the effect of the EH/TCLN treatment on anti-angiogenesis further.Results: When applied in combination with TCLN in MC-38 tumor-bearing mice, EH/TCLN significantly suppressed tumor growth with more than half of the mice showing tumor regression. In addition, EH/TCLN treatment resulted in noticeable changes in the tumor microenvironment. As compared with the control group, EH/TCLN treatment led to significantly reduced tumor angiogenesis and expression of tumor microenvironment-related cytokines (TMCs), increased proportion of CD8+ T cells in the spleen, lymph node and tumor, elevated activity of cytotoxic T lymphocytes (CTLs) and tumor cell apoptosis.Conclusion: The present study demonstrated that the EH/TCLN treatment effectively created a favorable immune microenvironment for the induction of antitumor immunity and improved antitumor immune responses.Graphical Abstract: Keywords: alginate, polydopamine, Endostar, colon tumor, angiogenesis, immunotherapy

Tao Liu,1,&ast; Xiulu Yang,2,&ast; Yanli Wu,1 Min Chen,1 Yu Yang,2 Yun Chen,2 Yiying Wang,1 Jie Zhou,1 Kelin Xu,2 Na Wang,2 Chaowei Fu2 1Guizhou Center for Disease Control and Prevention, Guiyang, 550004, People’s Republic of China; 2School of Public Health; NHC Key Laboratory of Health Technology Assessment, Fudan University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaowei Fu, School of Public Health; Key Laboratory of Public Health Safety; NHC Key Laboratory of Health Technology Assessment, Fudan University, Shanghai, 200032, People’s Republic of China, Tel/Fax +86 21 33563933, Email fcw@fudan.edu.cnPurpose: Few studies have explored the associations between diet patterns and incident obesity in China. This study aimed to explore associations between dietary patterns and incident obesity in a prospective community-population cohort in Southwest China.Patients and Methods: Totally, 5742 adult residents from Guizhou province were eligible for this analysis. Demographic characteristics, lifestyle, history of chronic diseases, and dietary patterns measured by hundred-item food frequency questionnaires (FFQs) were collected at the baseline study. Four dietary patterns were identified using factor analysis. Cox proportional hazard models stratified by physical activity were used to explore the association and estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI).Results: Among 5742 subjects, the average age was 45.06 ± 15.21 years old and more than half were women. During the follow-up of 40,524.15 person years (PYs), the overall incidence rate of obesity was 10.54/1000PYs. After the adjustment for possible confounding factors, subjects with the third (aHR: 1.51, 95% CI: 1.14– 2.00) and the fourth quartile (aHR: 1.46, 95% CI: 1.10– 1.94) of junk food patterns had statistically increased risk of incident obesity compared to those with the first quartile. Also, subjects with the third quartile of the western pattern had significantly higher risk of incident obesity (aHR: 1.33, 95% CI: 1.01– 1.75) than those with the first quartile.Conclusion: There was a high risk in incident obesity among Chinese community population of Southwest China and unhealthy diet significantly increased risk of developing obesity. The findings indicated that effective and targeted measures to improve dietary patterns need to be undertaken urgently in Southwest China.Keywords: dietary patterns, obesity, cohort study, factor analysis, China

Jing Luo,1 Nuoyan Wang,1 Ling Hua,1 Fei Deng,1 Dan Liu,1 Jun Zhou,1 Yue Yuan,1 Fumin Ouyang,1 Xuemin Chen,1 Shujuan Long,1 Yasi Huang,1 Zhanxing Hu,2,3 Hong Zhou1 1Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, People’s Republic of China; 2State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, People’s Republic of China; 3The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, People’s Republic of ChinaCorrespondence: Hong Zhou, Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, People’s Republic of China, Tel +86-085128643451, Fax +86-085128642303, Email zhouh64@163.com Zhanxing Hu, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, People’s Republic of China, Email huzhxi88@163.comBackground: The anti-inflammatory application of Guizhou ethnic medicine in the Karst area of China is mainly based on folk medicine experience, and there has been a lack of systematic research, leading to limited application of Guizhou ethnic medicine.Purpose: To evaluate the anti-inflammatory effects of compounds extracted from Guizhou ethnic medicine in the Karst area and investigate their molecular mechanisms.Methods and Results: Preliminarily, the anti-inflammatory effects of 181 compounds extracted from Guizhou ethnic medicine were screened in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and the 41 compounds with anti-inflammatory effects were selected. Then, these 41 compounds with anti-inflammatory effects were investigated for their druggability and 18 compounds were selected. Thirdly, compound Hx-150, named isocorydine, was selected as the candidate compound. In vitro and in vivo, isocorydine inhibited LPS-induced TNF-α and IL-6 release from LPS-treated mouse peritoneal macrophages. Isocorydine decreased TNF-α, IL-6, and IL-1β levels in the blood, lung, and spleen, and ameliorated lung tissue damage. Mechanistically, isocorydine had no effect on the mRNA expressions and protein levels of Tlr4, Myd88, and Traf6. Isocorydine also had no effect on the expression of RelA (encoding NFκB p65) mRNA, but inhibited phosphorylation of IκBα and NFκB p65 in the TLR4-mediated signaling pathway. Furthermore, isocorydine increased the cytoplasmic level of NFκB p65 and decreased its nuclear level in LPS-treated macrophages. Importantly, isocorydine upregulated Vdr mRNA (encoding the vitamin D receptor) expression and increased the nuclear VDR protein level.Conclusion: Many compounds from Guizhou ethnic medicine had potential anti-inflammatory activities. Among them, isocorydine has a strong anti-sepsis effect, which is tightly related to its upregulation of VDR expression and inhibition of NFκB p65 translocation into the nucleus, leading to reduced pro-inflammatory cytokines release and protection for LPS-challenged mice.Keywords: Guizhou ethnic medicine, LPS, Sepsis, Pro-inflammatory cytokines, NFκB, VDR

Wen Bao,1,&ast; Deqing Wu,1,&ast; Wei Han,1 Rui Kong,1 Nan Wang,1 Jie Lu2 1Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, 200072, People’s Republic of China; 2Department of Gastroenterology, Gongli Hospital, School of Medicine, Shanghai University, Shanghai, 200135, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Lu, Email kennisren@hotmail.comBackground: Extracorporeal shock wave lithotripsy (ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) are the main treatments for chronic calcific pancreatitis (CCP). However, clinical outcomes remain unclear for patients underwent different interventional therapies based on these two techniques.Methods: A total of 125 patients with CCP who underwent ESWL, ERCP or a combined treatment at two medical centers from January 2019 to January 2020 were considered. Patients were divided into four groups according to intervention types (ESWL-alone, ERCP-alone, ESWL-ERCP and ERCP-ESWL). A retrospective survey with a follow-up for 2 years was conducted. The main outcome measures were postoperative complications, abdominal pain and re-intervention during the follow-up. Possible prognostic factors were evaluated by multivariate analysis.Results: Patients in ESWL-ERCP group had the highest complete pain relief rate (49.28%), the lowest pain frequency (1 time/year) and intensity (VAS-score, 1.84± 1.93) during the follow-up, which were statistically significant compared with the other three groups. ESWL-ERCP group also had the lowest postoperative complication rate (6%), while the highest complication rate (16%) was observed in ESWL-alone group. Both ESWL-alone and ESWL-ERCP group had significant lower frequencies of re-interventions (0.44 ± 0.73, 0.57± 0.98, respectively) after the initial treatments. An analysis of treatment-based prognostic factors found significant interactions between age, course of CCP, max pancreatic duct stone diameter, calcium, glycosylated hemoglobin (HbA1c) and triglyceride.Conclusion: ESWL-ERCP was considered as the most effective interventional therapy for CCP with a better safety in a two-year follow-up. Prognostic factors may help to determine the patients who benefit by this technique.Keywords: chronic calcific pancreatitis, ESWL, ERCP, follow-up

Qianting Yang, Jiao Xie, Yan Cai, Na Wang, Yan Wang, Li Zhang, Youjia Li, Jingjie Yu, Ya Li, Haitao Wang, Kanghuai Zhang Department of Pharmacy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Kanghuai Zhang, Department of Pharmacy, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwu Road, Xi’an, 710004, People’s Republic of China, Tel +86-29-87679282, Email zhangkanghuai12@163.comPurpose: To determine whether combinations of antifungal drugs are effective and safe for patients in intensive-care units.Methods: This study compared the efficacy and safety of caspofungin (CAS), voriconazole (VOR), amphotericin B liposome (L-AmB), CAS+VOR, and CAS+L-AmB as empirical, preemptive, and targeted therapies for invasive fungal infection (IFI).Results: Comparing the CAS, VOR, and CAS+VOR groups revealed that there were no differences in response rates between all therapy types, IFI-associated death within 90 days was less common in the CAS+VOR group (1.8%) than the VOR group (14.3%), and there were more adverse events in the VOR group than in the CAS group (P < 0.05). For empirical or preemptive therapy, the CAS group had a better response rate (80.0%) than the CAS+VOR group (47.1%), and there were more adverse events in the VOR group than in the CAS group (P < 0.05). For targeted therapy, no differences were found for efficacy and safety. There were no differences among the CAS, L-AmB, and CAS+L-AmB groups in efficacy and safety.Conclusion: Patients who received CAS monotherapy as an empirical or preemptive therapy could achieve good outcomes. Patients who received CAS+VOR or CAS+L-AmB achieved almost the same outcomes when compared with those who received CAS, VOR, and L-AmB monotherapy as targeted therapies, but those who received CAS+VOR had a lower IFI mortality rate than did those who received VOR monotherapy.Keywords: caspofungin, voriconazole, amphotericin B liposome, combination therapy, invasive fungal infection, intensive-care units

Nan Wang,1 Xuanyu Huang,1 Qian Long2 1School of Life Science, Jiaying University, Meizhou, People’s Republic of China; 2Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Nan Wang; Qian Long, Email wangnan@jyu.edu.cn; dr_longqian@foxmail.comBackground: Altered lipid metabolism is associated with gastric cancer (GC) progression. Comprehensive analysis to identify critical lipid metabolic drivers for predicting overall survival (OS) is not fully elucidated in GC. Our study aim to explore a novel lipid metabolism-related prognostic marker for GC.Methods: Transcriptional status and clinical features were obtained from the TCGA-STAD database. The differentially expressed lipid metabolic genes and the risk prognostic model were developed by using bioinformatics and Cox regression analyses. ROC and Kaplan–Meier analysis were established to assess the performance of the risk predictive score model. GSE84437 dataset was used for external validation. Immunochemistry (IHC) was used to examine the expression of CYP19A1 in GC patients. Gene Set Enrichment Analysis (GSEA) was conducted to elucidate the underlying enriched mechanisms. TIMER and CIBERSORT analysis were performed to explore the relationship between CYP19A1 and immune microenvironment.Results: A novel lipid metabolic gene signature (including MTTP, CYP19A1, MYB, SERPINE1), and specifically CYP19A1, might be a promising prognostic factor for GC. Using the validation cohort, ROC curves indicate a good showing of our risk model. Based on the signature yielded a significant difference OS time between the low- and high-risk groups. Cox regression indicates that the signature is an independent prognostic variable. ROC curves present better and reliability predictive accuracy. The IHC data validate that high expression of CYP19A1 was found in GC tissues. GSEA analysis reveals that higher expression of CYP19A1 may significantly up-regulate genes involved in fatty acid metabolism and glycerolipid metabolism. CIBERSORT analysis suggests that CYP19A1 is related to the infiltration of multiple immune cells.Conclusion: CYP19A1 could be an independent prognostic factor and a novel metabolic-targeted treatment strategy for gastric cancer.Graphical Abstract: Keywords: gastric cancer, lipid metabolism, prognostic signature, CYP19A1, immune infiltration

Wang N, Feng Y, Xie J, Han H, Dong Q, Wang W. Cancer Manag Res. 2020;12:13285-13300. At the author’s request, we, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 5 and 7 with images from other unrelated articles. Specifically, The image for Figure 5G, HL-60, ZNF667-AS1 si+miR-206 inh, has been duplicated with the image for Figure 5d, H460, miR-520a control, from Xie Y, Xue C, Guo S, Yang L. MicroRNA-520a Suppresses Pathogenesis and Progression of Non-Small-Cell Lung Cancer through Targeting the RRM2/Wnt Axis. Analytical Cellular Pathology. 2021;2021: Article ID 9652420. https://doi.org/10.1155/2021/9652420. The image for Figure 7H, HL-60, miR-206 inh+NC, has been duplicated with the image for Figure 4H, HSC-1, TIMP3 si, from Yin S, Lin X. MicroRNA-21 Contributes to Cutaneous Squamous Cell Carcinoma Progression via Mediating TIMP3/PI3K/AKT Signaling Axis. Int J Gen Med. 2021;14:27-39. https://doi.org/10.2147/IJGM.S275016. In addition, Figure 5G, HL-60, ZNF667-AS1 si+miR-206 inh and Figure 7H, HL-60, miR-206 inh+NC, have been duplicated. When approached for an explanation, the authors were cooperative and provided some data for their study. However, the author’s explanation and the provided data did not sufficiently explain how the duplication of these images occurred and was unable to alleviate the journal’s concerns regarding the validity of the findings. As verifying the validity of published work is core to the integrity of the scholarly record, the authors requested to retract the article and the Editor and Publisher agreed with this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Neng Wang,&ast; Conglin Zhao,&ast; Congchen Tang, Lichun Wang Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lichun Wang, Center of Infectious Diseases, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, 610041, People’s Republic of China, Tel +86 288 542 2859, Fax +86 288 542 3052, Email mindywang0218@163.comBackground: Histoplasmosis is a deep fungal infection caused by Histoplasma capsulatum and can be classified as pulmonary, disseminated or central. Disseminated histoplasmosis is the most dangerous of all clinical types and is characterized by rapid onset, rapid progression, high mortality, and difficulty in diagnosis and treatment.Case Presentation: This report describes a 31-year-old female who presented with fever, with a maximum temperature of 39.8 °C. There were no concomitant symptoms, such as cough, sputum, abdominal pain and diarrhoea, before the onset of fever, and the illness lasted for more than 20 days. On examination, the liver and spleen were enlarged, and laboratory tests showed a significant decrease in CD4 cell count, suggesting immune deficiency. Broad-spectrum antibiotic treatment was ineffective, and specific infectious diseases and haematological neoplasms were considered likely. She was finally diagnosed with disseminated histoplasmosis after undergoing bone marrow aspiration and metagenomic next-generation sequencing (mNGS) and was treated with amphotericin B, fluorouracil and itraconazole, with good results.Conclusion: This case demonstrates that disseminated histoplasmosis infection can present with unexplained fever and that mNGS can be an important complement to bone marrow aspiration for the diagnosis of this disease.Keywords: disseminated histoplasmosis, immune deficiency, metagenomic next-generation sequencing, amphotericin B, case report

Na Wang,1,2,&ast; Hong Zhang,3,&ast; Yihua Yin,4,&ast; Xiaogang Xu,1 Li Xiao,5 Yang Liu1 1Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 2Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Clinical Laboratory, Shanghai Children’s Hospital, Shanghai Jiaotong University, Shanghai, 200062, People’s Republic of China; 4Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China; 5Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA&ast;These authors contributed equally to this workCorrespondence: Yang Liu, Institute of Antibiotics, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, People’s Republic of China, Tel +86-21-52888197, Email liuyang@fudan.edu.cn Li Xiao, Department of Medicine, University of Alabama at Birmingham, 1720 2nd Ave South, SHEL 206, Birmingham, AL, 35294, USA, Tel +1-205-996-1378, Email lixiao@uabmc.eduObjective: The current study investigated the recent genetic characteristics and antimicrobial susceptibility profiles of Mycoplasma pneumoniae (M. pneumoniae) in Shanghai, becoming a clinical reference for treating M. pneumoniae infection in Shanghai.Methods: Clinical strains were isolated from nasopharyngeal aspirates of the pediatric patients in Shanghai from 2017 to 2019. Nine antimicrobial agents of three antimicrobial classes macrolides, fluoroquinolones and tetracyclines, against M. pneumoniae isolates were investigated using the broth microdilution method. The mechanism of macrolide resistance was analyzed by evaluating the sequences of the 23S rRNA gene and the ribosomal protein genes L4 and L22. Molecular genotyping was undergone to classify the P1 subtypes and the multi-locus variable-number tandem-repeat analysis (MLVA) types.Results: A total of 72 isolates were resistant to macrolides (MICs > 64 mg/L for erythromycin) based on the A2063G mutation in the 23S rRNA gene. These strains were susceptible to tetracyclines and fluoroquinolones. P1 type 1 (166/182, 91.2%) and MLVA type 4-5-7-2 (165/182, 90.7%) were the dominant subtypes. MLVA type was associated with the P1 subtypes. The distribution of the P1 subtypes and MLVA types did not change over time. The macrolide-resistant rate in P1 type 2 and MLVA type 3-5-6-2 strains were increased during the three-year study. The 5-loci MLVA typing scheme revealed the clonal expansion of MLVA type 3-4-5-7-2 strains which are macrolide-resistant in 2019.Conclusion: Macrolide resistance in M. pneumoniae in Shanghai is very high and is evolving among certain subtypes. Cautions should be taken for the possible clonal spreading of macrolide-resistant genotypes within this populated region.Keywords: Mycoplasma pneumoniae, molecular genotyping, macrolide resistance, resistant mechanism

Nan Wang,1,2 HongZhan Sun1 1Department of Obstetrics and Gynecology, Taizhou People’s Hospital, Taizhou, Jiangsu Province, People’s Republic of China; 2Department of Graduate College, Dalian Medical University, Dalian, Liaoning Province, People’s Republic of ChinaCorrespondence: HongZhan Sun, Email sunzhureng@163.comAbstract: It’s been 100 years since the first intrauterine device (IUD) was invented in Germany in 1920. IUDS are widely favored by women of childbearing age for their efficiency, convenience, cheapness, and variety of materials. According to incomplete statistics, about 26 million people worldwide will need to have their IUDS removed from 2015 to 2025 alone. With such a large case base, we have to pay attention to the safety of IUD removal. There are few international guidelines on IUD placement and removal. Therefore, this paper will report a case of uterine artery rupture caused by ring removal, and discuss the important steps of ring removal surgery, so as to enhance the attention of physicians to the standard and safety of ring removal and improve the quality of medical treatment.Keywords: IUD removal, acute complications, case report

Yan Xuan,1,2,&ast; Wen Zhang,1,&ast; Yuying Wang,1 Bin Wang,1 Yi Chen,1 Fangzhen Xia,1 Kun Zhang,1 Qing Li,1 Ningjian Wang,1 Yingli Lu1 1Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Endocrinology, Luwan Branch, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingli Lu, Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China, Tel +86-13636352507, Fax +86-21-63136856, Email luyingli2008@126.comBackground: The aim of this study was measuring the association between the hypertriglyceridemic-waist (HTGW) phenotype and chronic kidney disease in a large type 2 diabetes population.Methods: A total of 4254 diabetic patients from the cross-sectional Environmental Pollutant Exposure and Metabolic Diseases in Shanghai (METAL) study were enrolled. The hypertriglyceridemic-waist (HTGW) phenotype was defined as the presence of an elevated waist circumference (WC) and elevated triglyceride (TG) concentration. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 or urinary albumin creatinine ratio (uACR) more than 30 mg/g. Linear and multiple logistic regression models were used for measuring the association between HTGW phenotype and chronic kidney disease.Results: The prevalence of CKD was 29% and 35.8% in total participants and participants with HTGW phenotype, respectively. Subjects in the HTGW phenotype group were more likely to have CKD (OR 1.47, 95% CI: 1.11, 1.95) compared with subjects in the normal waist circumference and normal triglycerides (NTNW) group. HTGW phenotype was both associated with the increasing risk of decreased eGFR (OR 1.31, 95% CI: 1.02, 1.75) and elevated uACR (OR 1.57, 95% CI: 1.18, 2.11). Furthermore, the stratified analysis showed that the strongest positive association between HTGW phenotype and CKD presence was found in the subgroup of presence of hypertension. The associations were all fully adjusted for age, sex, BMI, current smoking, current drinking and other confounding factors.Conclusion: Our study suggested a positive association between the HTGW phenotype and CKD in Chinese type 2 diabetes patients. Further prospective studies are needed to confirm our findings and to investigate the underlying biological mechanisms.Keywords: central obesity, type 2 diabetes mellitus, hypertriglyceridemia waist phenotype, chronic kidney disease

Ning Wang,1,2 Zhenjiang Guo,3 Xiaowei Gong,1 Shiwei Kang,1 Zhaobo Cui,2 Yadong Yuan1 1Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Hengshui People’s Hospital, Hengshui, People’s Republic of China; 3Department of Gastrointestinal Surgery, Hengshui People’s Hospital, Hengshui, People’s Republic of ChinaCorrespondence: Yadong Yuan, Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Tel/Fax +86-311-66003989, Email yuanyd1108@163.comBackground: Pulmonary hypertension (PH) is a life-threatening complication of chronic obstructive pulmonary disease (COPD). Timely diagnosis of PH in COPD patients is vital to achieve proper treatment; however, there is no algorithm to identify those at high risk. We aimed to develop a predictive model for PH in patients with COPD that provides individualized risk estimates.Methods: A total of 527 patients with COPD who were admitted to our hospital between May 2019 and December 2020 were retrospectively enrolled in this study. Using echocardiographic results as a standard, patients were stratified into a moderate- or high-PH probability group and a low-PH probability group. They were randomly grouped into either the training set (n = 368 patients) or validation set (n = 159 patients) in a ratio of 7:3. We utilized the least absolute shrinkage and selection operator (LASSO) regression model to select the feature variables. The characteristic variables selected in the LASSO regression were analyzed using multivariable logistic regression to construct the predictive model. The predictive model was displayed using a nomogram. We used the receiver operating characteristic curve, calibration curve, and clinical decision curve analysis (DCA) to evaluate model performance, and internal validation was assessed.Results: The predictive factors included in the prediction model were Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, emphysema, PaCO2, NT-pro-BNP, red blood cell (RBC) distribution width-standard deviation (RDW-SD), and neutrophil/lymphocyte ratio (NLR). The predictive model yielded an area under the curve (AUC) of 0.770 (95% confidence interval [CI], 0.719– 0.820); in the internal validation, the AUC was 0.741 (95% CI, 0.659– 0.823). The predictive model was well calibrated, and the DCA showed that the proposed nomogram had strong clinical applicability.Conclusion: This study showed that a simple nomogram could be used to calculate the risk of PH in patients with COPD which can be useful for the individualized clinical management of COPD patients who may be occur with PH. Further studies need to be confirmed by larger sample sizes and validated in the stable COPD population.Keywords: chronic obstructive pulmonary disease, pulmonary hypertension, nomogram, LASSO regression

Shuang Yang,1,2,* Xin Yin,3,* Yanan Zhang,4 Hanwei Zhao,4 Zixuan Zheng,2 Junqing Li,2 Xiaoying Hu,1 Juan Xie,2 Zhijun Jie,2 Na Wang,3 Jindong Shi2 1Department of General Medicine, Jiangchuan Community Healthcare Service Center of Minhang District, Shanghai, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Epidemiology, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 4Department of General Medicine, Zhuanqiao Community Healthcare Service Center of Minhang District, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jindong Shi, Department of Respiratory and Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, People’s Republic of China, Tel +86 18918168579, Email shijindong@5thhospital.com Na Wang, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 13564748559, Email na.wang@fudan.edu.cnPurpose: To evaluate the screening efficacy of a self-designed questionnaire for chronic obstructive pulmonary disease (COPD) and the potential gender disparity in its efficacy.Patients and Methods: A screening questionnaire, the COPD Screening Questionnaire-Minhang (COPD-MH), was designed with reference to the self-scored COPD population screener (COPD-PS) and the COPD screening questionnaire (COPD-SQ), incorporating characteristics of the local population in Shanghai, China. The revised questionnaire included only five questions. Each question scored 0– 4, with a highest total score of 20. The COPD-PS and COPD-SQ comprised 5 and 7 questions, respectively. Their scoring criteria were not consecutive integers and, thus, not easily counted. The COPD-MH focused on symptoms, and each item was set the same answers for convenience. Screening for COPD was conducted among residents over 40 years old in a community in Shanghai using the three aforementioned questionnaires. Each participant also received spirometry tests. A receiver operator characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated to assess the validity of each questionnaire.Results: A total of 1197 community residents in Minhang District completed the screening. A total of 1023 participants were finally included in analysis with a detected prevalence of 12.4% for COPD. The best cut-off values for the COPD-PS, COPD-SQ, and COPD-MH were 4, 16, and 7 points, respectively. The AUCs for these three questionnaires were > 0.5, but the sensitivity of the COPD-MH was higher than those of the COPD-PS and COPD-SQ. The sensitivity of COPD-MH was 80.77% for males and 77.5% for females. The COPD-MH had higher diagnostic efficiency and higher sensitivity with gender-specific cut-off values.Conclusion: The COPD-MH is comparable to and less time-consuming than the existing screening methods for COPD. Gender-related factors affect the optimal cut-off values of the COPD screening questionnaire, and rectifying this can improve the practical screening efficacy.Keywords: chronic obstructive pulmonary disease, screening questionnaire, gender, spirometry, ROC curve

Nan Wang,1 Yuanting Gu,1 Lin Li,1 Jiangrui Chi,1 Xinwei Liu,1 Youyi Xiong,1 Chaochao Zhong2 1Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Nan Wang, Email fccwangn2@zzu.edu.cnBackground: The changes of lipid metabolism have been implicated in the development of many tumors, but its role in breast invasive carcinoma (BRCA) remains to be fully established. Here, we attempted to ascertain the prognostic value of lipid metabolism-related genes in BRCA.Methods: We obtained RNA expression data and clinical information for BRCA and normal samples from public databases and downloaded a lipid metabolism-related gene set. Ingenuity Pathway Analysis (IPA) was applied to identify the potential pathways and functions of Differentially Expressed Genes (DEGs) related to lipid metabolism. Subsequently, univariate and multivariate Cox regression analyses were utilized to construct the prognostic gene signature. Functional enrichment analysis of prognostic genes was achieved by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Kaplan-Meier analysis, Receiver Operating Characteristic (ROC) curves, clinical follow-up results were employed to assess the prognostic potency. Potential compounds targeting prognostic genes were screened by Connectivity Map (CMap) database and a prognostic gene-drug interaction network was constructed using Comparative Toxicogenomics Database (CTD). Furthermore, we separately validated the selected marker genes in BRCA samples and human breast cancer cell lines (MCF-7, MDA-MB-231).Results: IPA and functional enrichment analysis demonstrated that the 162 lipid metabolism-related DEGs we obtained were involved in many lipid metabolism and BRCA pathological signatures. The prognostic classifier we constructed comprising SDC1 and SORBS1 can serve as an independent prognostic marker for BRCA. CMap filtered 37 potential compounds against prognostic genes, of which 16 compounds could target both two prognostic genes were identified by CTD. The functions of the two prognostic genes in breast cancer cells were verified by cell function experiments.Conclusion: Within this study, we identified a novel prognostic classifier based on two lipid metabolism-related genes: SDC1 and SORBS1. This result highlighted a new perspective on the metabolic exploration of BRCA.Keywords: lipid metabolism, breast invasive carcinoma, BRCA, prognostic classifier, SDC1, SORBS1