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Zhiheng Xiong,1,* Guomin Li,2,* Jiejia Chen,3 Li Peng1 1School of Humanities, Southeast University, Nanjing, People’s Republic of China; 2School of Education Science, Nanjing Normal University of Special Education, Nanjing, People’s Republic of China; 3School of Electronic and Information Engineering, Southwest University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Peng, Email pl_seu@163.comPurpose: Hearing-impaired college students often rely on smartphones for information exchange and social interaction due to their hearing limitations, which may increase their risk of smartphone addiction. This study aims to explore the impact of executive dysfunction on anxiety levels in hearing-impaired college students, investigating smartphone addiction as a mediator and academic procrastination as a moderator.Methods: We conducted a questionnaire survey using the Executive Function Scale, the Anxiety Scale, the Smartphone Addiction Scale, and the Academic Procrastination Scale. The survey included 609 hearing-impaired college students from three universities in Jiangsu, Hunan, and Heilongjiang Provinces, China.Results: After controlling for age, executive dysfunction was found to significantly predict higher anxiety levels in hearing-impaired college students. Additionally, smartphone addiction partially mediated the relationship between executive dysfunction and anxiety. Academic procrastination further moderated the relationship between smartphone addiction and anxiety.Conclusion: This study enhances the understanding of the complex interactions between executive dysfunction, smartphone addiction, and academic procrastination in contributing to anxiety among hearing-impaired college students. The findings offer valuable insights for developing strategies to promote the mental health of this population.Keywords: hearing-impaired, college students, mental health, executive dysfunction

Lingling Shan,1 Yudie Li,1 Yifan Ma,2 Yang Yang,1 Jing Wang,1 Lei Peng,1 Weiwei Wang,1 Fang Zhao,1 Wanrong Li,1 Xiaoyuan Chen3– 6 1Institute of Pharmaceutical Biotechnology, School of Biology and Food Engineering, Suzhou University, Suzhou, People’s Republic of China; 2Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 3Departments of Diagnostic Radiology, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, Singapore; 4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; 5Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; 6Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Singapore, SingaporeCorrespondence: Xiaoyuan Chen; Lingling Shan, Email chen.shawn@nus.edu.sg; ntlinger-300@163.comBackground: While nanoplatform-based cancer theranostics have been researched and investigated for many years, enhancing antitumor efficacy and reducing toxic side effects is still an essential problem.Methods: We exploited nanoparticle coordination between ferric (Fe2+) ions and telomerase-targeting hairpin DNA structures to encapsulate doxorubicin (DOX) and fabricated Fe2+-DNA@DOX nanoparticles (BDDF NPs). This work studied the NIR fluorescence imaging and pharmacokinetic studies targeting the ability and biodistribution of BDDF NPs. In vitro and vivo studies investigated the nano formula’s toxicity, imaging, and synergistic therapeutic effects.Results: The enhanced permeability and retention (EPR) effect and tumor targeting resulted in prolonged blood circulation times and high tumor accumulation. Significantly, BDDF NPs could reduce DOX-mediated cardiac toxicity by improving the antioxidation ability of cardiomyocytes based on the different telomerase activities and iron dependency in normal and tumor cells. The synergistic treatment efficacy is enhanced through Fe2+-mediated ferroptosis and the β-catenin/p53 pathway and improved the tumor inhibition rate.Conclusion: Harpin DNA-based nanoplatforms demonstrated prolonged blood circulation, tumor drug accumulation via telomerase-targeting, and synergistic therapy to improve antitumor drug efficacy. Our work sheds new light on nanomaterials for future synergistic chemotherapy. Keywords: DNA nanomaterials, targeting, imaging, synergistic therapy

Liqun Peng,1,2 Shaohua Xu,3 Jian-Liang Xu4 1Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, People’s Republic of China; 3Department of Clinical Laboratory, Center for Gene Diagnosis & Program of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 4Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Jian-Liang Xu, Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, People’s Republic of China, Tel +86-13580575810, Fax +8620-85253178, Email xujl6@mail.sysu.edu.cn Shaohua Xu, Department of Clinical Laboratory, Center for Gene Diagnosis & Program of Clinical Laboratory, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, People’s Republic of China, Email xshct4975@163.comIntroduction: Immunogenic cell death (ICD) can enhance the potency of immunotherapy in cancer treatment. Nevertheless, it is ambiguous how ICD-related genes (ICDRGs) contribute to hepatocellular carcinoma (HCC).Methods: Single-cell RNA sequencing (scRNA-seq) data were used to distinguish malignant cells from normal cells in the HCC tumor microenvironment(TME). Bulk RNA sequencing data was employed to acquire the landscape of the 33 ICDRGs. Unsupervised clustering identified two ICD molecular subtypes. The cellular infiltration characteristics and biological behavior in different subtypes were analyzed by ssGSEA. Subsequently, differentially expressed genes (DEGs) between the two subtypes were determined, based on which patients were classified into three gene clusters. Then, the prognostic model was constructed by Lasso-Cox analysis. Finally, we investigated the expression of risk genes in cancer cell line encyclopedia (CCLE) and validated the function of NKX3-2 in vitro experiments.Results: ICD scores and ICDRGs expression in malignant cells were significantly lower than in normal cells by scRNA-seq analysis. ICD-high subtype was characterized by ICD-related gene overexpression and high levels of immune infiltration abundance and immune checkpoints; Three DEGs-related gene clusters were likewise strongly linked to stromal and immunological activation. In the ICD-related prognostic model consisting of NKX3-2, CHODL, MMP1, NR0B1, and CTSV, the low-risk group patients had a better endpoint and displayed increased susceptibility to immunotherapy and chemotherapeutic drugs like 5-Fluorouracil, afatinib, bortezomib, cediratinib, lapatinib, dasatinib, gefitinib and crizotinib. Moreover, NKX3-2 amplification in HCC samples has been verified by experiments, and its disruption suppressed the proliferation and invasion of tumor cells.Conclusion: Our study highlighted the potential of the ICDRGs risk score as a prognostic indicator to aid in the accurate diagnosis and immunotherapy sensitivity of HCC.Keywords: Hepatocellular carcinoma, prognostic model, immunotherapy, immunogenic cell death

Xiaoyu Zhou,1– 3 Fei Du,1– 3 Wei Peng,4 Li Bai,5 Leyi Peng,1– 3 Xiaorong Hou1– 3 1College of Medical Informatics, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Medical Data Science Academy, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Chongqing Engineering Research Center for Clinical Big Data and Drug Evaluation, Chongqing, 400016, People’s Republic of China; 4The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400042, People’s Republic of China; 5Hospital of Zigong Mental Health Central, Sichuan, 643021, People’s Republic of ChinaCorrespondence: Xiaorong Hou, Chongqing Medical University, No. 1, Medical College Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Email xiaoronghou@cqmu.edu.cnPurpose: Long-term care facilities are increasingly challenged with meeting the diverse healthcare needs of the elderly population, particularly concerning medication management. Understanding medication information literacy and behavior among this demographic is imperative. Therefore, this qualitative study aims to explore medication information literacy and develop distinct medication profiles among elderly long-term care residents.Material and Methods: In this study, we conducted in-depth semi-structured interviews with 32 participants aged 65 or older residing in a long-term care facility. The interviews were designed to explore participants’ understanding of medication information, medication management practices, and experiences with healthcare providers. Thematic analysis was employed to analyze the interview data, allowing for the identification of common patterns and themes related to medication-taking behavior among the elderly residents.Results: The thematic analysis revealed four distinct medication behavior profiles among the elderly long-term care residents: (1) Proactive Health Self-Managers, (2) Medication Information Adherents, (3) Experience-Based Medication Users, and (4) Nonadherent Medication Users. These findings provide valuable insights into the diverse approaches to medication management within long-term care facilities and underscore the importance of tailored interventions to support the specific needs of each profile.Conclusion: This study highlights the necessity for tailored medication education and support to optimize medication management for the elderly. With the aging population expansion, addressing the unique medication challenges within long-term care facilities becomes increasingly critical. This research contributes to ongoing endeavors to enhance healthcare services for the elderly, striving for safer and more effective medication-taking behavior.Keywords: medication information literacy, medication profile, long-term care facility, qualitative study, elderly

Qiong Wu,1,* Shiying An,1,* RueyJyh Lee,1 Dongwen Gao,2 Yinyifan Zhou,1 Longping Peng,1 Chunrui Hu,1 Lei Yao,3 Chang Zhou,4 Li Zhou,5 Junjie Gao,6 Min Cao,1 Meijiao Mao,1 Guanghao Li,1 Bing Deng,1 Yingjia Xu,4 Youhua Wang1 1Department of Cardiology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Ultrasound, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Cardiology, Shanghai Fifth People’s Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 5Department of Cardiology, Shanghai Jiading Nanxiang Hospital, Shanghai, People’s Republic of China; 6Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingjia Xu, Shanghai Fifth People’s Hospital, Fudan University, Minhang District, 128 Ruili Road, Shanghai, 200240, People’s Republic of China, Tel +862164308151, Email xuyingjia@5thhospital.com Youhua Wang, Department of cardiology, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Xunhui, 725 South Wan-Ping Road, Shanghai, 200032, People’s Republic of China, Tel +862164385700, Email doctorwyh@163.comBackground: Dilated cardiomyopathy (DCM) is a severe heterogeneous cardiomyopathy characterized by cardiac enlargement and declining heart function, often leading to refractory heart failure and life-threatening outcomes, particularly prevalent in China. The challenge lies in the scarcity of targeted therapies with substantial efficacy for DCM. Additionally, traditional anti-heart failure drugs are constrained due to hypotension propensity or limited symptom improvement. Kuoxin Formula (KXF), internally endorsed at Longhua Hospital, demonstrates clear biological evidence for enhancing cardiac function and myocardial remodeling. Previous clinical studies suggest its potential to enhance patients’ quality of life. This trial aims to further evaluate KXF’s safety and efficacy in managing DCM-related heart failure.Methods: This prospective, randomized, double-blind, placebo-controlled, multicenter trial aims to recruit 230 DCM patients from five centers. Participants will be randomly assigned to either KXF or placebo for 12 weeks, with careful monitoring of key indicators and adverse events. The primary outcome measures the proportion of patients with NT-proBNP reduction exceeding 30%. Secondary outcomes include New York Heart Association functional classification, Traditional Chinese Medicine syndrome scores, 6-minute walk test, Lee’s heart failure score, and Minnesota Heart Failure Quality of Life Scale score. Ventricular remodeling will be assessed using cardiac ultrasound and ELISA. Safety metrics and adverse events will be meticulously recorded.Discussion: This study will be the first multicentered research conducted in China that utilizes a randomized, double-blind, placebo-controlled design to investigate the use of TCM in the treatment of DCM. It seeks to develop new theoretical frameworks and provide solid clinical data to support the integration of TCM and modern medicine in treating heart failure in DCM patients.Trial Registration: China Clinical Trial Registry, ChiCTR2300068937. Registered on March 1, 2023. https://www.chictr.org.cn/bin/project/edit?pid=190926.Keywords: dilated cardiomyopathy, heart failure, Kuoxin Formula, traditional Chinese medicine, clinical trials

Dingbin Yang,1,2 Yu Mao,3 Lu Peng,2 Shuqiong Huang,2 Lijun Zhou,2 Changqiang Li1 1Department of Dermatology, the Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Dermatology, People’s Hospital of Leshan, Leshan, 614000, People’s Republic of China; 3Department of Pathology, People’s Hospital of Leshan, Leshan, 614000, People’s Republic of ChinaCorrespondence: Changqiang Li, Department of Dermatology, the Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Email lcq-1973@163.comAbstract: Keratoacanthoma (KA) is a papule, plaque, or nodule in an exposed area, with a crater-like horn plug in the center. Multiple KAs are rare disorders, especially when the lesions are agglomerated together. Herein, we report a case of 65-year-old man who presented with four red nodules of different sizes on the right side of the chest. The lesions were clustered, with central keratotic cores, similar in appearance to a four-leaf clover. The nodules were completely removed by excisional surgery and the diagnosis of Agglomerate KAs was made based on clinical and pathological results. A 6-year follow-up found no recurrence.Keywords: agglomerate keratoacanthomas, four-leaf clover

Jiaqing Zhou,1 Huan Xu,2 Wen Du,1 Lijun Peng1 1Department of Respiratory Medicine, West China Fourth Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Scientific Affairs, Vision Medicals for Infectious Diseases, Guangzhou, People’s Republic of ChinaCorrespondence: Lijun Peng, Department of Respiratory Medicine, West China Fourth Hospital, Sichuan University, No. 17, Section 3, Renmin South Road, Wuhou District, Chengdu, 610041, People’s Republic of China, Tel +86 13208119408, Email penglijun711@163.comAbstract: We reported a 51-year-old male electric welder with stage I pneumoconiosis, who had no significant cough, sputum, fever, chest pain, or other discomfort. However, regular physical examination at our hospital revealed bilateral pulmonary nodules with cavity formation. Blood routine, liver or kidney function, and infection-related biomarkers, including interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and procalcitonin (PCT), were normal. Sputum and alveolar lavage fluid (BALF) acid-fast bacilli (AFB) smears, BALF Mycobacterium tuberculosis (TB) PCR, and T-SPOT.TB were negative. The nucleic acid sequence of Mycobacterium europaeum was detected by BALF metagenomic next-generation sequencing (mNGS), which was confirmed by the subsequent positive culture for NTM. Considering stable conditions, no significant discomfort, and no significant changes in the lung lesion, the patient was diagnosed with inactive nontuberculous mycobacterial pulmonary disease (NTM-PD).Keywords: pneumoconiosis, nontuberculous mycobacterial pulmonary disease, NTM-PD, Mycobacterium europaeum, metagenomic next-generation sequencing, mNGS

Hongwei Shen,1,* Qiaomin Zhang,1,* Liang Peng,2 Wen Ma,1 Jingdong Guo2 1Clinical Laboratory, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, People’s Republic of China; 2Department of Burns and Plastic Surgery, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingdong Guo; Hongwei Shen, Email guojingdong1996@163.com; hongweishen@smu.edu.cnAim: Mycobacterium abscessus is ubiquitous in the environment and seldom causes infections in immunocompetent individuals. However, skin and soft tissue infections caused by M. abscessus have been reported in recent years. Additionally, the cutaneous infections or outbreaks post cosmetic surgery caused by M. abscessus have been increasing due to the popularity of plastic surgery. The main modes of transmission are through contaminated saline, disinfectants, or surgery equipment, as well as close contact between patients. This article describes three patients who were admitted to our hospital between November 2019 and October 2020. They presented with long-term non-healing wounds caused by M. abscessus infection after undergoing plastic surgery. Symptoms presented by the three patients included swelling, ulceration, secretion, and pain. After identification of M. abscessus with Ziehl-Neelsen staining and MALDI-TOF MS system, the patients were treated with surgical debridement and clarithromycin.Conclusion: It is important to note that a long-term wound that does not heal, especially after plastic surgery, should raise suspicion for M. abscessus infection. The infection mechanism in these three patients may have been due to exposure to surgical equipment that was not properly sterilized or due to poor sterile technique by the plastic surgeon. To prevent such infections, it is important to ensure proper sterilization of surgical equipment and saline.Keywords: Mycobacterium abscessus, cutaneous infection, plastic surgery, treatment, antibiotic resistance

Xin Liu,1– 3,&ast; Zhen Wang,1,&ast; Chaoran Zhang,1 Jingwen Xu,4 Ziheng Shen,4 Lixin Peng,1 Yanyan Mi,2,3 Haibo Xu1– 3 1School of Management, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 2Center for Mental Health Education and Research, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 3Research Center for Psychological Crisis Prevention and Intervention of College Students in Jiangsu Province, Xuzhou medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 4The Second Clinical Medical School, Xuzhou medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haibo Xu; Yanyan Mi, Email xhb@xzhmu.edu.cn; miyanyan@126.comPurpose: Current interpersonal sensitivity among college students is easily linked to mood disorders such as anxiety, depression and other mood disorders. This study aims to examine the mediating role of psychological capital and its dimensions in the relationship between interpersonal sensitivity and depressive symptoms among undergraduates.Methods: The cross-sectional survey was conducted by using cluster stratified random sampling method across six Chinese universities between November and December 2022. The questionnaire consists of the Interpersonal Sensitivity sub-scale, the Patient Health Questionnaire, the Psychological Capital Questionnaire and the Socio-Demographic Feature Questionnaire.Results: A total of 2580 respondents participated in the survey, with the majority being females (69.73%) and an average age of 19.22± 1.28 years. Descriptive and correlation analyses were performed using SPSS v24.0, while direct and indirect effects were analyzed using PROCESS v3.4 macro. The findings revealed that interpersonal sensitivity had a significant direct effect on depression symptoms among undergraduates (β =0.416, 95% Boot CI [0.380, 0.453], p < 0.001) Additionally, psychological capital and its components were found to be negatively correlated with depression (p < 0.001). Further analysis demonstrated that hope, optimism, and resilience significantly mediated the association between interpersonal sensitivity and depressive symptoms (indirect effect: hope = 0.056, optimism = 0.074, resilience = 0.099; p < 0.001 for all).Conclusion: These results suggest that psychological capital, including its dimensions of hope, optimism, and resilience plays a crucial role in mitigating the negative effects of interpersonal sensitivity on depressive symptoms among undergraduates.Keywords: depressive symptoms, interpersonal sensitivity, psychological capital, Chinese undergraduates, multiple mediation

Jiaxin Zeng,1,&ast; Chen Zhou,2,&ast; Qun Yi,1,3 Yuanming Luo,4 Hailong Wei,5 Huiqing Ge,6 Huiguo Liu,7 Jianchu Zhang,8 Xianhua Li,9 Pinhua Pan,10 Mengqiu Yi,11 Lina Cheng,11 Liang Liu,12 Jiarui Zhang,1 Lige Peng,1 Jiaqi Pu,1 Haixia Zhou1 On behalf of the MAGNET AECOPD Registry Investigators1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Center of Infectious Diseases, Division of Infectious Diseases in State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3Sichuan Cancer Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, Sichuan Province, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Neijiang City, Neijiang, Sichuan Province, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 11Department of Emergency, First People’s Hospital of Jiujiang, Jiu jiang, Jiangxi Province, People’s Republic of China; 12Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Chengdu University, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86-28-85422571, Email zhouhaixia@wchscu.cnBackground: The Rome severity classification is an objective assessment tool for the severity of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) based on readily measurable variables but has not been widely validated. The aim of this study is to evaluate the validity of the Rome classification in distinguishing the severity of AECOPD based on short-term mortality and other adverse outcomes.Methods: The Rome severity classification was applied to a large multicenter cohort of inpatients with AECOPD. Differences in clinical features, in-hospital and 60-day mortality, intensive care unit (ICU) admission, mechanical ventilation (MV) and invasive mechanical ventilation (IMV) usage were compared among the mild, moderate and severe AECOPD according to the Rome proposal. Moreover, univariate logistic analysis and Kaplan Meier survival analysis were also performed to find the association between the Rome severity classification and those adverse outcomes.Results: A total of 7712 patients hospitalized for AECOPD were included and classified into mild (41.88%), moderate (40.33%), or severe (17.79%) group according to the Rome proposal. The rate of ICU admission (6.4% vs 12.0% vs 14.9%, P < 0.001), MV (11.7% vs 33.7% vs 45.3%, P < 0.001) and IMV (1.4% vs 6.8% vs 8.9%, P < 0.001) increased significantly with the increase of severity classification from mild to moderate to severe AECOPD. The 60-day mortality was higher in the moderate or severe group than in the mild group (3.5% vs 1.9%, 4.3% vs 1.9%, respectively, P < 0.05) but showed no difference between the moderate and severe groups (2.6% vs 2.5%, P > 0.05), results for in-hospital mortality showed the same trends. Similar findings were observed by univariate logistic analysis and survival analysis.Conclusion: Rome severity classification demonstrated excellent performance in predicting ICU admission and the need for MV or IMV, but how it performs in differentiating short-term mortality still needs to be confirmed.Keywords: AECOPD, the Rome severity classification, short-term mortality, intensive care unit admission, mechanical ventilation, multicenter cohort

Xuan Yi,1 Xinxing Wan,1 Md Asaduzzaman Khan,2,3 Xiaoying Sun,1 Zhouqi Wang,1 Ke Chen,1 Lin Peng4 1Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Research Division, Nature Study Society of Bangladesh, Dhaka, 1000, Bangladesh; 3Pulmonary Department, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, 02118, USA; 4Department of Nephrology, The First Hospital of Changsha, Changsha, People’s Republic of ChinaCorrespondence: Lin Peng, Department of Nephrology, The First Hospital of Changsha, Changsha, People’s Republic of China, Tel +86-731-8466-7510, Email plin1018@163.com Ke Chen, Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86-731-8861-8239, Email chenke520@yeah.netPurpose: Adipogenesis is one of the major pathways for generating obesity or overweight that can cause a range of metabolic disorders. Circular RNAs (circRNAs), a specific type of RNAs, have a significant influence on metabolic disorders. This study aims to find differentially expressed circRNAs (DECs) during human subcutaneous adipose tissue (SATs) adipogenesis.Patients and Methods: The human adipose tissue-derived stromal cells (hADSCs) were isolated from human SATs (n = 3), and then induced into adipocytes. Total RNAs were extracted from hADSCs and adipocytes, and he DECs were detected using circRNA microarray. The GO and KEGG pathways of DECs were analyzed by bioinformatic methods, and partial DECs were further validated by quantitative polymerase chain reaction (qPCR).Results: Our study detected a total of 1987 DECs, among which, 1134 were found upregulated and 853 were downregulated. GO analysis showed that the upregulated DECs have catalytic activity in intracellular organelle and cytoplasms, whereas downregulated DECs are enriched in organelle lumen, and are involved in positive regulation of developmental process. In addition, pathway results demonstrated that upregulated DECs are involved in platinum drug resistance and cellular senescence, and downregulated DECs are enriched in proteoglycans in cancer and focal adhesion pathway. Two circRNAs, namely has_circ_0001600 and has_circ_0001947 were validated to be significantly upregulated in adipocytes compared to hADSCs.Conclusion: Our study explored DECs between hADSCs derived from SATs and adipocytes, and report that two circRNAs named has_circ_0001600 and has_circ_0001947 might be important factors involved in human adipogenesis, however, the molecular mechanism should be further explored.Keywords: circRNA microarray, subcutaneous adipose tissue, human adipose tissue-derived stromal cells, adipogenesis, SAT

A new solid-state inorganic compound, indium dilead pentachloride, InPb2Cl5, was synthesized by melting InCl and PbCl2 in a vacuum-sealed quartz ampoule. The ampoule was heated to 793 K and then slowly cooled to room temperature to induce crystallization of InPb2Cl5. InPb2Cl5 crystallizes in the monoclinic crystal system adopting a space group of type P21/c, which is isostructural with other metal halides such as RbPb2Cl5, KPb2Cl5 and TlPb2Cl5. The bulk InPb2Cl5 exhibits a metallic black/grey colour, allowing it to be separated from white/yellow PbCl2 crystals. Due to the incongruent nature of the compound, the pure bulk InPb2Cl5 was not obtained. The black/grey InPb2Cl5 crystals were characterized by powder and single-crystal X-ray diffraction. InPbCl3 was also explored, however the growth was unsuccessful.

Yuan Wang,1– 3 Chengfeng Ma,1,2 Zhanbing Ma,1,2 Mengyi Yang,1,2 Jing Pu,1,2 Xiuhui Ma,1,2 Xi Wu,1,2 Liang Peng,1,2 Zhenghao Huo,1,2,&ast; Jie Dang1,2,&ast; 1School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Key Laboratory of Fertility Preservation and Maintenance of the Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 3Department of Dermatology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Dang; Zhenghao Huo, Department of Medical Genetics and Cell Biology, School of Basic Medicine, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750001, People’s Republic of China, Tel/Fax +86-951-6980049, Email djjune1978@163.comPurpose: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause systemic damage to multiple organs. This study aims to analyze the value and function of IFI44 in the diagnosis and pathology of SLE by bioinformatics and immune infiltration analysis.Patients and Methods: GSE49454 and GSE65391 of SLE were obtained from the GEO dataset, and R software was employed to identify DEGs and investigate their functions. The PPI network was utilized to identify hub genes associated with SLE. CIBERSORT was used to assess differences in immune cell infiltration in SLE patients and controls. ROC curve analysis was performed to evaluate the diagnostic value of IFI44 in SLE. The expression of IFI44 in PBMCs was detected by RT-qPCR, and the correlation between IFI44 expression and SLE-related clinical indicators was analyzed.Results: A total of 65 DEGs were identified from the GSE49454 and GSE65391 databases. Through PPI analysis, IFI44 and RSAD2 were identified as significantly aberrantly expressed in SLE patients. SLE patients and controls showed a significant difference in the proportion of immune cell infiltration. IFI44 expression was positively correlated with activated DCs, monocytes, PCs, neutrophils, and activated memory CD4+T cells, while negatively correlated with M0 and CD8+T cells. The expression of IFI44 was significantly higher in SLE patients (P< 0.01), especially in male patients (P=0.0376). ROC curve analysis demonstrated that IFI44 had a high diagnostic value for SLE. Correlation analysis indicated that IFI44 expression was correlated with levels of RBC, HGB, HCT, IgA, ESR, UPRO, C3, C4, and ENA in SLE patients.Conclusion: IFI44 may play a role in the pathogenesis of SLE by influencing the immune microenvironment of SLE patients, and thus has the potential to serve as a diagnostic marker and therapeutic target for SLE.Keywords: systemic lupus erythematosus, IFI44, bioinformatics, immune cell infiltration, sexual dimorphism

Jiarui Zhang,1,&ast; Yichun Qin,2,&ast; Chen Zhou,3 Yuanming Luo,4 Hailong Wei,5 Huiqing Ge,6 Hui-Guo Liu,7 Jianchu Zhang,8 Xianhua Li,9 Pinhua Pan,10 Mengqiu Yi,11 Lina Cheng,11 Liang Liu,12 Adila Aili,1 Lige Peng,1 Yu Liu,1 Jiaqi Pu,1 Qun Yi,1,13,&ast; Haixia Zhou1,&ast; 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, Sichuan Province, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Neijiang City, Neijiang, Sichuan Province, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 11Department of Emergency, First People’s Hospital of Jiujiang, Jiujiang, Jiangxi Province, People’s Republic of China; 12Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Chengdu University, Chengdu, Sichuan Province, People’s Republic of China; 13Sichuan Cancer Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou; Qun Yi, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86-28-85422571, Email zhouhaixia@wchscu.cn; yiqun925@126.comBackground: High blood urea nitrogen (BUN) is observed in a subset of patients with acute exacerbation of COPD (AECOPD) and may be linked to clinical outcome, but findings from previous studies have been inconsistent.Methods: We performed a retrospective analysis of patients prospectively enrolled in the MAGNET AECOPD Registry study (ChiCTR2100044625). Receiver operating characteristic (ROC) was used to determine the level of BUN that discriminated survivors and non-survivors. Univariate and multivariate Cox proportional hazards regression analyses were performed to assess the impact of BUN on adverse outcomes.Results: Overall, 13,431 consecutive inpatients with AECOPD were included in this study, of whom 173 died, with the mortality of 1.29%. The non-survivors had higher levels of BUN compared with the survivors [9.5 (6.8– 15.3) vs 5.6 (4.3– 7.5) mmol/L, P < 0.001]. ROC curve analysis showed that the optimal cutoff of BUN level was 7.30 mmol/L for in-hospital mortality (AUC: 0.782; 95% CI: 0.748– 0.816; P < 0.001). After multivariate analysis, BUN level ≥ 7.3 mmol/L was an independent risk factor for in-hospital mortality (HR = 2.099; 95% CI: 1.378– 3.197, P = 0.001), also for invasive mechanical ventilation (HR = 1.540; 95% CI: 1.199– 1.977, P = 0.001) and intensive care unit admission (HR = 1.344; 95% CI: 1.117– 1.617, P = 0.002). Other independent prognostic factors for in-hospital mortality including age, renal dysfunction, heart failure, diastolic blood pressure, pulse rate, PaCO2 and D-dimer.Conclusion: BUN is an independent risk factor for in-hospital mortality in inpatients with AECOPD and may be used to identify serious (or severe) patients and guide the management of AECOPD.Clinical Trial Registration: MAGNET AECOPD; Chinese Clinical Trail Registry NO.: ChiCTR2100044625; Registered March 2021, URL: http://www.chictr.org.cn/showproj.aspx?proj=121626.Keywords: AECOPD, inpatients, blood urea nitrogen, mortality, adverse outcomes

Tingting Li,1,2 Wenjing Han,1,2 Xinlu Yang,1 Yu Wang,1 Li Peng,1 Lingwei He,1 Lianjia Hu,1 Jiayuan Liu,1 Min Xia,1 Sheng Wang1,2 1Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 2Department of Anesthesiology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Sheng Wang, Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 17 Lujiang Road, Luyang District, Hefei, Anhui Province, People’s Republic of China, Tel +86 191 5600 7726, Email iamsheng2020@ustc.edu.cnPurpose: This study aimed to explore the effects of different injection rates of propofol on postoperative cognition in elderly patients undergoing laparoscopic inguinal hernia repair.Methods: A total of 180 elderly patients who planned to undergo laparoscopic inguinal hernia repair were randomly divided into three groups: slow injection of propofol (VS-Group, 30 mg kg− 1 h− 1); medium injection of propofol (VM-Group, 100 mg kg− 1 h− 1) or fast injection of propofol (VF-Group, 300 mg kg− 1 h− 1). Propofol was induced by microinfusion pump, and the depth of anesthesia was monitored by bispectral index (BIS). Propofol and remifentanil were continuously infused during anesthesia maintenance and adjusted according to BIS. The primary outcome was the use of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) to measure the incidence of postoperative cognitive decline (POCD) in elderly patients on the first and seventh postoperative day. Secondary outcomes included induced dose of propofol, incidence of burst suppression and maximum electroencephalographic (EEG) effect of propofol (BIS-min) during induction.Results: The incidence of POCD on the first and seventh day postoperatively was similar among the three groups (P > 0.05). However, with the increase of propofol injection rate, induced dose of propofol, incidence of burst suppression and BIS-min during induction, the number of patients requiring vasoactive agents were significantly increased (P < 0.001). Multivariate regression analysis showed that the brief duration of burst suppression during induction did not affect the occurrence of POCD, while age and duration of hospitalization were risk factors for POCD.Conclusion: For elderly patients undergoing laparoscopic inguinal hernia repair, lowering the injection rate of propofol (such as 30 mg kg− 1 h− 1) cannot decrease the incidence of early POCD, but reduces induction dose of propofol and use of vasoactive drugs, making the patient’s hemodynamics more stable.Keywords: propofol, injection rate, bispectral index, burst suppression, elderly, postoperative cognitive decline

Libin Liu,1,2,&ast; Guihua Wu,1,2 Jing Wang,1,2 Lijun Peng,1,2 Xiaoqun Xu,1,2 Long Cai1,2,&ast; 1Centre of Laboratory Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Long Cai, Centre of Laboratory Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, No. 208 East Huancheng Road, Hangzhou, 310003, People’s Republic of China, Email cailong317@hotmail.comPurpose: Exploring whether smoking is an influencing factor for the inconsistency between QuantiFERONTB Gold assay (QFT-GIT) and tuberculosis etiology.Patients and Methods: The clinical data of patients who were confirmed positive for Mycobacterium tuberculosis (MTB) after undergoing QFT-GIT testing from September 2017 to August 2021 were retrospectively analyzed. Chi-square and rank-sum tests were used to compare the differences in characteristics between smokers and non-smokers. Logistic regression was used to adjust for confounding factors affecting smoking. Propensity score matching (PSM) was used to verify the above conclusions again.Results: Positive results of tuberculosis etiology were adopted as the standard, the incidence of inconsistent results between QFT-GIT and tuberculosis etiology was 8.90% (108/1213), of which the false negative rate was 6.27% (76/1213) and the indeterminate rate was 2.64% (32/1213). In the overall population, the smokers had a lower level of basal IFN-γ (Z=− 2.079, P=0.038). Among 382 elderly (≥ 65 years old) patients, the smokers had lower levels of antigen-stimulated IFN-γ (Z=− 2.838, P=0.005). After performing BOX-COX transformation on all non-normally distributed data, logistic stepwise regression was used to adjust confounding factors. The results showed that smoking was an influencing factor for the inconsistency between QFT-GIT and tuberculosis etiology results (OR=1.69, P=0.020). Using PSM for 1:2 matching, the results showed that smoking was still an independent risk factor for the inconsistent results of QFT-GIT and tuberculosis etiology (OR= 1.95, P=0.019). Age-stratified analysis showed that smoking was an independent risk factor in discordance between QFT-GIT and tuberculosis etiology in patients aged ≥ 65 years (OR=2.40, P=0.005), but not in patients aged < 65 years (P > 0.05).Conclusion: Smoking can reduce the body’s IFN-γ release ability, and smoking (especially the elderly) is an influencing factor for the inconsistency between QFT-GIT and tuberculosis etiological results.Keywords: tuberculosis etiology, PSM, inconsistency, influencing factors

Xiangdong Wang,1,&ast; Dongpo Zhu,2,&ast; Leilei Peng,1 Yan Gao,3 Xiaodong Li4 1Department of Blood Purification, Baoding People’s Hospital, Baoding, 071030, People’s Republic of China; 2Department of Internal Medicine, Baoding People’s Hospital, Baoding, 071030, People’s Republic of China; 3Department of Nephrology, Affiliated Hospital of Hebei University, Baoding, 071030, People’s Republic of China; 4Department of Nephrology, Baoding No. 1 Central Hospital of Hebei Medical University, Baoding, 071000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodong Li, Department of Nephrology, Baoding No. 1 Central Hospital of Hebei Medical University, Baoding, Hebei, 071000, People’s Republic of China, Email lxd_765@sina.comObjective: One of the earliest echocardiographic features of the left ventricle explored extensively was left ventricular hypertrophy (LVH). Numerous studies have identified a few risk factors for LVH, however, there are few for people with diabetic kidney disease (DKD). Therefore, we evaluated the risk factors in DKD patients with LVH by analyzing laboratory data and clinical traits.Methods: In total, 500 DKD patients in the Baoding area from February 2016 and June 2020 were admitted and classified as an experimental group (240 cases, LVH group) and a control group (260 cases, non-LVH group). The clinical parameters and laboratory tests of the participants were collected and analyzed retrospectively.Results: Compared with the control group, low-density lipoprotein (LDL), body mass index (BMI), intact parathyroid hormone (iPTH), systolic blood pressure, and 24-hour urine protein were higher in the experimental group (all P< 0.01). Multivariable logistic regression analysis results confirmed that high BMI (OR=1.332, 95% CI 1.016– 1.537, P=0.006), LDL (OR=1.279, 95% CI 1.008– 1.369, P=0.014) and 24-hour urine proteins (OR=1.446, 95% CI 1.104– 1.643, P=0.016) were statistically significant. The ROC analysis illustrated that the optimum cutoff value of BMI, LDL, and 24-hour urine proteins for diagnosis of LVH in patients with DKD was 27.36 kg/m2, 4.18 mmol/L, and 1.42 g respectively.Conclusion: The increase in BMI, LDL, and 24-hour urine proteins quantification are independent risk factors for LVH in patients with DKD.Keywords: diabetic kidney disease, chronic kidney disease, risk factors, left ventricular hypertrophy

Ling Peng,1,2,&ast; Hong You,2,&ast; Mei-yu Xu,2 Zhou-yu Dong,2 Min Liu,2 Wen-jing Jin,2 Chao Zhou2 1Department of Critical Care Medicine, Qiannan Buyi and Miao Autonomous Prefecture People’s Hospital, Guizhou, People’s Republic of China; 2Department of Respiratory Medicine, Guangming Traditional Chinese Medicine Hospital of Pudong New Area, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Zhou, Department of Respiratory Medicine, Guangming Traditional Chinese Medicine Hospital of Pudong New Area, No. 43 DongMen Street. Pudong new District, Shanghai, 201399, People’s Republic of China, Tel +86-21-68019069, Email zhou2000sh@163.comBackground: Chronic obstructive pulmonary disease (COPD) has higher mortality when developing to acute exacerbation (AECOPD); hence, the early intervention of COPD is critical for preventing AECOPD. Exploring the serum metabolites associated with acute exacerbation in patients with COPD will contribute to the early intervention of COPD.Methods: In the study, a non-targeted metabolomics strategy combined with multivariate statistical methods was performed to explore the metabolic profiling of COPD developing acute exacerbation, to screen the potential metabolites associated with AECOPD and to analyze the potential value of these metabolites in predicting the development of COPD.Results: Serum lysine, glutamine, 3-hydroxybutyrate, pyruvate and glutamate levels were significantly higher, while 1-methylhistidine, isoleucine, choline, valine, alanine, histidine and leucine levels were significantly lower in AECOPD patients, compared with stable COPD patients after normalization based on the healthy controls. Moreover, eight metabolic pathways were significantly altered (P< 0.05) in the serum of AECOPD patients compared with the stable COPD population, including purine metabolism, glutamine and glutamate metabolism, arginine biosynthesis, butyrate metabolism, ketone body synthesis and degradation, and linoleic acid metabolism. In addition, the correlation analysis between metabolites and AECOPD patients demonstrated that an M-score based on a weighted sum of concentrations of four metabolites including pyruvate, isoleucine, 1-methylhistidine and glutamine were significantly associated with the acute exacerbation of pulmonary ventilation function in COPD patients.Conclusion: Altogether, the metabolite score based on a weighted sum of concentrations of four serum metabolites was associated with an increased risk of COPD developing acute exacerbation, which will provide a new insight for the understanding of COPD development.Keywords: COPD, AECOPD, acute exacerbation, metabolomics, metabolites

Jiaqi Pu,1,&ast; Qun Yi,1,2,&ast; Yuanming Luo,3 Hailong Wei,4 Huiqing Ge,5 Huiguo Liu,6 Xianhua Li,7 Jianchu Zhang,8 Pinhua Pan,9 Hui Zhou,10 Chen Zhou,11 Mengqiu Yi,12 Lina Cheng,12 Liang Liu,10 Jiarui Zhang,1 Lige Peng,1 Adila Aili,1 Yu Liu,1 Haixia Zhou1 On behalf of the MAGNET AECOPD Registry Investigators1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, Cancer Hospital Affiliate to School of Medicine, UESTC, Chengdu, People’s Republic of China; 3State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, the First People’s Hospital of Neijiang City, Neijiang, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Chengdu University, Chengdu, People’s Republic of China; 11West China School of Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 12Department of Emergency, First People’s Hospital of Jiujiang, Jiu Jiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86-28-85422571, Email zhouhaixia@wchscu.cnPurpose: The prognostic value of blood eosinophils in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains controversial. This study aimed to evaluate whether blood eosinophils could predict in-hospital mortality and other adverse outcomes in inpatients with AECOPD.Methods: The patients hospitalized for AECOPD were prospectively enrolled from ten medical centers in China. Peripheral blood eosinophils were detected on admission, and the patients were divided into eosinophilic and non-eosinophilic groups with 2% as the cutoff value. The primary outcome was all-cause in-hospital mortality.Results: A total of 12,831 AECOPD inpatients were included. The non-eosinophilic group was associated with higher in-hospital mortality than the eosinophilic group in the overall cohort (1.8% vs 0.7%, P < 0.001), the subgroup with pneumonia (2.3% vs 0.9%, P = 0.016) or with respiratory failure (2.2% vs 1.1%, P = 0.009), but not in the subgroup with ICU admission (8.4% vs 4.5%, P = 0.080). The lack of association still remained even after adjusting for confounding factors in subgroup with ICU admission. Being consistent across the overall cohort and all subgroups, non-eosinophilic AECOPD was also related to greater rates of invasive mechanical ventilation (4.3% vs 1.3%, P < 0.001), ICU admission (8.9% vs 4.2%, P < 0.001), and, unexpectedly, systemic corticosteroid usage (45.3% vs 31.7%, P < 0.001). Non-eosinophilic AECOPD was associated with longer hospital stay in the overall cohort and subgroup with respiratory failure (both P < 0.001) but not in those with pneumonia (P = 0.341) or ICU admission (P = 0.934).Conclusion: Peripheral blood eosinophils on admission may be used as an effective biomarker to predict in-hospital mortality in most AECOPD inpatients, but not in patients admitted into ICU. Eosinophil-guided corticosteroid therapy should be further studied to better guide the administration of corticosteroids in clinical practice.Keywords: acute exacerbation of chronic obstructive pulmonary disease, peripheral blood eosinophils, inpatients, in-hospital mortality, clinical outcomes

Lu Wang,1 Jingwei Liu,2 Liping Peng1 1Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Department of Pediatric Intensive Care Unit, The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Liping Peng, Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China, Email penglp@jlu.edu.cnPurpose: To summarize the clinical characteristics of progressive pneumonia caused by Chlamydia psittaci (C. psittaci) and to explore the effect of high-dose tigecycline on severe C psittaci.Patients and Methods: We retrospectively analyzed the clinical characteristics, treatment, and outcomes of three progressive pneumonia patients caused by C. psittaci in our hospital in the past three years.Results: All three patients showed high fever and progressive dyspnea, and all of them were finally diagnosed by bronchoalveolar lavage fluid (BALF) of metagenomic next-generation sequencing (mNGS). Case 1 rapidly developed into multilobar infiltration after raising a parrot with a normal appearance one week before. Respiratory failure occurred despite the use of moxifloxacin, requiring non-invasive ventilator-assisted ventilation. Case 2 developed discomfort one day after sightseeing in the forest park. Moxifloxacin was ineffective for her and she quickly developed respiratory failure, requiring invasive ventilator-assisted ventilation. Case 3 kept chickens and ducks at home. Respiratory failure and renal failure still occurred rapidly despite the use of doxycycline, requiring invasive ventilator-assisted ventilation and continuous renal replacement therapy (CRRT). After adjusting the antibiotic to high-dose tigecycline (100mg, I.V., q12h), all three patients were treated effectively and no side effects occurred.Conclusion: C. psittaci pneumonia is one of the causes of progressive pneumonia. High-dose tigecycline is safe and effective for the treatment of severe C. psittaci.Keywords: Chlamydia psittaci, progressive pneumonia, metagenomic next-generation sequencing, high-dose tigecycline

SathishKumar Moorthy,1,&ast; Linli Yu,1,&ast; Lin Peng,1 Liangliang Shen,1 Yu Han,1 Zikai Zhang,2 Yanqiao Li,3 Xin Huang1 1Department of Dermatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China; 2Department of Science, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China; 3Department of Dermatology, Institute of Dermatology and Venereology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, Sichuan, 610072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Huang, Department of Dermatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China, Email alida_huang@163.comBackground: Health-related quality of life (HRQoL) of androgenetic alopecia patients has become increasingly important, but the influencing factors associated with the different domains are poorly understood.Objective: This study aimed to investigate the influencing factors in HRQoL of androgenetic alopecia patients and identify its strongly associated domains.Patients and Methods: We enrolled 170 androgenetic alopecia patients. HRQoL was measured using the World Health Organization Quality of Life Brief Version (WHO-BREF), and Hairdex.Results: HRQoL was significantly impaired in patients < 30 years, (WHO-BREF: P=0.022, Hairdex: P=0.004), less educated (WHO-BREF: P=0.021, Hairdex: P=0.003), single patients (Hairdex: P=0.023), and urban residence (Hairdex: P=0.043). By domains, those < 30 years were impaired by physical health (P=0.038) and psychological (P=0.030) by WHO-BREF, and symptoms (P=0.002) and emotions (P=0.002) by Hairdex. Singles were impaired by symptoms (P=0.020), and emotions (P=0.009) by Hairdex. Less-educated individuals had impaired all domains in the WHO-BREF and Hairdex, except for physical health. Women had impaired symptoms (P=0.013) and stigmatization (P=0.041) in Hairdex.Conclusion: Androgenetic alopecia is associated with significantly reduced HRQoL in young, less educated, and single patients. Dermatologists should inquire about Quality of Life and appropriately support androgenetic alopecia patients.Keywords: quality of life, androgenetic alopecia, WHO-BREF, Hairdex

Chen Zhou,1,&ast; Yujie Guang,1,&ast; Yuanming Luo,2 Huiqing Ge,3 Hailong Wei,4 Huiguo Liu,5 Jianchu Zhang,6 Pinhua Pan,7 Jiarui Zhang,8 Lige Peng,8 Adila Aili,8 Yu Liu,8 Jiaqi Pu,8 Xia Zhong,1 Yixi Wang,1 Qun Yi,8,9 Haixia Zhou8 On behalf of the MAGNET AECOPD Registry Investigators1West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, Sichuan Province, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 9Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, Cancer Hospital Affiliate to School of Medicine, UESTC, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel +86-28-85422571, Fax +86-28-85422571, Email zhouhaixia@wchscu.cnBackground: The optimal tool for risk prediction of venous thromboembolism (VTE) in inpatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is still unknown. This study aimed to evaluate whether D-dimer could predict the risk of VTE in inpatients with AECOPD compared to the Padua Prediction Score (PPS).Methods: Inpatients with AECOPD were prospectively enrolled from seven medical centers in China between December 2018 and June 2020. On admission, D-dimer was detected, PPS was calculated for each patient, and the incidence of 2-month VTE was investigated. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of D-dimer and PPS on VTE development, and the best cut-off value for both methods was evaluated through the Youden index.Results: Among the 4468 eligible patients with AECOPD, 90 patients (2.01%) developed VTE within 2 months after admission. The area under the receiver operating characteristic curves (AUCs) of D-dimer for predicting VTE were significantly higher than those of the PPS both in the overall cohort (0.724, 95% CI 0.672– 0.776 vs 0.620, 95% CI 0.562– 0.679; P< 0.05) and the subgroup of patients without thromboprophylaxis (0.747, 95% CI 0.695– 0.799 vs 0.640, 95% CI 0.582– 0.698; P< 0.05). By calculating the Youden Index, the best cut-off value of D-dimer was determined to be 0.96 mg/L with an AUC of 0.689, which was also significantly better than that of the PPS with the best cut-off value of 2 (AUC 0.581, P=0.007). After the combination of D-dimer with PPS, the AUC (0.621) failed to surpass D-dimer alone (P=0.104).Conclusion: D-dimer has a superior predictive value for VTE over PPS in inpatients with AECOPD, which might be a better choice to guide thromboprophylaxis in inpatients with AECOPD due to its effectiveness and convenience.Clinical Trial Registration: Chinese Clinical Trail Registry NO. ChiCTR2100044625; URL: http://www.chictr.org.cn/showproj.aspx?proj=121626.Keywords: acute exacerbation of chronic obstructive pulmonary disease, inpatients, D-dimer, Padua Prediction Score, venous thromboembolism

Yujie Li,1,2 Linjia Peng,1,2 Ke Zhang,1,2 Yong Wu,3 Huifeng Gao,1,2 Hao Chen1,2 1Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Oncology, The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of ChinaCorrespondence: Hao Chen, Department of Integrative Oncology, Fudan University Shanghai Cancer Center, 270 Dong’an Road, Shanghai, People’s Republic of China, Tel +86-18017312356, Email chengkll@sina.comObjective: Ablation serves as a common local treatment for liver metastases from pancreatic cancer (PCLM), but the correlation between the prognosis of PCLM and inflammatory cytokines has been rarely reported. This study aimed to establish a cytokine-based prognostic model for patients with PCLM who are receiving ablation.Patients and Methods: Serum samples from peripheral blood were collected from patients with PCLM before their first ablation. Cytokines were measured using Luminex chips and ELISA. Cox regression and least absolute shrinkage and selection operator regression were used to select prognostic factors for overall survival (OS). Area under the receiver operating characteristic curve (AUC) was applied to compare the ability to predict survival.Results: The relationship between cytokines and clinical factors was evaluated and their prognostic value was compared. Six optimal predictors were selected, including IL-2, IL-7, HGF, IFN-γ, CA19-9 and CEA. The risk model based on these predictors was built and named circulating tumor-associated inflammatory index (CTII). The CTII (AUCs > 0.90) showed superior performance to systemic immune-inflammation index (SII, AUCs < 0.65) in OS.Conclusion: A circulating cytokine-based risk model for patients with PCLM before first ablation has been proposed and validated, which has demonstrated superior performance in predicting survival and has the potential to inform clinical treatment strategies.Keywords: inflammation, cytokines, advanced pancreatic cancer, ablation, prognosis

Jiaoquan Chen,&ast; Xin Tian,&ast; Nanji Yu, Liqian Peng, Huilan Zhu Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, 510095, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huilan Zhu, Department of Dermatology Guangzhou Institute of Dermatology, 56 Hengfu Road, Guangzhou, 510095, People’s Republic of China, Email Zhlhuilan@126.comAbstract: T-cell lymphoblastic lymphoma (T-LBL) is a heterogeneous malignancy derived from T-cells that more commonly affects teens and males. Most commonly, T-LBL exhibits signs of lymph nodes, bone marrow, and mediastinal mass invasion, but in rare cases, the disease manifests cutaneously. We present a case of both cutaneous and systemic presentation of T-LBL in 9-year-old man in which the skin immunophenotype analysis showed TdT expression with positivity of CD3, CD4 and CD99. Review of all currently described cases of cutaneous T-LBL revealed that the most frequently positive tumor markers were TdT (100%), CD3 (100%), CD4 (59.1%) and CD99 (40.9%). Cutaneous involvement may be a prognostic factor in treating T-LBL with chemotherapy.Keywords: T-cell lymphoblastic lymphoma, cutaneous lymphoma, diagnosis

Shaoyun Li,1,&ast; Yuefei Li,1,&ast; Xiyan Xu,1 Jian Shao,2 Ruifeng Xie,3 Sheng Liu,1 Li Peng,1 Jin Wang,1 Kaixin Zhou,3 Huyi Feng1 1The Fifth People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 2Guangzhou Laboratory, Guangzhou, People’s Republic of China; 3Department of Life Sciences, University of Chinese Academy of Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaixin Zhou; Huyi Feng, Email zhoukx@ucas.ac.cn; fenghuyi@hotmail.comIntroduction: Simple non-invasive biomarker is urgently needed to detect the largely silent osteopenia in order to prevent osteoporosis-related fracture later in life. The accumulation of advanced glycation end products (AGEs) has been related to reduced bone density and osteoporotic fractures. Whether lens autofluorescence (LAF) based AGEs (LAF-AGEs) measurement could be used to assess the risk of osteopenia is aimed to investigate in this paper.Methods: Through routine health examination, 368 individuals under the age of 50 were enrolled. A dual-energy X-ray absorptiometry (DXA) device was used to measure bone mineral density (BMD) of the forearm and determine osteopenia. AGE levels were derived with LAF along with the other demographic and laboratory parameters. After deriving the age-adjusted AGE levels (AALs), a linear regression analysis and an ordered logistic regression analysis were applied to examine the associations between osteopenia and LAF-AGEs as well as AALs.Results: Negative correlations (Pearson r = − 0.16, p < 0.001) were found between LAF-AGEs and T-scores. Higher AALs were significantly associated (p = 0.004) with escalated level of osteopenia in the ordered logistic analysis.Discussion: After reviewing the relevant studies, it is concluded that LAF-AGE is a more stable measure of long-term metabolic dysfunction than circulating AGE. LAF-AGEs are a valid, practical and non-invasive parameter for osteopenia risk evaluation. Further studies with longer follow-up will be helpful to clarify its effectiveness for osteoporosis risk assessment.Keywords: lens autofluorescence, LAF, osteopenia, advanced glycation end products, AGEs, bone mineral density, T-scores

Keke Zhang,1 Xinxing Wan,1 Md Asaduzzaman Khan,2 Xiaoying Sun,1 Xuan Yi,1 Zhouqi Wang,1 Ke Chen,1 Lin Peng3 1Department of Endocrinology, the Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2The Research Centre for Preclinical Medicine, Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Nephrology, the First Hospital of Changsha, Changsha, People’s Republic of ChinaCorrespondence: Lin Peng, Department of Nephrology, the First Hospital of Changsha, Changsha, People’s Republic of China, Tel +86-731-8466-7510, Email plin1018@163.com Ke Chen, Department of Endocrinology, the Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86-731-8861-8239, Email chenke520@yeah.netPurpose: Type 2 diabetes mellitus (T2DM) increases the incidence of diabetic nephropathy (DN) and eventually progresses to end-stage renal disease. Circular RNAs (circRNAs) are a class of non-coding RNAs that are promising as diagnostic biomarkers and therapeutic targets for human diseases. The aim of this study was to analyze the differential expression of circRNAs (DECs) in peripheral blood from patients with early type 2 diabetic nephropathy (ET2DN), T2DM and controls, which will facilitate to discover some new biomarkers for ET2DN.Patients and Methods: Twenty ET2DN patients, 20 T2DM patients, and 20 normal controls were included in this study. Blood samples from 3 random subjects of age- and sex-matched patients in each group, respectively, were used to detect circRNA expression profiles by circRNA microarray, and the circRNA expression of remaining subjects was validated by real-time quantitative polymerase chain reaction (qRT-PCR). Further functional assessment was performed by bioinformatic tools.Results: There were 586 DECs in ET2DN vs T2DM group (249 circRNAs were upregulated and 337 circRNAs were downregulated); 176 circRNAs were upregulated and 101 circRNAs were downregulated in T2DM vs control group; 57 circRNAs were upregulated and 5 circRNAs were downregulated in ET2DN vs control group. The functional and pathway enrichment of DECs were analyzed by GO and KEGG. qRT-PCR results revealed that hsa_circ_0001831 and hsa_circ_0000867 were significantly upregulated in ET2DN group compared to both of T2DM and control group. The ROC curve demonstrated that hsa_circ_0001831 and hsa_circ_0000867 have high sensitivity and specificity associated with ET2DN.Conclusion: Our study showed the expression profiles of circRNAs in ET2DN patients and demonstrated that hsa_circ_0001831 and hsa_circ_0000867 can be used as novel diagnostic biomarkers for ET2DN.Keywords: circRNAs microarray, diagnostic biomarkers, early type 2 diabetic nephropathy, inflammation

Yongjun Liu,1,2,&ast; Peng Lu,2,3,&ast; Lei Peng,2,3 Jie Chen,4 Chunlin Hu2,3 1Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Department of Emergency Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 4Department of Critical Care Medicine, Dongguan People’s Hospital, Dongguan, 523059, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunlin Hu, Department of Emergency Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China, Email huchunl@mail.sysu.edu.cn Jie Chen, Department of Critical Care Medicine, Dongguan People’s Hospital, Dongguan, 523059, People’s Republic of China, Email cj1982520@163.comObjective: Critical covid-19 patients have complications with acute myocardial injury is still unclear. We observed a series of critically ill patients, paying particular attention to the impact of myocardial injury at admission on short-term outcome.Methods: We prospectively collected and analyzed data from a series of severe covid-19 patients confirmed by real-time RT-PCR. Data were obtained from electronic medical records including clinical charts, nursing records, laboratory findings, and chest x-rays were from Feb 8, 2020, to April 7, 2020. The Acute Physiology and Chronic Health Evaluation (APACHE II) score, CURB-65 Pneumonia Severity Score, Sequential Organ Failure Assessment (SOFA) Score and pneumonia severity index (PSI) score were made within 24 hours of admission. Cardiac injury was diagnosed as hs-cTnI were above > 28 pg/mL. The short-term outcome was defined as mortality in hospital.Results: A total of 100 patients met the diagnostic criteria of severe patients with COVID-19 during 2020.02.08– 2020.04.07. The CURB 65, APACH2, SOFA, and PSI score were significantly higher in Critical group than in Severe group. Univariate regression analysis showed that oxygen flow, PO2/FiO2, SOFA and hs-cTnI were closely related to short-term outcome. The corresponding ROC of hs-cTnI, oxygen flow and SOFA for patient death prediction were 0.949, 0.906 and 0.652. hs-cTnI at 47.8 ng/liter predicted death, sensitivity 92.8%, specificity 92.9%; Oxygen flow at 5.5 liter/minute predicted death sensitivity 100%, specificity 77.9%; SOFA score at 5 predicted death sensitivity 100%, specificity 73.8%.Conclusion: Our cohort study demonstrated that inhaled oxygen flow, SOFA score, and myocardial injury at admission in critically ill COVID-19 patients were important indicators for predicting short-term death of patients, the hs-cTnI can be as a risk stratification, which may provide a simple method for the physicians to identify high-risk patients and give reasonable treatment in time.Keywords: COVID-19, high-sensitivity cardiac troponin I, short-term outcome

Hao Gao,1 Hao Yin,1 Li Peng,1 Han Wang2 1School of Journalism and Communication, Nanjing Normal University, Nanjing, 210097, People’s Republic of China; 2School of Journalism and Communication, Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of ChinaCorrespondence: Han Wang, School of Journalism and Communication, Jinan University, No. 601, West Huangpu Avenue, Guangzhou, Guangdong, 510632, People’s Republic of China, Email jacobwang0606@163.comBackground: With the widespread promotion of the COVID-19 vaccination in China, videos about the vaccination have become increasingly available on social video platforms. With the User Generated Content model, different creators’ interpretations of COVID-19 vaccines may influence the attitudes towards the vaccines and vaccination.Objective: To explore the overview of COVID-19 vaccine-related videos on Bilibili, discussing the communication effects of COVID-19 topic videos and its influencing factors.Methods: A content analysis was applied to the 202 video samples obtained through data mining regarding the creator’s information, video presentation, and COVID-19 vaccine-related content.Results: Individuals and medical professionals preferred VLOG videos, media chose to upload informational videos, and enterprises preferred to post showcase videos. Individuals were more likely to discuss the adverse reactions in their videos, while medical professionals were more likely to discuss the vaccination process for the COVID-19 vaccine. Videos with core issues positively influenced the video’s dissemination breadth. The attitudes toward the COVID-19 vaccine in the videos positively influence the recognition of the videos. The richness of knowledge points related to the COVID-19 vaccine negatively affected the recognition and participation.Conclusion: Social video platforms could play an active role in the vaccination promotion for the youth. Health promotion-related departments and individuals could strengthen agenda setting, grasp the characteristics of young groups, and express positive attitudes toward health issues to achieve better health (vaccine) promotion.Keywords: COVID-19 vaccine, social media, Bilibili, health promotion, vaccination

Jing Xiao,1 Jianjian Ge,1 Dingxin Zhang,1 Xinqiang Lin,1 Xiaoshuang Wang,1 Li Peng,2 Liqun Chen1 1Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Respiratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Liqun Chen, Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 4000416, People’s Republic of China, Tel +86 13883557769, Email cqll1970@163.comBackground: The diverse manifestations of tuberculosis (TB) in chronic kidney disease (CKD) patients can cause difficulty in diagnosis, delayed treatment, even death. Therefore, this study investigated the clinical characteristics and the risk factors for mortality in CKD patients with TB.Methods: This retrospective study included 167 patients diagnosed with active TB at two tertiary medical centers in Chongqing within six years. Clinical characteristics and outcomes of anti-TB treatment in patients with and without CKD were collected, and the predictive mortality values of variables were analyzed.Results: Of the 167 patients, 66.7% (44/66) hemodialysis (HD), 41.1% (21/51) pre-HD, and 32.0% (16/50) non-CKD patients had extrapulmonary TB. The pleura and lymph node were the common sites in CKD patients. Clinical presentations of cough and hemoptysis in CKD patients were less common than those in non-CKD patients, 13.7% (16/117) of CKD patients even not having any clinical symptoms. The positive rates of tuberculin skin test, TB-polymerase chain reaction and acid-fast bacilli in sputum in HD patients were lower than those in pre-HD and non-CKD patients (p< 0.05). CKD patients were more prone to gastrointestinal and neurological side effects during anti-TB treatment. The mortality rates of non-CKD, pre-HD and HD patients was 6.1%, 31.9% and 37.3%, respectively. Multivariate Cox analysis revealed that age≥ 40 years (HR: 5.871; p=0.019), hypoalbuminemia (HR:2.879; p=0.004), CKD stage 4– 5 (HR:4.719; p=0.018) and HD (HR:6.13; p=0.005) were associated with mortality.Discussion: CKD patients with TB have atypical clinical manifestations and high mortality. Age, hypoalbuminemia, CKD stage 4– 5, and HD were independent predictors of mortality.Keywords: chronic kidney disease, extrapulmonary TB, pulmonary TB, anti-TB therapy, treatment outcome, hemodialysis

Yan-Lei Tai,1 Li Peng,1 Ying Wang,2 Zi-Jun Zhao,3 Ya-Nan Li,1 Chun-Ping Yin,1 Zhi-Yong Hou,4 De-Cheng Shao,5 Ya-Hui Zhang,1 Qiu-Jun Wang1 1Department of Anesthesiology, Third Hospital Affiliated to Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Anesthesiology, Tangshan Gongren Hospital, Tangshan, Hebei, People’s Republic of China; 3Department of Anesthesiology, Hebei Chest Hospital, Shijiazhuang, Hebei, People’s Republic of China; 4Center of Emergency and Trauma, Third Hospital Affiliated to Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 5Department of Sport Medicine, Third Hospital Affiliated to Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Qiu-Jun Wang, Department of Anesthesiology, Third Hospital Affiliated to Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China, Tel +8618533112929, Email wangqiujunsy@163.comBackground: Femoral nerve block combined with general anesthesia is commonly used for patients undergoing knee arthroscopy in ambulatory care centers. An ideal analgesic agent would selectively (differentially) block sensory fibers, with little or no effect on motor nerves. Ropivacaine is considered to cause less motor block than others. This study investigated the median effective concentration (EC50) of ropivacaine for differential femoral nerve block in adults either younger or older than 60 years.Methods: Patients with American Society of Anesthesiologists physical status I–III and scheduled for knee arthroscopy were categorized as 18- to 60-years-old (Group 1), or older than 60 years (Group 2). Surgeries were performed under general anesthesia combined with femoral nerve block via 22 mL ropivacaine. The EC50 of ropivacaine for differential femoral nerve block was determined using the up-and-down method and probit regression. The primary outcome was the EC50 (95% confidence interval [CI]) of the 2 groups. Data on the sensory block, analgesic effect, complications, and hemodynamics during surgery were also recorded.Results: The EC50 of 22 mL ropivacaine for differential femoral nerve block of Group 1 (0.124%, 95% CI 0.097– 0.143%) was significantly higher than that of Group 2 (0.088%, 95% CI 0.076– 0.103%). The sensory block and hemodynamic data of the 2 groups were comparable. None of the patients experienced neurological complications.Conclusion: The EC50 of ropivacaine administered for differential femoral nerve block during knee arthroscopy was lower in patients older than 60 years, relative to younger adults.Keywords: femoral nerve block, ropivacaine, motor block, age groups, EC50

Li Peng,&ast; Ni Zhu,&ast; Dan Wang,&ast; Yanhong Zhou, Yifei Liu School of Stomatology and Ophthalmology, Xianning Medical College, Hubei University of Science and Technology, Xianning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanhong Zhou; Yifei Liu, Email zyh@hbust.edu.cn; liuyifei@hbust.edu.cnIntroduction: Nod-like receptor C4 (NLRC4) is a member of the Nod-like receptor (NLR) family, and its expression mediates the activation of caspase-1 (CASP1). Abnormal expression of NLRC4 and CASP1 is associated with multiple tumors. However, the expression differences, prognostic value and immune correlation of NLRC4 and CASP1 in colorectal cancer (CRC) remain to be determined.Methods: In this study, TCGA, CCLE, HPA, PrognoScan, STRING and GeneMANIA databases were used to analyze differences in expression, prognostic value, genetic alterations and immune cell infiltration of NLRC4 and CASP1 in CRC patients. Then, we further validated the expression of NLRC4 and CASP1 in CRC using immunohistochemistry (IHC).Results: NLRC4 and CASP1 were expressed low in CRC tissues and CRC cell lines. The expression of NLRC4 was significantly related to the patient’s gender and lymph node metastasis. NLRC4 and CASP1 down-regulated expression was observably correlated with poor survival and diverse immune cells infiltration in CRC patients. NLRC4 and CASP1 have a gene mutation alteration. NLRC4 and CASP1 had a significant positive correlation in CRC.Conclusion: This study will provide new ideas for the prognosis and treatment in CRC. NLRC4 and CASP1 are expected to be novel biomarkers and potential immunotherapy targets in CRC patients.Keywords: Nod-like receptor C4, caspase-1, colorectal cancer, bioinformatics, immunohistochemistry

Runan Zuo,1 Yan Zhang,1 Xiaorong Chen,1 Shiheng Hu,1 Xinhao Song,1 Xiuge Gao,1 Jiahao Gong,1 Hui Ji,1 Fengzhu Yang,1 Lin Peng,1 Kun Fang,2 Yingjun Lv,1 Junren Zhang,1 Shanxiang Jiang,1 Dawei Guo1 1Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, People’s Republic of China; 2The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, People’s Republic of ChinaCorrespondence: Dawei Guo; Shanxiang Jiang, Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal, Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, People’s Republic of China, Tel +86 25-84396215, Fax +86-25-84398669, Email gdawei0123@njau.edu.cn; nauvy@sina.comBackground: Halofuginone (HF)-loaded TPGS polymeric micelles (HTPM) were successfully fabricated using the thin-film hydration technique. HTPM via intravenous injection have been demonstrated to exert an excellent anticancer effect against triple-negative breast cancer (TNBC) cells and subcutaneous xenografts. In the present study, we further explored the potential treatment effect and mechanism of orally administered HTPM alone and in combination with surgical therapy on TNBC in subcutaneous and orthotopic mouse models.Methods: Herein, the stability and in vitro release behavior of HTPM were first evaluated in the simulated gastrointestinal fluids. Caco-2 cell monolayers were then used to investigate the absorption and transport patterns of HF with/without encapsulation in TPGS polymeric micelles. Subsequently, the therapeutic effect of orally administered HTPM was checked on subcutaneous xenografts of TNBC in nude mice. Ultimately, orally administered HTPM, combined with surgical therapy, were utilized to treat orthotopic TNBC in nude mice.Results: Our data confirmed that HTPM exhibited good stability and sustained release in the simulated gastrointestinal fluids. HF was authenticated to be a substrate of P-glycoprotein (P-gp), and its permeability across Caco-2 cell monolayers was markedly enhanced via heightening intracellular absorption and inhibiting P-gp efflux due to encapsulation in TPGS polymeric micelles. Compared with HF alone, HTPM showed stronger tumor-suppressing effects in subcutaneous xenografts of MDA-MB-231 cells when orally administered. Moreover, compared with HTPM or surgical therapy alone, peroral HTPM combined with partial surgical excision synergistically retarded the growth of orthotopic TNBC. Fundamentally, HTPM orally administered at the therapeutic dose did not cause any pathological injury, while HF alone led to weight loss and jejunal bleeding in the investigated mice.Conclusion: Taken together, HTPM could be applied as a potential anticancer agent for TNBC by oral administration.Graphical Abstract: Keywords: triple-negative breast cancer, Halofuginone hydrobromide, TPGS polymeric micelles, subcutaneous xenografts, orthotopic xenografts, oral administration

Renyu Zhou,1 Xiaoxi Zhu,2 Yulong Peng,1 Lijuan Zhong,1 Lilin Peng,1 Bo Yang,1 Yuhua Meng,3 Xuanzhao Chen,4 Yuanzhi Lu1,4 1Department of Pathology, First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 2Department of Oncology, First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 3Department of Pathology, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, 528300, People’s Republic of China; 4The Center of Pathological Diagnosis and Research, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524023, People’s Republic of ChinaCorrespondence: Yuanzhi Lu, Tel +86-20 38688984, Email yuanzhi.lu@jnu.edu.cnIntroduction: Amplification of the 11q13.3 locus has been observed in various tumors. This study sought to determine the correlation of gene amplification at the 11q13.3 locus with the immune status and survival of breast cancer.Methods: Amplification of the 11q13.3 locus was characterized by analyzing a publicly available database from the cBioPortal platform (TCGA). The correlation of amplified genes with immune cell infiltration in breast cancer was further analyzed using the TIMER2.0 platform. Immunohistochemical staining was used to determine the expression levels of Cyclin D1 (CCND1), Fas-associated death domain (FADD) and P53 in 156 clinical breast cancer samples.Results: This study revealed that amplification of the 11q13.3 amplicon in breast cancer is likely more frequently detected in luminal B breast cancer. Moreover, high expression or amplification of CCND1, fibroblast growth factor 3 (FGF3), fibroblast growth factor 4 (FGF4), fibroblast growth factor 19 (FGF19) and FADD was inversely correlated with the abundance of CD4+ T cells and dendritic cell infiltration in breast cancer (P < 0.05). Data analysis also demonstrated that high expression of CCND1, FGF4 and FADD mRNA levels was closely correlated with shorter recurrence-free survival (RFS) in patients with breast cancer (P < 0.05). The results of immunohistochemical staining from clinical samples further confirmed that high expression of CCND1 and FADD was frequently detected in luminal B and high-grade breast cancer with shorter metastasis-free survival times (P < 0.05).Conclusion: This study demonstrated that coamplification of genes located on the 11q13.3 amplicon is frequently detected in luminal B subtype breast cancer and is closely associated with worse survival in patients with breast cancer. Moreover, coamplification of the CCND1-FGF locus might decrease antitumor immune activity in breast cancer, indicating that coamplification of the 11q13.3 amplicon is likely to be a key determinant of therapeutic resistance and accelerate the aggressive evolution of breast cancer.Keywords: breast cancer, chromosomal amplification, 11q13.3 amplicon, prognosis, immune microenvironment

Lingli Jiang,1,&ast; Lei Peng,1,&ast; Miaoling Rong,2 Xiaozhi Liu,3 Qinxia Pang,1 Huaping Li,1 Ying Wang,1 Zhou Liu1 1Department of Obstetrics and Gynecology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 2Department of Obstetrics and Gynecology, First Maternity and Infant Hospital Affiliated to Tongji University, Shanghai, People’s Republic of China; 3Department of Ultrasound, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhou Liu, Department of Obstetrics and Gynecology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, No. 1500, Zhouyuan Road, Pudong New Area, Shanghai, 201318, People’s Republic of China, Tel +86 18930837705, Email zp_liuz@sumhs.edu.cnBackground: The majority of women who experience spontaneous preterm delivery (SPTD) have low-risk, asymptomatic pregnancies with a cervical length (CL) ≥ 25mm and no clear risk factors. Despite the fact that cervical elastography is a potential tool for predicting SPTD, there is currently no feasible solution to make a reliable prediction for preventing SPTD.Objective: The aim of this study was to construct a nomogram including multimodal transvaginal ultrasound parameters during the second trimester to predict SPTD in low-risk women.Methods: This multi-center study enrolled 1260 women with singleton pregnancies between 20 and 24 weeks’ gestation. CL and cervical elastography data were obtained when they were undergoing the second-trimester anomaly scan. Univariate and multivariate Logistic regression were utilized to screen predictors independently related to SPTD from the maternal characteristics and multimodal ultrasound data. Then construct a nomogram to determine the likelihood of SPTD in pregnant women.Results: A total of 66 pregnancies in the training cohort (7.8%, 66/842) and 37 pregnancies (8.9%, 37/418) in the validation cohort ended in SPTD. Age, uterine curettage, CL, and strain in the anterior lip of internal os were the independent predictors of SPTD (P < 0.001, < 0.001, = 0.007, and < 0.001, respectively). These predictors constituted a nomogram to predict the probability of SPTD for a pregnant woman in her second trimester. It showed good discrimination (C-index = 0.898 and 0.839), calibration (P = 0.258 and 0.115), and yielded net benefits both in the training and validation cohorts.Conclusion: The nomogram including data of multimodal transvaginal ultrasound at 20 to 24 weeks’ gestation is expected to identify women with SPTD in the low-risk, asymptomatic population.Keywords: cervical length measurement, elasticity imaging techniques, nomograms, pregnancy trimester, second, premature birth

Longxian Lv,1,&ast; Ling Peng,2,&ast; Ding Shi,1 Li Shao,3,&ast; Huiyong Jiang,1 Ren Yan1 1State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Respiratory Disease, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3Institute of Translational Medicine, Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiyong Jiang; Ren Yan, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, Zhejiang, 310003, People’s Republic Of China, Tel/Fax +86-571-87236453, Email jianghuiyong@zju.edu.cn; 1514090@zju.edu.cnBackground: Streptococcus pneumoniae (SP) is the most common cause of bacterial pneumonia, especially for people with immature or compromised immune systems. In addition to vaccination and antibiotics, immune regulation through microbial intervention has emerged in recent anti-SP infection research. This study investigated the therapeutic effect of a combination of live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus (CBLEB), a widely used probiotic drug, on SP infection in rats.Methods: An immunocompromised SP-infection rat model was established by intraperitoneal injection of cyclophosphamide and nasal administration of SP strain ATCC49619. Samples from SP-infected, SP-infected and CBLEB-treated, and healthy rats were collected to determine blood indicators, serum cytokines, gut microbiota, faecal and serum metabolomes, lung- and colon-gene transcriptions, and histopathological features.Results: CBLEB treatment alleviated weight loss, inflammation, organ damage, increase in basophil percentage, red cell distribution width, and RANTES levels and decrease in total protein and albumin levels of immunocompromised SP-infection rats. Furthermore, CBLEB treatment alleviated dysbiosis in gut microbiota, including altered microbial composition and the aberrant abundance of opportunistic pathogenic bacterial taxa such as Eggerthellaceae, and disorders in gut and serum metabolism, including altered metabolomic profiles and differentially enriched metabolites such as 2,4-di-tert-butylphenol in faeces and L-tyrosine in serum. The transcriptome analysis results indicated that the underlying mechanism by which CBLEB fights SP infection is mainly attributed to its regulation of immune-related pathways such as TLR and NLR signalling in the lungs and infection-, inflammation- or metabolism-related pathways such as TCR signalling in the colon.Conclusion: The present study shows a potential value of CBLEB in the treatment of SP infection.Keywords: Streptococcus pneumonia infection, probiotics, microbiota, metabolism, transcriptome

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

Yuliang Wang,1– 3 Linna Peng,1– 3 Hongyan Lu,1– 3 Zhanhao Zhang,1– 3 Shishi Xing,1– 3 Dandan Li,1– 3 Chunjuan He,1– 3 Tianbo Jin,1– 3 Li Wang1– 3 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, 712082, Shaanxi, People’s Republic of China; 2Engineering Research Center of Tibetan Medicine Detection Technology, Ministry of Education, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 3Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of ChinaCorrespondence: Li Wang Tel +86-15706028826Email wangli_xzmd@163.comBackground: We aimed to enrich the pharmacogenomic information of a Blang population (BP) from Yunnan Province in China.Methods: We genotyped 55 very important pharmacogene (VIP) variants from the PharmGKB database and compared their genotype distribution (GD) in a BP with that of 26 populations by the χ2 test. The minor allele frequency (MAF) distribution of seven significantly different single-nucleotide polymorphisms (SNPs) was conducted to compare the difference between the BP and 26 other populations.Results: Compared with the GD of 55 loci in the BP, among 26 studied populations, GWD, YRI, GIH, ESN, MSL, TSI, PJL, ACB, FIN and IBS were the top-10 populations, which showed a significantly different GD > 35 loci. CHB, JPT, CDX, CHS, and KHV populations had a significantly different GD < 20 loci. A GD difference of 27– 34 loci was found between the BP and 11 populations (LWK, CEU, ITU, STU, PUR, CLM, GBR, ASW, BEB, MXL and PEL). The GD of five loci (rs750155 (SULT1A1), rs4291 (ACE), rs1051298 (SLC19A1), rs1131596 (SLC19A1) and rs1051296 (SLC19A1)) were the most significantly different in the BP as compared with that of the other 26 populations. The genotype frequency of rs1800764 (ACE) and rs1065852 (CYP2D6) was different in all populations except for PEL and LWK, respectively. MAFs of rs1065852 (CYP2D6) and rs750155 (SULT1A1) showed the largest fluctuation between the BP and SAS, EUR, AFR and AMR populations.Conclusion: Our data can provide theoretical guidance for safe and efficacious personalized drug use in the Blang population.Keywords: Blang population, single-nucleotide polymorphism, SNP, very important pharmacogene, genotype distribution, pharmacogenomics, personalized drug use

Tong Lin,1 E Zhang,1 Zhimei Lin,1 Lisheng Peng2 1The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Department of Science and Education, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Lisheng PengDepartment of Science and Education, Shenzhen Traditional Chinese Medicine Hospital, No. 1 Fuhua Road, Futian District, Shenzhen, Guangdong Province, People’s Republic of ChinaEmail pls0556@gzucm.edu.cnBackground: The prognosis of patients with advanced hepatocellular carcinoma (HCC) remains poor. Lipid remodeling modulators are considered promising therapeutic targets of cancers, owing to their functions of facilitating cancer cells’ adaption to the limited environment. Lysophosphatidylcholine acyltransferases (LPCATs) are enzymes regulating bio-membrane remodeling, whose roles in HCC have not been fully illuminated.Methods: Multiple bioinformatic tools were applied to comprehensively evaluate the expression, genetic alterations, clinical relevance, prognostic values, DNA methylation, biological functions, and correlations with immune infiltration of LPCATs in HCC.Results: We found LPCAT1 was significantly overexpressed and the most frequently altered in HCC. The high-expression of LPCAT1/4 indicated clinicopathological advancements and poor prognoses of HCC patients. Even though the global DNA methylation of LPCATs in HCC showed no significant difference with that in normal liver, the hypermethylation of numerous CpG sites of them implied worse survivals of HCC patients. Thirty LPCATs’ interactive genes were identified, which were generally membrane components and partook in phospholipid metabolism pathways. Finally, we found the expression of LPCATs was extensively positively correlated with the infiltration of various stimulatory and suppressive tumor-infiltrating immune cells (TIICs) in the tumor microenvironment.Conclusion: This study addressed LPCAT1/4 were potential prognostic and immunotherapeutic biomarkers of HCC targeting bio-membrane lipid remodeling.Keywords: hepatocellular carcinoma, LPCATs, bioinformatics, biomarker, immune infiltration

Tong Lin,1 Yingzhao Zhang,1 Zhimei Lin,1 Lisheng Peng2 1The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Department of Science and Education, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Lisheng PengDepartment of Science and Education, Shenzhen Traditional Chinese Medicine Hospital, No. 1 Fuhua Road, Futian District, Shenzhen, Guangdong Province, People’s Republic of ChinaEmail pls0556@gzucm.edu.cnBackground: The prognosis of patients with advanced hepatocellular carcinoma (HCC) is still poor, effective therapeutic targets are needed. ZW10 interacting kinetochore protein (Zwint) is an essential component of the mitotic spindle checkpoint and is upregulated in cancers. Disappointing, the role of ZWINT in HCC has not been fully illuminated.Methods: Multiple tools, including TIMER2.0, Oncomine, GEPIA2, UALCAN, LinkedOmics, Kaplan–Meier Plotter, cBioPortal, and MethSurv, etc. were applied to comprehensively analyze the expression, genetic alternations, clinicopathological relevance, prognostic value, and DNA methylation of ZWINT, along with its correlations with immune infiltration in HCC. Besides, gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) analysis were performed for the correlated genes of ZWINT, closely interconnected clusters and hub proteins in the PPI network were discovered to learn the underlying biological mechanisms.Results: We found ZWINT was significantly upregulated in diverse cancers including HCC, compared with the corresponding normal controls. ZWINT upregulation was significantly associated with unfavorable clinicopathological features and survivals of HCC patients. Genetic alternations of ZWINT frequently occurred, which were linked to worse outcomes of HCC patients. The results of GSEA displayed ZWINT and its correlated genes might be components of condensed chromosomes and spindles, which participated in biological processes and signaling pathways involving DNA replication, cytokinesis, and cell cycle checkpoint, etc. Three highly interconnected clusters and 10 hub proteins were identified from the PPI network constructed with the correlated genes of ZWINT. Moreover, ZWINT expression was found positively correlated with infiltration levels of various immune cells, especially myeloid-derived suppressor cells.Conclusion: This study demonstrated ZWINT might be a promising unfavorable prognostic biomarker and a therapeutic target of HCC, which could regulate HCC progression through cell division and immunosuppression.Keywords: hepatocellular carcinoma, ZWINT, prognosis, immune infiltration, kinetochore

Peng L, Huang YT, Chen J, et al. Cancer Manag Res. 2018;10:5471–5477. The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised regarding the alleged duplication of flow cytometry images in Figure 3. Specifically, The image for Figure 3A, Ctrl, appears to have regions of unexpected duplication with the image for Figure 3A, 2 Gy. The image for Figure 3A, 5 Gy, appears to have regions of unexpected duplication with the image for Figure 3A, Osthole. The authors agreed with the concerns that had been raised and provided data related to the study, however it was unable to verify the validity of the published work. Therefore, the decision was made to retract the article and the authors were notified of this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Ying Sun,1,2,&ast; Beibei Chen,3,4,&ast; Jisheng Li,3,&ast; Ling Peng,5 Shuguang Li,3 Xuejun Yu,3 Li Li3 1Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, 250012, People’s Republic of China; 2Department of Medical Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, 266035, Shandong Province, People’s Republic of China; 3Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong Province, People’s Republic of China; 4Department of Radiation Oncology, Heze Municipal Hospital, Heze, 274031, Shandong Province, People’s Republic of China; 5Department of Respiratory Disease, Zhejiang Provincial People’s Hospital, Hangzhou, 310000, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Li; Xuejun YuDepartment of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Wenhua Xi Road 107, Jinan, 250012, Shandong Province, People’s Republic of ChinaTel +86 531-82169851Email drlili5060@163.com; yuxuejun@qiluhospital.comBackground: As a novel irreversible pan-ErbB inhibitor recently approved in China, pyrotinib has exhibited promising anticancer efficacy and acceptable safety profile in HER2-positive metastatic breast cancer (mBC). The aim of this retrospective study was to estimate the efficacy and safety of pyrotinib treatment in Chinese mBC patients.Methods: We retrospectively reviewed the real-world clinicopathological and treatment data of HER2-positive mBC patients receiving pyrotinib-based treatment from August 2018 to July 2019 in Qilu Hospital of Shandong University and other medical centers of Shandong Province in China.Results: A total of 64 patients treated with pyrotinib were included for analysis, and the median follow-up duration was 260 days (interquartile range, 199.0 to 339.0 days). Fifty-nine (92.2%) patients had been previously treated with trastuzumab and/or T-DM1, while 11 (17.2%) patients had been exposed to lapatinib. The objective response rate (ORR) of all patients was 73.4%, and the disease control rate (DCR) was 98.4%, with a clinical benefit rate (CBR) of 87.5%. Patients with exposure to lapatinib responded well to pyrotinib-based treatment, although the ORR was significantly lower compared with that of patients without exposure to lapatinib (44.1% vs 77.5%, p=0.037). Previous lapatinib exposure was negatively associated with the objective response of pyrotinib treatment (odds ratio [OR]=0.248, 95% confidence interval [CI] 0.063– 0.970, p=0.045). The median progression-free survival (mPFS) for patients with previous lapatinib exposure and patients with visceral metastasis was 299 days (95% CI 240.1– 357.9 days) and 359 days (95% CI 258.3– 459.7 days), respectively. But the mPFS of the whole cohort has not been reached until the cut-off date. Cox multivariate analysis revealed that only visceral metastasis was an independent predictor of significantly shorter PFS (p=0.041) but not previous exposure to lapatinib (p=0.092). Diarrhea (28.1%), hand-foot syndrome (17.2%), and neutropenia (9.4%) were the most common grade 3 adverse events associated with pyrotinib treatment.Conclusion: Pyrotinib is highly beneficial to HER2-positive metastatic breast cancer patients, even in patients with previous lapatinib exposure. Pyrotinib is a feasible replacement of lapatinib in combination with chemotherapeutic drugs or as a monotherapy. Adverse effects are tolerable and easily manageable.Keywords: breast cancer, HER2 positive, pyrotinib, adverse effect, objective response rate

Chunjuan He,1 Linna Peng,1 Shishi Xing,1 Dandan Li,1 Li Wang,1 Tianbo Jin1,2 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 2Key Laboratory for Basic Life Science Research of Tibet Autonomous Region, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of ChinaCorrespondence: Tianbo JinKey Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, #6, Wenhui East Road, Xianyang, 712082, Shaanxi, People’s Republic of ChinaTel/Fax +86-29-88895902Email jintianbo@gmail.comBackground: Genetic variation influences drug reaction or adverse prognosis. The purpose of this research was to genotype very important pharmacogenetic (VIP) variants in the Tibetan population.Methods and Materials: Blood samples from 200 Tibetans were randomly collected and 59 VIP variants were genotyped, and then compared our data to 26 other populations in the 1000 project to further analyze and identify significant difference.Results: The results showed that on comparing with most of the 26 populations from the 1000 project, rs4291 (ACE), rs1051296 (SLC19A1) and rs1065852 (CYP2D6) significantly differed in the Tibetan population. Furthermore, three significant loci were related to drug response. In addition, the allele frequency of Tibetans least differed from that of East Asian populations, and most differed from that of Americans.Conclusion: Three significant loci of variation ACE rs4291, SLC19A1 rs1051296 and CYP2D6 rs1065852 were associated with drug response. This result will contribute to improving the information of the Tibetan in the pharmacogenomics database, and providing a theoretical basis for clinical individualised drug use in Tibetans.Keywords: the Tibetan population, pharmacogenomics, VIP variants

Liping Zhu,1,&ast; Zhiqiang Wang,2,&ast; Justin Stebbing,3 Zibing Wang,4 Ling Peng5 1Department of Medical Oncology, Shouguang Hospital of Traditional Chinese Medicine, Shouguang, Shandong Province, People’s Republic of China; 2Department of Urology, Shouguang Hospital of Traditional Chinese Medicine, Shouguang, Shandong Province, People’s Republic of China; 3Division of Cancer, Department of Surgery and Cancer, Imperial College London, London, UK; 4Department of Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan Province, People’s Republic of China; 5Department of Respiratory Disease, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling PengDepartment of Respiratory Disease, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, People’s Republic of ChinaTel/Fax +86 571-85893509Email drpengling@hotmail.comZibing WangDepartment of Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan Province, People’s Republic of ChinaTel/Fax +86 37165587098Email zlyywzb2118@zzu.edu.cnAbstract: Immune checkpoint inhibitors (ICIs) including anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) and anti-programmed death cell protein 1 (anti-PD1) have extended patient survival benefit and revolutionized cancer treatment. As ICIs rely on immune regeneration to eliminate tumor cells, they can also lead to an imbalance of immune reactions often called immune-related adverse events (irAEs). Rare irAEs such as ocular or cardiac toxicity or vasculitis are seen in less than 1% of patients receiving ICIs. Immune-related cystitis remains a rare occurrence. Herein, we describe a patient with extensive-stage small cell lung cancer (SCLC) and a history of syphilis with a complete response to second-line treatment using nivolumab plus paclitaxel who complained of urinary irritation symptoms. At biopsy, we found infiltration of CD3+ and CD8+ lymphocytes in the urothelium. Although there are reports describing immune-related cystitis in cancer patients, our case has comprehensive pathological confirmation and a differentiation diagnosis. In this report, we review other cases to elucidate clinical characteristics and discuss suitable management of this rare irAE.Keywords: immunotherapy, cystitis, lung cancer, syphilis, immune checkpoint inhibitor

Li-Ping Zhu,1,&ast; Wei-Lan Yin,2,&ast; Lei Peng,1,&ast; Xiao-Hong Zhou,3 Peng Zhou,1 Shu-Xia Xuan,1 Ying Luo,1 Chen Chen,1 Bin Cheng,1 Jin-Duan Lin,1 Yan-Mei Liu,1 Feng-Jun Tan,4 Wei-Guo Yin1,&ast; 1Department of Molecular Diagnosis Center, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, 511518, Guangdong, People’s Republic of China; 2Department of Physiology & Institute of Neuroscience, University of South China, Hengyang, 421001, Hunan, People’s Republic of China; 3Kingmed Diagnostic Center for Clinical Laboratory, Guangzhou, 510330, Guangdong, People’s Republic of China; 4Department of Otorhinolaryngology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, 511518, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei-Guo YinDepartment of Molecular Diagnosis Center, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, No. B24, Xincheng Yinquan Road, Qingcheng District, Qingyuan, 511518, Guangdong, People’s Republic of ChinaTel +86 763 311 3890Email wgy09dr_mn@163.comObjective: This study explored the correlation between myocardial infarction (MI) and the Glu504Lys polymorphism in the aldehyde dehydrogenase 2 (ALDH2) gene in the Qingyuan area.Methods: The Glu504Lys polymorphism of the ALDH2 gene was analyzed using the polymerase chain reaction and deoxyribonucleic acid microarray analysis for 468 patients diagnosed with MI for the first time and 132 healthy subjects.Results: There was a significant difference in the distribution of the ALDH2 genotype between the MI group and the control group (P = 0.0492), but there was no significant difference in allele frequency between the two groups (P = 0.1363). The clinical data showed that there were statistically significant differences (P < 0.05) in the two groups’ gender and age distributions, rates of diabetes and hypertension, levels of alcohol and tobacco use, serological levels of heart markers, blood lipids and glucose. The subgroup analysis of ALDH2 genotypes found that alcohol consumption, high levels of myoglobin, and low levels of high-density lipoprotein cholesterol were significantly associated with a higher incidence of MI (P < 0.05). After adjusting for gender, hypertension, diabetes, and other related influencing factors, logistic regression analysis showed that the ALDH2 genotype GA/AA was an independent risk factor for MI (P < 0.05, OR = 1.479, 95% CI = 1.003– 2.179).Conclusion: The presence of risk alleles with the genetic effect (ALDH2 genotype GA/AA) is an independent risk factor for MI.Keywords: myocardial infarction, aldehyde dehydrogenase 2, polymorphism

Qiang Huang,1,* Long Peng,2,* Yuxiang Sun,1 Jiayu Huang,3 Tong Han,1 Yongjie Li,1 Hui Peng1 1Department of Nephrology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, People’s Republic of China; 2Department of Cardiovascular Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, People’s Republic of China; 3Department of Urology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui PengDepartment of Nephrology, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Ave, Guangzhou, Guangdong, 510630, People’s Republic of ChinaTel +86 020 85252865Email pengh@mail.sysu.edu.cnBackground: Accumulating evidence has indicated that dysregulation of microRNAs (miRNAs) contributes to the tumorigenesis of prostate cancer (PCa). Nevertheless, the role of miR-593-3p in the development of PCa remains unclear. The objective of this study was to investigate the role and mechanisms of miR-593-3p in PCa cells.Methods: RT-PCR was used to detect the expression levels of miR-593-3p. CCK-8, colony formation, spheroid formation and transwell assays were performed to examine the proliferation, migration and invasion of C4-2, DU145 and RWPE-1 cells. And then, transcriptome sequencing, dual-luciferase reporter assay and Western blot were taken to identify the target gene and downstream mechanisms of miR-593-3p.Results: Here, we found that miR-593-3p promoted PCa cell proliferation, colony formation, spheroid formation, migration and invasion. Further mechanistic studies revealed that miR-593-3p possessed binding sites of ADIPOR1 3ʹ-UTR and played an important role in 5ʹ-AMP-activated protein kinase (AMPK) signaling pathway and epithelial–mesenchymal transition (EMT) process. In addition, the transfection of si-ADIPOR1 also enhanced the PCa cell proliferation and invasion.Conclusion: Our study provides an empirical investigation of miR-593-3p, which exerts oncogenic function through targeting ADIPOR1 in PCa cells.Keywords: miR-593-3p, ADIPOR1, PCa, proliferation, invasion

Ling Peng,1,* Kui Xiao,2,* Jian Cui,3 Xiang-Hua Ye,4 Yong-Chang Zhang,5 Li Mao,6 Giovanni Selvaggi,7 Jennifer Yen,8 Justin Stebbing9 1Department of Pulmonary and Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 3Shanghai BioGenius Bioinformatics Institute, Shanghai, People’s Republic of China; 4Department of Radiotherapy, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 5Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, Hunan, People’s Republic of China; 6Betta Pharmaceuticals, Hangzhou, People’s Republic of China; 7X-Covery Holdings, Palm Beach Gardens, FL, USA; 8Guardant Health, Inc., Redwood City, CA, USA; 9Division of Cancer, Department of Surgery and Cancer, Imperial College London, London, UK*These authors contributed equally to this workCorrespondence: Ling PengDepartment of Pulmonary and Critical Care Medicine, Zhejiang Provincial People’s Hospital, No. 158 Shangtang Road, Hangzhou, Zhejiang Province, People’s Republic of ChinaTel/Fax +86-571-85893509Email drpengling@hotmai.comBackground: Alectinib is approved for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring ALK rearrangements. Although generally well tolerated, alectinib can cause serious or life-threatening side effects.Case Presentation: Here, we report a case of a patient with NSCLC with an EML4-ALK fusion and was treated with alectinib but who developed grade 4 hyperbilirubinemia after five months on therapy. Alectinib was discontinued, and an artificial liver support system (ALSS) was used with an impressive decline in bilirubin levels. After two months drug-free, the patient experienced disease progression. Ensartinib was initiated as second-line treatment with a best response of stable disease after three months of therapy with no evidence of hyperbilirubinemia.Conclusion: This is the first report of ensartinib treatment after alectinib-induced hyperbilirubinemia which was successfully relieved by ALSS treatment and targeted drug cessation.Keywords: ensartinib, alectinib, hyperbilirubinemia, NSCLC, ALK

Xiaoli Liu,1,* Linna Peng,1,* Dandan Li,1 Chunjuan He,1 Shishi Xing,1 Yuhe Wang,2 Yongjun He1 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 2Department of Clinical Laboratory, The Affiliated Hospital of Xizang Minzu University, Xianyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongjun HeKey Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, #6 East Wenhui Road, Xianyang, 712082, Shaanxi, People’s Republic of ChinaTel +86-18691008772Email 545139647@qq.comBackground: Rheumatoid arthritis (RA), an autoimmune systemic inflammatory disease, largely resulted from genetic factor. Our purpose was to explore the association for IL1R1 and IL1R2 genetic variants with RA susceptibility in the Chinese Han population.Patients and Methods: A total of 508 RA patients and 494 controls were involved in this case–control study; single-nucleotide polymorphisms (SNPs) genotyping was identified by the Agena MassARRAY platform. The relationship between polymorphisms and RA susceptibility was calculated using the Pearson’s Chi-square test with odds ratios and 95% confidence intervals (CIs) in multiple genetic models. The Pearson’s Chi-square test and Student’s t-test were used for sample basic characteristic analysis. And linkage disequilibrium (LD) analysis and haplotype analysis were performed by logistic regression analysis.Results: The result from this study showed that rs2072472 (IL1R2) was an increased risk factor of RA (adjusted OR = 1.41, p = 0.011). Stratified analysis indicated SNPs rs10490571, rs956730, rs3917318 of IL1R1, and SNPs rs4851527, rs719250, rs3218896, rs3218977, rs2072472 of IL1R2 had impacts on RA risk after stratification based on gender and average age (54 years). Finally, haplotype analysis revealed that Ars3218977Ars2072472 haplotype in IL1R2 was related to a decreased RA risk (adjusted OR = 0.79; 95% CI = 0.65– 0.94; p = 0.010). Yet, rs3917225(IL1R1) and rs11674595(IL1R2) were not significant in RA association analysis.Conclusion: We determined SNPs (rs3917318, rs956730, rs1049057) of IL1R1 and SNPs (rs3218977, rs719250, rs4851527, rs3218896, rs2072472) of IL1R2 were correlated with the RA susceptibility in the Chinese Han population.Keywords: rheumatoid arthritis, RA, IL1R1/IL1R2, single-nucleotide polymorphism, SNP, susceptibility

Chen Gao, Fenghua Peng, Xubiao Xie, Longkai Peng Department of Kidney Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaCorrespondence: Longkai PengDepartment of Kidney Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaEmail penglongkai@csu.edu.cnBackground: Circulating interleukin (IL)-10 is associated with adverse cardiovascular events in chronic kidney disease (CKD). Whether IL-10 predicts cardiovascular and all-cause mortality after kidney transplantation (KT) is unknown.Methods: The association between plasma IL-10 and cardiovascular and all-cause mortality was analyzed in a prospective cohort, which included 418 stable kidney transplant recipients, at a median of 3.6 (range=1.2– 8.4) years after transplantation. Multivariate Cox regression models were performed to adjusting related confounding factors.Results: Median level of IL-10 in KT patient was 22.3 pg/mL. Multivariate Cox regression analysis revealed that serum levels IL-10 were significantly and independently associated with cardiovascular mortality after adjusting for age, gender, BMI, current smoker, current drinker, cause of kidney disease, systolic and diastolic BP, laboratory indexes and medication (HR=1.26, 95% CI 1.19– 2.08, P-trend< 0.001). The multivariate Cox analysis also suggested that serum levels IL-10 were independently associated with all-cause mortality (HR=1.25, 95% CI 1.11– 1.8, P-trend=0.023) after controlling these same related confounding factors. Sensitivity and stratified analysis showed that the significant association can be affected by history of acute rejection.Conclusion: Plasma IL-10 is independently and significant associated with cardiovascular and all-cause mortality after kidney transplantation. The significant association is independent of cardiovascular risk factors and other related confounding factors.Keywords: IL-10, kidney transplantation, cardiovascular mortality, all-cause mortality, Cox regression, prognosis

Junjie Li,* Lijia Peng,* Wenya Bai, Peihua Peng, Wendong Chen, Wei Yang, Jianlin Shao Department of Anesthesiology, First Affiliated Hospital, Kunming Medical University, Kunming City, 650032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianlin ShaoDepartment of Anesthesiology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Wuhua, Kunming, Yunnan, 650000, People’s Republic of ChinaTel +86-871-6532488-2755Email cmushaojlmz@163.comBackground: We have previously demonstrated that biliverdin has neuroprotective effects that ameliorate cerebral ischemia/reperfusion (I/R) injury in rats. However, the underlying mechanism is unknown. This study aimed at elucidating on the modulatory role of miR-27a-3p on Rgs1 as a mechanism by which biliverdin affects cerebral I/R injury.Methods: Middle cerebral artery occlusion/reperfusion (MCAO/R) was used to establish I/R rat models while oxygen glucose deprivation/reoxygenation (OGD/R) was used to induce hippocampal neurons to establish I/R models in vitro. Infarct volume was assessed by TTC staining. Apoptotic analyses of ischemic cortical neurons and cells were performed by TUNEL staining and flow cytometry, respectively. Cell viability was assessed by the CCK-8 assay while the target of miR-27a-3p was determined by double luciferase reporter assay. Relative expression levels of miR-27a-3p and Rgs1 (in vivo and in vitro) as well as markers of inflammation and apoptosis (in vitro) were detected by RT-qPCR. Then, Elisa and western blot were used to assess protein expression levels of inflammatory and apoptotic markers in vitro.Results: Biliverdin suppressed inflammation and apoptosis in hippocampal neurons upon OGD/R, and reduced cerebral infarction volume as well as apoptosis in the MCAO/R rat model. Furthermore, biliverdin upregulated miR-27a-3p and downregulated hippocampal neuron Rgs1 after OGD/R as well as in rat brain tissues after cerebral I/R. Bioinformatic analysis revealed an miR-27a-3p docking site in the 3ʹ-UTR region of Rgs1. Luciferase reporter assays showed that Rgs1 is an miR-27a-3p target. Moreover, miR-27a-3p upregulation inhibited OGD/R-triggered inflammation and suppressed neuronal apoptosis. Rgs1 knockdown suppressed OGD/R-triggered inflammation and decreased neuronal apoptosis while miR-27a-3p downregulation reversed the protective effect of Rgs1 knockdown. Moreover, miR-27a-3p overexpression and Rgs1 silencing suppressed NF-κB (p65) expression.Conclusion: Biliverdin protects against cerebral I/R injury by regulating the miR-27a-3p/Rgs1 axis, thereby inhibiting inflammation and apoptosis.Keywords: cerebral ischemia/reperfusion, biliverdin, miR-27a-3p, Rgs1, inflammation, apoptosis

Yan Hao,1 Jie Miao,2 Wenjia Liu,1 Kangqin Cai,1 Xianli Huang,1 Li Peng1 1Department of Nephrology, The First People’s Hospital of Zigong, Zigong, 643000, Sichuan, People’s Republic of China; 2Department of Nephrology, The Health and Rehabilitation Vocational College of Sichuan, Zigong, 643000, Sichuan, People’s Republic of ChinaCorrespondence: Yan HaoDepartment of Nephrology, The First People’s Hospital of Zigong, No. 42, Shangyi Road, Daoshenghao Community, Ziliujing District, Zigong, 643000, Sichuan, People’s Republic of ChinaTel/Fax +86-13990087106Email haoyan12301@163.comBackground: Mesenchymal stem cell (MSC)-derived exosomes have seen great advances in human disease control in a minimally invasive manner. This research aimed to explore the function of MSC-derived exosomes in diabetic nephropathy (DN) progression and the molecules involved.Methods: A rat model with DN and rat glomerular mesangial cell (GMC) models treated with high glucose (HG) were established, which were treated with exosomes from adipose-derived-MSCs (adMSCs). The levels of blood glucose, serum creatinine, and urinary protein, the urine albumin-to-creatinine ratio (UACR), kidney weight/body weight, and mesangial hyperplasia and kidney fibrosis in rats were determined. The expression of interleukin-6 (IL-6), collagen I (Col. I), fibronectin (FN), Bax and Bcl-2 in HG-treated GMCs was assessed. The microRNA (miRNA) carried by adMSC-exosomes was identified, and the implicated down-stream molecules were analyzed.Results: adMSC-derived exosomes decreased levels of blood glucose, serum creatinine, 24-h urinary protein, UACR and kidney weight/body weight, and they suppressed mesangial hyperplasia and kidney fibrosis in DN rats. The exosomes also suppressed levels of IL6, Col. I and FN in HG-treated GMCs and promoted cell apoptosis. miR-125a was at least partially responsible for the above protective events mediated by adMSC-exosomes. miR-125a directly bound to histone deacetylase 1 (HDAC1), while HDAC1 further regulated endothelin-1 (ET-1) activation. Up-regulation of HDAC1 blocked the functions of adMSC-exosomal miR-125a.Conclusion: This study suggested that adMSC-derived exosomes inhibit DN progression and alleviate the symptoms by carrying miR-125a, during which HDAC1 and ET-1 were inhibited. This study may provide novel effects into DN treatment.Keywords: exosomes, miR-125a, HDAC1, ET-1, diabetic nephropathy