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Yurong Ou, Ningqi Wu, Lishan Shu, Yang Zhao, Yunfang Bao, Qiong Wu Department of Pathology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, People’s Republic of ChinaCorrespondence: Qiong Wu, Department of Pathology, The First Affiliated Hospital of Bengbu Medical University, 287, Changhuai Road, Bengbu, Anhui Province, People’s Republic of China, Tel +86-18607490054, Email wuqiong@bbmc.edu.cnBackground: Existing research shows inducing ferroptosis can improve the effectiveness of tumor treatment. Glutathione peroxidase 4 (GPX4) is a ferroptosis inhibitor. Solute carrier family 7, membrane 11 (SLC7A11) plays a key role in glutathione homeostasis, which is important for protecting cells from oxidative stress. β-catenin is the key protein the Wnt/β-catenin signaling pathway. The purpose of this study was to investigate the expression of SLC7A11 and GPX4 in colorectal cancer (CRC) and their relationship with β-catenin and to analyze the association of these two factors with several clinicopathological features and patient survival.Methods: This study retrospectively collected paraffin-embedded tissue samples from 120 CRC patients, who received surgical resection between 2017 and 2018. We examined the patterns of expression of SLC7A11, GPX4 and β-catenin by using immunohistochemistry. Analyzing the relationships between SLC7A11, GPX4, β-catenin and clinical pathological parameters and their relationships with overall survival (OS).Results: Expression of SLC7A11 and GPX4 were high expression in 60.83% and 64.17% among the patients, respectively, and were higher than those in normal tissue. SLC7A11, GPX4 and β-catenin were positively correlated with each other (P< 0.05). Expression of SLC7A11 and GPX4 significantly correlates with tumor stage and lymph node metastasis (P < 0.05). The β-catenin was related to lymph node metastasis, TNM stage and tumor grade. Kaplan–Meier analysis showed that patient’s OS in the SLC7A11 and GPX4 were reduced (P< 0.05). Univariate and multivariate analyses showed that SLC7A11 and GPX4 were independent risk factors for CRC prognosis.Conclusion: SLC7A11 and GPX4 overexpression is associated with β-catenin and poor prognosis and may be important for predicting CRC invasion, metastasis, and prognosis.Keywords: colorectal cancer, SLC7A11, GPX4, β-catenin, prognosis

Xiyao Yang,1,&ast; Alayi Bolatai,2,&ast; Jiaxin An,2 Na Wu1,3 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, People’ s Republic of China; 2Department of Student Affairs, Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, People’ s Republic of China; 3Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, 110004, People’ s Republic of China&ast;These authors contributed equally to this workCorrespondence: Na Wu, Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, 110004, People’ s Republic of China, Email 3441535223@qq.comAbstract: With changes in lifestyle, sedentary behavior or lack of physical exercise increases the risk of various glycolipid metabolic disorders. Glycolipid metabolic dysregulation refers to abnormalities in the metabolism of carbohydrates and lipids, including diseases such as diabetes, obesity, and metabolic syndrome. In-depth research into the molecular mechanisms of glycolipid metabolic dysregulation can help develop more effective treatment strategies and preventive measures to prevent the occurrence of long-term complications such as cardiovascular diseases. Alternative polyadenylation (APA) is an important form of RNA modification that helps regulate gene expression and generate protein diversity. This modification can affect processes such as RNA stability, post-transcriptional modification, and translational regulation. Recent studies have confirmed that APA can influence the expression of genes involved in glucose and lipid metabolism, increasing the probability of developing immune, endocrine, and metabolic diseases. The review explains the research progress of APA involvement in various metabolic diseases and explores these mechanisms, providing new insights and directions for novel metabolic disorder treatment strategies.Keywords: APA, alternative polyadenylation, glycolipid metabolic diseases, 3’UTRs, diabetes, obesity, metabolism, dysfunction

Rong Yang,1,&ast; Qing Ma,1,2,&ast; Xiaolin Zhang,3 Qian Zhao,1,4,5 Suilan Zeng,6 Hechun Yan,7 Yi Lei,1,5 Shanye Yi,1 Xin Chen,8 Nianxi Wu9 1General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2West China School of Nursing, Sichuan University, Chengdu, People’s Republic of China; 3Preventive Health Section, Dayi County Shaqu Street Community Health Service Center, Chengdu, People’s Republic of China; 4Teaching & Research Section, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5General Practice Medical Center and General Practice Research Institute, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Guan Ge Center Health Center, Guangan, People’s Republic of China; 7Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, People’s Republic of China; 8Big Buddha Street Community Health Service Center, Leshan, People’s Republic of China; 9Chongqing Magic MedTech Co., Ltd., Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Zhao, Email 27355151@qq.comPurpose: Osteoporosis is a major health concern among the elderly, underscoring the importance of investigating its prevalence across different geographical regions. There is a current research gap regarding the incidence of osteoporosis and its variation by altitude within Sichuan, China. This study aimed to assess the prevalence of osteoporosis among populations residing at different altitudes in western Sichuan Province.Basic Procedures: This study utilized data from a population-based cohort in Sichuan, China. Representative locations were selected, and cluster random sampling was employed to conduct cohort studies across multiple sites in southwestern China. T Baseline data were collected from populations in Mianzhu, Kangting, and Sertar between July 2020 and August 2021. To assess differences in osteoporosis incidence among populations at different altitudes and with varying characteristics, we applied Chi-square and rank-sum tests.Main Findings: The study involved 4074 participants, including 1404 males (34.46%) and 791 individuals diagnosed with osteoporosis (19.42%). The prevalence of osteopenia in mid-altitude and high-altitude regions was 20.05% and 16.28%, respectively, while the prevalence of osteoporosis was significantly different, at 25.85% in mid-altitude areas compared to 13.00% in high-altitude areas (P < 0.001). Further analysis identified statistically significant differences in the prevalence of osteopenia and osteoporosis among females (P< 0.001), middle-aged (P=0.015) and elderly populations (P=0.038), as well as among individuals who were underweight (P=0.011), normal weight (P< 0.001), overweight (P< 0.001), and obese (P=0.038). As altitude increased, the prevalence of osteoporosis decreased in all groups except the elderly, while the prevalence of osteopenia decreased among women and across various BMI categories, but increased among middle-aged and elderly individuals. Additionally, in high-altitude regions, Kangting recorded an 18.10% prevalence of osteopenia and a 14.26% prevalence of osteoporosis, compared to Sertar, which exhibited a 6.54% prevalence of osteopenia and a 6.23% prevalence of osteoporosis, indicating significant differences (P< 0.001).Conclusion: This study demonstrates that higher altitudes are associated with a decreased prevalence of osteopenia and osteoporosis, particularly among females and middle-aged individuals. These results emphasize the importance of developing region-specific osteoporosis prevention strategies.Keywords: osteoporosis, aging, prevalence, altitude, Sichuan province

Jiahua Wu, Xihua Lin, Xueyao Yin, Zhiye Xu, Nan Wu, Ziyi Zhang, Jiaqiang Zhou,&ast; Hong Li&ast; Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Li; Jiaqiang Zhou, Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, People’s Republic of China, Email srrshnfm@zju.edu.cn; zjq8866@zju.edu.cnPurpose: Metabolic syndrome (MetS) is an increasingly prevalent issue in China’s public health landscape. Few studies have investigated the metabolic syndrome (MetS) in overweight people. We proposed to analyze and contrast the occurrence of MetS in normal-weight and overweight individuals and identify potential indicators for forecasting MetS in adults in Zhejiang Province.Methods: This cohort study included 359 adults aged 40– 65 years and followed up for five years in Zhejiang Province. The study assessed the predictive capabilities of five indicators linked to obesity and lipid levels, namely body mass index (BMI), waist-to-height ratio (WHtR), triglyceride-glucose index (TyGi), and their combined indices (TyG-BMI, TyG-WHtR). The evaluation was done employing the area under the Receiver Operating Characteristic (ROC) Curve (AUC). DeLong test was applied to compare area under different ROC curves.We evaluated the relationships between five variables and MetS using multivariate logistic regression.Results: In normal-weight individuals, the five-year cumulative incidence of MetS was 21.85%, but in overweight people, it was 60.33%. After adjusting for confounding factors, BMI, WHtR, TyGi, TyG-BMI, and TyG-WHtR were independently linked to MetS in normal-weight individuals, while BMI, TyGi, TyG-BMI, and TyG-WHtR were independently linked to MetS in overweight individuals. In normal-weight individuals, the WHtR (AUC=0.738 and optimal threshold value =0.469) and TyG-WHtR (AUC=0.731 and optimal threshold value =4.121) had the larger AUC, which was significantly greater than that of the different three indicators. The TyG-BMI (AUC=0.769 and optimal threshold value = 211.099) was the best predictor of MetS in overweight individuals.Conclusion: The five-year cumulative incidence of MetS in overweight people was approximately triple that of normal-weight people in Zhejiang Province. In the overweight population, the TyG-BMI performed better than the other indices in predicting MetS. WHtR and TyG-WHtR outperformed BMI, TyGi, and TyG-BMI in anticipating MetS in a normal-weight population.Keywords: metabolic syndrome, normal weight, overweight, WHtR, BMI, TyG

Hongmei Xu,1 Ningning Wu,2 Hui Yu,3 Chuanqing Wang,4 Jikui Deng,5 Hongmei Wang,5 Chunzhen Hua,6 Yinghu Chen,6 Xuejun Chen,7 Ting Zhang,8 Hong Zhang,9 Yiping Chen,10 Shifu Wang,11 Qing Cao,12 Huiling Deng,13 Sancheng Cao,14 Jianhua Hao,15 Wei Gao,16 Chunmei Jing2 1Infectious Disease Department, Children’s Hospital of Chongqing Medical University; National Clinical Research Center for Child Health and Disorders; Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, People’s Republic of China; 2Department of Clinical Laboratory, Children’s Hospital of Chongqing Medical University; National Clinical Research Center for Child Health and Disorders; Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, People’s Republic of China; 3Infectious Disease Department, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, People’s Republic of China; 4Department of Clinical Microbiology Laboratory, Nosocomial Infection Control Department, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, People’s Republic of China; 5Infectious Disease Department, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 6Infectious Disease Department, Children’s Hospital of Zhejiang University, Zhejiang, People’s Republic of China; 7Department of Medical Laboratory, Children’s Hospital of Zhejiang University, Zhenjiang, People’s Republic of China; 8Digestive and Infectious Disease Department, Children’s Hospital of Shanghai Jiaotong University, Shanghai, People’s Republic of China; 9Department of Medical Laboratory, Children’s Hospital of Shanghai Jiaotong University, Shanghai, People’s Republic of China; 10Pediatric Infectious Disease Department, Second Affiliated Hospital, and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 11Department of Medical Laboratory, Qilu Children’s Hospital, Shandong University, Shandong, People’s Republic of China; 12Infectious Disease Department, Shanghai Children’s Medical Center, Shanghai, People’s Republic of China; 13Infectious Disease Department, Xi’an Children’s Hospital, Xi’an, People’s Republic of China; 14Department of Medical Laboratory, Xi’an Children’s Hospital, Xi’an, People’s Republic of China; 15Infectious Disease Department, Children’s Hospital of Kaifeng City, Kaifeng, People’s Republic of China; 16Department of Medical Laboratory, Children’s Hospital of Kaifeng City, Kaifeng, People’s Republic of ChinaCorrespondence: Chunmei Jing, Department of Clinical Laboratory, Children’s Hospital of Chongqing Medical University, Chongqing Medical University, No. 136 Zhongshan Er Road, Yu Zhong District, Chongqing, 400014, People’s Republic of China, Email jcm791203@163.comObjective: Aim to investigate the pathogens distribution and drug resistance of gram-negative bacteria causing bloodstream infection (BSIs) in Infectious Disease Surveillance of Pediatric from 2016 to 2022. The prevalence of four important drug resistance phenotypes was studied: difficult-to-treat resistance, fluoroquinolone resistance, carbapenem resistance, and extended-spectrum cephalosporin resistance, and to provide reference basis for preventing and treating BSIs diseases in children.Methods: Strain identification and antimicrobial susceptibility tests were independently performed at each hospital. Data were analyzed using Whonet 5.6 and GraphPad Prism 8 software. The Mann–Whitney U-test was used to examine and compare temporal changes.Results: A total of 39977 BSIs strains were isolated, with 27.1% of the negative bacteria causing BSIs (10824 strains). The highest bacteria detected were E. coli and S. maltophilia in the neonatal and pediatric groups. The detection rate of carbapenem-resistant-K. pneumoniae (CRKPN) in neonate group was 31.4%, significantly increased compared with pediatric group, whose detection rate was 24.7%. The rates of resistance to levofloxacin and trimethoprim/sulfamethoxazole were significantly lower in neonatal groups than pediatric groups in BSIs caused by K. pneumoniae. To imipenem and meropenem were 3.6% and 3.9% among neonatal isolates, which was lower than 4.7% and 5.8 among pediatric BSIs caused by E. coli. Isolated from neonatal BSIs caused by A. baumannii showed lower resistance ratios to all the agents tested than those from pediatric. However, only the prevalence of piperacillin/tazobactam resistance was statistically lower than that in pediatric BSIs caused by P. aeruginosa. The average detection rates of carbapenem resistance, extended-spectrum cephalosporin resistance, and fluoroquinolone resistance for K. pneumoniae and E. coli were 28.1%,41.4%,11.6% and 4.0%,24.3%,31.1%, respectively.Conclusion: The detection rate of gram-negative pathogens showed an increasing trend among the bloodstream infection. The detection rate of CRKPN assumed a downward trend in 2018. There are differences types of pathogens between the neonatal group and the pediatric group, The detection rate of CRKPN in the neonate group was significantly higher than pediatric group. The first average detection rates for carbapenem resistance, extended-spectrum cephalosporin resistance, and fluoroquinolone resistance were obtained for A. baumannii, K. pneumoniae, and Escherichia coli, respectively. Those data showed a high level of antimicrobial resistance, which has posed an urgent threat to Children’s health, suggested that effective monitoring of antimicrobial resistance and antimicrobial stewardship among children in China are required.Keywords: bloodstream infection, pathogenic bacterium, difficult-to-treat resistance, carbapenem resistance, extended-spectrum cephalosporin resistance, fluoroquinolone resistance

Bingyang Xu,1 Biao Yu,2 Zining Xu,1 Shuhong Ye,1 Yuxin Qing,1 Hong Sun,3 Bin Zhao,4 Na Wu,5 Jiawen Wu1 1Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Dermatology, Taihe Hospital, Hubei University of Medicine, Shi’yan, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 4Department of Dermatology, Xi’an International Medical Center Hospital, Xi’an, People’s Republic of China; 5Department of Nursing, Xi’an Jiaotong University Medical School, Xi’an, People’s Republic of ChinaCorrespondence: Jiawen Wu, Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China, Email jiawen702@126.comPurpose: Psoriasis is not yet completely curable, and its etiology and pathogenesis are unclear. Necroptosis, also known as programmed necrosis, is a regulated mode of necrotic cell death. The interaction between inflammatory diseases and necrotic apoptosis has recently attracted significant attention. We explored the molecular mechanisms of necrotic apoptosis-related genes in psoriasis using bioinformatics methods to identify potential biomarkers for psoriasis.Patients and Methods: In this study, we screened psoriasis differentially expressed genes from the datasets GSE13355 and GSE14905 and took intersections with necrotic apoptosis-related genes for the next analysis. We used multiple machine learning algorithms to screen key genes and perform enrichment analysis. In addition, we performed an immune infiltration analysis. Transcription factors were predicted by the R package “RcisTarget”. We also observed the cellular clustering of key genes in different cell types at the single-cell sequencing level. We used real-time fluorescence-based quantitative-polymerase chain reaction, Western blot, and immunohistochemistry to analyze gene expression in clinical samples. We constructed an imiquimod-induced psoriasis-like dermatitis model in mice for further validation.Results: Seven key genes were screened as follows: AIM2, CARD6, HPSE, MYD88, PYCARD, RAI14, and TNFSF10. Enrichment analysis showed that the key genes were mainly involved in inflammatory pathways. Immune infiltration analysis showed significantly higher levels of CD8 T cells, CD4 initial T cells, and CD4 memory-activated T cells in the disease group’s samples than in the normal patients’ samples. The key gene expression in single cells analyzed showed that PYCARD was significantly expressed in keratinocytes. PYCARD was selected for gene expression analysis; the results showed that its expression was significantly elevated in the skin lesion tissues of patients with psoriasis. We also verified that PYCARD might play a vital role in the development of psoriasis skin lesions using animal experiments.Conclusion: PYCARD plays a vital role in psoriasis development and is a potential biomarker for psoriasis.Keywords: necrotic apoptosis-related gene, bioinformatics, inflammatory disease, immune disease

Wenzhen Ge,1 Ning Wu,1 Chieh-I Chen,1 Timothy J Inocencio,1 Patrick R LaFontaine,2 Frank Seebach,3 Matthew Fury,4 James Harnett,1 Emily S Ruiz5 1Department of Health Economics and Outcomes Research, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA; 2Department of Global Health Economics & Outcomes Research, Sanofi, Cambridge, MA, USA; 3Department of Regulatory Affairs, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA; 4Department of Clinical Sciences, Oncology, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA; 5Department of Dermatology, Dana-Farber Cancer Institute, Boston, MA, USACorrespondence: Wenzhen Ge, Regeneron Pharmaceuticals, Inc, 1 Rockwood Road, Sleepy Hollow, NY, 10591, Tel +1 914-847-7000, Email wenzhen.ge@regeneron.comBackground: Prior to the Food and Drug Administration approval of cemiplimab in 2018, the median overall survival (OS) for adult patients with advanced CSCC receiving systemic therapy was approximately 8 to 15 months. Limited real-world data are available on cemiplimab for this indication in the US.Patients and Methods: This retrospective cohort study included US patients with advanced CSCC initiating cemiplimab monotherapy in a real-world database (2018– 2021). A clinical trial–like sub-cohort was identified using select criteria. Time to treatment discontinuation (TTD), time to next treatment (TTNT), and OS were estimated using Kaplan–Meier methods. Cox proportional hazard models were used to examine prognostic factors associated with OS in the main cohort.Results: The main cohort included 622 patients (n = 240 in the trial-like cohort). In the main cohort, the median age was 78 years, 77.8% were male, 21.4% were immunocompromised/immunosuppressed, and 63.8% had metastatic CSCC. Median (95% CI) TTD and TTNT were 8.0 (6.6– 9.0) months and 16.4 (13.3– 21.0) months, respectively, in the main cohort. Median (95% CI) OS was 24.8 (21.8– 29.1) months in the main cohort (not reached in the trial-like cohort). In multivariable analyses, age < 60 years (hazard ratio [HR], 0.37), Eastern Cooperative Oncology Group performance status < 3– 4 (HR range, 0.13– 0.57), and primary CSCC location in the head and neck only versus extremities only (HR, 0.59) were associated with better OS. Similar OS was observed between patients who had immunosuppressing/immunocompromising conditions and those without.Conclusion: These findings confirm the effectiveness of cemiplimab among a heterogenous, real-world advanced CSCC patient population and substantiate the efficacy of cemiplimab observed in clinical trials.Keywords: cutaneous squamous cell carcinoma, cemiplimab, immune checkpoint inhibitor, real-world study, skin cancer

Yongyi Xie,1,&ast; Nanhui Wu,1,&ast; Suwei Tang,1,&ast; Zhiyu Zhou,1 Jiashe Chen,1 Jie Li,1 Fei Wu,1 Mingyuan Xu,1 Xiaoxiang Xu,1 Yeqiang Liu,1 Xin Ma1,2 1Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yeqiang Liu; Xin Ma, Shanghai Skin Disease Hospital, Institute of Dermatology, Baode Road 1278 Street, Shanghai, 200433, People’s Republic of China, Email 1500156@tongji.edu.cn; Nicole.ma@me.comAbstract: The endoplasmic reticulum (ER) is the main site of protein synthesis, transport, and modification. Its abnormal status has now emerged as an established cause of many pathological processes, such as tumors and autoimmune diseases. Recent studies also demonstrated that the defective functions of ER may lead to pigmentary diseases. Vitiligo is a depigmenting ailment skin disorder whose pathogenesis is now found to be associated with ER. However, the detailed mechanism is still unclear. In this review, we try to link the association between ER with its inter- and intra-organellar interactions in vitiligo pathogenesis and focus on the function, mechanism, and clinical potential of ER with vitiligo. Expand ER is found in melanocytes of vitiligo and ER stress (ERS) might be a bridge between oxidative stress and innate and adaptive immunity. Meanwhile, the tight association between ER and mitochondria or melanosomes in organelles levels, as well as genes and cytokines, is the new paradigm in the pathogenesis of vitiligo. This undoubtedly adds a new aspect to the understanding of vitiligo, facilitating the design of targeted therapies for vitiligo.Keywords: vitiligo, endoplasmic reticulum, organelles, cellular interactions, oxidative stress

Nengwen Wu,&ast; Xiaoqing Shen,&ast; Jianwei Li, Miaolian Chen, Guishen Wu, Haiming Niu, Hongkai Liang, Ting Yang Department of Critical Care Medicine, Zhongshan People’s Hospital, Zhongshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongkai Liang; Ting Yang, Department of Critical Care Medicine, Zhongshan People’s Hospital, Zhongshan, 528400, People’s Republic of China, Email 1019978382@qq.com; 53103334@qq.comAbstract: Septic cardiomyopathy (SCM) is often associated with bacterial infections but also occurs with infections with viruses such as influenza and spirochetes, including syphilis. However, there has been no systematic investigation into whether Aspergillus infections can cause septic cardiomyopathy. We report on such a case for the first time in a patient without immunodeficiency. Therefore, clinicians should be concerned with septic cardiomyopathy caused by some atypical or rare pathogens when admitting such patients.Keywords: septic cardiomyopathy, aspergillus, extracorporeal membrane oxygenation, metagenomic next-generation sequencing

Yang Liu,1 Dan Yang Li,1 Alayi Bolatai,2 Na Wu1,3 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’ s Republic of China; 2Department of Student Affairs, Affiliated Hospital of China Medical University, Shenyang, Liaoning, People’ s Republic of China; 3Medical Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’ s Republic of ChinaCorrespondence: Na Wu, Email 3441535223@qq.comAbstract: Gestational diabetes mellitus (GDM) and preeclampsia (PE) are common complications in pregnancy, with incidence rates of 1– 5% and 9.4%, respectively, in China. Both these phenomena can cause adverse pregnancy outcomes and are extremely harmful to the mother and fetus. In this study, we observed that several predictive factors have important value in GDM and PE. Among the GDM group, abnormal levels of adiponectin (APN), C-reactive protein (CRP), and Leptin were observed. The coexistence of PE and GDM in the pregnant population is not uncommon. Ultimately, we discovered abnormal levels of factors such as Visfatin, Advanced oxidative protein product (AOPP), Fibroblast growth factor 21 (FGF21), and resistin in both GDM and PE groups. Particularly, the FGF21 factor holds significant importance in our research. Therefore, we need to complete the analysis and discussion of relevant predictive factors to enable early prediction and disease monitoring of GDM, PE, and other pregnancy-related disorders, ultimately contributing to the long-term health of pregnant women.Keywords: gestational diabetes mellitus, preeclampsia, predictor of the GDM and PE

Yutong Liu,1 Xiuyan Liu,2 Na Wu2,3 1Student Affairs Department, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China; 2Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China; 3Medical Department, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaCorrespondence: Na Wu, Email 3441535223@qq.comAbstract: Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are two very common autoimmune thyroid diseases (AITD). In this review, we use “HT in the hyperthyroidism stage” to refer to early HT with clinical manifestations of hyperthyroidism. In clinical practice, it is not easy to distinguish between HT in the hyperthyroidism stage and GD as they exhibit very similar clinical symptoms. The current literature lacks so far studies that systematically compare and summarize hyperthyroidism due to HT and GD from varied aspects. It is necessary to focus on all the clinical indices of HT in the hyperthyroidism stage and GD, for accurate diagnosis. Multiple databases such as PubMed, CNKI, WF Data, and CQVIP Data were used to search the literature concerning HT in the hyperthyroidism stage and GD. The information extracted from the relevant literature was summarized and further analyzed. To differentially diagnose hyperthyroidism as HT or GD, it is recommended to first focus on serological tests, followed by imaging tests, as well as the thyroid I131 uptake index. In pathology, fine needle aspiration cytology (FNAC) is the gold standard for the differential diagnosis of HT and GD. Test results from cellular immunology and genetics could also be used to accurately diagnose between the two diseases, which may be further developed and studied in the future. In this paper, we reviewed and summarized the difference between HT in the hyperthyroidism stage and GD from the following six aspects: blood tests, imaging, thyroid I131 uptake, pathology, cellular immunology, and genetics.Keywords: Hashimoto’s thyroiditis, Graves’ disease, diagnosis, differential diagnoses

Xuebin Tian,1,2,&ast; Yiwen Xie,1,2,&ast; Jingjing Chen,3,&ast; Wanpeng Yin,1,2 Yu Long Zhao,1 Peng Yao,4 Mingqing Dong,4 Changzhong Jin,1,2 Nanping Wu1,2 1Cell Biology Research Platform, Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, People’s Republic of China; 2State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Hospital Office, Shandong Second Provincial General Hospital, Jinan, Shandong, People’s Republic of China; 4Department of Infectious Disease, Zhejiang Qingchun Hospital, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changzhong Jin; Nanping Wu, Email changzhongjin@163.com; flwnp2013@163.comBackground: Microbial translocation (MT) is a characteristic of human immunodeficiency virus (HIV) infection. Whether MT is also a biomarker of different immune responses to antiretroviral therapy (ART) received by people living with HIV (PLWH) is not known.Methods: We examined the presence of MT in a cohort of 33 HIV-infected immunological responders (IRs) and 28 immunological non-responders (INRs) (≥ 500 and < 200 cluster of differentiation (CD)4+ T-cell counts/μL after 2 years of HIV-1 suppression, respectively) with no comorbidities. Plasma samples were used to measure the circulating levels of MT markers. All enrolled study participants had received 2 years of viral-suppression therapy.Results: Levels of lipopolysaccharide (P = 0.0185), LPS-binding protein (P < 0.0001), soluble-CD14 (P < 0.0001), and endogenous endotoxin-core antibody (P < 0.0001) at baseline were significantly higher in INRs than in IRs and were associated with an increased risk of an immunological non-response, whereas the level of intestinal fatty acid-binding protein did not show this association. Analysis of receiver operating characteristic (ROC) curves demonstrated the utility of these individual microbial markers in discriminating INRs after ART in people living with HIV with high sensitivity, specificity, and area under the ROC curve.Conclusion: INRs in HIV infection are characterized by increased MT at baseline. These markers could be used as a rapid prognostic tool for predicting immune responses in people infected with the HIV.Keywords: HIV, immunological non-responders, microbial translocation

Bo Li,1,2 Li Jiang,1,2 Ni Wu,1,2 Yao Chen,1,2 Zhi Xu,3 Fengcheng Xu,2,4 Heping Chen,1 Tianhu Liu2,4 1Clinical Pharmacy Department, The Third Affiliated Hospital of Chengdu Medical College, Pidu District People’s Hospital, Chengdu, Sichuan, People’s Republic of China; 2Drug Clinical Trial Management Center, The Third Affiliated Hospital of Chengdu Medical College, Pidu District People’s Hospital, Chengdu, Sichuan, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Chengdu Medical College, Pidu District People’s Hospital, Chengdu, Sichuan, People’s Republic of China; 4Department of Cardiovascular Medicine, The Third Affiliated Hospital of Chengdu Medical College, Pidu District People’s Hospital, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Bo Li, Clinical Pharmacy Department, The Third Affiliated Hospital of Chengdu Medical College, Pidu District People’s Hospital, Chengdu, Sichuan, People’s Republic of China, Email lbydcg@163.com Tianhu Liu, Department of Cardiovascular Medicine, The Third Affiliated Hospital of Chengdu Medical College, Pidu District People’s Hospital, Chengdu, Sichuan, People’s Republic of China, Email lthzgl@163.comBackground: In 2021, National Health Commission of the People’s Republic of Chinese issued a document that no longer recommended the routine skin test for cephalosporin (RSTC). However, there is still resistance to the cancellation of RSTC in a primary hospital. The study aimed to explore the potential factors for hindering the abolition of the RSTC in a county-level hospital based on the PRECEDE model.Methods: The cross-sectional study was conducted on healthcare workers in the Pidu District People’s Hospital, Chengdu, by online questionnaire from September 10 to September 25 in the 2021.The PRECEDE model was used to divide the potential factors of healthcare professionals in hindering the abolition of the RSTC into predisposing factors, enabling factors and reinforcing factors. Data were analyzed by ANOVA, Chi-square test, multiple linear and multiple logistic regression analysis.Results: We collected 605 respondents’ valid questionnaires. 254 healthcare professionals were against cancellation of the RSTC, accounting for 41.98%. Multiple linear regression analysis showed that working for 6~10 years (β = 1.953, P = 0.024), medium (β = 1.995, P = 0.030) or senior (β = 4.003, P = 0.007) professional qualification, pharmacists (β = 3.830, P = 0.013) and working in surgical department (β= 4.462, P < 0.001) were significantly associated with higher score of predisposing factors, enabling factors, and reinforcing factors on abolition of RSTC. Furthermore, multiple logistic regression analysis showed that pharmacists (OR=3.113, 95% CI: 1.341– 7.223, P=0.030), medium professional qualification (OR=1.272, 95% CI: 0.702– 2.302, P=0.008), scores of predisposing factors (OR=1.335, 95% CI: 1.033– 1.726, P=0.009), and scores of enabling factors (OR=1.208, 95% CI: 1.109– 1.315, P< 0.001) were independently associated with the positive anticipated behavior on the abolition of RSTC. While nurses (OR=0.516, 95% CI: 0.284– 0.938, P< 0.001) were independently associated with anticipated negative behavior.Conclusion: Pharmacists, medium professional qualification, and healthcare professionals with higher scores of predisposing and enabling factors were more likely to have a positive anticipated behavior on the abolition of RSTC, while nurses did not.Keywords: cephalosporin, skin test, potential factors, PRECEDE model, cross-sectional study

Yaolin Wang,1– 3,&ast; Kai Zhao,4,5,&ast; Nanling Wu,1– 3 Tao Ji,1– 3 Gaowei Su,1– 3 Xiaojie Cui,1– 3 Yushan Dong,1– 3 Xiuxia Chen1– 3 1NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4Department of Anesthesiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, Anhui, People’s Republic of China; 5Department of Anesthesiology, Anhui Provincial Hospital, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuxia Chen, Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China, Tel +86 18052268332, Email cxxlxy@sina.comPurpose: This study was designed to investigate the effects of different doses of butorphanol on postoperative shivering and quality of recovery in elderly patients.Patients and Methods: A total of 147 elderly patients (aged 60 or older) scheduled for elective transurethral resection of the prostate were enrolled in the current study. Patients were randomly and evenly assigned into four groups: Group C (0.9% normal saline), Group B1 (butorphanol 0.01 mg/kg), Group B2 (butorphanol 0.02 mg/kg) and Group B3 (butorphanol 0.03 mg/kg). All drugs were diluted to 5mL and injected intravenously slowly 5 min before induction of anesthesia. The primary outcome measure was the incidence of postoperative shivering in the post-anesthesia care unit. Quality of Recovery-40 (QoR-40) scores were assessed on postoperative day (POD) 1, 2 and 3. Perioperative core and skin temperature, extubation time and adverse events were also recorded.Results: Patients among the four groups had comparable baseline characteristics. Compared with Group C, the incidence of shivering was significantly lower in Group B2 and B3 (P = 0.006 and P = 0.005, respectively). The QoR-40 scores on POD1 were significantly higher in all butorphanol groups than that in Group C (P < 0.0083). In Group B2 and B3, patients experienced lower pain intensity (P < 0.001). In addition, the incidence of catheter-related bladder discomfort (CRBD) was lower in all butorphanol groups than in Group C (P < 0.0083).Conclusion: Butorphanol 0.02 or 0.03 mg/kg could effectively prevent the occurrence of postoperative shivering in elderly patients scheduled for transurethral resection of the prostate, provided effective postoperative recovery and postoperative analgesia.Keywords: butorphanol, elderly patients, postoperative shivering, recovery quality, postoperative pain

Yujing He,1 Na Wu1,2 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Medical Service Quality, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Na Wu, Email 3441535223@qq.comObjective: To study the characteristics of selective polyadenylation (APA) in gestational diabetes mellitus (GDM) by poly(A) site sequencing and to explore the role of APA process in the pathogenesis of GDM.Methods: Three pregnant women diagnosed as GDM in our hospital were randomly selected as the GDM group, and three healthy pregnant women at the same time as the control group. The placental tissues of two groups of pregnant women after delivery were collected for high-throughput transcriptome sequencing (RNA-seq) and poly(A) site sequencing (PAS-seq) to screen differentially expressed genes and variable 3’UTR genes in GDM. Gene Ontology (GO) analysis and pathway analysis were used to analyze the functional classification and pathway of differential genes, and preliminarily explore the susceptible genes in GDM.Results: Compared with the control group, there were 202 TTS loci in the GDM group, including 103 genes with shortened TTS loci and 99 genes with delayed TTS loci. There were 57 genes with significant difference in TTS (P< 0.05). Subsequently, we found that VCPIP1 and LGR4 were differentially expressed in RNA-seq. The genes in advance of TTS locus were enriched in biological processes such as cell development, protein transport and phosphorylation, signal transduction, etc. Delayed TTS genes are enriched in biological processes such as transcriptional regulation, cell migration and cycle, DNA repair and damage.Conclusion: The abnormality of APA process may be involved in the occurrence and development of GDM. The genes with significantly different changes in TTS locus may become biomarkers or predictors for GDM to assess the incidence, disease progression and disease severity, and may also become potential targets for GDM treatment.Keywords: gestational diabetes mellitus, high-throughput sequencing, LGR4, leucine-rich repeat containing G protein-coupled receptor 4, VCPIP1, valosin-containing protein interacting protein 1, micro-RNA

Wenzhen Ge,1 Ning Wu,1 Jessica J Jalbert,1 Ruben GW Quek,1 Jinjie Liu,2 Petra Rietschel,1 Jean-Francois Pouliot,1 James Harnett,1 Melinda Laine Hsu,3 Josephine L Feliciano4 1Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 2Genesis Research, LLC, Hoboken, NJ, USA; 3University Hospitals, Cleveland Medical Center, Cleveland, OH, USA; 4Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USACorrespondence: Josephine L Feliciano, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA, Tel +1 410 550 1711, Email jfelici4@jhmi.eduBackground: Immune checkpoint inhibitors (ICIs) are standard-of-care for patients with advanced non-small cell lung cancer (aNSCLC) and programmed cell death-ligand 1 (PD-L1) expression ≥ 50%.Methods: A retrospective cohort study was conducted using the US de-identified electronic health record-derived Flatiron Health aNSCLC database (January 1, 2018, to July 31, 2021) among patients with PD-L1 ≥ 50% initiating first-line ICIs with or without chemotherapy. A clinical trial-like sub-cohort was also identified with Eastern Cooperative Oncology Group performance status 0– 1, adequate organ function, and no brain metastases or other primary cancers. Kaplan–Meier methods were used to estimate time to treatment discontinuation, time to next treatment, progression-free survival and overall survival (OS) by ICI regimen (ICI+chemotherapy, ICI monotherapy) and PD-L1 expression (50– 69%, 70– 89%, 90– 100%). Cox proportional hazard models were used to examine associations between ICI regimen, PD-L1 level, and OS, adjusting for baseline demographic and clinical variables.Results: A total of 2631 patients with aNSCLC initiating ICI+chemotherapy (n = 992) or ICI monotherapy (n = 1639) were included; median (Q1, Q3) age was 71 (63– 78) years and 51.6% were male. The trial-like sub-cohort (n = 1029) generally had better outcomes vs. the overall cohort. Patients receiving ICI+chemotherapy generally had longer median OS vs. ICI monotherapy. Multivariable analyses showed no association between ICI regimen and OS among patients with PD-L1 70– 89% (hazard ratio [HR]: 0.90, 95% confidence interval [CI]: 0.73– 1.09) or 90– 100% (HR: 0.91, 95% CI: 0.77– 1.08), but patients with PD-L1 50– 69% receiving ICI+chemotherapy had longer OS (HR: 0.80, 95% CI: 0.64– 0.99).Conclusion: Outcomes in real-world clinical trial-like patients with aNSCLC approached those reported in pivotal ICI trials in high PD-L1 expressers. ICI monotherapy offers a potential alternative in patients with PD-L1 ≥ 70% while avoiding potential chemotherapy toxicity exposure; the benefits are less clear in patients with PD-L1 50– 69%. Future studies should confirm these findings.Keywords: immune checkpoint inhibitors, non-small cell lung cancer, PD-L1 expression, real-world data, overall survival, progression-free survival

Ning Wu,1 Mingzi Li2 1Department of Nursing, Shanxi Provincial People’s Hospital, Taiyuan, 030012, People’s Republic of China; 2Peking University, School of Nursing, Beijing, 100191, People’s Republic of ChinaCorrespondence: Mingzi Li, Peking University, School of Nursing, No. 38 Xueyuan Road, Haidian District, Beijing, 100191, People’s Republic of China, Tel +86 010-82805230, Email limingzi@bjmu.edu.cnObjective: To examine the developmental characteristics and trends affecting clinical research nurses (CRNs) in China and provide a reference for the training and employment of nursing talents in this specialty.Methods: Literature pertaining to CRNs published from the year in which the database was constructed to 2020 was searched. The databases used were the China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature and Weipu, while CiteSpace software was used to conduct a bibliometric analysis of literature quantity, annual distribution, literature journals and regional distribution, literature authors, subject funding status and literature type and keywords. The characteristics and trends affecting CRNs in China were then evaluated using a descriptive analysis.Results: A total of 3735 pieces of literature were retrieved, and after deduplication and screening, 199 pieces of literature were retained for this study. Overall, the number of publications increased year-on-year. Of these publications, 17 papers (8.5% of the retained papers) were published in the Chinese Journal of Modern Nursing and 9138 papers (69.3%) were published in the top 10 regions according to the location of the first author (of these, 31 [15.6%] were published in Beijing and 42 [21.1%] were funded by scientific research funds). The research fell mainly in the experience summary category, with 107 articles (53.8%) taking this approach. The top five research hotspots were clinical research, good clinical practice (GCP), research nurses, management and clinical trials. The practice and exploration of CRNs were regionalised, accounting for varying degrees of development. CRNs were found to be at the forefront of developments in oncology specialties.Conclusion: In China, CRNs are currently in a period of rapid development. Research into CRNs mainly involves single-centre studies and lacks financial support. In the future, it will be necessary to increase capital investment, strengthen cross-regional cooperation between authors and institutions to narrow the regional development gap, and promote strict and standardised CRN training models and qualification certification to improve the quality of clinical research nursing.Keywords: clinical research nurses, CRNs, clinical trials, bibliometric analysis, CiteSpace, development trends

Ping Yang,1,2 Chao Liu,3 Zhenchao Wu,2 Jiajia Zheng,4 Juan Yi,1 Nan Wu,2 Zhangli Wu,1,2 Ming Lu,2,3 Liyan Cui,4,&ast; Ning Shen1– 3,&ast; 1Institute of Medical Technology, Peking University Health Science Center, Beijing, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 3Department of Infectious Diseases, Peking University Third Hospital, Beijing, People’s Republic of China; 4Department of Laboratory Medicine, Peking University Third Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liyan Cui; Ning Shen, Email cliyan@163.com; shenningputh@163.comPurpose: This study aimed to identify the clinical outcomes, microbiological features and risk factors for difficult-to-treat resistance (DTR) Klebsiella pneumoniae (Kp) infection.Materials and Methods: A retrospective study was conducted at Peking University Third Hospital from January 2020 to March 2021. DTR was defined as resistance to ≥ 1 carbapenem, ≥ 1 extended-spectrum cephalosporin, and ≥ 1 fluoroquinolone. Hypervirulent Kp (HvKp) was defined as peg-344-, iroB-, iucA-, rmpA-, or rmpA2-positive. Clinical data were collected. Antimicrobial susceptibility testing and string tests were performed to determine resistance and hypermucoviscosity phenotype. Whole genome sequencing was performed to analyze the sequence type (ST), capsular serotypes, resistance and virulence genes. Risk factors for 30-day mortality were analyzed.Results: Fifty DTR-Kp (50.0%) strains were identified among 100 patients. Compared to non-DTR-Kp group, a significant number of patients with DTR-Kp infection experienced ICU admission (44.0% versus 10.0%, P< 0.001) and mechanical ventilation after Kp detection (26.0% versus 10.0%, P=0.037). Notably, the percentage of hvKp among the DTR-Kp isolates increased consistently over the 15 months evaluated. Most DTR-Kp strains belonged to ST11 (82.0%), followed by ST15 (12.0%), ST86 (2.0%), ST996 (2.0%), and ST3157 (2.0%). DTR-Kp isolates possessed various resistance genes, such as blaKPC-2, blaTEM-1D and fosA3 (90.0%, 80.0% and 72.0%, respectively). Importantly, the yersiniabactin genes were significantly clustered in DTR group (48/50, 96.0%). The 30-day mortality was significantly higher in patients with DTR-Kp infection than non-DTR-Kp group (38.0% versus 8.2%, P=0.001). DTR-Kp infection (odds ratio [OR] = 4.196) was an independent risk factor for the 30-day mortality of Kp-infected patients. Additionally, cerebrovascular disease (OR = 2.780) and Charlson comorbidity index (OR= 1.584) were independent risk factors for DTR-Kp infections.Conclusion: DTR-hvKp is rapidly emerging. The DTR-Kp strains harbored various resistance genes and high rates of yersiniabactin siderophore genes. DTR-Kp infection was an independent risk factor for mortality, suggesting that enhanced awareness essential.Keywords: Klebsiella pneumoniae, difficult-to-treat resistance, mortality, risk factor

Xiao-Fan Xu,1– 3 Jian-Wei Fan,2 Jia-Qi Xin,4 Nan Wu,4 He Gao,2 Li-Fang Duan,2 Wen-Bin Zou,3 Hong Zhang,2,5 Zhao-Shen Li3 1School of Clinical Medicine, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 2Basic Medical Academy, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China; 3Department of Gastroenterology, Changhai Hospital, Shanghai, People’s Republic of China; 4Department of Gastroenterology, Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich (TUM), Munich, Germany; 5Shaanxi International Cooperation Base, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of ChinaCorrespondence: Zhao-Shen Li; Hong Zhang, Email zhaoshenli@smmu.edu.cn; zhangh1227@sntcm.edu.cnAim: Chronic pancreatitis (CP) is a complex and intractable disease mainly manifested as chronic inflammation and fibrosis. Aspirin(acetylsalicylic acid, ASA) has been reported to be used in the treatment of acute pancreatitis (AP), but its effectiveness on CP is unclear. This study aimed to investigate the therapeutic effects of ASA in CP mice.Methods: A murine model of CP was induced by intraperitoneal injection with 20% L-arginine. After one week of L-arginine administration, mice in the ASA treatment group were administered aspirin (100mg/kg/d) by intragastric gavage. At two, four, and six weeks after the first injection of L-arginine, mice were euthanized and the pancreas was collected for histological and molecular analysis. A second model of CP (caeruelin-induced) was used as a validation experiment to test the effect of ASA.Results: L-arginine-induced CP resulted in over-expression of the inflammatory enzyme cyclooxygenase (COX)-2. COX-2 expression decreased after ASA treatment. Pancreatic-injury inflammatory response (measured by changes in amylase, CK-19, F4/80, CD3, MCP-1, IL-6) and fibrosis degree (measured by expression of COL1A1, MMP-1 and TIMP-1) was reduce in ASA -treated mice model. The therapeutic effect of ASA was also observed in caeruelin-induced CP.Conclusion: ASA has an ameliorating effect in murine models of CP through inhibition of pancreatic inflammation and fibrosis, which may be a promising option for clinical treatment.Keywords: chronic pancreatitis, fibrosis, inflammation, aspirin, COX-2

Cong Shi,1,&ast; Shengping Gong,2,&ast; An Wu,3 Tingting Niu,1 Ningning Wu,1 Yi Zhang,1 Guifang Ouyang,3 Qitian Mu1 1Laboratory of Stem Cell Transplantation, Ningbo First Hospital, Ningbo, Zhejiang, People’s Republic of China; 2Cancer Radiotherapy and Chemotherapy Center, Ningbo First Hospital, Ningbo, Zhejiang, People’s Republic of China; 3Hematology Department, Ningbo First Hospital, Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guifang Ouyang; Qitian Mu, Email nbhematology@163.com; muqitian@163.comBackground: Myelodysplastic syndrome (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. It has been demonstrated that fibrinogen (FIB) is associated with disease risk in several cancer types. Coagulation and fibrinolysis problems are widespread in MDS patients. Therefore, FIB might be one of these indicators. We thus examined the role of FIB levels in the prognosis of MDS.Methods: A cohort of 198 MDS patients were retrospectively analyzed to explore the prognostic value of the plasma FIB levels at diagnosis. Patients were divided into the high FIB group and low FIB group. The prognostic significance of FIB was determined by univariate and multivariate Cox hazard models.Results: In our cohort, the FIB levels in 198 MDS patients were higher than those in 100 healthy donors (3.9 g/L vs 2.9 g/L, P < 0.0001). MDS patients with high FIB levels had significantly shorter overall survival (OS; P = 0.001) and decreased leukemia-free survival (LFS; P = 0.036). Multivariate cox proportional hazards regression analysis indicated that, in addition to older age, gender, lower HB, poorer karyotype for OS, lower NE, and higher bone marrow blast percentage for OS and LFS, elevated FIB level was also an independent adverse prognostic factor for OS (P = 0.045) but not for LFS (P = 0.188).Conclusion: Elevated FIB levels may be associated with mortality risk among MDS patients and could predict disease progress and patient prognosis. Thus, assessment of FIB levels may promote the determination of the prognosis of MDS patients.Keywords: myelodysplastic syndrome, IPSS-R, prognostic, overall survival, fibrinogen

Shuai Yin,1,&ast; Zhen-Hua Zhang,1,&ast; Yi-Niu Chang,2,&ast; Jin Huang,2 Ming-Li Wu,1 Qi Li,1 Jin-Qi Qiu,1 Xiao-Dong Feng,1,2 Nan Wu2 1Rehabilitation Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, People’s Republic of China; 2School of Rehabilitation Medicine, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Dong Feng, Rehabilitation Center, The First Affiliated Hospital of Henan University of Chinese Medicine, No. 19, Renmin Road, Zhengzhou, 450000, People’s Republic of China, Tel +8615303828605, Email fxd0502@163.com Nan Wu, School of Rehabilitation Medicine, Henan University of Chinese Medicine, No. 156, Jinshui East Road, Zhengzhou, 450046, People’s Republic of China, Tel +8613540484550, Email wunanwy@126.comPurpose: Abnormal central nervous system function is the key central pathological factor leading to chronic pain in patients with knee osteoarthritis (KOA). Acupuncture can effectively relieve the pain of KOA patients. However, the central nervous mechanism of acupuncture treating KOA is not fully understood. This trial will use functional magnetic resonance imaging (fMRI) analysis techniques to investigate the potential central nervous mechanism of acupuncture treatment of KOA.Materials and Methods: A total of 108 patients will be randomized (in a 1:1:1 ratio) into three groups, this trial will include 4-week treatment, patients in groups A and B will receive 20 acupuncture and sham acupuncture sessions, respectively, patients in group C will not receive any intervention, and all patients will receive fMRI scans before and after the intervention. The Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) will be the primary clinical outcome. Then, we will explore the functional changes of the cognitive control network (CCN) in the brains of KOA patients through whole brain functional connectivity (FC) analysis and seed-based functional connectivity (sFC) analysis. Pearson correlation coefficient will be used to analyze the relationship between the improved value of the clinical correlation scale and the change of fMRI data.Discussion: This trial will analyze the efficacy of verum acupuncture, sham acupuncture and the waiting-list for KOA and explore the activity of the CCN in three groups of patients by fMRI, so as to reveal the central nervous mechanisms of acupuncture in the treatment of KOA.Study Registration: This study is approved by the Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine (No: 2019HL-133-01) and registered in the Chinese Clinical Trial Registry, ChiCTR2000038554.Keywords: knee osteoarthritis, acupuncture, cognitive control network, randomized controlled trial

Kai Zhao,1,&ast; Yushan Dong,1,&ast; Gaowei Su,1 Yaolin Wang,1 Tao Ji,1 Nanling Wu,1 Xiaojie Cui,1 Wenzhan Li,1 Yanming Yang,1 Xiuxia Chen1,2 1Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuxia Chen, Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China, Tel +86 18052268332, Fax +0516-8346-9496, Email cxxlxy@sina.comPurpose: Lidocaine has been gradually used in general anesthesia. This study was designed to investigate the effect of systemic lidocaine on postoperative quality of recovery (QoR) in patients undergoing supratentorial tumor resection, and to explore its brain-injury alleviation effect in neurosurgical anesthesia.Patients and Methods: Sixty adult patients undergoing elective supratentorial tumor resection. Patients were randomly assigned either to receive lidocaine (Group L: 1.5 mg/kg bolus completed 10 min before anesthesia induction followed by an infusion at 2.0 mg/kg/h) or to receive normal saline (Group C: received volume-matched normal saline at the same infusion rate). Primary outcome measures were Quality of Recovery-40 (QoR-40) scores on postoperative day (POD) 1 and 2. Plasma concentrations of S100B protein (S100B), neuron specific enolase (NSE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) before anesthesia induction and at the end of surgery were assessed. Visual Analogue Scale (VAS) scores were assessed at 1, 2, 6, 12, 24 and 48 h after surgery. Perioperative parameters and adverse events were also recorded.Results: Patients between two groups had comparable baseline characteristics. Global QoR-40 scores on POD 1 and POD 2 were significantly higher (P < 0.001) in group L (165.5± 3.8 vs 173.7± 4.7) than those in group C (155.6± 4.0 vs 163.2± 4.5); and scores of physical comfort, emotional state, and pain in group L were superior to those in group C (P < 0.05). In group L, patients possessed lower plasma concentration of pro-inflammatory factors (IL-6, TNF-α) and brain injury-related factors (S100B, NSE) (P < 0.05), consumed less remifentanil and propofol, and experienced lower pain intensity. Multiple linear regression analysis demonstrated age and pain were correlated with postperative recovery quality.Conclusion: Systemic lidocaine improved early recovery quality after supratentorial tumor resection with general anesthesia, and had certain brain-injury alleviation effects. These benefits may be attributed to the inflammation-alleviating and analgesic properties of lidocaine.Keywords: lidocaine, brain neoplasm, supratentorial tumor resection, recovery quality, brain protection, postoperative pain

Xiyao Yang,1 Na Wu1,2 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 2Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Na WuDepartment of Endocrinology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Heping District, Shenyang, Liaoning Province, 110004, People’s Republic of China, Tel +86 18940258445, Email 3441535223@qq.comAbstract: Gestational diabetes mellitus (GDM) is defined as glucose intolerance that occurs during the second or third trimester of pregnancy. As the incidence of GDM rises, so does the risk of maternal and fetal complications with short- and long-term consequences. As a result, early diagnosis and treatment of this condition are important to avoiding adverse pregnancy outcomes. Exosomes are tiny vesicles secreted by living cells which contain a variety of bioactive substances. They are released by cells to facilitate cell-to-cell communication and regulate a variety of biological processes such as cellular immune response, inflammatory response, and apoptosis, among others. Many studies have recently confirmed that changes in the expression and secretion of exosomal miRNAs can be used as novel markers for the diagnosis, prognosis, and treatment of GDM. In this review, we summarized the various roles of exosomal miRNAs and circulating miRNAs in GDM. We found that the changes in the expression of certain miRNAs could be used to diagnosing GDM. Exosomal miRNAs target metabolic pathways, resulting in insulin resistance. We also highlighted the potential for miRNAs and exosomal miRNAs to be used as biomarkers for diagnosis or therapeutic agents.Keywords: GDM, exosomal miRNA, biomarker, insulin resistance, pregnancy

Ning Wu,1,&ast; Taohua Yuan,1,&ast; ZhiXin Yin,1 Xiaotian Yuan,1 Jianfei Sun,1 Zunqiu Wu,1 Qilong Zhang,1 Carl Redshaw,2 Shenggang Yang,1 Xiaotian Dai3 1Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Chemistry, University of Hull, Hull, Yorkshire, HU6 7RX, UK; 3Department of Mathematics and Statistics, University of Calgary, Calgary, AB, Canada&ast;These authors contributed equally to this workCorrespondence: Shenggang Yang, Guizhou Medical University, Guiyang, Guizhou, 550025, People’s Republic of China, Tel/Fax +86 13158000576, Email yangshenggang2021@126.com Xiaotian Dai, Department of Mathematics and Statistics, University of Calgary, Calgary, AB, T2N 1N4, Canada, Tel/Fax +1 435 754 4980, Email xiaotian.dai@uCalgary.caPurpose: This study aimed to investigate the molecular mechanisms of Compound Sidaxue (SX), a prescription of Chinese Miao medicine, in treating rheumatoid arthritis (RA) using network pharmacology and in vivo experimental approaches.Methods: Network pharmacology was adopted to detect the active components of four Traditional Chinese herbal medicine (TCM) of SX, and the key targets and signaling pathways in the treatment of RA were predicted, and the key components and targets were screened for molecular docking. The predicted targets and pathways were validated in bovine type II collagen and incomplete Freund’s adjuvant emulsifier-induced rat RA model.Results: In this study, we identified 33 active components from SX, predicted to act on 44 RA-associated targets by network pharmacology. PPI network demonstrated that TNF-α, VEGF-A, IL-2, IL-6, AKT, PI3K, STAT1 may serve as the key targets of SX for the treatment of RA. The main functional pathways involving these key targets include PI3K-AKT signaling pathway, TNF signaling pathway, NF-κB signaling pathway. Molecular docking analysis found that the active components β-amyrin, cajanin, eleutheroside A have high affinity for TNF-α, VEGFA, IL-2, AKT, and PI3K, etc. SX can improve joint swelling in Collagen-induced arthritis (CIA) rats, reduce inflammatory cell infiltration and angiogenesis in joint synovial tissue, and down-regulate IL-2, IL-6, TNF-α, VEGF, PI3K, AKT, p-AKT, NF-κBp65, the expression of p-NF-κBp65, STAT1, and PTGS2 are used to control the exacerbation of inflammation and alleviate the proliferation of synovial pannus, and at the same time play the role of cartilage protection to achieve the effect of treating RA.Conclusion: Through a network pharmacology approach and animal study, we predicted and validated the active compounds of SX and their potential targets for RA treatment. The results suggest that SX can markedly alleviate CIA rat by modulating the VEGF/PI3K/AKT signaling pathway, TNF-α signaling pathway, IL/NF-κB signaling pathway.Keywords: network pharmacology, molecular docking, rheumatoid arthritis, Sidaxue, VEGF/PI3K/AKT signaling pathway, TNF-α signaling pathway, IL/NF-κB signaling pathway

Ya-Jun Wu,1,&ast; Jie Rao,1,&ast; Xin Huang,2 Na Wu,1 Ling Shi,1 Hui Huang,1 Si-Yu Li,1 Xiao-Lin Chen,1 Shui-Qin Huang,1 Pei-Pei Zhong,1 Xiao-Rong Wu,1 Jun Wang3 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 2Department of Ophthalmology, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 3Department of Respiratory Disease, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Wang Email wangjun5087@163.comPurpose: Converging evidence demonstrated that bronchial asthma (BA) individuals with hypoxia were associated with functional and morphological reorganization in the brain. However, the alterations of the interhemispheric functional connectivity in BA individuals remain unknown. The purpose of this study was to assess the interhemispheric functional connectivity changes in individuals with hypoxia due to middle-aged BA using voxel-mirrored homotopic connectivity (VMHC) methods.Methods: In total, 31 BA individuals and 30 healthy controls (HCs) closely matched in age, sex, and education underwent resting-state magnetic resonance imaging (MRI) scans. VMHC analysis was performed to investigate differences in interhemispheric functional connectivity between the two groups. Then, a seed-based resting-state functional connectivity (rsFC) analysis was conducted to further reveal the abnormal functional connectivity between the altered VMHC regions and the whole brain.Results: Compared with HCs, BA individuals had significantly lower VMHC values in the bilateral basal ganglia/thalamus/insula, cuneus/calcarine/lingual gyrus, precentral and postcentral gyrus. [voxel level P < 0.01, Gaussian random field (GRF) correction, cluster level P < 0.05]. Taking VMHC altered brain areas as seed points, the rsFC values of left insula/supramarginal/postcentral gyrus (PostCG)/inferior parietal lobule (IPL) brain areas in BA were increased.Conclusion: The abnormal resting-state functional connectivity of middle-aged BA is altered in specific brain regions related to the basal ganglia network, visual network, and sensorimotor network, which may be related to the neuropathogenesis of asthma patients. Furthermore, these VMHC and FC values may be important clinical indicators for the diagnosis and treatment of asthma patients.Keywords: bronchial asthma, voxel-mirrored homotopic connectivity, functional magnetic resonance imaging, basal ganglia network, visual network, sensorimotor network

Qian Feng,1 Liang-Jie Tang,2 Ding-Hai Luo,3 Ying Wang,1 Nan Wu,1 Hao Chen,1 Meng-Xia Chen,1 Lei Jiang,4 Rong Jin1,5 1Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 3Department of Gastroenterology, Taizhou Hospital of Zhejiang Province, Taizhou, 317000, People’s Republic of China; 4Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 5Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Rong JinDepartment of Gastroenterology, Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaEmail jinrongjrjr@163.comLei JiangCentral Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaTel +86-577-55579127Fax +86-577-55578999Email jiangleistone79@163.comPurpose: Hyperuricemia and metabolic syndrome (MetS) have been shown to correlate with prognosis in patients with malignant tumors. The present study evaluated the relationship between preoperative hyperuricemia and MetS in colorectal cancer (CRC) patients and analyzed the effect of this combination on prognosis within 5 years.Patients and Methods: The study enrolled patients who had undergone radical CRC resection at three independent medical centers from January 2014 to December 2016. Patients were preoperatively categorized into four groups, those with hyperuricemia alone (H), those with MetS alone (MS), those with MetS-related hyperuricemia (MSH), and those with neither condition (control [C] group). The disease-free survival (DFS) and overall survival (OS) rates of these four groups were compared.Results: The study population consisted of 1271 patients, with 114, 201, 101, and 855 patients categorized into the H, MS, MSH and C groups, respectively. Preoperative MetS was found to be significantly associated with hyperuricemia (P < 0.001). Multivariate Cox regression analysis showed that MetS-related hyperuricemia (hazard ratio [HR] = 2.728; P < 0.001) and MetS alone (HR = 1.631; P < 0.001) were independent predictors of death, whereas simple hyperuricemia was not (P > 0.1). Relative to the C group, the MSH group had the highest rate of tumor recurrence or metastasis (HR = 5.103, P < 0.001), followed by the MS (HR = 2.231, P < 0.001) group. In contrast, prognosis did not differ significantly in the H and C groups (P > 0.1). MetS was significantly associated with poor prognosis, with MetS-related hyperuricemia resulting in a significantly poorer prognosis. In contrast, hyperuricemia alone had no effect on the long-term prognosis of CRC patients.Conclusion: This study highlights the prognostic importance of MetS-related hyperuricemia on the survival of patients with CRC.Keywords: colorectal cancer, metabolic syndrome, hyperuricemia, prognosis

Huijing Lin,1,&ast; Alayi BoLatai,2,&ast; Na Wu1,3 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’ s Republic of China; 2Student Affairs Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’ s Republic of China; 3Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’ s Republic of China&ast;These authors contributed equally to this workCorrespondence: Na WuDepartment of Endocrinology, Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaEmail 3441535223@qq.comAbstract: Diabetic foot is a serious infection of the lower limbs. It is caused by diabetic neuropathy and vascular disease. It is also the primary cause of disability and death in patients with severe diabetes, so prompt treatment is essential for positive outcomes. The clinical use of nano-silver dressings can be considered to further optimize the treatment process and improve the treatment efficacy in diabetic foot patients. Nano-silver dressings have a larger contact surface and a stronger bactericidal effect when compared to ordinary silver dressings. Besides, it can be disinfected repeatedly to better wound infection control and promote wound healing. The current article discusses the pathogenesis of diabetic foot, diabetic foot dressing treatment, the application of nanotechnology in diabetic foot treatment, the efficacy evaluation of different dressings, and the practical prospects of adopting nanotechnology in the treatment of diabetic foot.Keywords: nano-silver, diabetic foot, antibacterial dressings

Donghui Hou,1 Weihua Li,2 Sicong Wang,3 Yao Huang,1 Jianwei Wang,1 Wei Tang,1 Lina Zhou,1 Linlin Qi,1 Ning Wu,1,4,&ast; Shijun Zhao1,&ast; 1Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3GE Healthcare, Life Sciences, Beijing, People’s Republic of China; 4PET-CT Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shijun Zhao; Ning WuDepartment of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing, 10021, People’s Republic of ChinaTel +86-10-8778-8550; Tel/Fax +86-10-8778-7523Email zsj.2001@163.com; cjr.wuning@vip.163.comPurpose: Although patients with primary and acquired epidermal growth factor receptor (EGFR) T790M positive non-small-cell lung cancer (NSCLC) respond to osimertinib treatment, the optimal treatment strategy differs for these two groups of patients. This study aimed to compare the clinicopathologic and computed tomography (CT) imaging characteristics between primary and acquired EGFR T790M mutations in patients with NSCLC before treatment.Patients and Methods: We enrolled two groups of patients with primary or acquired EGFR T790M mutation NSCLC (n = 103 per group) from January 2012 to December 2019. We analyzed their clinicopathologic and CT characteristics and differences between the groups. The groups were further categorized based on 21L858R and 19del to exclude the effect of coexistent mutations.Results: Primary, compared to acquired, T790M mutation tends to coexist with 21L858R (P < 0.001), exhibiting earlier tumor stage (P < 0.001), higher differentiation (P = 0.029), higher proportion of lepidic subtype adenocarcinoma (P < 0.001), and significant associations with some CT features (multiple primary lung cancers, ground-glass opacity, air bronchogram, and vacuole sign [all P < 0.001]). The combined model, composed of clinicopathologic and conventional CT signature and CT-radiomic signature, showed good discriminative ability with the area under the receiver operating characteristic curve 0.90 and 0.91 in the training and validation datasets, respectively. The T790M mutation contributed to these differences independently of coexistent mutations.Conclusion: We identified clinicopathologic and CT imaging differences between primary and acquired T790M mutations. These findings provide insights into developing future personalized T790M mutation status-based theranostic strategies.Keywords: non-small-cell lung cancer, T790M mutation, osimertinib, clinicopathologic characteristic, computed tomography

Runyu Du, Na Wu, Ling Li Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of ChinaCorrespondence: Ling LiDepartment of Endocrinology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, Liaoning Province, 110004, People’s Republic of ChinaTel +86 18940251181Fax +86 24-25944460Email liling8864@hotmail.comAbstract: Gestational diabetes mellitus (GDM), one of the most common complications during pregnancy, is associated with a high risk of short- and long-term adverse effects on the mother and offspring. Placenta-derived hormones and cytokines aggravate maternal insulin resistance (IR) during pregnancy, which in turn contribute to GDM. The hyperglycemia and IR in GDM result in aberrant placental structure and function adversely affecting fetal growth and well-being. Therefore, it is reasonable to assume that structural and functional alterations in the placenta contribute to the pathogenesis of GDM and GDM-related complications. Increasing evidence suggests that multiple non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, and circular RNAs, are dysregulated in placentas of patients with GDM and linked to abnormal placental structure, metabolism, and function. Manipulation of ncRNA expression led to some key pathophysiological features of GDM, such as trophoblast dysfunction, changes in intracellular glucose metabolism, and inflammation. Moreover, placenta-specific ncRNAs may be potential diagnostic biomarkers and even therapeutic targets for GDM. This review summarizes data published on the involvement of aberrantly expressed placental ncRNAs in GDM and provides information on their role in the pathogenesis of GDM and GDM-associated complications.Keywords: dysregulated ncRNA, pregnancy disorder, placental dysfunction, pregnancy-related complications, trophoblast dysfunction

Ying Wang,1 Na Wu,2 Haitao Shen3 1Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China; 2Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China; 3Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaCorrespondence: Haitao Shen Tel +86-18940256180Email pianzhang6@163.comAbstract: Preeclampsia has a significant long-term effect on the health of both mothers and babies. Preeclampsia-related pregnancy complications increase the morbidity and mortality of pregnant women and their fetuses by 5– 8%. The recent advancement of assisted reproductive technology, combined with a rise in the number of elderly pregnant women, has resulted in pregnancy incidence with twins. Twins pregnant women have a 2– 3 times greater risk of developing preeclampsia than singleton pregnant women, and it happens sooner and progresses faster. It is more severe and may appear in an atypical way. End-organ damage, such as renal failure, stroke, cardiac arrest, pulmonary edema, placental abruption, and cesarean section, are related maternal complications. Fetal growth retardation, stillbirth, and premature delivery with obstetric signs are all fetal complications. According to studies, all multiple pregnancies can take low-dose aspirin (60– 150 mg) to minimize the risk of preeclampsia. To improve pregnancy outcomes and reduce the inherent risk of pregnancy with twins, twins should be handled as a high-risk pregnancy and treated differently than singletons. The literature on twin pregnancy with preeclampsia is the subject of this review. It will examine the current state of research on preeclampsia in pregnancy with twins, including the occurrence, diagnosis, and pathophysiological process. Moreover, the effect of pregnancy with twins on the perinatal outcome and pregnancy management of pregnancy with twins, including blood pressure management and preeclampsia prevention and treatment, is examined in this literature review. The goal is to figure out what kind of diagnosis and care you may need.Keywords: twins, pregnancy, preeclampsia

Weibo Ma,1,* Yuewen Liu,1,* Ning Wu,1 Hui Zhang,1 Peipei Han,1 Feng Wang,1 Jingru Wang,1 Fandi Xie,2 Shumeng Niu,2 Hao Hu,2 Chenyu Zhang,1 Nuo Chen,1 Yichen Zhang,1 Qi Guo,1 Ying Yu1 1Department of Rehabilitation Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 2Department of Clinical Laboratory Center, Shanghai Jiangwan Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qi GuoDepartment of Rehabilitation Medicine, Shanghai University of Medicine and Health Sciences, No. 279 Zhouzhu Road, Pudong New Area, Shanghai, 201318, People’s Republic of ChinaTel +86-21-8333-6977Fax +86-21-8333-6977Email guoqijp@gmail.comYing Yu Email yuying@sumhs.edu.cnObjective: We examined the association between obesity and physical performance under different metabolic status.Methods: The sample included 1395 Chinese community-dwelling participants (mean age, 71.88 ± 5.87 years; 40.9% men). Being metabolically healthy was defined as having the presence of < 3 of 5 components of metabolic syndrome (MetS); obesity was defined as having a BMI > 28 kg/m2. Participants were divided into four groups based on BMI (non-obese/obese) and metabolic health (healthy/unhealthy). Physical performance was measured by grip strength, 4-m walking speed, and the timed up and go test (TUGT).Results: After multiple adjustments, compared with metabolically healthy non-obese group, the metabolically unhealthy obese group showed lower relative grip strength, lower 4-m walking speed, and higher TUGT (P all < 0.05), and only relative grip strength of the metabolically healthy obese group was significantly lower than that of metabolically healthy non-obese (P < 0.01). Relative grip strength was negatively associated with impaired fasting glucose (β = − 0.071), elevated triglycerides (β = − 0.062), abdominal obesity (β = − 0.230) and general obesity (β = − 0.225) (P all < 0.01). Walking speed and TUGT were only associated with general obesity, rather than other metabolic components. The associations of MetS with physical performance were mainly driven by abdominal obesity.Conclusion: Even in those who are metabolically healthy, obesity (especially general obesity) increases the risk of poor physical performance. Elderly people with general obesity and MetS, whether in combination or alone, have an increased risk of muscle dysfunction, and that combination produces a higher risk of impaired mobility.Keywords: metabolic health, obesity, physical performance, grip strength, 4-m walking speed, TUGT

Xinyan Liu,1 Na Wu,1,2 Abdulrahman Al-Mureish1 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China; 2Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaCorrespondence: Na Wu Email 3441535223@qq.comAbstract: Glycosylated hemoglobin (HbA1C) and glycated albumin (GA) can be used for blood glucose management of a person with diabetes as a result of their convenience and stability. However, there is no corresponding standard for the application of glycosylated hemoglobin and glycosylated albumin in gestational diabetes mellitus (GDM). In this review, we summarize the published research and discuss three aspects of the significance of HBA1C and GA in GDM patients: screening of gestational diabetes mellitus, blood glucose monitoring and the relationship with pregnancy outcome. At present, studies suggest that HBA1C can be used as a screening indicator for pregnant women, but it cannot completely replace OGTT. HbA1C and GA can be used for blood glucose management in patients with GDM to reduce the incidence of GDM complications. However, the application of HBA1C and GA in GDM still needs more research and clinical practice support.Keywords: blood glucose, diabetes mellitus, fasting blood glucose

Yujing He,1 Na Wu1,2 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, People’ s Republic of China; 2Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Na WuShengjing Hospital of China, 36 Sanhao Road, Heping District, Shenyang, Liaoning Province, 110004, People’s Republic of ChinaTel +86 18940258445Email 3441535223@qq.comAbstract: Gestational diabetes mellitus (GDM) is the onset or first recognition of diabetes during pregnancy in women with normal glucose metabolism or potentially impaired glucose tolerance before pregnancy. Studies have shown that vascular endothelial cells (VECs) are an important target organ of insulin, which is injured by multiple factors in the case of GDM, thereby leading to worsened insulin resistance (IR) and the further development of GDM. When VECs are abnormal, there will be changes in the content of a variety of cell markers, which may be helpful for the clinical prediction and diagnosis of GDM. This study attempted to investigate the mechanism and markers of VECs injury in GDM patients.Keywords: gestational diabetes mellitus, endothelial cells, biomarkers

Yuxin Liu,1 Na Wu2,3 1Student Affairs Department, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China; 2Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China; 3Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaCorrespondence: Na WuShengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaEmail 3441535223@qq.comAbstract: Diabetic retinopathy (DR) is a chronic diabetes complication that progressively manifests itself as blurred vision, eye floaters, distorted vision, and even partial or total loss of vision as a result of retinal detachment in severe cases. Clinically, patients who have undergone variations in the microcirculation of the ocular fundus are treated with laser photocoagulation to improve the circulation of retina; but for patients with macular edema, anti-vascular endothelial growth factor (anti-VEGF) drugs are generally injected to eliminate macular edema and improve vision. The worst cases are patients with fundus hemorrhage or proliferative vitreoretinopathy, for whom vitrectomy has been performed. At present, these clinical treatment methods have widely been used, providing satisfactory results. However, considering the low bioavailability and potential side effects of drugs and the inevitable risks in major surgery, DR prevention, and treatment as well as nerve tissue regeneration in the later stage have always been the focus of research. In recent years, nanotechnology has been increasingly applied in the medical field, leading to new ideas for DR treatment. This study aims to systematically review the research progress of nanotechnology in DR treatment.Keywords: diabetes mellitus, diabetic retinopathy, nanotechnology, drug delivery

Ning Wu,1 Andreas Kuznik,1 Degang Wang,1 Chad Moretz,2 Ann Xi,2 Shambhavi Kumar,2 Laurie Hamilton2 1Health Economics and Outcomes Research, Regeneron Pharmaceuticals, Tarrytown, NY, USA; 2Avalere Health, Washington, DC, USACorrespondence: Andreas KuznikHealth Economics and Outcomes Research, Regeneron Pharmaceuticals, Tarrytown, NY, USATel +1 914 847 1889Email andreas.kuznik@regeneron.comBackground: Emerging trial data for treatment of COVID-19 suggest that in addition to improved clinical outcomes, these treatments reduce length of hospital stay (LOS). However, the economic value of a shortened LOS is unclear.Objective: To estimate incremental costs per day of hospitalization for a patient with influenza or viral pneumonia, as a proxy for COVID-19; ICU costs associated with invasive mechanical ventilation (iMV) were also determined.Methods: Retrospective analysis of claims-based data was conducted using the IBM MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Care and the Medicare Fee-for-Service claims databases for hospitalizations due to influenza/viral pneumonia between January 2018 and June 2019. Cases were stratified as uncomplicated hospitalizations or with ICU. Ordinary least squares regression, excluding LOS or costs exceeding the 99th percentile (base case), was used to estimate incremental costs per day; a sensitivity analysis included all qualified hospitalizations. Additional sensitivity analyses used weighting methodology.Results: Among 6055 and 118,419 hospitalizations in the commercially insured and Medicare databases, respectively, 5958 and 116,552 hospitalizations, respectively, represented the base case. Estimated incremental base case costs per additional inpatient day were $2158 and $3900 in the commercial population for uncomplicated hospitalizations and hospitalizations with ICU, respectively, and $475 and $668, respectively in the Medicare population. Estimated incremental base case costs per additional ICU day were $5254 and $608 for Commercial and Medicare populations, respectively. Higher absolute costs were estimated in the sensitivity analysis on all qualified hospitalizations; the weighted sensitivity analyses generally showed that estimates were stable. Use of iMV increased costs by $35,482 and $13,101 in the commercial and Medicare populations, respectively.Conclusion: The incremental daily cost of a hospitalization is substantial for US patients with commercial insurance and for Medicare patients. These findings may help quantify the economic value of COVID-19 treatments that reduce LOS.Keywords: viral pneumonia, hospitalizations, intensive care unit, length of stay, mechanical ventilation, costs

Simin Yu,1,* Ning Wu,2,* Jianmin Zhu,3 Ying Liu,4 Jinbin Han1 1Department of Traditional Chinese Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Pudong New Area Gongli Hospital, Shanghai, People’s Republic of China; 3Shanghai Clinical Center, Chinese Academy of Sciences/Xuhui Central Hospital, Shanghai, People’s Republic of China; 4Department of Oncology, Yunnan Provincial Hospital of Chinese Medicine, Kunming, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinbin Han Tel +862123271699Fax +862163136856Email 18621100359@163.comPurpose: To investigate whether pyrrolidine dithiocarbamate (PDTC) could facilitate arsenic trioxide (ATO) to induce apoptosis in pancreatic cancer cells via perturbing ubiquitin-proteasome pathway.Methods: Mass spectrometry was performed to examine the interaction between PDTC and ATO, and the data showed they could form a complex termed PDTC-ATO. Inhibiting effects on cell viability were examined by CCK-8 test, and apoptosis was examined by flow cytometry. Four treatment arms (n = 6), including the control, PDTC, ATO, and PDTC-ATO, were evaluated using BALB/c nude mouse models bearing a xenograft tumor of SW1990 human pancreatic cancer line. Western blot, immunohistochemistry assays were to detect the mechanism.Results: The results showed that PDTC-ATO had higher inhibiting effects on proliferation of pancreatic cancer cells than ATO in vitro. In bearing-tumor mice, PDTC-ATO inhibited tumor growth by 79%, being more potent than ATO (by 46%) or PDTC (by 35%) compared to the control. Results of Western blot and immunohistochemistry showed proteasome inhibition and apoptotic cell death, together with obvious suppression of associating E3 ubiquitin ligase activity, occurred more frequently in tumors treated with PDTC-ATO than those with ATO.Conclusion: PDTC demonstrated the function to facilitate ATO against pancreatic cancer due to forming a stable complex to perturb ubiquitin-proteasome pathway.Keywords: arsenite, ubiquitin ligase, pancreatic cancer cell, dithiocarbamate, complex

Meichen Qian,1 Na Wu,1,2 Ling Li,1 Wenshu Yu,1 Hong Ouyang,1 Xinyan Liu,1 Yujing He,1 Abdulrahman Al-Mureish2 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China; 2Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of ChinaCorrespondence: Na WuDepartment of Endocrinology, Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of ChinaEmail 3441535223@qq.comAbstract: Ketone bodies are one of the products of fat metabolism which can be used as an alternative energy source for the human body in states of glucose deficiency. Normal pregnant women may develop ketosis due to physiological changes during pregnancy, while pregnant women with abnormal glucose metabolism are more likely to develop ketosis due to abnormal insulin secretion. Animal experiments and clinical studies have shown that exposure to high-ketone environments during pregnancy is closely related to adverse maternal and infant outcomes. However, there is no unified conclusion on whether ketone bodies should be routinely monitored during pregnancy. This review summarizes the existing studies on ketone body levels and pregnancy outcomes in the case of abnormal blood glucose during pregnancy, elaborates the current guidelines on the level of ketone bodies, provides the detection and treatment of ketosis in pregnant women with abnormal blood glucose in the clinical practice.Keywords: diabetic ketoacidosis, gestational diabetes mellitus, ketoacidosis, pregestational diabetes mellitus, diabetes mellitus

Yujing He,1 Na Wu,1,2 Wenshu Yu,1 Ling Li,1 Hong OuYang,1 Xinyan Liu,1 Meichen Qian,1 A Al-Mureish1 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 2Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaCorrespondence: Na WuDepartment of Endocrinology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Heping District, Shenyang, Liaoning Province 110004, People’s Republic of ChinaTel +86 18940258445Email 3441535223@qq.comAbstract: Gestational diabetes mellitus (GDM) refers to different degrees of abnormal glucose metabolism during pregnancy, where blood glucose levels do not reach the level of overt diabetes, accounting for 80– 90% of pregnancy with hyperglycemia. Hyperglycemia affects the pregnancy process, leading to a series of adverse maternal outcomes that have a profound impact on the future of the offspring. The establishing of an appropriate GDM model will provide theoretical basis for study GDM pathogenesis involves, the choice of resonable drugs and the observation the disease trends and outcomes. At present, there are many methods for establishing experimental GDM animal models and animal choices. This paper examines the different GDM models and their induction methods.Keywords: gestational diabetes mellitus, animal model, chemical induction, high-sugar and high-fat diet, genetic manipulation

Qian Sun,1 Hongyan Sun,2 Lele Cong,1 Yang Zheng,1 Nan Wu,1 Xianling Cong1 1Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Tissue Bank, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Xianling CongDepartment of Dermatology, China-Japan Union Hospital of Jilin University, Xiantai Road 126, Changchun, Jilin 130033, People’s Republic of ChinaTel +86-15904420533Fax + 86-431-89876626Email congxl@jlu.edu.cnAbstract: Epidemiological findings on the effects of hormones on melanoma risk have been inconsistent. We therefore conducted a meta-analysis to examine the relationship between exogenous hormonal and reproductive factors and the risk of melanoma in women. We performed a search of PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) database through April 2020 for relevant studies. Based on heterogeneity, we performed the meta-analysis of the risk estimates using either fixed effect or random effect models. We identified 38 studies that met the analytical criteria, involving 3,571,910 participants. The results showed that long-term use of oral contraceptives (OC) may increase the risk of melanoma in women (≥ 5 years [pooled RR=1.18; 95% CI: 1.07– 1.31; I2=0%] and ≥ 10 years [pooled RR=1.25; 95% CI: 1.06– 1.48; I2=0%]). Women who first used OC 15– 19 years previously were more likely to develop melanoma (pooled RR=1.52; 95% CI: 1.03– 2.24; I2=0%), while the years since the last use and the age at first use were not associated with the development of melanoma in women. Hormone replacement therapy (HRT) increased the incidence of melanoma in women (pooled RR=1.12, 95% CI: 1.02– 1.24; I2=50%) and was especially associated with an increased risk of superficial spreading melanoma (SSM) (pooled RR=1.26; 95% CI: 1.17– 1.37; I2=0%), and estrogen and estradiol may be the main active agents that contribute to the increased risk of melanoma, but these results may be due to a combination of sun exposure factors. With regard to reproductive factors, decreased parity and being aged ≥ 20 years at first birth may be associated with an increased risk of melanoma in females, while menopausal status and age at menarche are not associated with the incidence of melanoma in females. Further large-scale prospective studies are necessary to reveal new pathophysiological mechanisms and new therapeutic targets for cutaneous melanoma.Keywords: oral contraceptives, hormone replacement therapy, menopause, menarche, parity

Wenshu Yu,1 Na Wu,1 Ling Li,1 Hong OuYang,1 Meichen Qian,1 Haitao Shen2 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, People’ s Republic of China; 2Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Na WuDepartment of Endocrinology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Heping District, Shenyang, Liaoning Province 110004, People’ s Republic of ChinaTel +86 18940258445Email 3441535223@qq.comAbstract: Gestational diabetes mellitus (GDM) is associated with many adverse obstetric outcomes and neonatal outcomes, including preeclampsia, Cesarean section, and macrosomia. Active screening and early diabetes control can reduce the occurrence of adverse outcomes. Glycosylated hemoglobin (HbA1c) only reflects average blood glucose levels, but not glycemic variability (GV). Studies have shown that GV can cause a series of adverse reactions, and good control of GV can reduce the incidence of adverse pregnancy outcomes in patients with GDM. In order to provide clinicians with a better basis for diagnosis and treatment, this study reviewed the measurement, evaluation, and control of GV, the importance of GV for patients with GDM, and correlations between GV and maternal and neonatal outcomes.Keywords: gestational diabetes mellitus, glycemic variability, outcomes, self-monitoring of blood glucose, continuous glucose monitoring

Fan Yang,1 Pengzhen Lei,2 Weihui Zeng,3 Jianwu Gao,1 Na Wu1 1Department of Dermatology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi 710068, People’s Republic of China; 2Department of Orthopedics, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi 710068, People’s Republic of China; 3Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710048, People’s Republic of ChinaCorrespondence: Fan YangDepartment of Dermatology, Shaanxi Provincial People’s Hospital, No. 256 Youyi West Road, Xi’an, Shaanxi 710068, People’s Republic of ChinaEmail fanfanniu1985@126.comPurpose: Long intergenic non-protein-coding RNA 173 (LINC00173) plays crucial roles in lung cancer. However, the expression and biological functions of LINC00173 in melanoma have not yet been investigated. In this study, we aimed to characterize the involvement of LINC00173 in melanoma and elucidate its mechanisms of action.Materials and Methods: Reverse-transcription quantitative PCR was performed to measure LINC00173 expression in melanoma. A CCK-8 assay, flow cytometry, and migration and invasion assays were applied to examine melanoma cell proliferation, apoptosis, migration, and invasion, respectively. A xenograft tumor experiment was performed to determine the tumorous growth of melanoma cells in vivo.Results: We found that LINC00173 was upregulated in melanoma tissues and cell lines. High LINC00173 expression was closely associated with TNM stage, lymph node metastasis, and shorter overall survival of patients with melanoma. Functional assays revealed that LINC00173 downregulation inhibited melanoma cell proliferation, migration, and invasion and induced apoptosis, suggesting that LINC00173 acts as an oncogenic RNA. LINC00173 knockdown retarded the tumorous growth of melanoma cells in vivo. Mechanistically, LINC00173 increased insulin receptor substrate 4 (IRS4) expression by sponging microRNA-493 (miR-493), thereby acting as a competing endogenous RNA. The effects of LINC00173 knockdown on the malignant phenotype of melanoma cells were reversed by overexpression of IRS4 or knockdown of miR-493.Conclusion: The LINC00173–miR-493–IRS4 pathway regulates melanoma characteristics by increasing the expression of IRS4 via competitive binding of LINC00173 to miR-493, suggesting that this pathway is a potential target for the diagnosis, prognosis, and/or treatment of melanoma.Keywords: LINC00173, miR-493, melanoma, therapeutic target

Huimin Yang,* Xin Xin,* Hang Yu, Yandong Bao, Pengyu Jia, Nan Wu, Dalin Jia Department of Cardiology, The Central Laboratory, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dalin Jia; Nan WuDepartment of Cardiology The Central Laboratory, The First Affiliated Hospital of China Medical University, 155th North of Nanjing Street, Heping District, Shenyang, Liaoning 110001, People’s Republic of ChinaEmail jdl2001@126.com; imwunan@163.comPurpose: A high-fat diet (HFD) can lead to cardiac dysfunction, hypertrophy, and fibrosis. This study aimed to explore microRNA expression profiles in the myocardium of HFD-induced obesity rat.Materials and Methods: Wistar rats were randomly divided into two groups, and fed with normal chow diet (NCD) or HFD for 20 weeks. Cardiac function was evaluated by echocardiography. Left ventricular myocardium was harvested to assess the extent of myocardial morphology alteration. MicroRNA expression was analyzed using Agilent miRNA microarray and quantitative real-time PCR (qRT-PCR) was used to validate the microarray data. The mirdbV6 database was used to forecast the miRNA target genes. The role of microRNAs in palmitate-induced cardiac hypertrophy and fibrosis in primary neonatal rat cardiomyocytes was evaluated by loss- and gain-of-function experiments.Results: Significant changes in cardiac function, hypertrophy, fibrosis, and apoptosis were found in HFD rats as compared with NCD rats. miR-141-3p and miR-144-3p were also significantly upregulated in the myocardium of HFD-induced obesity rat. A series of genes involved in essential biological processes, including anatomical structure development and metabolic process, was targeted by these two miRNAs. These target genes were also implicated in signaling pathways involved in the PI3K-Akt signaling pathway, Wnt signaling pathway, autophagy, and protein processing in the endoplasmic reticulum. Inhibition of miR-141 or overexpression of miR-144 attenuated palmitate-induced cardiac hypertrophy and fibrosis. In contrast, overexpression of miR-141 or inhibition of miR-144 aggravated palmitate-induced cardiac hypertrophy and fibrosis.Conclusion: This study identifies that miR-141 and miR-144 are candidate miRNAs associated with the development of HFD-induced cardiac dysfunction and structure alteration.Keywords: high-fat diet, obesity, microRNA, cardiac dysfunction, cardiac remodeling

Qian Sun,1 Hongyan Sun,2 Lele Cong,1 Yang Zheng,1 Nan Wu,1 Xianling Cong1 1Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Tissue Bank, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Xianling Cong, Department of Dermatology, China-Japan Union Hospital of Jilin University, Xiantai Road 126, Changchun, Jilin, 130033, People’s Republic of China, Tel +86 15904420533, Fax +86 431-89876626, Email congxl@jlu.edu.cn View the original paper by Dr Sun and colleagues This is in response to the Letter to the Editor

Xuying Li,1,* Pengyu Jia,1,* Zijun Huang,1 Shuang Liu,1 Jiaxin Miao,1 Yuxuan Guo,1 Nan Wu,2 Dalin Jia11Department of Cardiology; 2The Central Laboratory, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People’s Republic of China*These authors contributed equally to this workBackground: Mitochondria permeability transition pore (MPTP) is an important therapeutic target for myocardial ischemia-reperfusion injury (MIRI). Lycopene (LP) is a potent antioxidant extracted from the mature fruits of plants and has been reported to protect against MIRI; however, its mechanism of action has yet to be completely elucidated. The present study aimed to investigate the role of MPTP in the cardioprotection of LP.Methods: H9c2 cells were pretreated with LP for 12 hrs and were subjected to 12-hr hypoxia/1-hr re-oxygenation, and cell viability was measured by a Cell Counting Kit-8 (CCK-8) assay. Male rats were subsequently intraperitoneally injected with LP for 5 consecutive days. At 24 hrs following the final injection, the rat hearts were isolated and subjected to 30-min ischemia/120-min reperfusion using Langendorff apparatus. The myocardial infarct size was measured by a TTC stain. Opening of the MPTP was induced by CaCl2 and measured by colorimetry. The change in mitochondrial transmembrane potential (ΔΨm) was observed under a fluorescence microscope. Apoptosis was measured by flow cytometry and a TUNEL stain, and the expression of apoptosis-related proteins was detected by Western blotting.Results: LP pretreatment significantly increased cell viability, reduced myocardial infarct size and decreased the apoptosis rate. In addition, opening and the decrease of ΔΨm were attenuated by LP and the expressions of cytochrome c, APAF-1, cleaved caspase-9 and cleaved caspase-3 were also decreased by LP. However, these beneficial effects on MIRI were abrogated by the MPTP opener (atractyloside). Furthermore, LP treatment markedly increased Bcl-2 expression, decreased Bax expression and the Bax/Bcl-2 ratio.Conclusion: The results of the present study demonstrated that LP protects against MIRI by inhibiting MPTP opening, partly through the modulation of Bax and Bcl-2.Keywords: myocardial ischemia reperfusion injury, lycopene, mitochondrial permeability transition pore, apoptosis

Pengyu Jia,1 Nan Wu,2 Dalin Jia,1 Yingxian Sun11Department of Cardiology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People‘s Republic of China; 2The Central Laboratory of the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People‘s Republic of ChinaPurpose: The increased level of saturated fatty acids (SFAs) is found in patients with diabetes, obesity, and other metabolic disorders. SFAs can induce lipotoxic damage to cardiomyocytes, but the mechanism is unclear. The long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) acts as a key regulator in palmitic acid (PA)-induced hepatic steatosis, but its role in PA-induced myocardial lipotoxic injury is still unknown. The aim of this study was to explore the role and underlying mechanism of MALAT1 in PA-induced myocardial lipotoxic injury.Methods: MALAT1 expression in PA-treated human cardiomyocytes (AC16 cells) was detected by RT-qPCR. The effect of MALAT1 on PA-induced myocardial injury was measured by Cell Counting Kit-8, lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) assays. Apoptosis was detected by flow cytometry. The activities of cytokines and nuclear factor (NF)-κB were detected by enzyme-linked immunosorbent assay. The interaction between MALAT1 and miR-26a was evaluated by a luciferase reporter assay and RT-qPCR. The regulatory effects of MALAT1 on high mobility group box 1 (HMGB1) expression were evaluated by RT-qPCR and western blotting.Results: MALAT1 was significantly upregulated in cardiomyocytes after PA treatment. Knockdown of MALAT1 increased the viability of PA-treated cardiomyocytes, decreased apoptosis, and reduced the levels of LDH, CK-MB, TNF-α, and IL-1β. Moreover, we found that MALAT1 specifically binds to miR-26a and observed a reciprocal negative regulatory relationship between these factors. We further found that the downregulation of MALAT1 represses HMGB1 expression, thereby inhibiting the activation of the Toll-like receptor 4 (TLR4)/NF-κB-mediated inflammatory response. These repressive effects were rescued by an miR-26a inhibitor.Conclusion: We demonstrate that MALAT1 is induced by SFAs and its downregulation alleviates SFA-induced myocardial inflammatory injury via the miR-26a/HMGB1/TLR4/NF-κB axis. Our findings provide new insight into the mechanism underlying myocardial lipotoxic injury.Keywords: metastasis-associated lung adenocarcinoma transcript 1, saturated fatty acids, microRNA, high mobility group box-1 protein, inflammation

Yong Tao,1 Danping Yuan,1 Hongshuang Pang,1 Hongbiao Wu,1 Dongfang Liu,1 Ningning Jin,1 Ningning Wu,1 Jianming Qiu,2 Yuepeng Cao11Department of Colorectal Surgery, Ningbo City First Hospital, Ningbo, Zhejiang, 86-315000, People’s Republic of China; 2Department of Colorectal Surgery, Hangzhou Third People’s Hospital, Hangzhou, 86-310009, People’s Republic of ChinaBackground: Inflammatory cellular response is implicated in the pathogenesis of colorectal cancer (CRC). Nevertheless, the dynamic effects of inflammatory index coNLR (neutrophil-to-lymphocyte ratio)-PLR (platelet-to-lymphocyte ratio) during chemotherapy remain elusive.Methods: The baseline clinical data and laboratory parameters of 480 CRC patients who received palliative resection of primary tumors and FOLFOX-based chemotherapy from January 2007 to January 2013 were retrospectively analyzed. Receiver operating characteristic curves were plotted to obtain the predictive NLR and PLR values, and to calculate the coNLR-PLR score. The Kaplan–Meier method was used to estimate the rates of recurrence-free survival (RFS) and overall survival (OS), and the Cox proportional hazards model was employed for analysis.Results: The dynamic cut-off values of NLR during four periods of chemotherapy were 3.029, 2.466, 2.102 and 1.795, respectively, and those of PLR were 216.438, 187.572, 169.027 and 174.368, respectively. A higher coNLR-PLR was significantly associated with lower rates of RFS and OS (P

Xiang Li,1,* Shaolei Li,1,* Shi Yan,1 Yaqi Wang,1 Xing Wang,1 Alan DL Sihoe,2 Yue Yang,1 Nan Wu1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China; 2Department of Surgery, University of Hong Kong, Hong Kong *These authors contributed equally to this work Objectives: This meta-analysis aimed to demonstrate the impact of preoperative exercise therapy on surgical outcomes in patients with lung cancer and COPD. Pulmonary function and muscle capacity were investigated to explore their potential links with outcome improvements after exercise. Methods: Articles were searched from PubMed, Embase, and the Cochrane Library with criteria of lung cancer patients with or without COPD, undergoing resection, and receiving preoperative exercise training. Key outcomes were analyzed using meta-analysis. Results: Seven studies containing 404 participants were included. Patients receiving preoperative exercise training had a lower incidence of postoperative pulmonary complications (PPCs; OR 0.44, 95% CI 0.27–0.71) and shorter length of hospital stay (standardized mean difference –4.23 days, 95% CI –6.14 to –2.32 days). Exceptionally, pneumonia incidence remained unchanged. Patients with COPD could not obviously benefit from exercise training to reduce PPCs (OR 0.44, 95% CI 0.18–1.08), but still might achieve faster recovery. No significant difference in pulmonary function was observed between the two groups. However, 6MWD and VO2 peak were significantly improved after exercise training. Conclusion: Preoperative exercise training may reduce PPCs for lung cancer patients. However, for patients with COPD undergoing lung cancer resection, the role of exercise is uncertain, due to limited data, which calls for more prospective trials on this topic. Rehabilitation exercise strengthens muscle capacity, but does not improve impaired pulmonary function, which emphasizes the possible mechanism of the protocol design. Keywords: preoperative exercise, lung cancer, COPD, postoperative pulmonary complications, 6MWD, VO2 peak

Yang F, Lei P, Zeng W, Gao J, Wu N. Cancer Manag Res. 2020;12:3131–3144. The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised over the tumor xenograft data presented in the article. The authors responded to our initial queries but were unable to provide satisfactory original data for their study. Given concerns relating to the validity of the study’s findings the Editor advised for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Chao Chen,1 Ning Wu,2 Crystal Watson2 1Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA; 2Value and Access, Biogen, Cambridge, MA, USA Background: Real-world outcomes from staying on an interferon beta (IFNβ) vs switching to another IFNβ could help guide treatment decisions. This study’s objective was to compare outcomes of stable multiple sclerosis (MS) patients on an IFNβ who stayed on therapy vs those who switched to another IFNβ.Methods: MS patients were identified from the Optum Insights Clinformatics Data Mart Multi-Plan who were 18–64 years old and relapse-free (stable) over 1 year while continuously being treated with an IFNβ. Patients were propensity score matched 3:1 using age, gender, initial IFNβ, adherence, and month and year for patients who stayed on the initial IFNβ (No Switch) to patients who switched to another IFNβ (Switch). Patients had to be continuously enrolled for 1 year prior to and 1 year after the index date (date of the first claim of the switched-to IFNβ or the match date when continuing on initial IFNβ treatment). Patients were enrolled with index dates between January 1, 2005 and September 30, 2014. Relapses were recorded during the 1-year follow-up period after index date.Results: After matching, there were 381 patients in the Switch group and 1,143 in the No Switch group. Baseline characteristics were well matched between groups (average age 46 years, 72% female). The percentage of patients experiencing a relapse during the follow-up was significantly higher in the Switch group than in the No Switch group (21% vs 12%, P