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Qingyi Liu,1,2 Qiongdan Zhang,1,2 Zhijian Yao,1,2 Gangqiang Yi,2 Yeonseok Kang,3 Yixing Qiu,1,2 Yupei Yang,1,2 Hanwen Yuan,1,2 Ronggeng Fu,2 Wenbing Sheng,1,2 Lidong Cheng,4 Wei Wang,1,2 Huizhen Wang,1,2 Caiyun Peng1,5 1TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 3College of Korean Medicine, Wonkwang University, Jeonbuk, Korea; 4Hunan Yirentang Chinese Herbal Pieces Co., Ltd, Changde, People’s Republic of China; 5Institute of Innovation and Applied Research in Chinese Medicine Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Huizhen Wang; Caiyun Peng, Tel +86-151-1648-1295 ; +86-138-7480-7689, Email whuiz0086@163.com; caiyunpeng@hnucm.edu.cnAbstract: Extracellular vesicles (EVs) are microparticles released from cells in both physiological and pathological conditions and could be used to monitor the progression of various pathological states, including neoplastic diseases. In various EVs, tumor-derived extracellular vesicles (TEVs) are secreted by different tumor cells and are abundant in many molecular components, such as proteins, nucleic acids, lipids, and carbohydrates. TEVs play a crucial role in forming and advancing various cancer processes. Therefore, TEVs are regarded as promising biomarkers for the early detection of cancer in liquid biopsy. However, the currently developed TEV detection methods still face several key scientific problems that need to be solved, such as low sensitivity, poor specificity, and poor accuracy. To overcome these limitations, DNA walkers have emerged as one of the most popular nanodevices that exhibit better signal amplification capability and enable highly sensitive and specific detection of the analytes. Due to their unique properties of high directionality, flexibility, and efficiency, DNA walkers hold great potential for detecting TEVs. This paper provides an introduction to EVs and DNA walker, additionally, it summarizes recent advances in DNA walker-based detection of TEVs (2018– 2024). The review highlights the close relationship between TEVs and DNA walkers, aims to offer valuable insights into TEV detection and to inspire the development of reliable, efficient, simple, and innovative methods for detecting TEVs based on DNA walker in the future. Keywords: EVs, TEVs, DNA walker, detection

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

Ne Yan,1,2 Ying Long,2 Huiling Yuan,3 Xiaofei Zhou,3,4 Bin Xie,2 Ying Wang1,3 1Department of Psychiatry, Xi’an Honghui Hospital, Xi’an, Shaanxi, 710054, People’s Republic of China; 2Department of Psychology, Xi’an Physical Education University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Psychiatry, Xi’an International Medical Center Hospital, the Affiliated Hospital of Northwest University, Xi’an, Shaanxi, People’s Republic of China; 4The College of Life Sciences and Medicine, Northwest University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Ying Wang, Xi’an Honghui Hospital, 666 Jianyuan 2nd Road, Economic and Technological Development Zone, Xi’an City, Shaanxi Province, 710000, People’s Republic of China, Email fgx995@163.comBackground: The 18– 24 age group has a much higher rate of depression risk than other age groups, and this age group has the highest proportion among users of mobile social media. The relationship between the use of mobile social media and depressive mood is inconsistent and the mechanism of action is controversial.Purpose: This study explored the relationship among the intensity of social media use, upward social comparison, cognitive overload and depressive mood.Methods: In this research, we used the Brief Self-rating Depression Scale (PHQ-9), the Social Media Usage Intensity Questionnaire, the Social Comparison Scale on Social Networking Sites and the Social Networking Site Cognitive Overload Scale to investigate the depressive mood and mobile social media use of 568 college students.Results: The intensity of mobile social media use, social networking site upward social comparison, and social networking site cognitive overload are all positively correlated with depressive mood. The intensity of mobile social media use has a positive predictive effect on depressive mood, with upward social comparison and cognitive overload acting as independent mediators in the relationship between mobile social media use intensity and depressive symptoms, as well as exhibiting a chained mediating effect of upward social comparison-cognitive overload.Conclusion: The upward social comparison and cognitive load that occur during the use of mobile social media are important predictive factors for the occurrence of depressive mood. This study is a supplement to the mechanism of the relationship between mobile social media use and depression, providing more evidence-based evidence and intervention directions for university teachers, mobile social media developers, and psychologists.Keywords: mobile social media, upward social comparison, cognitive overload, depressive mood, chain mediation

Ziyan Wang,1,2,* Chengxin Liu,1,2,* Jiaming Wei,2,3 Hui Yuan,1,2 Min Shi,2,3 Fei Zhang,2,3 Qinghua Zeng,2,3 Aisi Huang,2,3 Lixin Du,4 Ya Li,4 Zhihua Guo2,3 1First Clinical College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China; 2Hunan Key Laboratory of Colleges and Universities of Intelligent Traditional Chinese Medicine Diagnosis and Preventive Treatment of Chronic Diseases of Hunan Universities of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China; 3School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China; 4School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ya Li; Zhihua Guo, Email 003872@hnucm.edu.cn; 004294@hnucm.edu.cnObjective: This study aims to explore the mechanism of action of Yixintai in treating chronic ischemic heart failure by combining bioinformatics and experimental validation.Materials and Methods: Five potential drugs for treating heart failure were obtained from Yixintai (YXT) through early mass spectrometry detection. The targets of YXT for treating heart failure were obtained by a search of online databases. Gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted on the common targets using the DAVID database. A rat heart failure model was established by ligating the anterior descending branch of the left coronary artery. A small animal color Doppler ultrasound imaging system detected cardiac function indicators. Hematoxylin-eosin (HE), Masson’s, and electron microscopy were used to observe the pathological morphology of the myocardium in rats with heart failure. The network pharmacology analysis results were validated by ELISA, qPCR, and Western blotting.Results: A total of 107 effective targets were obtained by combining compound targets and eliminating duplicate values. PPI analysis showed that inflammation-related proteins (TNF and IL1B) were key targets for treating heart failure, and KEGG enrichment suggested that NF-κB signaling pathway was a key pathway for YXT treatment of heart failure. Animal model validation results indicated the following: YXT can significantly reduce the content of intestinal microbiota metabolites such as trimethylamine oxide (TMAO) and improve heart failure by improving the EF and FS values of heart ultrasound in rats and reducing the levels of serum NT-proBNP, ANP, and BNP to improve heart failure. Together, YXT can inhibit cardiac muscle hypertrophy and fibrosis in rats and improve myocardial ultrastructure and serum IL-1β, IL-6, and TNF-α levels. These effects are achieved by inhibiting the expressions of NF-κB and PKC.Conclusion: YXT regulates the TMAO/PKC/NF-κB signaling pathway in heart failure.Keywords: heart failure, yixintai, TMAO, PKC/NF-κB pathway, traditional Chinese medicine, network pharmacology

Haohua Yuan,1 Huan Gui,1 Shuanghui Chen,1 Lan Zhu,1 Chenglv Wang,1 Qianyu Jing,2 Hang Lv,1 Quan Wan,2 Shuyi Wang,1 Shengwen Zhou,1 Xiaodong Ren,1 Yingjie Nie,1,3 Linzhao Li1 1Medical College, Guizhou University, Guizhou Province, 550025, People’s Republic of China; 2School of Preclinical Medicine of Zunyi Medical University, Zunyi, Guizhou Province, 563000, People’s Republic of China; 3NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, 550002, People’s Republic of ChinaCorrespondence: Yingjie Nie; Linzhao Li, Medical College of Guizhou University, Guiyang, Guizhou Province, 550025, People’s Republic of China, Tel +86-085188274013; +86-085188274016, Email nienyj@hotmail.com; lzli@gzu.edu.cnPurpose: This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-β-CD).Methods: R848-loaded PLGA nanoparticles modified with 2-HP-β-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo.Results: The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-β-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival.Conclusion: The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.Keywords: R848, 2-HP-β-CD, anti-TNFR2, TIME, immunotherapy

Mingjie Wang,1,* Wenxiang Xue,2,* Hanghang Yuan,2 Zhicheng Wang,2 Lei Yu1 1Department of Radiotherapy, Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, Jilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhicheng Wang; Lei Yu, Tel +86-431-85619443, Email zhicheng@jlu.edu.cn; yul0826@163.comAbstract: Currently, pancreatic cancer (PC) is one of the most lethal malignant tumors. PC is typically diagnosed at a late stage, exhibits a poor response to conventional treatment, and has a bleak prognosis. Unfortunately, PC’s survival rate has not significantly improved since the 1960s. Cancer-associated fibroblasts (CAFs) are a key component of the pancreatic tumor microenvironment (TME). They play a vital role in maintaining the extracellular matrix and facilitating the intricate communication between cancer cells and infiltrated immune cells. Exploring therapeutic approaches targeting CAFs may reverse the current landscape of PC therapy. In recent years, nano-drug delivery systems have evolved rapidly and have been able to accurately target and precisely release drugs with little or no toxicity to the whole body. In this review, we will comprehensively discuss the origin, heterogeneity, potential targets, and recent advances in the nano-drug delivery system of CAFs in PC. We will also propose a novel integrated treatment regimen that utilizes a nano-drug delivery system to target CAFs in PC, combined with radiotherapy and immunotherapy. Additionally, we will address the challenges that this regimen currently faces.Keywords: nanoparticle, nano-drug delivery system, cancer-associated fibroblasts, pancreatic cancer, tumor microenvironment

Qi Wang,1– 3,* Jiaxin Dong,4,* Mengxian Du,1,3,* Xinna Liu,1– 3 Shiqi Zhang,1 Di Zhang,1,3 Wanyun Qin,1,3 Xikun Xu,1,2 Xianghui Li,1,3 Ruidong Su,1,2 Leyi Qiu,1,2 Baoqiang Li,4,5 Huiping Yuan1 1Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry Education, Harbin, People’s Republic of China; 3Future Medical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, People’s Republic of China; 5Laboratory of Dynamics and Extreme Characteristics of Promising Nanostructured Materials, Saint Petersburg State University, St. Petersburg, Russia*These authors contributed equally to this workCorrespondence: Huiping Yuan, Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China, Email yuanhp2013@126.com Baoqiang Li, Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, 150081, People’s Republic of China, Email libq@hit.edu.cnIntroduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications.Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined.Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1β and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-β. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function.Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy. Keywords: retina, ischemia/reperfusion injury, rapamycin, carbon dots, microglial polarization, autophagy

Qiongdan Zhang,1,2,* Huizhen Wang,1,2,* Qingyi Liu,1,2 Ni Zeng,1,2 Gang Fu,1,2 Yixing Qiu,1,2 Yupei Yang,1,2 Hanwen Yuan,1,2 Wei Wang,1,2 Bin Li1,2 1TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Wang; Bin Li, Tel +86-136-5743-8606 ; +86-158-7410-0917, Email wangwei402@hotmail.com; libin@hnucm.edu.cnAbstract: Exosomes, small extracellular vesicles derived from cells, are known to carry important bioactive molecules such as proteins, nucleic acids, and lipids. These bioactive components play crucial roles in cell signaling, immune response, and tumor metastasis, making exosomes potential diagnostic biomarkers for various diseases. However, current methods for detecting tumor exosomes face scientific challenges including low sensitivity, poor specificity, complicated procedures, and high costs. It is essential to surmount these obstacles to enhance the precision and dependability of diagnostics that rely on exosomes. Merging DNA signal amplification techniques with the signal boosting capabilities of nanomaterials presents an encouraging strategy to overcome these constraints and improve exosome detection. This article highlights the use of DNA signal amplification technology and nanomaterials’ signal enhancement effect to improve the detection of exosomes. This review seeks to offer valuable perspectives for the enhancement of amplification methods applied in practical cancer diagnosis and prognosis by providing an overview of how these novel technologies are utilized in exosome-based diagnostic procedures. Keywords: tumor, exosomes, nanomaterials, DNA signal amplification

Chenxi Xie,1,* Xiaopei Hao,2,* Hao Yuan,1 Chongyu Wang,3 Razinah Sharif,4,5 Haibo Yu1 1Hepatobiliary Center, Department of Hepatobiliary Surgery, People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of China; 3The First Clinical Medical College of Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Center for Healthy Ageing & Wellness, Faculty of Health Sciences, University Kebangsaan Malaysia, Kuala Lumpur, 50300, Malaysia; 5Biocompatibility Laboratory, Centre for Research and Instrumentation, University Kebangsaan Malaysia, UKM, Bangi, Selangor Darul Ehsan, 43600, Malaysia*These authors contributed equally to this workCorrespondence: Haibo Yu, The People’s Hospital of Zhengzhou University, 7 Weiwu Road, Jinshui District, Zhengzhou, 450003, People’s Republic of China, Tel +86- 371 – 65580213, Email yhb2101661@zzu.edu.cn Razinah Sharif, Center for Healthy Ageing & Wellness, Faculty of Health Sciences, University Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, 50300, Malaysia, Tel +60- 3 – 60193009360, Email razinah@ukm.edu.myAbstract: Hepatocellular carcinoma (HCC) is one of the most common aggressive tumors in the world. Despite the availability of various treatments, its prognosis remains poor due to the lack of specific diagnostic indicators and the high heterogeneity of HCC cases. CircRNAs are noncoding RNAs with stable and highly specific expression. Extensive research evidence suggests that circRNAs mediate the pathogenesis and progression of HCC through acting as miRNA sponges, protein modulators, and translation templates. Tumor microenvironment (TME) has become a hotspot of immune-related research in recent years due to its effects on metabolism, secretion and immunity of HCC. Accordingly, understanding the role played by circRNAs in TME is important for the study of HCC. This review will discuss the crosstalk between circRNAs and TME in HCC. In addition, we will discuss the current deficiencies and controversies in research on circRNAs and predict future research directions.Keywords: CircRNAs, hepatocellular carcinoma, characteristics, tumor microenvironment, biomarker

Qinglin Ye,1,* Guiling Xu,1,* Hao Yuan,2,3 Junhao Mi,2,3 Yuli Xie,2,3 Haoyu Li,1 Zhejun Li,1 Guanwen Huang,1 Xuesong Chen,1 Wei Li,1 Rirong Yang2,3 1Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, People’s Republic of China; 2Centre for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Department of Immunology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rirong Yang, Centre for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Department of Immunology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Fax +86 0771 5317061, Email yangrirong@sr.gxmu.edu.cn; 520yrr@163.com Wei Li, Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, People’s Republic of China, Email liwei030514@126.comBackground: Diabetic kidney disease (DKD) is a chronic renal disease which could eventually develop into renal failure. Though albuminuria and estimated glomerular filtration rate (eGFR) are helpful for the diagnosis of DKD, the lack of specific biomarkers reduces the efficiency of therapeutic interventions.Methods: Based on bulk-seq of 56 urine samples collected at different time points (including 11 acquired from DKD patients and 11 from healthy controls), in corporation of scRNA-seq data of urine samples and snRNA-seq data of renal punctures from DKD patients (retrieved from NCBI GEO Omnibus), urine-kidney specific genes were identified by Multiple Biological Information methods.Results: Forty urine-kidney specific genes/differentially expressed genes (DEGs) were identified to be highly related to kidney injury and proteinuria for the DKD patients. Most of these genes participate in regulating glucagon and apoptosis, among which, urinary PART1 (mainly derived from distal tubular cells) and PLA2R1 (podocyte cell surface marker) could be used together for the early diagnosis of DKD. Moreover, urinary PART1 was significantly associated with multiple clinical indicators, and remained stable over time in urine.Conclusion: Urinary PART1 and PLA2R1 could be shed lights on the discovery and development of non-invasive diagnostic method for DKD, especially in early stages. Keywords: diabetic kidney disease, urine, non-invasive, diagnosis, biomarker

Puxin Yang,* Xiao Liang,* Xingzhu Xu, Qingtao Liu, Zhiyuan Guo, Hongru Yuan, Hui Wang, Wenyuan Ding Department of Spine Surgery, HeBei Medical University Third Hospital, Shijiazhuang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenyuan Ding; Hui Wang, Department of Spine Surgery, HeBei Medical University Third Hospital, Shijiazhuang, The People’s Republic of China, Tel +86 311 88602317, Fax +86 311 87023626, Email dingwymanuscript@163.com; wanghuiwenxian@163.comIntroduction: To explore the incidence and predictive factors of new onset postoperative sacroiliac joint pain (PSJP) after posterior lumbar fusion surgery for degenerative lumbar disease.Methods: Three hundred and sixty-seven patient medical records from January 2020 to December 2021 were retrieved. The patients were divided into two groups: PSJP group and N-PSJP (non-postoperative sacroiliac joint pain group). To investigate potential risk factors for PSJP, HU value (Hounsfield unit value) was assessed on CT scans. ImageJ software was used to assess the fat and muscle of the lumbar multifidus muscle (LMM) in the axial MRI image, the red area was marked as fat and the rest were muscles to calculate the ratio of fatty infiltration. Patient characteristics, surgical variables and radiographic parameters were analyzed statistically.Results: Twenty of 367 patients were diagnosed with PJSP at postoperative follow-up. Patients with PSJP presented with significantly higher HU value. For surgical variables, PSJP patients received more operations including distal fusion level at sacrum than the N-PSJP group. For radiographic parameters, most of the patients in the PSJP group had more severe fatty atrophic muscle in the LMM compared to the N-PSJP group. There was no statistically significant difference between the two groups in preoperative and postoperative lumbar lordosis (LL), angle of lumbar lordosis of fixed lumbar vertebrae (FV-LL), pelvic incidence (PI), sacrum slope (SS). The bivariate logistic regression model revealed preoperative fat infiltration rate of the LMM, and higher HU value were independently associated with PSJP.Conclusion: PSJP for degenerative lumbar disease was 5.4%, the predictive factors included preoperative severe infiltration of LMM, distal fusion level at sacrum and higher HU value.Keywords: sacroiliac joint pain, lumbar instrumented fusion surgery, bone mineral density, paraspinal muscles

Meat colour is one of the primary factors affecting the acceptability of retail meat cuts. Therefore, displaying the natural bright-red colour of meat is a major goal of the meat industry. Consumers frequently reject to retail meat cuts with discolouration even at low levels of surface browning and/or darkening, which in turn results in significant food waste and economic loss. Thus, understanding the factors that influence meat colour deviations such as discolouration or darkening is crucial in developing effective strategies to minimise the display colour-related quality issues. Numerous factors influence series of biochemical reactions of post-mortem muscles and the chemical state of myoglobin, which ultimately affects meat colour and colour stability. Recent studies have demonstrated the incidence of dark-cutting beef post-mortem can be attributed to the combination of lower glycolytic potential, less glycolytic metabolites, enzymes and dysregulated energy metabolism. This review will focus on the role of post-mortem bioenergetics and mitochondria dynamics that affect beef colour chemistry.

Qi Yang,1– 4 Yalan Luo,1– 3 Peng Ge,1– 3 Bowen Lan,1– 3 Jin Liu,1– 3 Haiyun Wen,1– 3 Yinan Cao,1– 3 Zhenxuan Sun,1– 3 Guixin Zhang,1– 3 Huiming Yuan,5 Lihua Zhang,5 Hailong Chen1– 3 1Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 2Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 3Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 4Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, People’s Republic of China; 5CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic Research and Analysis Center, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, 116023, People’s Republic of ChinaCorrespondence: Hailong Chen, Email chenhailong@dmu.edu.cnBackground: Numerous preclinical investigations have exhibited the beneficial impact of emodin (EMO) on the management of severe acute pancreatitis (SAP)-associated acute lung injury (ALI). However, the potential of EMO to mitigate organ damage through the modulation of exosome (Exo)-specific miRNA expression profiles remains unclear.Methods: The SAP rat model was established by retrograde injection of 5% sodium taurocholate into the pancreatic bile duct. Rats received intragastric administration of EMO at 2 h and 12 h post-modeling. Plasma and bronchoalveolar lavage fluid (BALF)-derived exosomes were isolated and purified from SAP rats treated with EMO. The therapeutic effects of these Exos in SAP rats were assessed using hematoxylin-eosin staining and measurement of inflammatory factor levels. MicroRNA (miRNA) sequencing was conducted on plasma and BALF-derived Exos, and rescue experiments were performed to investigate the function of NOVEL miR-29a-3p in the treatment of SAP using EMO.Results: EMO exhibits ameliorative effects on pancreatic and lung injury and inflammation in rats with SAP. Plasma/BALF-derived Exos from EMO-treated SAP rats also have therapeutic effects on SAP rats. The miRNA expression profile of plasma and BALF-derived Exos in SAP rats underwent significant changes upon exposure to EMO. In particular, 34 differentially expressed miRNAs (DEmiRNAs) were identified when comparing BALF-SAP+EMO-Exo and BALF-SAP-Exo. 39 DEmiRNAs were identified when comparing plasma-SAP+EMO-Exo to plasma-SAP-Exo. We found that SAP rats treated with Exos derived from BALF exhibited a more potent therapeutic response than those treated with Exos derived from plasma. EMO may rely on NOVEL-rno-miR-29a-3p expression to prevent pulmonary injury in SAP rats.Conclusion: The mechanism of action of EMO is observed to have a significant impact on the miRNA expression profile of Exos derived from plasma and BALF in SAP rats. NOVEL-rno-miR-29a-3p, which is specific to Exos, and is derived from BALF, may play a crucial role in the therapeutic efficacy of EMO. Plain Language Summary: Exosomes extracted from plasma/BALF of EMO-treated SAP rats show a substantial therapeutic impact on SAP-Associated ALI, with BALF-derived exosomes having a higher therapeutic effect than plasma-derived exosomes.EMO dramatically altered the miRNA expression patterns of plasma and BALF-derived exosomes in SAP rats.The lung protective effect of EMO in SAP rats is somewhat reliant on Novel-rno-miR-29a-3p expression.Keywords: severe acute pancreatitis, acute lung injury, emodin, exosome, microRNA

Hongjie Yuan,1 Xiaobin Yi2 1Department of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Pain Division, Department of Anesthesiology, Washington University in St Louis, St Louis, MO, USACorrespondence: Xiaobin Yi, Email yix@wustl.eduBackground: Lumbar spinal stenosis (LSS) is a common pain condition that causes lumbar back pain, radiating leg pain, and possible functional impairment. MILD is an emerging minimally invasive treatment for LSS. It is an image-guided percutaneous procedure designed to debulk hypertrophied ligamentum flavum. However, the exact short- and long-term efficacy, safety profile, indication criteria, and certain procedure details reported in medical literature vary.Objective: This narrative review was to elucidate efficacy, safety profile, certain procedure details, advantages, and limitations of MILD.Study Design: This is a narrative review.Setting: All included articles are clinic trials including analytic studies and descriptive studies.Methods: PubMed, Cochrane Library, and Scopus were searched. Only clinical trials of MILD procedure were included. Information of indications, contraindications, VAS scores, ODI scores, effective rate, efficacy durations, and certain procedure details was focused on.Results: According to the literature, for the MILD procedure, the VAS score could be reduced from a pre-treatment level of 6.3– 9.6 to a post-treatment level of 2.3– 5.8. The ODI score could be reduced from a pre-treatment level of 38.8– 55.3 to a post-treatment level of 27.4– 39.8. The effective rate of the MILD procedure was reported to be 57.1%– 88%. A 2-year postoperative stability of efficacy was also supported. One RCT study testified superior efficacy of MILD over epidural steroid injection.Limitations: There is few high-quality literature in the review. Moreover, the long-term efficacy of MILD cannot be revealed according to the current literature.Conclusion: Based on the reviewed literature, MILD is an effective and safe procedure. MILD can reduce pain intensity and improve functional status significantly. Therefore, it is a preferable option for LSS patients who failed conservative treatments, but not for those who require immediate invasive decompression surgery.Keywords: lumbar spinal stenosis, minimally invasive lumbar decompression, mild ®, low back pain, lumbar radiculopathy, neurogenic claudication, ligamentum flavum

Hu Yuan,1,&ast; Caihong Wang,2,&ast; Li Liu,3 Chun Wang,3 Zhenlin Zhang,3 Shen Qu4 1Department of Endocrinology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215001, People’s Republic of China; 2Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215001, People’s Republic of China; 3Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Disease, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China; 4Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, Clinical Medical College of Nanjing Medical University, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenlin Zhang; Shen Qu, Email zhangzl@sjtu.edu.cn; qushencn@tongji.edu.cnPurpose: The aim of this study was to explore the association between CTSK polymorphisms and the response to alendronate treatment in postmenopausal Chinese women with low bone mineral density.Patients and Methods: In this study, 460 postmenopausal women from Shanghai were included. All of them were treated with weekly oral alendronate 70 mg, daily calcium 600 mg and vitamin D 125 IU for a year. Four tag single nucleotide polymorphisms (SNPs) in CTSK gene were genotyped. Bone mineral densities of lumbar spine (L1-L4), femoral neck and total hip were measured at baseline and after 12 months of treatment, respectively.Results: After 1-year of treatment, there was no significant differences in BMI between baseline and follow-up. After alendronate treatment, the BMD of L1– 4, femoral neck and total hip all increased significantly (all P < 0.001), with average increases of 4.33 ± 6.42%, 1.85 ± 4.20%, and 2.36 ± 3.79%, respectively. There was no significant difference in BMD at L1-L4, the femoral neck and total hip between different genotype groups at baseline (P> 0.05). After 1-year treatment with alendronate, rs12746973 and rs10847 were associated with the % change of BMD at L1-L4 (P=0.038) and % change of BMD at femoral neck (P=0.038), respectively. Furthermore, rs10847 was associated with BMD response at femoral neck (P=0.013). However, the associations were not significant after Bonferroni correction.Conclusion: We concluded that the common variations of CTSK gene were potentially associated with the therapeutic response to alendronate treatment in Chinese women with low bone mineral density. However, further validation is needed.Keywords: CTSK gene, alendronate, postmenopausal, low bone mineral density, osteoporosis

Tao Wang,1,2,&ast; Yanan Li,2,&ast; Shuai Miao,1,2 Chunxiao Yang,3 Wei Xie,1,2 Huijuan Yuan,3 Wenhao Bai,1,2 Han Xiao,1,2 Shengyuan Yu1,2 1Department of Neurology, the First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Medical School of Chinese PLA, Beijing, People’s Republic of China; 3College of Medicine, Nankai University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengyuan Yu, Email yusy1963@126.comBackground: Migraine treatment research has made much great progress over the past decade. However, there have been few bibliometric studies conducted so far. In this study, bibliometric analysis was used to explore the current status and future trends of migraine treatment research.Methods: Migraine treatment-related articles were retrieved from the Web of Science Core Collection on December 7, 2022. Quantitative variables were analyzed by the R-tool bibliometrix and Excel 2020. VOS viewer and CiteSpace software were used to visualize citation, co-authorship, co-occurrence, and co-citation analysis of countries/regions, organizations, authors, references, and keywords.Results: A total of 3294 articles were included with the global publication output showing a slow upward trend. The United States was the most productive country with 1116 papers and gained the most citations. Albert Einstein College of Medicine was the most active institution with 176 papers. Headache published the most articles in this domain, while Cephalalgia was the most commonly co-cited journal. Lipton, RB published the most articles and had the most citations. Tepper S, 2017, Lancet neurology and Silberstein S, 2004, Cephalalgia were defined as classic articles. The current research mainly focuses on CGRP-related therapeutics, such as fremanezumab, erenumab and ubrogepant.Conclusion: Based on the analysis of bibliometric data on migraine treatment over the past decade, the trends and the knowledge graph of the country, organization, author, reference, and the keyword were identified, providing accurate and quick positioning of the critical information in the domain.Keywords: migraine, treatment, bibliometric analysis, research trends, hot spots

Lu Huang,&ast; Xiuli Dong, Hang Yuan, Lihua Wang&ast; Business School of Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihua Wang, Business School of Sichuan University, Chengdu, Sichuan, People’s Republic of China, Tel +86 +28-85415451, Fax +86 +28-85418379, Email 2470610738@qq.comPurpose: The short video APP has entered the stage of competition for stock, making it crucial to keep users engaged in their APP to promote continuous usage. Previous studies on the continuous use intention of mobile short video APP were relatively limited, with most studies focusing only on promoting factors. Therefore, based on the dual-factor theory of “enabling-inhibiting”, and drawing on the Information System Continuance Model (ECM-ISC) and Cognitive Load Theory, this study extracted two variables, satisfaction and fatigue, to construct an integrated model to explore their enabling and inhibiting effects on continuous use intention.Methods: This study selected TikTok APP users as the respondents, obtained 681 valid questionnaires and analyzed with structural equation modeling (SEM) using SPSS24.0 and Amos23.0 software.Findings: The study investigated the factors that influence users’ continuous use intention of short video APP. It shows that in enabling mechanism, perceived usefulness and social influence will increase user satisfaction and thus promote their continuous use intention, and perceived playfulness has a direct effect on the continuous use intention. In inhibiting mechanism, information overload and communication overload are positively correlated with emotional fatigue, which further reduces the continuous use intention.Contribution/Conclusion: Based on the dual-factor theory of “enabling-inhibiting”, the study established an integration model to more comprehensively reveal the impact mechanism of short video APP users’ continuous use intention. The study found that the fatigue caused by information and communication overload can inhibit users’ continuous use intention of short video APP. Therefore, to improve users’ continuous use intention, short video APP should not only increase users’ satisfaction but also reduce the fatigue caused by overload.Keywords: short video APP, continuous use intention, satisfaction and fatigue, enablers, inhibitors, ECM-ISC model

Mu-Lan Xu,1,2,&ast; Xiang-Bo Wu,1,&ast; Ying Liang,3,&ast; Ning Li,1 Xu Hu,1 Xiao-Dong Lin,1 Miao-Qiao Sun,1 Chun-Qiu Dai,1 Dan Niu,1 Yan-Rong Zhang,1 Hui Cao,1 Chen-Guang Zhao,1 Xiao-Long Sun,1 Hua Yuan1 1Department of Rehabilitation Medicine, Xi-Jing Hospital, Air Force Medical University (Fourth Military Medical University), Xi’an, Shaanxi, People’s Republic of China; 2Department of Rehabilitation Medicine, Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shanwei, Guangdong, People’s Republic of China; 3Department of Health Statistics, Air Force Medical University (Fourth Military Medical University), Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Yuan; Xiao-Long Sun, Department of Rehabilitation Medicine, Xi-Jing Hospital, Air Force Medical University (Fourth Military Medical University), No. 15, Changle West Road, Xi’an, Shaanxi, 710032, People’s Republic of China, Tel/Fax +86-29-84775437 ; +86-29-84775439, Email yuanhua@fmmu.edu.cn; xlsun@fmmu.edu.cnBackground: Neuropathic pain (NP) is a common and severe problem following spinal cord injury (SCI). However, its relationship with functional outcome remains unclear.Methods: A retrospective explorative analysis was performed on SCI patients admitted to a tertiary academic medical center between January 2018 and June 2022. The candidate predictor variables, including demographics, clinical characteristics and complications, were analyzed with logistic and linear regression. Spinal Cord Independence Measure (SCIM) scores at discharge and mean relative functional gain (mRFG) of SCIM were as outcome parameters.Results: A total of 140 SCI patients included for the final analysis. Among them, 44 (31.43%) patients were tetraplegics, and 96 (68.57%) patients were paraplegics; 68 (48.57%) patients developed NP, and 72 (51.43%) patients did not. Logistic and linear regression analyses of SCIM at discharge both showed that NP [OR=3.10, 95% CI (1.29,7.45), P=0.01; unstandardized β=11.47, 95% CI (4.95,17.99), P< 0.01; respectively] was significantly independent predictors for a favorable outcome (SCIM at discharge ≥ 50, logistic regression results) and higher SCIM total score at discharge (linear regression results). Besides, NP [unstandardized β=15.67, 95% CI (8.94,22.41), P< 0.01] was also independently associated with higher mRFG of SCIM scores. Furthermore, the NP group had significantly higher mRFG, SCIM total scores and subscales (self-care, respiration and sphincter management, and mobility) at discharge compared to the non-NP group. However, there were no significant differences in mRFG, SCIM total score or subscales at discharge among the NP subgroups in terms of locations (at level pain, below level pain, and both) or timing of occurrence (within and after one month after SCI). This study also showed that incomplete injury, lumbar-sacral injury level and non-anemia were significantly independent predictors for a favorable outcome, and higher mRFG of SCIM scores (except for non-anemia).Conclusion: NP appears independently associated with better functional recovery in SCI patients, suggesting the bright side of this undesirable complication. These findings may help to alleviate the psychological burden of NP patients and ultimately restore their confidence in rehabilitation.Keywords: spinal cord injury, neuropathic pain, functional outcome, SCIM, mRFG, retrospective study

Ting Lan,1,&ast; Yang Zhao,1,2,&ast; Yu Du,1,3,&ast; Chunyi Ma,1 Rui Wang,1 Qianlei Zhang,1 Shanshan Wang,1 Wenxian Wei,4 Honghua Yuan,2 Qingli Huang1,2 1Medical Technology School of Xuzhou Medical University, Xuzhou City, Jiangsu, 221000, People’s Republic of China; 2Public Experimental Research Center of Xuzhou Medical University, Xuzhou City, Jiangsu, 221004, People’s Republic of China; 3Xuzhou Center for Disease Control and Prevention, Xuzhou City, Jiangsu, 221006, People’s Republic of China; 4Testing Center, Yangzhou University, Yangzhou City, Jiangsu, 225009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Honghua Yuan, Public Experimental Research Center of Xuzhou Medical University, Tong Shan No. 209, Xuzhou, 221004, People’s Republic of China, Tel/Fax +86-516-83262091, Email XUYIyhh@xzhmu.edu.cn Qingli Huang, Medical Technology School, Public Experimental Research Center of Xuzhou Medical University, Tong Shan No. 209, Xuzhou, 221004, People’s Republic of China, Tel/Fax +86-516-83262091, Email qlhuang@xzhmu.edu.cnPurpose: A novel CYPA-targeted, SiO2 encapsulated Au star@AgAu yolk-shell nanostructure (YSNS) was synthesized and used for ovarian cancer early diagnosis and therapy.Methods: Diverse spectroscopic and microscopic methods were utilized to investigate the pattern of the yolk-shell nanostructure. In addition, in vitro and in vivo experiments were carried out.Results: It can be found that the ratio of HAuCl4 and AgNO3 played a critical role in the constitution of the yolk-shell nanostructure. The as-prepared yolk-shell nanostructure showed excellent SERS performance, which could be utilized as SERS substrate for specific sensitivity analysis of ovarian cancer markers cyclophilin A (CYPA) with detectable limit of 7.76&ast;10− 10 μg/mL. In addition, the as-prepared yolk-shell nanostructure possessed outstanding photothermal performance, which could be used as photothermal agent for ovarian cancer therapy. Experiments in vitro and in vivo proved that the as-prepared yolk-shell nanostructures are ideal candidate for early diagnosis and therapy for ovarian cancer in one platform.Conclusion: This work holds promise to offer a new method for the detection and therapy of ovarian cancer in the early stage.Graphical Abstract: Keywords: yolk-shell nanostructure, surface-enhanced Raman scattering, early diagnosis, cancer targeted therapy

Yuan H, Zhao J, Yang Y, et al. Cancer Manag Res. 2020;12:13273–13284. We, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Following publication of the article, concerns were raised regarding the duplication of images from Figure 2 with images from other unrelated articles. Images for Figure 2F have been duplicated with images for Figure 3F from Zhu Z, Wang H, Pang Y, Hu H, Zhang H, Wang W. Exosomal long non-coding RNA UCA1 functions as growth inhibitor in esophageal cancer. Aging (Albany NY). 2020;12:20523-20539. https://doi.org/10.18632/aging.103911 (RETRACTED) and Figure 4D from Zhong X, Wen X, Chen L, Gu N, Yu X, Sui K. Long non-coding RNA KCNQ1OT1 promotes the progression of gastric cancer via the miR-145-5p/ARF6 axis. J Gene Med. 2021;23:e3330. https://doi.org/10.1002/jgm.3330. In addition, the images of Figure 2E, LOVO, vector-NC and si-NC, have been duplicated. The authors responded to our queries but were unable to provide an explanation for the duplicated images or provide 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 agree 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”.

Zhang Qing, Huang Yuan, Xiong Hao, Peng Jie Department of Radiology, Jingzhou No 1 People’s Hospital and First Affiliated Hospital of Yangtze University, Jingzhou City, Hubei Province, 434000, People’s Republic of ChinaCorrespondence: Peng Jie, Department of Radiology, The Jingzhou No 1 People’s Hospital and First Affiliated Hospital of Yangtze University, Hangkong Road, Shashi District, Jingzhou City, Hubei Province, 434000, People’s Republic of China, Tel +86 181 6313 1595, Email 18163131595vip@sina.comObjective: To explore the potential value of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) magnetic resonance imaging (MRI) in the diagnosis of hepatocellular carcinoma (HCC) in LR-3/4 lesions by adding computed tomography (CT) delayed images based on the Liver Imaging Reporting And Data System (LI-RADS).Methods: The differences in clinical and imaging characteristics between hepatocellular carcinoma and non-HCC were compared, and logistic regression was used to analyze the imaging risk factors for the diagnosis of HCC. Based on the main and HCC-specific auxiliary features of Gd-EOB-DTPA MRI, the HCC diagnostic model 1 was established, and the diagnostic efficacy was analyzed. Based on model 1, delayed phase CT images were added to establish model 2 to find reliable predictors of HCC diagnosis. Receiver operating characteristic (ROC) analysis and the DeLong test were used to compare the two models.Results: There was a significant difference in serum AFP between HCC and non-HCC (P = 0.008). Based on main and HCC-specific auxiliary features of Gd-EOB-DTPA MRI, enhancing capsule (OR = 0.197, 95% CI = 0.06– 0.595, P = 0.005) and washout (OR = 10.345, 95% CI = 3.460– 30.930, P < 0.001) were independent risk factors in Model 1. After adding CT delayed-phase images to build model 2, enhancing capsule (OR = 0.132, 95% CI = 0.139– 0.449, P = 0.001), MRI and (or) CT washout (OR = 0.052, 95% CI = 0.016– 0.172, P < 0.001) were reliable predictors for HCC diagnosis. The AUC of model 1 was 0.808, sensitivity was 63.46%, and specificity was 85.00%. The AUC of model 2 was 0.854, the sensitivity was 71.20%, and the specificity was 85.00%. DeLong test (P = 0.040) demonstrated the diagnostic efficacy of model 2 significantly superior than model 1.Conclusion: Tumor washout and enhanced capsule are reliable factors for the diagnosis of HCC. Gd-EOB-DTPA MRI with delayed phase CT images can improve the sensitivity and diagnostic efficiency of HCC in LR-3/4 lesions on the premise of maintaining high specificity. Future studies are required to reinforce our finding.Keywords: liver imaging reporting and data system, gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid, computed tomography, hepatocellular carcinoma, diagnostic performance

Jian Tang,1 Hong Yuan,2 Yun Long Wu,1 Shui Fu,3 Xiao Yong Pan4 1Department of Intensive Care, First People’s Hospital of Linping District, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Cardiology, First People’s Hospital of Linping District, Hangzhou, Zhejiang Province, People’s Republic of China; 3Clinical Laboratory Department, First People’s Hospital of Linping District, Hangzhou, Zhejiang Province, People’s Republic of China; 4Clinical Laboratory Department, The People’s Hospital of Cangnan Zhejiang, Wenzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xiao Yong Pan, Clinical Laboratory Department, The People’s Hospital of Cangnan Zhejiang, Wenzhou, Zhejiang Province, People’s Republic of China, Email pxy01234567892023@163.comObjective: To explore the serial measurement of heparin-binding protein and D-dimer in the prediction of 28-day mortality and efficacy evaluation of critically-ill patients with sepsis.Methods: We recruited a total of 51 patients with sepsis in the ICU of our hospital. They were divided into a survival group or a death group according to their prognosis 28 days after treatment. The HBP and D-dimer levels in these patients were determined on the 1st (24h), 3rd, and 5th days. Besides, the sequential organ failure assessment (SOFA) score of these patients was recorded at admission. The patients in both groups were subjected to comparison regarding HBP and D-dimer levels and SOFA scores within 24h of admission. Additionally, a correlation between the levels of HBP and D-dimer and the SOFA score was statistically measured, while the predictive effectiveness of these factors for the prognosis of patients with sepsis was also determined. Moreover, the dynamic changes in HBP and D-dimer during the treatment of both groups were analyzed.Results: The HBP and D-dimer levels and the SOFA scores in the survival group were considerably lower than those in the death group, and the differences were statistically significant (P< 0.05). Additionally, the levels of HBP and D-dimer in sepsis patients were positively correlated with the SOFA score (P< 0.05). The area under the curve (AUC) of HBP, D-dimer, and their combination in predicting the prognosis of patients with sepsis was 0.824, 0.771, and 0.830, respectively. Besides, the sensitivity and specificity of their combination in predicting the prognosis of patients with sepsis were 68.42% and 92.31%, respectively. The HBP and D-dimer levels presented a downward trend in the survival group during treatment, while they exhibited an upward trend in the death group.Conclusion: HBP and D-dimer realize high predictive effectiveness for the prognosis of patients with sepsis, while the combined use of these two factors achieves superior effectiveness. Thus, they can be applied to the prediction of 28-day mortality and efficacy evaluation of sepsis patients.Keywords: sepsis, heparin-binding protein, HBP, D-dimer, sequential organ failure assessment score, SOFA, prognosis

Cui Shao,1,&ast; Mengxue Sun,2,&ast; Wanwen Liu,2 Shaoyang Zhao,1 Yang Liu,2 Yuna Chen,1 Shu-Nung Liang,2 Haoyu Yuan,2 Huacheng Sui,2 Baohua Wang,1 Saimei Li1 1Department of Endocrinology, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baohua Wang; Saimei Li, Department of Endocrinology, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China, Tel +8613580515855 ; +8615818159018, Fax +86 20-36588726, Email wangbaohua@gzucm.edu.cn; lsm@gzucm.edu.cnPurpose: We aimed to assess the efficacy of the Jiang Tang San Huang (JTSH) tablet for the treatment of patients with type 2 diabetes mellitus (T2DM).Methods: All data for this retrospective cohort study were acquired from the outpatient clinic database of our institution, and all enrolled patients received JTSH tablet for at least two months. Overall, 147 patients were included in the analysis. The primary outcome was patient-reported outcomes on the efficacy of the JTSH tablets using a questionnaire survey. Correlation analysis evaluated the duration of JTSH tablet administration and glycemic control in patients with T2DM. The secondary outcome measures included: changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2-hour postprandial blood glucose, homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) after 2 months of treatment with JTSH tablets.Results: Overall,120 patients (81.63%) reported a JTSH tablet treatment satisfaction score of ≥ 60 points, and believed that JTSH tablets had satisfactory hypoglycemic effects and could improve symptoms. The average duration of JTSH tablet treatment was 2.57± 1.45 years. Overall, 111 patients achieved good blood glucose control, while 36 patients had poor glycemic control. Multivariate logistic regression model analysis showed that taking JTSH tablets for 1 year might reduce the risk of poor hypoglycemic effect by 17.00% (Risk ratio=0.830, 95% confidence interval:0.578, 1.021, P=0.066). Compared with the baseline data, the levels of HbA1c, FPG and HOMA-IR decreased significantly and HOMA-β levels increased significantly (P< 0.05).Conclusion: Good blood glucose control may be positively correlated with the duration of JTSH tablets administration. Patients with T2DM were satisfied with the anti-diabetic effects of JTSH tablets, which can significantly reduce blood glucose and insulin resistance, and improve the function of islet cells.Keywords: type 2 diabetes mellitus, Jiang Tang San Huang tablet, patient-reported outcomes, blood glucose control, multiple logistic regression

Yongping Li,1 Xiaofei Jiang,1 Ming Zhong,1 Bo Yu,2 Hao Yuan1 1Department of Breast Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, People’s Republic of China; 2Department of Vascular Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, People’s Republic of ChinaCorrespondence: Hao Yuan, Department of Breast Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong New Area, Shanghai, 201399, People’s Republic of China, Tel +86 18918790382, Email zhougg1984@hotmail.com Bo Yu, Department of Vascular Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong New Area, Shanghai, 201399, People’s Republic of China, Tel +86 18918922698, Email yuboshpd@163.comObjective: Because tumor tissues are most frequently heterogeneous and hard to characterize, the resulting therapeutic strategy could be misled. The most active and invasive tumor cells are circulating tumor cells (CTCs). In this study, we investigated the feasibility of individualized treatment of breast cancer patients based on whole genome sequencing (WGS) of single cell CTC.Methods: Twenty-four CTCs were identified in three breast cancer patients. For each patient, one polyploid CTC was captured, and on which the WGS was performed. WGS was considered due to its sequencing robustness compared to conventional sequencing approaches. Based on the histopathological Her-2 status in tumor tissue and the HER2 gene status in WGS results of CTC, we adjusted treatment strategies and monitored disease progression.Results: Patients ID1 and ID2 are found to be Her-2 positive in primary tumors and HER2 gene amplification in the DNA of CTCs. In-patient ID3, histopathological examination of the primary tumor and liver metastases revealed Her-2 negative, but the WGS analysis of CTC showed HER2 gene amplification. After adjusting treatment by adding Her-2 inhibitors according to the results of CTC sequencing, liver metastases and pleural effusion were significantly reduced two months later, CTC number and ctDNA burden were decreased, and 18-months progression-free survival (PFS) was recorded. In addition, some potential therapeutic targets and mutations in drug-resistant genes were detected.Conclusion: The results of CTC sequencing effectively guided the treatment of a patient with HER2 gene amplification in CTC but with Her-2 negative on tumor tissue. Therefore, CTC sequencing could help resolve the heterogeneity of tumors and provide precision medicine for patients.Keywords: single circulating tumor cell, breast cancer, heterogeneity, whole genome sequencing, HER2 gene

Zengxin Jiang,1,&ast; Zeng Zhang,1,&ast; Shuo Li,2,&ast; Sen Lin,3 Hengfeng Yuan1 1Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Joint Bone Disease Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 3National Engineering Research Center, East China University of Science and Technology, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sen Lin; Hengfeng Yuan, Email linsen@ecust.edu.cn; yuanhf@shsmu.edu.cnBackground: Degenerative joint disease or osteoarthritis (OA) is a leading cause of disability worldwide. Intra-articular injection is the mainstay nonsurgical treatment for OA. However, dense cartilage and a lack of vasculature often limit the ability of drugs to reach cell or tissue targets at the concentrations necessary to elicit the desired biological response. Kartogenin (KGN), a small molecular compound, possesses a strong capacity to promote chondrogenic differentiation of mesenchymal stem cells (MSCs). However, the rapid clearance of KGN from the intra-articular cavity limits its feasibility.Materials and Methods: We constructed a magnetically guided biodegradable nanocarrier system (MNP) which enabled intracartilaginous delivery of KGN to promote chondrogenic differentiation by MSCs embedded within the articular matrix. Moreover, in preclinical models of OA, KGN-loaded MNPs exhibited increased tissue penetration and retention within the joint matrix under external magnetic guidance.Results: Histological examination showed that compared with KGN alone, KGN-loaded MNPs enhanced chondrogenic differentiation and improved the structural integrity of both articular cartilage and subchondral bone.Conclusion: This study demonstrates a practical method for intracartilaginous delivery using engineered nanocarriers, thus providing a new strategy to improve the efficacy of molecular therapeutic agents in the treatment of OA.Graphical Abstract: Keywords: osteoarthritis, kartogenin, magnetic nanoparticles, intracartilaginous

Hang Yuan,1 Yu Peng,1 Xiren Xu,2 Shiliang Tu,1 Yuguo Wei,3 Yanqing Ma2 1Department of Colorectal Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital of Hangzhou Medical College), Hangzhou, People’s Republic of China; 2Department of Radiology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital of Hangzhou Medical College), Hangzhou, People’s Republic of China; 3GE Healthcare, Precision Health Institution, Hangzhou, People’s Republic of ChinaCorrespondence: Yanqing Ma, Department of Radiology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital of Hangzhou Medical College), Hangzhou, People’s Republic of China, Email 704180026@qq.comObjective: To predict the status of microsatellite instability (MSI) of rectal carcinoma (RC) using different machine learning algorithms based on tumoral and peritumoral radiomics combined with clinicopathological characteristics.Methods: There were 497 RC patients enrolled in this retrospective study. The tumoral and peritumoral CT-based radiomic features were calculated after tumor segmentation. The radiomic features from two radiologists were compared by way of inter-observer correlation coefficient (ICC). After methods of variance, correlation, and dimension reduction, six machine learning algorithms of logistic regression (LR), Bayes, support vector machine, random forest, k-nearest neighbor, and decision tree were conducted to develop models for predicting MSI status of RC. The relative standard deviation (RSD) was quantified. The radiomics and significant clinicopathological variables constituted the radiomics-clinicopathological nomogram. The receiver operator curve (ROC) was made by DeLong test, and the area under curve (AUC) with 95% confidence interval (95% CI) was calculated to evaluate the performance of the model.Results: The venous phase of CT examination was selected for further analysis because the proportion of radiomic features with ICC greater than 0.75 was higher. The tumoral and peritumoral model by LR algorithm (M-LR) with minimal RSD showed good performance in predicting MSI status of RC with the AUCs of 0.817 and 0.726 in the training and validation set. The radiomic-clinicopathological nomogram performed better in both the training and validation set with AUCs of 0.843 and 0.737.Conclusion: The radiomics-clinicopathological nomogram demonstrated better predictive performance in evaluating the MSI status of RC.Keywords: rectal carcinoma, microsatellite instability, computed tomography, machine learning, radiomics, nomogram

Xiaodan Jiang,1,2,&ast; Yu Wan,1,2,&ast; Hao Yuan,1,2,&ast; Liming Zhao,3,&ast; Min Sun,4,&ast; Yanhui Xu,5,&ast; Xiangyang Xin,6,&ast; Jing Dong,7,&ast; Die Hu,8,&ast; Dongmei Chen,9,&ast; Xuemin Li1,2 1Department of Ophthalmology, Peking University Third Hospital, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Beijing, People’s Republic of China; 3Department of Ophthalmology, Beijing Fengtai Hospital, Beijing, People’s Republic of China; 4Department of Ophthalmology, Huabei Petroleum General Hospital, Renqiu, Hebei, People’s Republic of China; 5Department of Ophthalmology; Hebei Provincial Eye Hospital, Xingtai, Hebei, People’s Republic of China; 6Department of Ophthalmology, Inner Mongolia Baogang Hospital, Baotou, Inner Mongolia, People’s Republic of China; 7Department of Ophthalmology, the First Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia, People’s Republic of China; 8Department of Ophthalmology, Baoding Zhuozhou GEM Flower Hospital, Zhuozhou, Hebei, People’s Republic of China; 9Department of Ophthalmology, Baoding GEM Flower Eastern Hospital, Zhuozhou, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemin Li, Department of Ophthalmology, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, No. 49 Huayuan North Road, Haidian District, Beijing, 100191, People’s Republic of China, Tel +86 10 8226 6312, Fax +86 10 8208 9951, Email lxmlxm66@sina.comObjective: To investigate the incidence of acute postoperative endophthalmitis (POE) after cataract surgery in Northern China from 2013 to 2019, evaluate the efficacy of prophylaxis and analyze the predictors of visual prognosis among POE patients.Methods: The study was conducted as a retrospective multi-center research, with seven hospitals in Northern China enrolled. The diagnosis of acute-onset POE was made on the basis of clinical manifestations within six weeks after initial surgery. By reviewing electronic medical system, the number of cataract surgeries and acute POE cases were recorded to estimate the overall incidence and incidences by different years and hospitals. Perioperative measures for preventing infection in different hospitals were collected. The correlations between unfavorable final vision and potential factors including basic information and clinical characteristics were examined to determine the predictive factors for final visual prognosis.Results: Of 72,255 cataract surgeries performed during seven years in the seven hospitals, 19 cases developed acute POE, yielding an overall incidence of 0.026%. The average incidence of acute POE among seven hospitals significantly declined annually during the past 7 years (p = 0.021). In Hospital-D, the incidence of acute POE significantly decreased after the application of 0.5% povidone-iodine (PVP-I) for conjunctival washing (p = 0.003). Two hospitals adopting tobramycin in the irrigation solution achieved a significant lower incidence of POE than the other hospitals (p = 0.044). The positive rate of pathogen culture was just 17.6% (3/19). Patients with presenting BCVA of CF or better were more likely to present with unfavorable final vision than those with worse presenting BCVA (p = 0.003).Conclusion: The overall incidence of acute POE after cataract surgery from 2013 to 2019 in Northern China was 0.026%, and the incidence declined annually over the period. Presenting BCVA could be a significant prognosis factor for predicting the final visual outcomes of acute POE patients.Keywords: endophthalmitis, cataract surgery, infection prophylaxis, prognosis predictors

The objective of this study was to characterize the major proteomes and metabolites in beef exudate and determine their relationship to color and oxidative quality of beef muscles. Beef loin (LD) and tenderloin (PM) muscles were cut into sections, individually vacuum-packaged, and aged for 9, 16 and 23 days at 2 °C. Following aging, beef exudates were collected and analyzed for both proteomics and metabolomics profiles. Proteome analysis indicated clustering by muscle types, while metabolomics profiling further clustered the samples based on the aging periods. The PM exudate had a greater concentration of oxidative enzymes, while the LD exudate contained more glycolytic enzymes. Greater lipid, nucleotide, carnitine and glucoside metabolites were observed in LD and 23d exudates. HSP70 and laminin proteins, together with glucosides metabolites, were correlated to muscle oxidative stability. The results indicated that meat exudate could be a viable analytical matrix to determine changes in quality attributes of meat with aging.

Fang Peng,1 Hao Yuan,1 Yi-Feng Zhou,2 Si-Xian Wu,1 Zhen-Yi Long,1 Ya-Meng Peng1 1Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China; 2Operating Room, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of ChinaCorrespondence: Hao Yuan, Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China, Tel +8613677366519, Email yuanhao666@hunnu.edu.cnPurpose: We aimed to explore the clinical diagnostic value of combined detection via protein induced by vitamin K absence or antagonist II (PIVKA-II), alpha-fetoprotein (AFP), and D-dimer (D-D) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).Materials and Methods: We analyzed PIVKA-II, AFP, and D-D levels in 291 subjects comprising liver cirrhosis (LC) patients (n = 143) and HCC patients (n = 148). Receiver operating characteristic (ROC) curves were used to analyze and compare the clinical diagnostic value of the three biomarkers for HBV-related HCC alone and in combination.Results: The levels of PIVKA-II, AFP, and D-D were positively correlated with tumor size in HCC patients. The levels of PIVKA-II and AFP in early-stage HCC, advanced HCC, HBV DNA+ HCC, and HBV DNA- HCC patients were higher than those in LC patients, while the levels of D-D were lower. The area under the curve for combined detection was greater than that for single-index detection in early-stage HCC, advanced HCC, HBV DNA+ HCC, and HBV DNA- HCC patients.Conclusion: D-D may be a useful biomarker for the diagnosis of HBV-related HCC. The combined detection of PIVKA-II, AFP, and D-D had better diagnostic value for different types of HCC than the detection of individual biomarkers.Keywords: PIVKA-II, alpha-fetoprotein, D-dimer, biomarker, hepatocellular carcinoma, hepatitis B virus

Xueying Zhang,1– 3,* Chen He,1– 3,* Peijun Ju,4,* Qingrong Xia,1– 3 Jianliang Gao,1– 3 Loufeng Zhang,1– 3 Xuequan Chen,1– 3 Hui Yuan,1– 3 Hua Gao,1– 3 Yang Zhang,1– 3 Junwei Yan,1– 3 Wen Xie,1– 3,* Cuizhen Zhu1– 3,* 1Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Clinical Center for Psychiatry and Mental Health, Hefei Fourth People’s Hospital, Hefei, People’s Republic of China; 3Anhui Mental Health Center, Hefei, People’s Republic of China; 4Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wen Xie; Cuizhen Zhu, Affiliated Psychological Hospital of Anhui Medical University, No. 316 Huangshan Road, Shushan District, Hefei, Anhui, People’s Republic of China, Tel +86 13339102285 ; +86 13705535258, Fax +86 055163616000, Email xiewen0808@sina.com; zhucuizhen88@126.comPurpose: The study aimed to clarify the cognitive impairments of schizophrenia with metabolic syndrome while evaluating their potential as risk factors.Patients and Methods: We recruited 153 participants and divided them into three groups according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria and the guideline standards for the prevention and treatment of dyslipidemia in Chinese adults in 2007 for metabolic syndrome, as follows: healthy control group (n = 47); nonmetabolic syndrome group (n = 58); and metabolic syndrome group (n = 48). Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale. Cognitive function and automatic thinking were estimated using the Montreal Cognitive Assessment Scale, Verbal Fluency Test, and Automatic Thoughts Questionnaire. Serum biochemical parameters were measured by automatic biochemistry analyzer.Results: One-way ANOVA analysis revealed that differential cognition impairments in schizophrenia patients compared to controls. Furthermore, results of multiple comparisons showed that more serious barriers in orientation, language fluency, and negative automatic thinking existed in the metabolic syndrome group than in the healthy and non-metabolic syndrome groups. Spearman correlation and stepwise linear regression analyses showed that psychopathological symptoms, high waist circumference, and high triglyceride were the predictive factors for negative automatic thoughts, orientation, and language fluency. Those results collectively revealed that high waist circumference, high triglyceride and negative automatic thinking had validity and effectiveness in predicting the cognitive function impairments of the metabolic syndrome group.Conclusion: The present findings strongly supported the notion that aberrant parameters of high waist circumference, high triglyceride and high negative automatic thoughts had validity and effectiveness predictive role for cognitive impairments in the schizophrenics with metabolic syndrome. The schizophrenia patients with metabolic syndrome should receive regular monitoring and adequate treatment for metabolic and psychological risk factors.Keywords: second-generation antipsychotics, negative symptoms, diet, Montreal Cognitive Assessment Scale, Verbal Fluency Test

Fred Cohen, Hsiangkuo Yuan Jefferson Headache Center, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, 19107, USACorrespondence: Hsiangkuo Yuan, Jefferson Headache Center, Department of Neurology, Thomas Jefferson University, 900 Walnut St. Suite 200, Philadelphia, PA, 19107, USA, Tel +1 215-955-2243, Fax +1 215-955-2060, Email hsiangkuo.yuan@jefferson.eduAbstract: Advances in molecular biology and neuroscience have led to the discovery of calcitonin gene-related peptide (CGRP), a 37 amino-acid neuropeptide that plays a critical role in the pathogenesis of migraine. CGRP receptor antagonist, also known as gepant, is an oral medication that inhibits the CGRP-related nociceptive signaling pathway. To date, three gepants are approved by the FDA for migraine treatment. Atogepant is a 2nd-generation gepant that non-competitively antagonizes CGRP receptors inhibiting neurogenic inflammation and pain sensitization. With its long half-life and minimal cardiovascular or liver toxicity, it is the first in its class approved primarily for migraine prevention. This article will discuss the evidence, safety, and rationale of atogepant for use in clinical practice.Keywords: treatment, migraine, CGRP, gepant

This study was performed to evaluate the effects of wet-aging (3, 7, 14, 21, and 28 d at 2 °C) on beef (longissimus lumborum muscles) exudate proteome and meat quality changes. The pH, purge loss, and tenderness of beef increased with aging (P

Qiyun Jiang,1,2 Dan Gong,1,2 Huiqi Li,3 Donglan Zhang,4 Suzhen Hu,5 Qinghua Xia,6 Hong Yuan,7 Peng Zhou,6 Yiying Zhang,7 Xing Liu,8 Mei Sun,1,2 Jun Lv,1,2 Chengyue Li1,2 1Department of Health Policy and Management, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2Research Institute of Health Development Strategies, Fudan University, Shanghai, People’s Republic of China; 3School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; 4Department of Health Policy and Management, College of Public Health, University of Georgia, Athens, GA, USA; 5Department of Medical Affairs, Liaocheng People’s Hospital, Liaocheng, People’s Republic of China; 6Department of Chronic Disease Prevention and Control, Changning District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 7Department of Chronic Disease Prevention and Control, Jiading District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 8Department of Epidemiology, School of Public Health, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Chengyue Li; Jun Lv, Department of Health Policy and Management, School of Public Health, Fudan University, P.O. Box 177, 130 Dong’an Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-33561022 ; +86-21-33563953, Fax +86-21-33563380, Email lichengyue@fudan.edu.cn; lujun@shmu.edu.cnPurpose: This study aimed to develop a screening tool based on a risk scoring approach that could identify individuals at high risk for hypertension in Shanghai, China.Methods: A total of 3147 respondents from the 2013 Shanghai Chronic Disease and Risk Factor Surveillance were randomly divided into the derivation group and validation group. The coefficients obtained from multivariable logistic regression were used to assign a score to each variable category. The receiver operating characteristic (ROC) curve was used to find the optimal cut-off point and to evaluate the screening performance.Results: Age, family history of hypertension, having diabetes, having dyslipidemia, body mass index, and having abdominal obesity contributed to the risk score. The area under the ROC curve was 0.817 (95% CI: 0.797– 0.836). The optimal cut-off value of 20 had a sensitivity of 83.4%, and a specificity of 64.3%, demonstrating good performance.Conclusion: We developed a simple and valid screening tool to identify individuals at risk for hypertension. Early detection could be beneficial for high-risk groups to better manage their conditions and delay the progression of hypertension and related complications.Keywords: Eastern China, high-risk population, hypertension, risk scoring method, screening tool

Huiyang Wang,1,&ast; Siqi Wang,2,&ast; Xisong Zhu,3 Wenxiu Ding,4 Tianlun Shen,2 Hongjie Fan,1 Yanhua Zhang,5 Lijun Peng,6 Hong Yuan,6 Xiangrui Liu,7 Jun Ling,2 Jihong Sun1 1Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China; 2MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, People’s Republic of China; 3Department of Radiology, Quzhou Central Hospital Affiliated to Zhejiang Chinese Medical University, Quzhou, 324002, People’s Republic of China; 4Department of Ultrasound Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, People’s Republic of China; 5Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China; 6College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310030, People’s Republic of China; 7Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jihong Sun, Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China, Tel +13857176538, Fax +571-86006762, Email sunjihong@zju.edu.cn Jun Ling, MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, People’s Republic of China, Tel +13645717301, Fax +571-87953739, Email lingjun@zju.edu.cnPurpose: To develop an iron-based solid lipid nanoparticle (SLN) absorbable by the intestinal wall and assess the differential diagnostic value of intestinal lesions in magnetic resonance imaging (MRI).Methods: SLNs were prepared with the simultaneous loading of trivalent Fe ions (Fe3+), levodopa methyl ester (DM), and fluorescein isothiocyanate (FITC). We evaluated the particle size, loading rate, encapsulation efficiency, and cytotoxicity of SLNs. The T1 contrast effects of the FeDM-FITC-SLNs and gadolinium-based contrast agent (GBCA) were compared in different mouse models: acute ulcerative colitis (AUC), chronic ulcerative colitis (CUC), colon adenocarcinoma (COAD), and normal control. MRI was performed in the same mouse with intravenous injection of GBCA on day 1 and enema of FeDM-FITC-SLNs on day 2. The signal-to-noise ratios (SNRs) were compared using one-way analysis of variance. Tissues were then collected for histology.Results: The average particle size of FeDM-FITC-SLN was 220 nm. The mean FeDM loading rate was 94.3%, and the encapsulation efficiency was 60.3%. The relaxivity was 4.02 mM− 1·s− 1. After enema with FeDM-FITC-SLNs, MRI showed the following contrast enhancement duration: AUC = COAD > normal > CUC. Confocal fluorescence microscopy confirmed that FeDM-FITC-SLNs were mainly distributed in the intestinal mucosa and tumor capsule.Conclusion: Iron-based SLNs are promising alternatives for contrast enhancement at T1-weighted MRI and will help in the differential diagnosis of intestinal bowel diseases (IBDs).Keywords: solid lipid nanoparticles, magnetic resonance imaging, contrast agent, ferric iron, intestinal bowel diseases

Root-lesion nematodes, Pratylenchus spp., are economically important pathogens because of their detrimental and economic impact on a wide range of crops. In August 2018, two samples of both roots and rhizosphere soil were collected from a corn field in Liangyuanqu of Shangqiu city, Henan Province, China. Root-lesion nematodes were recovered from the roots and soil samples using the modified Baermann funnel extraction method. Both the morphological characters and molecular analysis of the internal transcribed spacer (ITS) and D2-D3 expansion region of 28S ribosomal RNA sequences confirmed that the root-lesion nematode population collected from corn in this study was P. neglectus. Phylogenetic analyses showed that this isolate formed a highly supported clade with other P. neglectus isolates. To the best of our knowledge, this is the first report of P. neglectus on corn in Henan Province of China. This study reports the first partial sequences of 28S D2-D3 region of P. neglectus on corn in China. Due to the great harmfulness of root-lesion nematodes to corn, care should be taken to prevent the spread of P. neglectus to other regions in China. At the same time, further study on the biological characteristics of P. neglectus is needed, which will be helpful to develop corresponding management and control strategies.

Junwei Tong,1– 3,&ast; Xiangui Meng,1– 3,&ast; Qingyang Lv,1– 3,&ast; Hongwei Yuan,1– 3 Weiquan Li,1– 3 Wen Xiao,1– 3 Xiaoping Zhang1– 3 1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518000, People’s Republic of China; 3Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Zhang; Wen XiaoDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of ChinaFax +86 85776343Email xzhang@hust.edu.cn; xiaowenx11@163.comBackground: Increasing evidence indicated that the aberrant expression of the cytoplasmic FMR1-interacting protein (CYFIP) family might possess critical role and potential functions in cancer. But the role of CYFIP2 in clear cell renal cell carcinoma (ccRCC) is still uncharacteristic.Methods: We investigated the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database for the expression profile, clinicopathological variables, clinical prognosis information, and promoter methylation levels of CYFIPs in ccRCC. The aberrant CYFIP2 protein expression was validated by the Human Protein Atlas (HPA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to uncover CYFIP2 mRNA levels in 28 pairs of ccRCC cancer tissues. Kaplan–Meier analysis, univariate and multivariate Cox proportional hazard regression were performed to assess CYFIPs’ prognosis value. Gene set enrichment analysis (GSEA) was used to determined hallmark functions, gene ontology of CYFIP2. TIMER database was utilized to assess the correlation with immune infiltration in ccRCC.Results: Results showed CYFIP2 was downregulated in ccRCC, relative to paired normal tissues in TCGA-KIRC database and 28 pairs of clinical samples (P < 0.0001). Similarly, a decreased CYFIP2 protein expression was confirmed by ccRCC tissues. The results showed CYFIP2 was negatively regulated by promoter DNA methylation. Survival analysis results showed CYFIP2 could be an independent biomarker for ccRCC and its reduction predicted a poor overall survival (OS) and disease-free survival (DFS). GSEA showed CYFIP2 was involved in metabolic pathways and epithelial–mesenchymal transition (EMT). Immune infiltration analysis revealed that a list of immune markers was significantly correlated with CYFIP2 expression especially with CD4+ cells and CD8+ cells in ccRCC.Conclusion: These results show that CYFIP2 was downregulated in ccRCC patients and predicted an unfavorable prognosis. CYFIP2 might be a potential novel prognostic molecule, and related to immune infiltration, the metabolism, as well as EMT process in ccRCC. CYFIP2 could act as tumor suppressor gene in ccRCC and positive modulation of CYFIP2 might lead to development of a novel strategy for ccRCC treatment.Keywords: CYFIP2, ccRCC, methylation, prognosis, immune infiltration

Zhen-Yi Long,1,&ast; Yi-Feng Zhou,2,&ast; Hao Yuan,1 Ya-Meng Peng,1 Si-Xian Wu,1 Fang Peng1 1Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China; 2Operating Room, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao YuanDepartment of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of ChinaTel +86-13677366519Fax +86-731-82278012Email yuanhao666@hunnu.edu.cnPurpose: We explored the expression levels of IgG4 and interleukin (IL)-21 in the serum and ankle joints of collagen-induced arthritis (CIA) rats at different disease stages.Materials and Methods: Wistar rats were randomly divided into normal and model groups, and the latter group was administered bovine type II collagen to induce arthritis. Enzyme-linked immunosorbent assay was performed at 21, 28, 35, and 42 days to detect IgG4 and IL-21 in the serum, followed by histological and immunohistochemical analyses of IgG4 and IL-21r in the ankle joint of rats.Results: The contents of IgG4 and IL-21 in the serum of the CIA model group were positively correlated and increased with disease progression. The expression of IgG4 and IL-21 receptors in the ankle joint of the CIA model group was significantly higher than that in the control group. These proteins were closely related to the pathological score. The serum IL-21 level in the model group was closely related to the level of IL-21 receptor in the ankle joint.Conclusion: IL-21 may promote the occurrence and development of rheumatoid arthritis by combining with IL-21r to regulate the content of IgG4.Keywords: rheumatoid arthritis, immunoglobulin, interleukin, interleukin receptor

Xiangui Meng,1– 3,&ast; Hongwei Yuan,1– 3,&ast; Weiquan Li,1– 3,&ast; Wen Xiao,1– 3 Xiaoping Zhang1– 3 1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518000, People’s Republic of China; 3Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Zhang; Wen XiaoDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of ChinaTel +86-18602752025Fax +86 2785776343Email xzhang@hust.edu.cn; xiaowenx11@163.comBackground: Studies report that conventional treatment of clear cell renal cell carcinoma (ccRCC) is effective, but several advanced patients present with poor prognosis. The current study explored potential new tumor markers and therapeutic targets in advanced ccRCC.Methods: Biomarker gene expression of ccRCC was retrieved from GEO database and the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database. Gene ontology (GO) analysis and protein–protein interaction (PPI) networks of biomarker genes were constructed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool. Kaplan–Meier analysis and receiver operating characteristic curve (ROC) analysis were performed to explore the prognostic and diagnostic roles of these genes. Gene set enrichment analysis (GSEA) analysis was used to determine hallmark functions of the biomarker genes. qRT-PCR was used to verify the reliability of the analysis results in tumor tissues.Results: A total of 21 upregulated genes were identified between advanced ccRCC and early ccRCC (grade III+IV vs grade I+II). Gene ontology analysis showed that the 21 upregulated genes were mainly implicated in biological processes including metabolic and lipid transport. The findings showed that 7 out of the 21 genes were significantly upregulated in 72-paired samples retrieved from the TCGA-KIRC. High expression of 5 genes indicated a poor prognosis of overall survival and disease-free survival in KIRC. Three genes effectively distinguished renal cancer tissue and adjacent renal tissues in a total of 533 ccRCC samples. GSEA showed that the 3 biomarkers were significantly enriched in epithelial–mesenchymal transition, G2M checkpoint, and angiogenesis. The results of qRT-PCR showed that STEAP3, IBSP, and AQP9 had a significant identification effect in ccRCC.Conclusion: The findings showed that 3 biomarkers were significantly upregulated in advanced ccRCC and could be used for diagnosis, prediction, and potential novel therapeutic targets for progression of ccRCC.Keywords: advanced ccRCC, biomarker, progression, differentially expressed genes

Yongfang Zhang,1,&ast; Di Wang,2,&ast; Weiqun Liu,1 Yin Zhang,3 Lina Zhou,4 Hanhuan Yuan,5 Jiaming Yao,6 Ming Li7 1Department of Nursing, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 2Department of Nursing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 3The Party and Government Office, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 4Department of Publicity, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 5Infectious Disease Control and Disinfection Management Section, Shanghai Pudong New Area Center for Disease Control and Prevention, Fudan University Pudong Institute of Preventive Medicine, Shanghai, People’s Republic of China; 6Columbia University School of Nursing, New York, NY, USA; 7Dean’s Office, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming LiShanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, 1500 W Zhouyuan Road, Pudong New Area, Shanghai, 201318, People’s Republic of ChinaTel +86 2168135590 Ext. 6001Fax +86 21-68135715Email liming1070@126.comJiaming YaoColumbia University School of Nursing, 560 W 168th Street, New York, NY, 10032, USATel +1-6463391188Email jy2349@cumc.columbia.eduObjective: To implement epidemic prevention among entry personnel, Shanghai has launched a number of Medical Observation Sites (Observation Site) for which high expectations are set. Ours is one such Observation Site.Methods: As part of a novel project, we did not have any previous experience to use as reference. Despite some challenges, we achieved satisfactory outcomes by establishing a stepwise approach to inbound passenger management, including the division of the working area of the Observation Site, dynamic management of the rooms, closed-loop management of the isolated personnel.Results: As of May 14, 2020, a total of 42 Observation Sites were operational in Pudong New Area. The following are the detailed descriptions of our Temporary Medical Observation Site set up and work flow.Conclusion: Early screening of inbound passengers as well as prompt and dynamic management of information about passengers’ close contacts play an active role in preventing an influx of cases. As a pilot program, we have a model that is effective despite some limitations.Keywords: COVID-19, observation, pandemic, screening, airport, room

Zhaoping Wang,1 Xiaolin Ni,1,2 Danni Gao,2,3 Liang Sun,1 Xiaoquan Zhu,1 Juan Jiao,4 Qi Zhou,1 Chen Chen,1 Nan Zhang,1 Zhu Wu,1 Ze Yang,1 Huiping Yuan1 1The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, National Center for Gerontology, Beijing, 100730, People’s Republic of China; 2Graduate School of Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 3Peking University Fifth School of Clinical Medicine (Beijing Hospital), Beijing, 100730, People’s Republic of China; 4Clinical Laboratory Department, The Seventh Medical Center, PLA General Hospital, Beijing, 100730, People’s Republic of ChinaCorrespondence: Huiping YuanThe MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Dongdan DaHua Road 1#, Beijing, 100730, People’s Republic of ChinaTel +86-10-58115043Fax +86-10-65237929Email yuanhuiping@126.comPurpose: To our knowledge, the normal fasting plasma glucose (FPG), blood pressure (BP), and blood lipids (BL) interval values have not been well-established in the longevity population. This study aims to provide a reference for the establishment of normal BP, FPG, and BL interval values in the longevity people in China.Patients and Methods: A total of 7417 people were selected from the natural longevity cohort in Guangxi, with an age range of 20– 110 years old, including 7093 classified as the non-longevity (20– 89 years old) (94.02%) and 324 classified as the longevity (≥ 90 years old) (5.98%); there were 4309 men (58.1%) and 3108 women (41.9%). FPG, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels were defined as desirable levels when they were below the 75th percentile (P75), borderline levels from the 75th to 90th percentile (P75–P90), and high levels above P90; triglyceride (TG) levels above P90 were defined as high; and high-density lipoprotein cholesterol (HDL-C) levels below the 5th percentile (P5) were defined as low levels.Results: The reference interval values of FPG in the longevity were as follows: desirable levels < 6.15 mmol/L, borderline levels 6.15– 7.45 mmol/L, high levels ≥ 7.45 mmol/L. Reference interval values of systolic blood pressure (SBP) were as follows: desirable levels < 160.00 mmHg, borderline levels 160.00– 174.50 mmHg, high levels ≥ 175.00 mmHg. DBP reference interval values were as follows: desirable levels < 88.00 mmHg, borderline levels 88.00– 90.00 mmHg, high levels ≥ 90.00 mmHg. TC reference interval values were as follows: desirable levels < 5.59 mmol/L, borderline levels 5.59– 6.45 mmol/L, high levels ≥ 6.45 mmol/L. LDL-C reference interval values were as follows: desirable levels < 3.30 mmol/L, borderline levels 3.30– 3.85 mmol/L, high levels ≥ 3.85 mmol/L. TG reference interval values were as follows: desirable levels < 2.82 mmol/L, high levels ≥ 2.82 mmol/L. HDL-C reference interval values were as follows: low levels < 0.80 mmol/L, desirable levels ≥ 0.80 mmol/L.Conclusion: The reference interval values of BP, FPG, and BL are different between the longevity population and the non-longevity population, and the interval values change with increasing age.Keywords: longevity, blood pressure, fasting plasma glucose, blood lipids, reference interval values

Hua Yuan,* Yu-Zhao Zhang,* Hong Jie, Shi-Lian Li Department of Ophthalmology, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shi-Lian LiDepartment of Ophthalmology, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, No. 100 Hongkong Road, Wuhan, 430016, People’s Republic of ChinaTel +86 13971212408Fax +8627-82433375Email lisldrli@163.comObjective: To discuss a rapid and effective treatment used for children with eyelid lacerations during the COVID-19 lockdown in Wuhan to limit the risk of cross-infection.Methods: A comparative study was conducted of forty-five patients with eyelid lacerations who attended the Ophthalmology Department of Wuhan Children’s Hospital between January 23, 2020 and March 6, 2020. The tissue glue Histoacryl was used to bond the wounds in 24 cases, while the traditional suture method was used for 21 cases. The wound healing time, complications, treatment satisfaction, and number of visits of the two groups were compared.Results: The two groups had similar baseline characteristics. The wound healing time (from wound disinfection to wound dressing) was shorter in the tissue glue group (4.35 ± 0.47min versus 11.71 ± 1.85 min, P< 0.01). There was 1 case of wound dehiscence in the tissue glue group. Twenty-two cases in the tissue glue group were satisfied, 2 cases were basically satisfied, and 0 were dissatisfied. Eleven cases in the traditional suture group were satisfied, 9 cases were basically satisfied, and 1 case was dissatisfied. The difference was statistically significant (P < 0.05). In terms of the number of visits, the tissue glue group visited (1.54 ± 0.88) times, while the traditional suture group visited (2.38 ± 0.59) times. The difference between the two groups was statistically significant (P < 0.01). The real-time reverse transcriptase polymerase chain tests for severe acute respiratory syndrome coronavirus 2 of all medical staff in the ophthalmology emergency room were negative.Conclusion: Compared with the traditional suture method, tissue glue used in eyelid laceration in children has the advantages of painlessness, shorter operation duration, higher safety and satisfaction, greater ease of care, and fewer hospital visits. Tissue glue can be widely used to reduce the risk of cross-infection.Keywords: coronavirus disease 2019, COVID-19, tissue glue, acrylate cyanide, children, eyelid, laceration

Qi Zhou,1,* Guofang Pang,2,* Zhirong Zhang,3 Huiping Yuan,1 Chen Chen,1 Nan Zhang,1 Ze Yang,1 Liang Sun1,4 1The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Guangxi Jiangbin Hospital, Nanning, Guangxi, People’s Republic of China; 3Fengtai Center for Disease Control and Prevention, Beijing, People’s Republic of China; 4NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang SunThe Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, 100730, People’s Republic of ChinaTel +86-10-85115043Email sunbmu@foxmail.comObjective: Akkermansia muciniphila is among the most abundant bacterial species in the human intestine; however, its relationship to metabolic syndrome (MetS)—which is linked to gut dysbiosis—is not known. In this study, we investigated the association between Akkermansia abundance and risk of MetS and its components, as well as dose–response effects and the influence of microbial interactions on the association.Methods: This cross-sectional study included 6896 Chinese participants aged 18 to 97 years from the Guangdong Gut Microbiome Project. MetS was defined according to Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults criteria. The abundance of Akkermansia was assessed by 16S rRNA sequencing. Logistic regression analysis with adjustment for common confounders was performed to evaluate the association between Akkermansia and MetS and its components. Models with restricted cubic splines and interaction terms were used to examine the dose–response association and microbial interactions, respectively.Results: The prevalence of MetS was 20.4%, and the median abundance of Akkermansia was 0.08% (interquartile range: 0.04– 0.93%). Increased Akkermansia abundance was associated with decreased risk of MetS (Pnonlinear< 0.05), but this effect was not observed until the Akkermansia level was 0.2% of the total gut microbiota abundance (odds ratio=0.96, 95% confidence interval: 0.94– 0.98). Of the 5 MetS components, obesity and hypertriglyceridemia showed the strongest association with Akkermansia, followed by reduced high-density lipoprotein cholesterol, hypertension, and hyperglycemia. Microbial interaction analyses showed that Ruminococcaceae and Lachnospiraceae were the predominant bacterial families and were not only correlated with Akkermansia abundance but also influenced the Akkermansia–MetS association.Conclusion: There is a dose–response association between reduced risk of MetS and increased abundance of Akkermansia. The association between Akkermansia and 5 MetS components is variable and affected by microbial interactions.Keywords: metabolic syndrome, gut microbiota, Akkermansia muciniphila, dose–response, microbial interaction

Xin Jiang,1,* Wenqi Zhao,1,* Tiantian Zhao,2,* Mei Yang,1 Hongbin Yuan,1 Jun Qian,2 Zhenghua Xiang3 1Department of Anesthesiology, Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of General Surgery, Affiliated Xinchang Hospital of Shaoxing University, Zhejiang, People’s Republic of China; 3Department of Neurobiology, Key Laboratory of Molecular Neurobiology, Ministry of Education, Naval Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenghua XiangDepartment of Neurobiology, Key Laboratory of Molecular Neurobiology, Ministry of Education, Naval Medical University, No. 800 Xiangyin Road, Shanghai, 200433, People’s Republic of ChinaTel +86 21 81871044Fax +86 21 81885822Email xiang-zhenghua@163.comJun QianDepartment of General Surgery, Affiliated Xinchang Hospital of Shaoxing University, No. 117 Middle Gushan Road, Xinchang, Zhejiang, 312500, People’s Republic of ChinaTel +86 575 8638079Email qianj001@163.comPurpose: To detect the spatio-temporal expression of S100A4 in a spinal nerve ligation (SNL) rat model. Also to figure out which other molecules directly interact with S100A4 to explore the possible mechanisms which might be involved in neuropathic pain.Methods: Seven-week-old male SD rats were used for the SNL model construction. Immunofluorescence and Western blotting were used to detect the spatio-temporal expression of S100A4 in the model. S100A4 was co-labeled with a number of related molecules and marker molecules that can distinguish between cell types. After intrathecal injection of S100A4 neutralizing antibody, the behavioral changes of SNL rats were recorded, and molecular changes compared. The direct interaction between S100A4 and other related molecules was verified by co-immunoprecipitation (co-IP) to explore its possible mechanism.Results: After spinal nerve ligation, the content of S100A4 in the dorsal root ganglion (DRG) and spinal dorsal horn increased significantly. Intrathecal injection of S100A4 neutralizing antibody could effectively relieve the mechanical pain in rats. co-IP revealed a direct interaction between S100A4 and RAGE.Conclusion: The content of S100A4 in the DRG and spinal dorsal horn of SNL rats increased, compared with that of the control group. Intrathecal injection of S100A4 neutralizing antibody could effectively relieve the mechanical pain in SNL rats. S100A4 may be involved in the production of neuropathic pain through RAGE or other ways, but the specific mechanism needs to be further studied.Keywords: neuropathic pain, S100 calcium binding protein A4, receptor for advanced glycation end products, spinal nerve ligation model

Hao Wang,1,* Zengxin Jiang,1,* Zhiying Pang,1 Guobin Qi,1 Bingxuan Hua,1 Zuoqin Yan,1 Hengfeng Yuan2 1Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Orthopaedic Surgery, Shanghai Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zuoqin YanDepartment of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of ChinaTel +86 13818009668Email yan.zuoqin@zs-hospital.sh.cnHengfeng YuanDepartment of Orthopaedic Surgery, Shanghai Sixth People’s Hospital, Shanghai Jiaotong University, 600 Yishan Road, Xuhui District, Shanghai, 200233, People’s Republic of ChinaTel +86 13917398796Email yuan.hengfeng@hotmail.comPurpose: Osteoarthritis (OA) is a progressive disease characterized by pain and impaired joint functions. Engeletin is a natural compound with anti-inflammatory and antioxidant effects on other diseases, but the effect of engeletin on OA has not been evaluated. This study aimed to elucidate the protective effect of engeletin on cartilage and the underlying mechanisms.Methods: Chondrocytes were isolated from rat knee cartilage, and TNF-α was used to simulate OA in vitro. After treatment with engeletin, the expression of extracellular matrix (ECM) components (collagen II and aggrecan) and matrix catabolic enzymes (MMP9 and MMP3) was determined by Western blotting and qPCR. Chondrocyte apoptosis was evaluated using Annexin V-FITC/PI and flow cytometry. Apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) were evaluated by Western blotting. The mitochondrial membrane potential of chondrocytes was measured with JC-1, and intracellular reactive oxygen species (ROS) levels were determined with DCFH-DA. Changes in signaling pathways (Nrf2, NF-κB and MAPK) were evaluated by Western blotting. In vivo, anterior cruciate ligament transection (ACLT) was used to induce the rat OA model, and engeletin was administered intraarticularly. The therapeutic effect of engeletin was analyzed by histopathological analysis.Results: Pretreatment with engeletin alleviated TNF-α-induced inhibition of ECM components (collagen II and aggrecan) and upregulation of matrix catabolic enzymes (MMP9 and MMP3). Engeletin ameliorated chondrocyte apoptosis by inhibiting Bax expression and upregulating Bcl-2 expression. Engeletin maintained the mitochondrial membrane potential of chondrocytes and scavenged intracellular ROS by activating the Nrf2 pathway. The NF-κB and MAPK pathways were inhibited by treatment with engeletin. In vivo, ACLT-induced knee OA in rats was alleviated by intraarticular injection of engeletin.Conclusion: Engeletin ameliorated OA in vitro and in vivo. It may be a potential therapeutic drug for OA.Keywords: engeletin, osteoarthritis, OA, apoptosis, reactive oxygen species, ROS, mitochondrial membrane potential

Abstract Apoptosis has been suggested as the first step in the process of conversion of muscle into meat. While a potential role of apoptosis in postmortem proteolysis has been proposed, the underlying mechanisms by which metabolome changes in muscles would influence apoptotic and proteolytic process, leading to meat quality variation, has not been determined. Here, apoptotic and proteolytic attributes and metabolomics profiling of longissimus dorsi (LD) and psoas major (PM) muscles in pigs from two different production cycles (July–Jan vs. Apr–Sep) were evaluated. PM showed higher mitochondrial membrane permeability (MMP), concurrent with less extent of calpain-1 autolysis and troponin T degradation and higher abundance of HSP27 and αβ-crystallin compared to LD (P

Hongmei Yuan,1,2 Huilan Lei,2 Peng Gu,2 Lang Ma,1 Li Qiu1 1Department of Medical Ultrasound, Laboratory of Ultrasound Imaging Drug, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Ultrasound, Sichuan Key Laboratory of Medical Imaging, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, People’s Republic of ChinaCorrespondence: Li QiuDepartment of Medical Ultrasound, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, People’s Republic of ChinaTel +86-18980602044Fax +86-28-85164146Email qiulihx@scu.edu.cnAbstract: Multiple myeloma (MM) in the breast has been rarely documented. However, there are no reports on concurrent masses of chest wall soft tissue and breast as the primary symptoms for MM. Herein, we report a case of a 68-year-old woman presented with masses in her right breast and chest wall for 1 month. She recalled having xerophthalmia and xerostomia for 2 years without taking any test to search for the cause of these symptoms. Ultrasonography (US) and computed tomography (CT) examination revealed masses in the right breast and chest wall. Both lesions of the breast and chest wall were confirmed to be plasma cell tumors by ultrasound-guided puncture biopsy and MM was confirmed by bone marrow examination. Meanwhile, Sjogren’s syndrome (SS) was diagnosed by the positive expression of antibodies against antinuclear, Ro/SSA and La/SSB. After three courses of chemotherapy for MM, the symptoms of SS were significantly alleviated and the masses in the chest wall and breast disappeared.Keywords: multiple myeloma, Sjogren’s syndrome, breast neoplasms, chest wall tumors

The reduction of copper content in converting slag using process control is significant to copper smelter. In this study, the slags produced from the Ausmelt Converting Process for copper matte was analyzed using X-ray diffraction and chemical analysis. Thermodynamic calculation and effects of various conditions including the lance submerging depth in molten bath, the molten bath temperature, the addition of copper matte, and airflow rate were carried out to lower the content in the slag. Thermodynamic analysis indicated that the decrease of copper content was achieved by reducing Fe3O4, CuFe2O4, and Cu2O in the slag, decreasing the magnetism of slag and lowering the viscosity of slag, which was feasible at the operating temperature of the molten bath. Experiments showed that the optimal combination of operating conditions were found to be the addition of copper matte between 5,000 – 7,000 kg/h, a lance airflow rate of 13,000-14,000 Nm3/h, and a lance submergence depth into the molten bath of 700-900 mm, in which the copper content in the slag was effectively reduced from 22.74 wt. % to 7.70 wt. %. This study provides a theoretical support and technical guidance for promoting the utilization of slags from the Ausmelt Converting Process.

Huaqin Yuan,1,* Jun Zhao,2,* Yang Yang,3 Rongfu Wei,1 Liangxue Zhu,1 Jie Wang,1 Meiqing Ding,1 Mingyun Wang,1 Yanhong Gu4 1Department of Oncology, Nanjing Gaochun People’s Hospital Affiliated to Yangzhou University, Nanjing, Jiangsu 211316, People’s Republic of China; 2Department of Orthopedics, Nanjing Gaochun People’s Hospital Affiliated to Yangzhou University, Nanjing, Jiangsu 211316, People’s Republic of China; 3Department of Oncology, Gulou Hospital Affiliated to Medical College of Nanjing University, Nanjing, Jiangsu 210000, People’s Republic of China; 4Department of Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu 210029, People’s Republic of China*These authors contributed equally to this work.Correspondence: Mingyun WangDepartment of Oncology, Nanjing Gaochun People’s Hospital Affiliated to Yangzhou University, 53 Maoshan Road, Gaochun, Nanjing, Jiangsu 211316, People’s Republic of ChinaTel +86-18262636619Fax +86-25-57311232Email Mingyun18748@126.comYanhong GuDepartment of Oncology, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, People’s Republic of ChinaTel +86-18262643578Fax +86-25-57311232Email guluer@163.comPurpose: Colon cancer is a common malignant tumor of the digestive system. This project verified the negative role of protein tyrosine phosphatase (SHP-2) in the regulation of colon cancer and further clarified the key targets and molecular mechanisms in the regulation process.Patients and Methods: The expression levels of SHP-2 in colon cancer tissues, adjacent tissues, normal colon cell lines, and cancer cell lines were detected via Quantitative Real-time PCR (qRT-PCR). The effect of SHP-2 on colon cancer cell function was verified using cell proliferation, Transwell, scratch, and apoptotic assays. CD81 was identified as the interaction protein of SHP-2 by immunoprecipitation.Results: The expression of SHP-2 was decreased in colorectal cancer compared with that in adjacent tissues. This expression was also decreased in colon cancer cells compared with that in intestinal epithelial cells. In addition, the tumor tissues of patients with metastatic colon cancer exhibited downregulated expression of SHP-2 compared with those of patients with non-metastatic colon cancer. Cell proliferation, Transwell, scratch, and apoptotic assay showed that the overexpression of SHP-2 inhibited proliferation, adhesion, and metastasis of colon cancer cell lines and promoted apoptosis. CO-IP proved that SHP-2 could interact with CD81 and inhibit the function of CD81. Recovery experiments confirmed that the overexpression of CD81 reversed the anti-cancer effect of SHP-2.Conclusion: Overexpression of SHP-2 inhibited malignant progression of colon cancer. Mechanism experiments showed that the anti-cancer effect of SHP-2 was realized through the interaction with CD81. This study elucidated the molecular mechanism of SHP-2 regulation in colon cancer and provided guidance for the diagnosis and prognosis assessment of colon cancer.Keywords: SHP-2, CD81, EMT, colorectal cancer

Zhaoping Wang,1 Xiaolin Ni,1,2 Li Zhang,1 Liang Sun,1 Xiaoquan Zhu,1 Qi Zhou,1 Ze Yang,1 Huiping Yuan1 1The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China; 2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Huiping YuanThe MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Dongdan DaHua Road 1#, Beijing 100730, People’s Republic of ChinaTel +86-10-58115043Fax +86-10-65237929Email yuanhuiping@126.comAbstract: Patients with type-2 diabetes mellitus (T2DM) display chronic low-grade inflammation induced by activation of the innate immune system. Toll-like receptor (TLR)4 is a pattern recognition receptor that plays a vital part in activation of the innate immune system. Results from animal and computer-simulation studies have demonstrated that targeting TLR4 to block the TLR4-nuclear factor-kappa B (NF-κB) pathway reduces the inflammatory response and complications associated with T2DM. Therefore, TLR4-targeted therapy has broad prospects. Here, we reviewed the role of TLR4 in inflammation during chronic hyperglycemia in T2DM and its therapeutic prospects.Keywords: T2DM, TLRS, TLR4, inflammation, TLR4 treatment