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Kun Xu,1,2 Jiefan Zhang,1,2 Wei Ma,1,2 Yongyu Wang,1,2 Bo Chen,1,2 Ningyang Gao,1,2 Jian Pang,1,2 Hongsheng Zhan1,2 1Shi’s Center of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Institute of Traumatology & Orthopedics, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Hongsheng Zhan; Jian Pang, Email shgsyjs@139.com; pangjian2004@gmail.comObjective: Shi’s Knee Daoyin (SKD) exercise is a treatment derived from Traditional Chinese exercise (TCE) specifically designed for lower limb health care. This study aimed to assess the feasibility of conducting a randomized controlled trial to explore the effectiveness of SKD exercise in treating knee osteoarthritis (KOA).Methods: Participants were randomized to receive Health Education (HE) or SKD exercise. The primary outcomes were feasibility and safety outcomes, including participant recruitment rate, retention rate, as well as adherence to intervention. The secondary outcomes included Visual Analogue Scale (VAS) scores for pain, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, the 20-Meter Walk Test (20-MWT) and the 5-times Chair-Stand Test (5-CST).Results: The results indicate that out of 89 individuals invited to participate in the study, 72 were eligible and agreed to participate, resulting in a recruitment rate of 80.9%. All participating patients completed the follow-up and were included in the analysis; no patients dropped out of the study due to adverse events. The secondary outcome measures showed that after twelve weeks of treatment, the VAS score, WOMAC total score, WOMAC pain score, WOMAC stiffness score, and WOMAC function score of patients in the HE group and SKD group all improved, but the improvement was more significant in the SKD group. The 20-MWT of SKD group after treatment was significantly shorter than before treatment (P< 0.001); There was no significant difference in 20-MWT between the HE group and baseline after treatment. The performance of the two groups of patients improved in 5-CST, but there was no statistical difference between the two groups after treatment (P=2.439).Conclusion: This study evaluated the feasibility and effectiveness of home-based SKD exercise intervention in alleviating symptoms in patients with symptomatic KOA, providing valuable information for designing an appropriate randomized controlled study.Keywords: knee osteoarthritis, pilot, exercise, randomized controlled trial

Yang Liu,1 Lanxi Zhang,2 Jie Zhao,1,3 Ruilong Lu,1 Xuejie Shao,1 Kexin Xu,1 Jiansheng Li,1,3,4,&ast; Yange Tian1,3,&ast; 1Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People’s Republic of China, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2School of Basic Medicine (Zhongjing School), Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiansheng Li; Yange Tian, Email li_js8@163.com; yange0910@126.comPurpose: The main objective of this study was to explore the mechanism of effective component compatibility of Bufei Yishen formula III (ECC-BYF III) in inhibiting mitochondrial oxidative stress in a rat model of chronic obstructive pulmonary disease (COPD).Methods: A549 cells exposed to cigarette smoke extract (CSE) were used to establish a model of mitochondrial oxidative damage. The cells were treated with the plasmid encoding Pkm2 and the enzymes and proteins involved in oxidative stress and mitochondrial function were measured. A rat model of COPD was established using CS and bacteria. Two different treatments were established, ECC-BYF III (5.5 mg/kg/d) and N-acetylcysteine (54 mg/kg/day). Animals were tested for pulmonary function (Vt, PEF, FVC, FEV0.1s and Cdyn) after eight weeks of therapy and were sacrificed. Pulmonary H&E staining was performed, and the total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) content were measured. The mitochondrial function was also examined. Furthermore, the Pkm2/Nrf2 signaling pathway was evaluated.Results: Overexpression of Pkm2 dramatically ameliorated the CS-induced mitochondrial oxidative damage. Further studies indicated that ECC-BYF III significantly improved mitochondrial function and inhibited oxidative stress in the lung tissues of COPD rats. Moreover, it can upregulate mitochondrial respiratory chain enzyme activity. ECC-BYF III also decreased the MDA content and increased T-SOD, GSH-Px, and T-AOC expression to facilitate oxidative homeostasis. Finally, our results indicated that the Pkm2/Nrf2 pathway is regulated by ECC-BYF III in A549 cells and lung tissue.Conclusion: These results indicate that ECC-BYF III exerts a strong effective therapeutic effect against cigarette smoke combined with bacteria-induced COPD in rats by activating the Pkm2/Nrf2 signaling pathway and restoring mitochondrial oxidative stress. Although more in vivo animal model research is needed to confirm these findings, this study contributes new data to support the conventional usage of ECC-BYF III.Keywords: chronic obstructive pulmonary disease, oxidative stress, ECC-BYF III, Pkm2, Nrf2

Kaiwu Xu,1 Cailing Xiang,1 Zhige Yu,1 Jia Li,2 Changjun Liu2 1Department of Gastrointestinal Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 410005, People’s Republic of China; 2Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 410005, People’s Republic of ChinaCorrespondence: Changjun Liu, Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), 61 Jiefang West Road, Changsha, Hunan Province, 410005, People’s Republic of China, Tel +86-0731-83928052, Email liuchangjun712@163.comPurpose: Strategies therapy for hepatocellular carcinoma (HCC) beyond oligometastasis are limited. The optimal sequence of systemic treatment for advanced HCC is not yet clear. Our study aims to evaluate the effectiveness of simultaneous lenvatinib combined PD-1 inhibitor on advanced HCC beyond oligometastasis.Patients and Methods: A total of 232 patients were enrolled in our retrospective study. Patients divided into three groups. (a) Lenvatinib plus simultaneous PD-1 inhibitor (Simultaneous group, n=58); (b) patients received PD-1 inhibitor before the tumor progression with continued lenvatinib administration (Before PD group, n=77); (c) patients received PD-1 inhibitor after the tumor progression (After PD group, n=97). To analyze overall survival (OS) and progression-free survival (PFS) among the three groups.Results: The estimated 6-, 12-, 18- and 24-mon OS for Simultaneous group patients were 100%, 93.1%, 63.4%, 48.3%, whereas the OS rates were 100%, 78%, 36.3%, 23.6% in Before PD group, and 99%, 61.2%, 22.1%, 7.5% in After PD group. The OS rates were obviously improved with the use of simultaneous PD-1 inhibitor among the three groups (P < 0.001). The estimated 3-, 6-, 9- and 12-month PFS rates for patients were 89.6%, 44.8%, 24.6%, 6% in After PD group, 90.9%, 59.7%, 27.3%, 12.4% in Before PD group and 98.3%, 81%, 51.7%, 39.7% in Simultaneous group, respectively. PFS rate was significantly different among the three groups (P < 0.001).Conclusion: Synchronous administration of lenvatinib and PD-1 inhibitors improved survival rate significantly. The synchronous combination could represent a promising strategy in HCC beyond oligometastasis.Keywords: lenvatinib, PD-1 inhibitor, hepatocellular carcinoma beyond oligometastasis, simultaneous, prognosis

Shenjiao Wang,1,2,&ast; Xin Zou,3– 5,&ast; Jianguang Fu,1 Fei Deng,1 Huiyan Yu,1 Huan Fan,1 Qigang Dai,1 Qingxiang Shang,5 Ke Xu,1 Changjun Bao1,5 1Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing, Jiangsu Province, People’s Republic of China; 2Ili Kazakh Autonomous Prefecture Center for Disease Control and Prevention, Ili, Xinjiang, People’s Republic of China; 3Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 4Chongqing Key Laboratory of Viral Infectious Diseases, Chongqing, People’s Republic of China; 5School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Xu; Changjun Bao, Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), No. 172, Jiangsu Road, Gulou District, Nanjing, Jiangsu Province, 210009, People’s Republic of China, Tel +86-18915999237, +86-18118996911, Email xuke923@163.com; bao2000_cn@163.comBackground: Human adenovirus (HAdV) is common pathogens that cause various respiratory diseases. The genetic diversity of viruses caused by recombination is considered to be the main source of emerging outbreaks. The aim of this study is to explore the evolutionary relationship and recombination events of HAdV genome in respiratory tract infections in Jiangsu Province.Methods: Whole-genome sequencing (WGS) technology was used to sequence 66 patients with HAdV infection (37 patients with influenza-like illness (ILI) and 29 hospitalized patients with pneumonia) from Jiangsu Province. Epidemiological analysis was performed on hospitalized pneumonia and ILI patients infected with HAdV. Subsequently, phylogenetic, recombination, and nucleotide and amino acid identity analyses were performed.Results: Epidemiological analysis of patients undergoing WGS showed that 75.7% of ILI patients were infected with the HAdVB strain and 69.0% of hospitalized pneumonia patients were infected with the HAdVC strain. Moreover, the hospitalized pneumonia and ILI patients infected with HAdV were different in region and time. The strains of HAdVB3 and HAdVB7 genotypes were mainly infected in 2015 and 2017, and the strains of HAdVC1 and HAdVC2 genotypes were mainly infected in 2020. The results of histogram analysis showed that the HAdV strain mainly infected children under 5 years old. In addition, 36 novel recombinant strains were identified. The discovery of these recombinant strains may contribute to understanding the epidemiology of HAdV and research on related vaccines. Furthermore, the percentage of nucleotide and amino acid identities revealed a high level of genetic conservation within isolates from HAdVB3, HAdVB7, HAdVC1, HAdVC2 and HAdVC5 genotypes.Conclusion: The WGS analysis reveals the evolutionary relationships and recombination events of HAdV strains in Jiangsu Province, which is helpful to deepen the understanding of HAdV epidemiology and evolution. In addition, it provides a basis for the formulation of public health strategies in Jiangsu Province.Keywords: human adenovirus, whole genome sequencing, phylogenetic analysis, recombination

Jiongfeng Zhang,1,&ast; Xiaohui Luo,1,&ast; Ruiling Zhou,2,&ast; Chong Guo,1 Kai Xu,1 Gaoyang Qu,1 Le Zou,1 Wenye Yao,1 Shifan Lin,1 Zhiping Zhang1 1Department of Orthopedics, the 3rd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330008, People’s Republic of China; 2Department of Dermatology, Jiangxi Provincial Dermatology Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shifan Lin, Email 66031226@qq.com; Zhiping Zhang, Tel +86 791-88862249, Email ndsfy001425@ncu.edu.cnObjective: To explore the suitable population of CT value for predicting low bone mineral density (low-BMD).Methods: A total of 1268 patients who underwent chest CT examination and DXA within one-month period retrospectively analyzed. The CT attenuation values of trabecular bone were measured in mid-sagittal plane from thoracic vertebra 7 (T7). Receiver operating characteristic (ROC) curves were used to evaluate the ability to diagnose low-BMD.Results: The AUC for diagnosing low BMD was larger in women than in men (0.894 vs 0.744, p < 0.05). The AUC increased gradually with the increase of age but decreased gradually with the increase in height and weight (p < 0.05). In females, when specificity was adjusted to approximately 90%, a threshold of 140.25 HU has a sensitivity of 69.3%, which is higher than the sensitivity of 36.5% in males for distinguishing low-BMD from normal. At the age of 70 or more, when specificity was adjusted to approximately 90%, a threshold of 126.31 HU has a sensitivity of 76.1%, which was higher than that of other age groups.Conclusion: For patients who had completed chest CTs, the CT values were more effective in predicting low-BMD in female, elderly, lower height, and lower weight patients.Keywords: bone mineral density, chest computed tomography, dual-energy X-ray absorptiometry, attenuation value

Yuli Ji,1,2,&ast; Liangyu Mi,1,2,&ast; Miaomiao Zhao,1,2 Xiaoyao He,1,2 Yuting Hu,1,2 Yanan Gao,1,2 Chengliang Yin,3 Ke Xu1,2 1Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China; 2Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Faculty of Medicine, Macau University of Science and Technology, Macau, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Xu, Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, No. 99 Longcheng Street, Taiyuan, Shanxi Province, People’s Republic of China, Email xukesxbqeh@hotmail.comAbstract: Autoimmune diseases refer to a group of conditions where the immune system produces an immune response against self-antigens, resulting in tissue damage. These diseases have profound impacts on the health of patients. In recent years, with the rapid development in the field of biomedicine, engineered exosomes have emerged as a noteworthy class of biogenic nanoparticles. By precisely manipulating the cargo and surface markers of exosomes, engineered exosomes have gained enhanced anti-inflammatory, immunomodulatory, and tissue reparative abilities, providing new prospects for the treatment of autoimmune diseases. Engineered exosomes not only facilitate the efficient delivery of bioactive molecules including nucleic acids, proteins, and cytokines, but also possess the capability to modulate immune cell functions, suppress inflammation, and restore immune homeostasis. This review mainly focuses on the applications of engineered exosomes in several typical autoimmune diseases. Additionally, this article comprehensively summarizes the current approaches for modification and engineering of exosomes and outlines their prospects in clinical applications. In conclusion, engineered exosomes, as an innovative therapeutic approach, hold promise for the management of autoimmune diseases. However, while significant progress has been made, further rigorous research is still needed to address the challenges that engineered exosomes may encounter in the therapeutic intervention process, in order to facilitate their successful translation into clinical practice and ultimately benefit a broader population of patients.Keywords: engineered exosomes, autoimmune diseases, genetic engineering, anti-inflammatory applications

Jialing Xu,1,2 Hao Zhang,1,2 Dan Chen,2 Kaiyong Xu,1,2 Zifa Li,1,2 Hongyun Wu,3 Xiwen Geng,1,2 Xia Wei,4 Jibiao Wu,1,2 Wenqiang Cui,3 Sheng Wei1,2 1The Key Laboratory of Traditional Chinese Medicine Classic Theory of Ministry of Education, Shandong University of Traditional Chinese Medicine, Ji’nan, Shandong, People’s Republic of China; 2Chinese Medicine and Brain Science Interdisciplinary Research Institute, Shandong University of Traditional Chinese Medicine, Ji’nan, Shandong, People’s Republic of China; 3Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji’nan, Shandong, People’s Republic of China; 4NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Institute for Food and Drug Control, Ji’nan, Shandong, People’s Republic of ChinaCorrespondence: Sheng Wei, Email weisheng@sdutcm.edu.cn; Wenqiang Cui, Email wqcui16@fudan.edu.cnAbstract: Chronic pain (CP) is a leading cause of disability and a potential factor that affects biological processes, family relationships, and self-esteem of patients. However, the need for treatment of CP is presently unmet. Current methods of pain management involve the use of drugs, but there are different degrees of concerning side effects. At present, the potential mechanisms underlying CP are not completely clear. As research progresses and novel therapeutic approaches are developed, the shortcomings of current pain treatment methods may be overcome. In this review, we discuss the retinal photoreceptors and brain regions associated with photoanalgesia, as well as the targets involved in photoanalgesia, shedding light on its potential underlying mechanisms. Our aim is to provide a foundation to understand the mechanisms underlying CP and develop light as a novel analgesic treatment has its biological regulation principle for CP. This approach may provide an opportunity to drive the field towards future translational, clinical studies and support pain drug development.Keywords: chronic pain, light therapy, photoanalgesia, brain regions, molecular targets

Yushan Shi,1,&ast; Zhangmeng Xu,2,&ast; Shuangshuang Pu,1 Kanghong Xu,1 Yanan Wang,1 Chunlai Zhang1 1Department of Laboratory Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 25000, People’s Republic of China; 2School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunlai Zhang, Department of Laboratory Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jingshi Road, Lixia, Jinan, Shandong, 25000, People’s Republic of China, Tel +86+15863139900, Email qd07@163.comPurpose: This study sought to examine the potential association between serum Klotho levels and the prevalence of COPD in the United States.Patients and Methods: This study was a cross-sectional analysis involving 4361 adults aged 40– 79 years participating in the US National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Our investigation utilized multivariate logistic regression and restricted cubic spline (RCS) regression to explore the potential correlation between serum Klotho concentrations and the prevalence of COPD. Additionally, we conducted stratified and interaction analyses to evaluate the consistency and potential modifiers of this relationship.Results: In this study encompassing 4631 patients (with an average age of 57.6 years, 47.5% of whom were male), 445 individuals (10.2%) were identified as having COPD. In the fully adjusted model, ln-transformed serum Klotho was negatively associated with COPD (OR = 0.71; 95% CI: 0.51– 0.99; p = 0.043). Meanwhile, compared with quartile 1, serum Klotho levels in quartiles 2– 4 yielded odds ratios (ORs) (95% CI) for COPD were 0.84 (0.63~1.11), 0.76 (0.56~1.02), 0.84 (0.62~1.13), respectively. A negative relationship was observed between the ln-transformed serum Klotho and occurrence of COPD (nonlinear: p = 0.140). the association between ln-transformed serum Klotho and COPD were stable in stratified analyses.Conclusion: Serum Klotho was negatively associated with the incidence of COPD, when ln-transformed Klotho concentration increased by 1 unit, the risk of COPD was 29% lower.Keywords: α-Klotho (Klotho), chronic obstructive pulmonary disease, cross-sectional study, National Health and Nutrition Survey, NHANES

Chongchong Zhou,1,2,&ast; Jingxuan Wei,1,&ast; Kai Xu,1 Yingtao Lin,3,4 Lingli Zhang,1 Xin Li1,4,5 1Department of Pharmaceutical Regulatory Science and Pharmacoeconomics, School of Pharmacy, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Research Management, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 3Department of Drug Clinical Trial Institution, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 4Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 5Department of Health Policy, School of Health Policy and Management, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Li; Lingli Zhang, School of Pharmacy, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, People’s Republic of China, Email xinli@njmu.edu.cn; zhanglingli@njmu.edu.cnBackground: Tislelizumab plus chemotherapy improved overall survival compared to chemotherapy alone, while maintaining an acceptable level of safety. But it’s still unclear which strategy is the most cost-effective. The objective of the study was to compare the cost-effectiveness of tislelizumab plus chemotherapy as first-line therapy for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) versus chemotherapy alone.Methods: A partitioned survival model with three states was constructed based on the RATIONALE-306 trial. The model’s time horizon was ten years, and its cycle was three weeks. Only direct medical costs were considered from the healthcare perspective in China. Calculations were performed on total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way sensitivity and probabilistic sensitivity analysis (PSA) were performed to determine the uncertainty regarding model parameters.Results: Tislelizumab plus chemotherapy provided 1.35 QALYs for &dollar;26,450.77, while chemotherapy alone provided 0.89 QALY for &dollar;16,687.15. Compared to chemotherapy alone, tislelizumab had an ICER of &dollar;21,062.09/QALY. At the threshold of three times the Chinese GDP per capita (&dollar;38,253/QALY), the PSA indicated that tislelizumab had a 96.4% likelihood of being designated cost-effective. At the threshold of 1.5 times the Chinese GDP per capita (&dollar;19,126.5/QALY), the PSA indicated that tislelizumab had a probability of 48.7% of being designated cost-effective.Conclusion: Tislelizumab plus chemotherapy as the first treatment for patients with advanced or metastatic ESCC may be a cost-effective option compared to chemotherapy alone at 3 times Chinese GDP per capita.Keywords: esophageal squamous cell carcinoma, cost-effectiveness, partitioned survival model, tislelizumab

Lianpeng Wu,1– 3 Yong Pan,1,2 Ke Xu1– 3 1Department of Clinical Laboratory Medicine, The Ding Li Clinical College of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Clinical Laboratory Medicine, Wenzhou Central Hospital, Wenzhou, 325000, People’s Republic of China; 3Key Laboratory of Diagnosis and Treatment of New and Recurrent Infectious Diseases of Wenzhou, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Ke Xu, Wenzhou Central Hospital, Key Laboratory of Diagnosis and Treatment of New and Recurrent Infectious Diseases of Wenzhou, The Ding Li Clinical College of Wenzhou Medical University, No. 252 Baili East Road, Lucheng District, Wenzhou, 325000, People’s Republic of China, Tel +86-13566290303, Email wzxuke72@163.comPurpose: To analyze the clinical characteristics of AIDS with dTSM, especially in patients with poor prognosis.Patients and Methods: One hundred and seventy AIDS patients were enrolled in this single-center retrospective study. The epidemiological characteristics, clinical manifestations, laboratory tests, imaging examination, and treatment outcome were collected. Logistic regression analysis was used to estimate the risk of mortality in AIDS patients with dTSM. The predictive value was evaluated using the receiver operating characteristic (ROC) curve.Results: From 2015 to 2022, the incidence of AIDS with dTSM in the Wenzhou region increased yearly, mainly in young adults. The mortality rate was 16.47%. The most common clinical manifestations were lymph-node enlargement (92.35%) and fever (78.24%). Multivariate logistic regression analysis showed that procalcitonin (PCT), blood urea nitrogen (BUN), shock, and antiretroviral therapy (ART) were the risk factors for poor outcomes. The model comprised four risk factors and showed an excellent prediction performance, with an AUC of 0.987 in the training cohort (95% CI: 0.946– 0.999) and 0.976 in the validation cohort (95% CI: 0.887– 0.999).Conclusion: This study suggested that PCT, BUN, shock, and ART were associated with the prognosis and outcome of AIDS with dTSM and had a specific predictive value.Keywords: acquired immunodeficiency syndrome, Talaromycosis marneffei, clinical characteristics, risk factor, prediction model, poor prognosis

Haishi Zheng,1,2 Yirixiati Aihaiti,2 Yongsong Cai,2 Qiling Yuan,2 Mingyi Yang,2 Zheng Li,2 Ke Xu,2 Peng Xu1,2 1Department of Orthopedics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Joint Surgery, HongHui Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Peng Xu, Department of Orthopedics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China, Tel +86 13772090019, Email xupeng369@mail.xjtu.edu.cnPurpose: The goal of this study was to explore the expression characteristics of RNA modification-related genes, reveal immune landscapes and identify novel potential diagnostic biomarkers in osteoarthritis (OA) and rheumatoid arthritis (RA) patients.Patients and Methods: RNA microarray and single-cell sequencing (scRNA-seq) data were downloaded from gene expression omnibus (GEO) database. Differentially expressed RNA modification-related genes were identified and then functionally annotated. Univariate logistic regression and lasso regression analysis were used to identify primary disease genes for OA and RA. Validation was done using scRNA-seq analysis and immunohistochemistry (IHC) in human knee synovial tissues and a murine destabilization of the medial meniscus (DMM) model. Through WGCNA analysis, genes associated with cell pyroptosis or autophagy in OA and RA were identified, which were then combined with differentially expressed RNA modification-related genes to construct a PPI interaction network. Furthermore, hub genes were selected for ceRNA interaction network analysis, correlation analysis with OA and RA molecular subtypes, as well as correlation analysis with 22 immune cells.Results: Six RNA modification-related genes (ADAMDEC1, IGHM, OGN, TNFRSF11B, SCARA3 and PTN) were identified as potential OA and RA pathogenesis biomarkers. Their expression was validated in human knee synovial tissues and a murine DMM model. Functional enrichment of differentially expressed RNA modification-related genes between RA and OA was analyzed using GO, KEGG, GSEA, and GSVA. Based on WGCNA and PPI analysis, the six hub genes related to pyroptosis and RNA modification (CXCL10, CXCL9, CCR7, CCL5, CXCL1, and CCR2) were identified as central nodes for ceRNA interaction, correlation with OA and RA molecular subtypes, and association with 22 immune cells.Conclusion: Our research revealed the significance of RNA modification-related genes in the development of OA and RA pathogenesis, thereby providing a novel research direction for understanding the mechanisms, diagnosis, and treatment of OA and RA.Keywords: m6A, m5C, m1A, osteoarthritis, rheumatoid arthritis, single-cell sequencing

Lianpeng Wu,1– 3 Dandan Xia,1– 3 Ke Xu1– 3 1Department of Clinical Laboratory Medicine, The Ding Li Clinical College of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Clinical Laboratory Medicine, Wenzhou Central Hospital, Wenzhou, 325000, People’s Republic of China; 3Key Laboratory of Diagnosis and Treatment of New and Recurrent Infectious Diseases of Wenzhou, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Ke Xu, Department of Clinical Laboratory Medicine, Wenzhou Central Hospital, Wenzhou, 325000, People’s Republic of China, Tel +86 135 6629 0303, Email wzxuke72@163.comPurpose: Although highly active antiretroviral therapy (HA-ART) can effectively suppress the disease process in patients with acquired immunodeficiency syndrome (AIDS), opportunistic infections, mainly bloodstream infections (BSI), are still the main cause of death in people living with HIV. There is no effective diagnostic strategy for HIV-infected people with BSI. This study aimed to develop an AI diagnostic model with high sensitivity to improve the early detection of HIV-infected people with BSI.Patients and Methods: This study retrospectively analyzed the 40 clinical factors of 498 HIV-infected people (171 with BSI positive and 327 with BSI negative) who admitted to Wenzhou Central Hospital from September 2014 to July 2021. This study used the hospital information management system to collect the clinical characteristics, laboratory and imaging examination results, and clinical diagnosis of the two groups. The diagnostic results of all patients were in line with the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of AIDS (2021 Edition), and the BSI diagnosis was in line with the diagnostic criteria of sepsis and bacteremia in Practical Internal Medicine (13th Edition). On this basis, various risk prediction models were established by combining 8 artificial intelligence (AI) algorithms in the training set and validating the diagnosis performance in the testing set. The model with the best diagnostic performance was selected as the final diagnostic model.Results: The clinical characteristics of HIV-infected people with BSI are atypical, and the pathogens in this area are mainly fungi. Ten risk factors were selected: low level of hemoglobin, CD4+T cell and platelets, high level of lactate dehydrogenase and blood urea nitrogen, splenomegaly, without ART treatment, strip shadow, nodular shadow, and shock. The combination of the ten risk factors, age, gender and the “svmRadial” model can identify the HIV-infected people with BSI from the HIV-infected people without BSI with an area under the curve of 0.916 and a sensitivity and specificity of 0.824 and 0.855, respectively.Conclusion: The model showed excellent performance in diagnosing HIV-infected people with BSI. Internal and external validation showed that the diagnosis model had high clinical application value.Keywords: acquired immunodeficiency syndrome, bloodstream infections, clinical risk factors, diagnosis, artificial intelligence model

Ke Xu,1,2 Dara Charles,3 Salami Ismael,3 Jun Zhang4 1Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, People’s Republic of China; 2Laboratory and Anatomical Pathology Department of the Mali Hospital, Bamako, Mali; 3Neurosurgery Department of the Mali Hospital, Bamako, Mali; 4Department of Orthopedics, Zhejiang Provincial People’s Hospital Bijie Hospital, Bijie, Guizhou, People’s Republic of ChinaCorrespondence: Jun Zhang, Department of Orthopedics, Zhejiang Provincial People’s Hospital Bijie Hospital, 112 Guanghui Road, Bijie, Guizhou, 551700, People’s Republic of China, Tel +86-13868140717, Fax +86-857-8294072, Email spinezhangjun@aliyun.comAbstract: Highly invasive infections caused by Klebsiella pneumonia, which includes bacteremia, liver abscess, meningitis, septic arthritis, and osteomyelitis, in not commonly seen in adult immunocompetent and immunocompromised patients. Here, we report an adult case of chronic multifocal osteomyelitis with severe cranial involvement caused by Klebsiella pneumonia. The patient has a 5-year history of orbital abscess and multiple scalp traumas. CT scan showed right temporal and periorbital osteolysis, multiple parietal osteolysis. The pus was collected twice and routine culture was positive for Klebsiella pneumoniae. Good clinical outcome was achieved with debridement and antibiotic treatment. Microbiologists and clinicians should promptly perform bacteriological cultures on biopsy specimens to facilitate diagnosis when imaging or intraoperative findings of bone infection are suspected, especially in the Mali population.Keywords: osteomyelitis, skull, Klebsiella pneumoniae, multifocal

Han Li,1,&ast; Ke Su,1,&ast; Lu Guo,2,&ast; Yi Jiang,1 Ke Xu,1 Tao Gu,1 Jiali Chen,1 Zhenying Wu,1 Pan Wang,3 Xi Zhang,4 Yushan Yan,1 Siyuan Li,1 Xue Wu,1 Lei Han,5 Kun He,6 Lianbin Wen,7 Bo Li,4 Yunwei Han1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Clinical Research Institute, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 4Department of General Surgery (Hepatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China; 6Clinical Medical College, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 7Sichuan Provincial People’s Hospital, Chengdu, 610072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunwei Han; Bo Li, The Affiliated Hospital of Southwest Medical University, 25 TAIPING Street, Luzhou City, Sichuan Province, People’s Republic of China, Tel +86-830-3165598 ; +86-830-3165613, Email lanpaoxiansheng@126.com; liboer2002@126.comBackground: At present, it is not known whether targeting plus immunotherapy combined with transarterial chemoembolization (TACE) can improve the efficacy of hepatocellular carcinoma (HCC). The aim of this retrospective experiment was to explore the difference in clinical efficacy between antiangiogenic drugs plus PD-1 inhibitors combined with and without TACE.Methods: Clinical data of 145 patients with HCC who received anti-angiogenesis therapy plus PD-1 inhibitor combined with TACE (TACE-P-T) (n = 62) or anti-angiogenesis therapy combined with PD-1 inhibitor (P-T) (n = 83) in China from October 2018 to December 2022 were collected and reviewed. We used propensity matching (PSM) to create two groups with comparable baseline scores, compared their median survival time (mOS) and median progression-free survival time (mPFS), and performed subgroup analysis.Results: Before PSM, the mOS and mPFS of patients were 20.3 and 5.0 months in the triple therapy group and 13.6 and 7.4 months in the control group, respectively. After PSM, the mOS and mPFS of patients were 19.7 and 6.6 months in the triple treatment group and 10.5 and 3.7 months in the control group, respectively. Therefore, the TACE-P-T group showed better survival outcomes than P-T. In the subgroup analysis, compared with the control group, the mOS was 10.7 vs 20.3 months in the alpha fetoprotein (AFP) (≥ 400ng/mL/< 400ng/mL) group, 29.3 vs 7.4 months in the alkaline phosphatase (ALP) (≥ 125u/L/< 125u/L) group and 10.5 vs 20.0 months in the Portal vein invasion (PVTT) group.Conclusion: Antiangiogenic therapy combined with PD-1 inhibitors combined with TACE has significant survival benefits for HCC patients.Keywords: HCC, PD-1 inhibitors, antiangiogenic therapy, TACE

Jiajun Wu,1,2,&ast; Lei Gao,1,2,&ast; Qiao Shi,3 Chunhui Qin,4 Kai Xu,1,2 Zhaoshun Jiang,1,2 Xixue Zhang,1,2 Ming Li,5 Jianjian Qiu,6,&ast; Weidong Gu1,2,&ast; 1Department of Anesthesiology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 2Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, 200040, People’s Republic of China; 3Department of Anesthesiology, International Peace Maternity and Child Health Hospital of China, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China; 4Department of Pain Management, Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 5Department of Radiology, Huadong Hospital affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 6Department of Radiation Oncology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Gu; Jianjian Qiu, Email hdmz0800@163.com; qiujianjian@fudan.edu.cnPurpose: To evaluate the accuracy of mixed reality (MR)-guided visualization technology for spinal puncture (MRsp).Methods: MRsp involved the following three steps: 1. Lumbar spine computed tomography (CT) data were obtained to reconstruct virtual 3D images, which were imported into a HoloLens (2nd gen). 2. The patented MR system quickly recognized the spatial orientation and superimposed the virtual image over the real spine in the HoloLens. 3. The operator performed the spinal puncture with structural information provided by the virtual image. A posture fixation cushion was used to keep the subjects’ lateral decubitus position consistent. 12 subjects were recruited to verify the setup error and the registration error. The setup error was calculated using the first two CT scans and measuring the displacement of two location markers. The projection points of the upper edge of the L3 spinous process (L3↑), the lower edge of the L3 spinous process (L3↓), and the lower edge of the L4 spinous process (L4↓) in the virtual image were positioned and marked on the skin as the registration markers. A third CT scan was performed to determine the registration error by measuring the displacement between the three registration markers and the corresponding real spinous process edges.Results: The setup errors in the position of the cranial location marker between CT scans along the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) axes of the CT bed measured 0.09 ± 0.06 cm, 0.30 ± 0.28 cm, and 0.22 ± 0.12 cm, respectively, while those of the position of the caudal location marker measured 0.08 ± 0.06 cm, 0.29 ± 0.18 cm, and 0.18 ± 0.10 cm, respectively. The registration errors between the three registration markers and the subject’s real L3↑, L3↓, and L4↓ were 0.11 ± 0.09 cm, 0.15 ± 0.13 cm, and 0.13 ± 0.10 cm, respectively, in the SI direction.Conclusion: This MR-guided visualization technology for spinal puncture can accurately and quickly superimpose the reconstructed 3D CT images over a real human spine.Keywords: mixed reality, spinal puncture, immobilization, superimposition, setup error, registration error

Baohu Zhang,1,&ast; Jie Zhou,1,&ast; Guancong Xie,2,&ast; Li Zhang,1 Yang Zhang,1 Kangli Xu,1 Tianyuan Feng,1 Shucai Yang1 1Department of Clinical Laboratory, Pingshan General Hospital, Southern Medical University (Pingshan District People’s Hospital of Shenzhen), Shenzhen, Guangdong, People’s Republic of China; 2Department of Cardiovascular Medicine, Pingshan General Hospital, Southern Medical University (Pingshan District People’s Hospital of Shenzhen), Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shucai Yang; Tianyuan Feng, Email shucaiyang@link.cuhk.edu.hk; psyyfty@sina.comAbstract: S. mitis/oralis has been previously reported in isolated cases of bacterial endocarditis and liver abscesses. Its presence in urine is generally considered a contaminant. A 66-year-old male patient was admitted to the hospital due to recurrent chest tightness and four-year history of exertional dyspnea. On the second day of admission, the patient presented with urgent and frequent urination, as well as dysuria. Both initial and subsequent urine cultures showed S. mitis/oralis infection, with polymorphonuclear leukocyte phagocytosis observed in the second sample. MALDI-TOF results confirmed the isolated strain as S. mitis/oralis. Drug susceptibility testing revealed multidrug resistance to penicillin, ceftriaxone, cefepime, levofloxacin, ofloxacin, and tetracycline, but sensitivity to quinupristin/dalfopristin, vancomycin, and linezolid. The clinician then prescribed vancomycin for anti-infective treatment, which proved effective. Keywords: S. mitis/oralis, UTI, MDR, phagocytosisKeywords: Streptococcus mitis/oralis, UKI, multidrug resistant, phagocytosis

Han Li,1,&ast; Lu Guo,2,&ast; Ke Su,1,&ast; Changlun Li,3 Yi Jiang,1 Pan Wang,4 Jiali Chen,1 Zhenying Wu,1 Ke Xu,5 Tao Gu,1 Hao Zeng,1 Kun He,6 Hao Chi,1 Wenxi Zhao,7 Lei Han,3 Yunwei Han1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China; 4Clinical Skills Center, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5Department of Oncology, Chongqing General Hospital, Chongqing, 401147, People’s Republic of China; 6Clinical Research Institute, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 7Clinical Medical College, Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunwei Han, The Affiliated Hospital of Southwest Medical University, 25 TAIPING Street, Luzhou City, Sichuan Province, People’s Republic of China, Tel +86-830-3165598, Email Lanpaoxiansheng@126.com Lei Han, Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China, Email hanleixxf@126.comBackground: TACE and TACE with or without targeted immunotherapy are crucial comprehensive therapies for middle and advanced HCC. However, a reasonable and concise score is needed to evaluate TACE and TACE combined with systemic therapy in HCC treatment.Methods: The HCC patients were grouped into two groups: training group (n = 778) (treated with TACE) and verification group (n = 333). The predictive value of baseline variables on overall survival was analyzed using COX model, and easy-to-use ALR (AST and Lym-R) scores. The best cut-off value of AST and Lym-R were determined using X-Tile software based on total survival time (OS) and further verified via a restricted three-spline method. Meanwhile, the score was further verified using two independent valid sets: TACE combined with targeted therapy and TACE with targeted combined immunotherapy.Results: In multivariate analysis, baseline serum AST> 57.1 (p < 0.001) and Lym-R≤ 21.7 (p < 0.001) were identified as independent prognostic factors. The OS of patients in the TACE pooled cohort with 0, 1, and 2 scores were 28.1 (95% CI 24– 33.8) months, 15 (95% CI 12.4– 18.6) months, and 7.4 (95% CI 5.7– 9.1) months, respectively. The time-varying ROC curve based on ALR showed that the AUC values for predicting 1, -2-and 3-year OS were 0.698, 0.718, and 0.636, respectively. These results are confirmed in two independent valid sets of TACE combined with targeted therapy and TACE with targeted combined immunotherapy. And we established a nomogram after COX regression to predict the 1 -, 2- and 3-year survival time.Conclusion: Our study confirmed that ALR score can predict the prognosis of HCC treated with TACE or TACE combined with systemic therapy.Keywords: TACE, immunotherapy, targeted therapy, nomogram

Zijun Wu,1,2,&ast; Qin Yang,3,&ast; Kai Xu,2 Juanjuan Wu,2 Bin Yang1,2 1The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Burn and Plastic Surgery, General Hospital of Central Theater Command, Wuhan, People’s Republic of China; 3Department of Laboratory Medicine, General Hospital of Central Theater Command, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Yang, The First School of Clinical Medicine, Southern Medical University, Nos.1023-1063, Shatai South Road, Baiyun District, Guangzhou, Guangdong, 510515, People’s Republic of China, Tel +86-18062601971, Email sszxkyb1@163.comBackground: IL-27 involves psoriasis pathogenesis potentially by promoting excessive keratinocyte proliferation. However, the underlying mechanisms remain unclear. This study aims to explore the key genes and molecular mechanisms of IL-27-induced keratinocyte proliferation.Methods: Primary keratinocytes and immortalized human keratinocyte HaCaT cells were treated with different concentrations of IL-27 for 24 h and 48 h respectively. CCK-8 assay was used to detect cell viability and Western blot was used to detect the expression of CyclinE and CyclinB1. Primary keratinocytes and HaCaT cells were treated with IL-27, and their differentially expressed (DE) genes were obtained by transcriptome sequencing. Then Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed to predict related pathways, and the long non-coding RNA-microRNA-messenger RNA network and protein-protein interaction network were constructed to screen key genes. Biochemical experiments were performed to assess the content of glucose (Glu), lactic acid (LA), and ATP. Flow cytometry and Mito-Tracker Green staining were used to detect mitochondrial membrane potential and the number of mitochondria respectively. Western blot was performed to assess the expression of glucose transporter 1 (GLUT1), hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), phosphoglycerate kinase 1 (PGK1), phosphorylated dynamin-related protein 1 (p-DRP1) (s637) and mitofusin 2 (MFN2).Results: IL-27 concentration-dependently increased keratinocyte viability and the expression of CyclinE and CyclinB1. Bioinformatics analysis showed that the enriched pathways of DE genes were closely associated with cellular metabolism. miR-7-5p, EGFR, PRKCB, PLCB1 and CALM3 were key genes. IL-27 increased the content of LA, mitochondrial membrane potential, and the expression of GLUT1, HK2, LDHA, PGK1, p-DRP1 (s637), and MFN2, accompanied by decreased contents of Glu and ATP (P< 0.001).Conclusion: IL-27 potentially promotes keratinocyte proliferation by enhancing glycolysis, mitochondrial function, and mitochondrial fusion. The findings of this study may be conducive to revealing the role of IL-27 in the pathogenesis of psoriasis.Keywords: psoriasis, RNA-seq, glycolysis, mitochondria

Su Zhang,1 Ke Xu,2 Su-Xiao Liu,3 Xiao-Lan Ye,1 Ping Huang,1 Hong-Juan Jiang1 1Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3Center for Reproductive Medicine, Department of Obstetrics, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Hong-Juan Jiang, Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 571 85893143, Fax +86 571 87666666, Email tigergirl@126.comPurpose: Ureaplasma urealyticum and Mycoplasma hominis began to show resistance to azithromycin, a macrolide antibiotic commonly used in pregnancy. Unfortunately, there are few effective and safe drugs in the clinic for genital mycoplasmas in pregnant women. In the present study, we investigated the prevalence of azithromycin-resistant U. urealyticum and M. hominis infections in pregnant women. The secondary research objects were possible influencing factors and consequences of insensitive Mycoplasma infection.Patients and methods: A retrospective analysis was carried out in pregnant women who underwent cervical Mycoplasma culture between October 2020 and October 2021 at a large general hospital in eastern China. The sociological characteristics and clinical information of these women were collected and analyzed.Results: A total of 375 pregnant women were enrolled, and 402 cultured mycoplasma specimens were collected. Overall, 186 (49.60%) patients tested positive cervical Mycoplasma infection, and 37 (9.87%) had infections caused by azithromycin-resistant Mycoplasma. In total, 39 mycoplasma samples were insensitive to azithromycin in vitro, also showing extremely high resistance to erythromycin, roxithromycin, and clarithromycin. Azithromycin was the only antibiotic used in women with Mycoplasma cervical infection, regardless of azithromycin resistance in vitro. Statistical results showed that azithromycin-resistant cervical Mycoplasma infection in pregnant women was unrelated to age, body mass index (BMI), gestational age, number of embryos, and assisted reproductive technology (ART) use, but led to a significantly increased incidence of adverse pregnancy outcomes (spontaneous abortion (SA), preterm birth (PTB), preterm prelabor rupture of membranes (PPROM), and stillbirth).Conclusion: Azithromycin-resistant U. urealyticum and M. hominis cervical infections are relatively common during pregnancy, and can increase the risk of adverse pregnancy outcomes; however, there is currently a lack of safe and effective drug treatments. Herein, we show that azithromycin-resistant mycoplasma infection requires timely intervention.Keywords: azithromycin resistance, Ureaplasma urealyticum, Mycoplasma hominis, pregnant women

Mengjie Chen,1,&ast; Kan Xu,2,&ast; Yuting He,1,&ast; Jianjun Jin,3 Ruolin Mao,1 Lei Gao,1 Yi Zhang,4 Gang Wang,5 Peng Gao,6 Min Xie,7 Chunfang Liu,8 Zhihong Chen1 1Department of Respiratory and Critical Care Medicine of Zhongshan Hospital, Shanghai Institute of Respiratory Disease, Fudan University, Shanghai, People’s Republic of China; 2Geriatric Department of Zhongshan Hospital, Shanghai Institute of Respiratory Disease, Fudan University, Shanghai, People’s Republic of China; 3Research Center of Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Air Liquide Holding Co., Ltd, Shanghai, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Department of Respiratory Medicine, The Second Affiliated Hospital of Jilin University, Changchun, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji Medical 10 College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 8Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihong Chen, Department of Respiratory and Critical Care Medicine of Zhongshan Hospital, No. 180 Fenglin Road, Shanghai, People’s Republic of China, Tel +86-21-64041990-2445, Fax +86-21-64187165, Email chen.zhihong@zs-hospital.sh.cn Chunfang Liu, Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, 12&num; Wlmq Road, Shanghai, People’s Republic of China, Email Chunfang_liu@fudan.edu.cnPurpose: The progression of an abnormal inflammatory response plays a crucial role in the lung function decline of chronic obstructive pulmonary disease (COPD) patients. Compared to serum biomarkers, inflammatory biomarkers in induced sputum would be a more reliable reflection of inflammatory processes in the airways.Patients and Methods: A total of 102 COPD participants were divided into a mild-to-moderate group (FEV1%pred≥ 50%, n=57) and a severe-to-very-severe group (FEV1%pred< 50%, n=45). We measured a series of inflammatory biomarkers in induced sputum and analyzed their association with lung function and SGRQ in COPD patients. To evaluate the relationship between inflammatory biomarkers and the inflammatory phenotype, we also analyzed the correlation between biomarkers and airway eosinophilic phenotype.Results: We found increased mRNA levels of MMP9, LTB4R, and A1AR and decreased levels of CC16 mRNA in induced sputum in the severe-to-very-severe group. After adjustment for age, sex and other biomarkers, CC16 mRNA expression was positively associated with FEV1%pred (r=0.516, p=0.004) and negatively correlated with SGRQ scores (r=− 0.3538, p=0.043). As previously known, decreased CC16 was related to the migration and aggregation of eosinophils in airway. It was also found that CC16 had a moderate negative correlation with the eosinophilic inflammation in airway (r=− 0.363, p=0.045) in our COPD patients.Conclusion: Low CC16 mRNA expression levels in induced sputum were associated with low FEV1%pred and a high SGRQ score in COPD patients. Sputum CC16 as a potential biomarker for predicting COPD severity in clinical practice might attribute to the involvement of CC16 in airway eosinophilic inflammation.Keywords: COPD, induced sputum, airway inflammation, biomarkers, lung function, CC16

Jinjuan Zhang,1 Caifang Bu,1 Liwei Yao,1,&ast; Kan Xu2,&ast; 1Department of Nursing, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liwei Yao, Department of Nursing, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, No. 208 East Huancheng Road, Hangzhou, Zhejiang, People’s Republic of China, Email ylwmed@163.com Kan Xu, Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, No. 208 East Huancheng Road, Hangzhou, Zhejiang, People’s Republic of China, Email xukanmed@163.comPurpose: To assess the accuracy of the Mycobacterium tuberculosis (MTB)-RNA assay using pericardial tissue specimens for tuberculous pericarditis (TBP) diagnosis.Methods: MTB culture and MTB-RNA assay were performed for patients with suspected TBP. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of these two assays were analyzed.Results: This study included 79 patients. The sensitivity, specificity, PPV, NPV, and AUC were 28.1% (18/64), 100.0% (15/15), 100.0% (18/18), 24.6% (15/61), and 0.64 for the MTB culture and 37.5% (24/64), 100.0% (15/15), 100.0% (24/24), 27.3% (15/55), and 0.69 for the MTB-RNA assay, respectively. Patients with positive pericardial tissue culture were defined as having definite TBP; in other words, culture was the gold standard for this group of patients and had a sensitivity, specificity, PPV, and NPV of 100% and an AUC of 1.00. However, these values were found to be 72.2% (13/18), 100.0% (15/15), 100.0% (13/13), 75.0% (15/20), and 0.86 for the MTB-RNA assay, respectively. Among patients with probable TBP (culture-negative patients), the sensitivity, specificity, NPV, and AUC of MTB culture were 0.0% (0/46), 100.0% (15/15), 24.6% (15/61), and 0.50, respectively, but the PPV could not be determined. These values were found to be 23.9% (11/46), 100.0% (15/15), 100.0% (11/11), 30.0% (15/50), and 0.62 for the MTB-RNA assay, respectively.Conclusion: MTB-RNA assay using pericardial tissues had limited diagnostic efficacy for TBP. In culture-positive TBP, the diagnostic accuracy of MTB-RNA was good. In contrast, in culture-negative TBP, its diagnostic accuracy was unsatisfactory.Keywords: tuberculous pericarditis, RNA, culture, polymerase chain reaction, accuracy

Meina Feng,&ast; Wenxian Tu,&ast; Qin Zhou, Yuanmin Du, Kang Xu, Yunfeng Wang Department of Neurology, Wuhan Brain Hospital, General Hospital of the YANGTZE River Shipping, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunfeng Wang, Email wyf4get@aliyun.comPurpose: The objective of this paper is to explore the role of circHECTD1 in vascular smooth muscle cells (VSMCs) and atherosclerosis (AS).Methods: VSMCs were treated with platelet-derived growth factor-BB (PDGF-BB) in vitro, and the level of circHECTD1 was determined using qRT-PCR. Cell proliferation, migration, and invasion were analyzed using CCK8 and transwell assays. Cell apoptosis and cell cycle were analyzed using flow cytometry. The binding interaction between circHECTD1 and KHDRBS3 or EZH2 was investigated using the RIP, RNA pull-down.Results: CircHECTD1 was upregulated in PDGF-BB-induced VSMCs with a dose-dependent and time-dependent manner. Knockdown of circHECTD1 suppressed VSMCsproliferation and migration and enhanced cell apoptosis in VSMCs, while circHECTD1 overexpression yielded opposite effects. Mechanistically, circHECTD1 could interact with KHDRBS3, thus enhanced the stability of EZH2 mRNA and increased EZH2 protein level. In addition, silencing EZH2 in VSMCs reversed the proliferation-enhancing effect of circHECTD1 overexpression.Conclusion: Our findings provided providing a potential prognostic and therapy biomarker for AS.Keywords: circHECTD1, KHDRBS3, EZH2, VSMCs, atherosclerosis

Yiran Chen,1,2,&ast; Xiaoling Wu,3,&ast; Xi Chen,1,2 Deliang Guo,1,2 Weijie Ma,1,2 Yonghua Guo,1,2 Kequan Xu,1,2 Shuxian Ma,1,2 Yufeng Yuan,1,2,4 Qian Zhu1,2 1Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 2Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, Hubei, 430071, People’s Republic of China; 3Department of Liver Surgery, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yufeng Yuan; Qian Zhu, Email yuanyf1971@whu.edu.cn; zhuqian@whu.edu.cnIntroduction: Hepatocellular carcinoma (HCC) was the sixth most prevalent cancer worldwide. Long non-coding RNA TGFB2-OT1 has been proven to mediate inflammation and autophagy in vascular endothelial cells. However, its function in HCC is still unknown.Methods: We analyzed the relationship between TGFB2-OT1 expression and the clinicopathological features of 202 HCC patients. RT-qPCR was used to analyze the TGFB2-OT1 expression in HCC cell lines and tissues. In vitro and in vivo assays were conducted to verify the effect of TGFB2-OT1 on the phenotype of HCC. RNA pull-down assays were applied to reveal the proteins binding to the TGFB2-OT1. Western-blot assays were conducted to analyze the protein expression in HCC cell lines.Results: TGFB2-OT1 was found to be highly expressed in HCC samples and hepatoma cells. TGFB2-OT1 expression was significantly associated with age (P = 0.001), cirrhosis (P = 0.003), tumor size (P < 0.001), tumor encapsulation (P = 0.029), tumor protruding from the liver surface (P = 0.040), and alpha fetoprotein (AFP, P < 0.001) levels. TGFB2-OT1 promoted proliferation, migration, invasion, and angiogenesis in HCC cells, both in vitro and in vivo. TGFB2-OT1 binds to β-catenin and competitively impaired the binding of β-catenin to GSK3β, thus suppressing the phosphorylation of β-catenin at Ser33, Ser37, and Thr41.Conclusion: TGFB2-OT1 is overexpressed in HCC and predicts the poor prognosis of HCC patients. TGFB2-OT1 impedes the phosphorylation of β-catenin and acts as an alternative activator of the Wnt/β-catenin pathway to promote the progression and angiogenesis of HCC.Keywords: TGFB2-OT1, HCC, β-catenin, angiogenesis, phosphorylation

Ke Su,1,&ast; Weihong Huang,2,&ast; Xueting Li,3,&ast; Ke Xu,4,&ast; Tao Gu,1 Yanlin Liu,1 Juan Song,2 Keyi Qian,5 Yaoyang Xu,2 Hao Zeng,1 Yipei Yang,6 Lu Guo,7 Yunwei Han1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Clinical Medical College, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Oncology, 363 Hospital, Chengdu, 610041, People’s Republic of China; 4Department of Oncology, Chongqing General Hospital, Chongqing, 401147, People’s Republic of China; 5Department of Nursing, Sichuan University, Chengdu, 610065, People’s Republic of China; 6Department of Orthopedic Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, 518000, People’s Republic of China; 7Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunwei Han; Lu Guo, The Affiliated Hospital of Southwest Medical University, 25 TAIPING Street, Luzhou City, Sichuan Province, People’s Republic of China, Tel +86-830-3165598 ; +86-830-3165613, Email hanyunwei@swmu.edu.cn; guolu68@163.comBackground: Tumor proliferation is frequently accompanied by aberrant enzyme production. We aim to investigate the potential predictive value of both plasma alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in patients with HCC and to develop a nomogram to assess the prognosis of HCC.Methods: The trial involved 2327 patients between May 2015 and March 2022. Within 7 days of enrollment, the levels of ALP and LDH were measured, and their association with survival was assessed. And we had developed and validated a new nomogram based on ALD and ALP.Results: Using X-tile software, the optimal cut-off values were determined to be ALP = 172 U/L and LDH = 241 U/L. The high ALP (≥ 172), LDH (≥ 241), and ALP/LDH (≥ 0.91) groups had lower median overall survival (mOS) than low ALP (< 172), LDH (< 241), and ALP/LDH (< 0.91) groups (all p < 0.001). In addition, elevated ALP and LDH levels are independent negative prognostic indicators. Moreover, we established that the area under the curve (AUC) values of the predicted 1-, 2-, and 3-year survival rates of receiver operating characteristic curve (ROC) based on the nomogram were 0.79, 0.77, and 0.74, respectively. In addition, the calibration curves and decision curve analyses (DCA) demonstrated that this model possessed strong predictive capability.Conclusion: ALP, LDH and ALP/LDH can be employed as biomarkers for predicting the prognosis of HCC. Furthermore, the nomograph based on ALH and ALP demonstrates good HCC prediction performance. For HCC patients with high ALH or ALP or ALP/LDH, close surveillance program and adjuvant therapy should be considered.Keywords: lactate dehydrogenase, alkaline phosphatase, hepatocellular carcinoma, overall survival, nomogram

Yue Dai,1,2,&ast; Xuan Sha,1,&ast; Xiaoxi Song,1 Xiuli Zhang,1,2 Mengyuan Xing,1 Siwen Liu,1 Kai Xu,1,2 Jingjing Li1,2 1School of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Xu; Jingjing Li, Email xkpaper@163.com; qingchao0124@163.comPurpose: Early diagnosis and treatment of atherosclerosis (AS) vulnerable plaque has important clinical significance for the prognosis of patients. In this work, the integrated diagnosis and treatment nanoparticles based on Gd-doped Prussian blue (GPB) were constructed for the fluorescence/MR dual-mode imaging and anti-ROS treatment of vulnerable AS plaques in vitro and in vivo.Methods: To fabricate the theranostic NPs, GPB was modified with water-soluble polymer polyethyleneimine (PEI), fluorescence molecule rhodamine (Rd), and targeted molecule dextran sulfate (DS) step by step via electrostatic adsorption to construct GPRD NPs. The fluorescence/MR imaging ability and various nano-enzymes activity of GPRD NPs were detected, and the biocompatibility and safety of GPRD were also evaluated. Subsequently, RAW264.7 cells and ApoE -/- model mice were used to evaluate the effect of GPRD NPs on the targeted dual-mode imaging and anti-ROS treatment of vulnerable plaque in vitro and in vivo.Results: The experimental results showed that our fabricated GPRD NPs not only displayed excellent MR/fluorescence dual-modality imaging of vulnerable plaque in vivo but also effectively utilized the nano-enzyme activity of GPB to inhibit the AS progress by ROS scavenging and the following reduction of inflammation, apoptosis, and foam cells’ formation, providing a new avenue for the diagnosis and treatment of AS vulnerable plaque.Conclusion: The fabricated multimodal imaging nanoparticles with ROS-scavenging ability provided a new avenue for the diagnosis and treatment of AS vulnerable plaques.Graphical Abstract: Keywords: vulnerable plaques, ROS scavengers, nano-enzyme, MRI, fluorescence imaging

Xiaofang Wen,1,&ast; Nan Zeng,1,&ast; Ningbo Zhang,1,2,&ast; Tingting Ou,1 Xiaowei Li,1 Xiaoying Li,1 Wangen Li,1 Kang Xu,3 Tao Du1 1Department of Endocrinology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, People’s Republic of China; 2Department of Endocrinology, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Du; Kang Xu, Email dutao@gzhmu.edu.cn; xukang@mail.sysu.edu.cnBackground: Although flash continuous glucose monitoring systems (FCGM) accuracy has been extensively studied in diabetes, its accuracy is still not fully evaluated in type 2 diabetes (T2D) patients in real-world settings. In the present study, we aim to assess the effects of diabetes complications and related comorbidities on FCGM accuracy in T2D patients with diabetes complications and related comorbidities in the real world.Methods: FCGM data were collected at eight-time points daily (3 AM, 7 AM, 9 AM, 11 AM, 1 PM, 5 PM, 7 PM, and 9 PM) from 742 patients with T2D and compared with simultaneous fingertip capillary blood glucose (reference blood glucose, REF), and the difference was evaluated using Parkes error grid (PEG), surveillance error grid (SEG), and logistic regression analysis.Results: In total, 25,579 FCGM/REF data pairs were included in the study. The FCGM values were lower than the paired REF values in 75% of the pairs. The maximum bias (− 23.0%) and maximum mean absolute relative difference (24.5%) were observed at 3 AM among eight-time points. SEG analysis also demonstrated the highest percentage of paired readings in moderate and great risk zone (C and D) at 3 AM than PEG analysis (7.33% vs 0.43%, P< 0.001). According to the SEG classification, hypoglycemia, infection, diabetic foot, diabetic ketoacidosis, and hypertension were independent risk factors that impaired FCGM accuracy in patients.Conclusion: FCGM commonly underestimates blood glucose levels. Compared with PEG, SEG analysis seems more conducive to the analysis of FCGM performance. The present data highlights the impairment of diabetes complications and related comorbidities on the FCGM accuracy in T2D patients.Keywords: flash continuous glucose monitoring system, type 2 diabetes, surveillance error grid, Parkes error grid, diabetes complications

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

Qixian Sun,1 Xinrong Tao,1– 4 Bing Li,1 Hangbing Cao,1 Haoming Chen,1 Yuanjie Zou,1 Huihui Tao,1– 4 Min Mu,1– 4 Wenyang Wang,1 Keyi Xu1– 4 1Center for Medical Research, Medical School, Anhui University of Science and Technology, Huainan, People’s Republic of China; 2Key Laboratory of Industrial Dust Control and Occupational Health, Ministry of Education, Anhui University of Science and Technology, Huainan, People’s Republic of China; 3Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety, Anhui Higher Education Institutes, Anhui University of Science and Technology, Huainan, People’s Republic of China; 4Engineering Laboratory of Occupational Safety and Health, Anhui Province, Anhui University of Science and Technology, Huainan, People’s Republic of ChinaCorrespondence: Xinrong Tao, Medical School, Anhui University of Science and Technology, Huainan, People’s Republic of China, Email xrtao1116@hotmail.comBackground: Silicosis is a severe pulmonary disease caused by inhaling dust containing crystalline silica. The progression of silicosis to pulmonary fibrosis is usually unavoidable. Recent studies have revealed positivity for the overexpression of C-X-C chemokine receptor type 4 (CXCR4) in pulmonary fibrosis and shown that the CXCR4 inhibitor AMD3100 attenuated pulmonary fibrosis after bleomycin challenge and paraquat exposure. However, it is unclear whether AMD3100 reduces crystalline silica-induced pulmonary fibrosis.Methods: C57BL/6 male mice were instilled intranasally with a single dose of crystalline silica (12 mg/60 μL) to establish an acute silicosis mouse model. Twelve hours later, the mice were injected intraperitoneally with 5 mg/kg AMD3100 or control solution. Then, the mice were weighed daily and sacrificed on day 7, 14, or 28 to collect lung tissue and peripheral blood. Western blotting was also applied to determine the level of CXCR4, while different histological techniques were used to assess pulmonary inflammation and fibrosis. In addition, the level of B cells in peripheral blood was measured by flow cytometry.Results: CXCR4 and its ligand CXCL12 were upregulated in the lung tissues of crystalline silica-exposed mice. Blocking CXCR4 with AMD3100 suppressed the upregulation of CXCR4/CXCL12, reduced the severity of lung injury, and prevented weight loss. It also inhibited neutrophil infiltration at inflammatory sites and neutrophil extracellular trap formation, as well as reduced B-lymphocyte aggregates in the lung. Additionally, it decreased the recruitment of circulating fibrocytes (CD45+collagen I+CXCR4+) to the lung and the deposition of collagen I and α-smooth muscle actin in lung tissue. AMD3100 also increased the level of B cells in peripheral blood, preventing circulating B cells from migrating to the injured lungs.Conclusion: Blocking CXCR4 with AMD3100 delays pulmonary inflammation and fibrosis in a silicosis mouse model, suggesting the potential of AMD3100 as a drug for treating silicosis.Keywords: CXCR4, silicosis, pulmonary fibrosis, inflammation, AMD3100, mice

Xiaoqun Xu1,2 &ast;, Houyong Zhu3 &ast;, Long Cai1,2 &ast;, Xinyu Zhu,4 Hanxin Wang,5 Libin Liu,1,2 Fengwei Zhang,1,2 Hongjuan Zhou,1,2 Jing Wang,1,2 Tielong Chen,3 Kan Xu1,2 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; 3Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4Department of Cardiology, The Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kan Xu, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, No. 208 East Huancheng Road, Hangzhou, 310003, People’s Republic of China, Email xukan3787@qq.com Tielong Chen, Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Hangzhou, 310007, People’s Republic of China, Email ctlppp@foxmail.comBackground: This study aimed to investigate whether nutrition levels in patients with active pulmonary tuberculosis (TB) affect their risk of all-cause mortality during hospitalization and to further evaluate the predictive ability of Geriatric Nutritional Risk Index (GNRI) and Body Mass Index (BMI) for risk of all-cause mortality.Methods: Patients from January 1, 2020 to December 31, 2021 were retrieved, and a total of 1847 were included. The primary outcome was all-cause mortality. Propensity score matching (PSM) was performed for risk adjustment, and receiver operating characteristic (ROC) curve analysis was performed to assess the predictive ability of GNRI and BMI for all-cause mortality.Results: Malnourished TB patients were older, had more congestive heart failure, and had more chronic obstructive pulmonary disease or asthma. Under the nutrition level grouping defined by GNRI, the all-cause mortality in the malnourished group did not appear to reach a statistical difference compared with the nonmalnourished group (P = 0.078). When grouped by level of nutrition as defined by BMI, the all-cause mortality was higher in the malnourished group (P = 0.009), and multivariate logistic regression analysis revealed that malnutrition was an independent risk factor for all-cause mortality. After propensity score matching, the results showed that the all-cause mortality was higher in the malnutrition group, regardless of BMI or GNRI defined nutrition level grouping, compared with the control group (both P < 0.001). The ROC curve analysis revealed that the area under the curve (AUC) was 0.811 ([95% confidence interval (CI) 0.701– 0.922], P < 0.001) for GNRI and 0.728 ([95% CI 0.588– 0.869], P = 0.001) for BMI.Conclusion: In the clinical treatment of patients with active TB, more attention should be paid to the management of nutritional risk. GNRI may be a highly effective and easy method for predicting short-term outcomes in patients with active pulmonary TB.Keywords: tuberculosis, malnutrition, Geriatric Nutritional Risk Index, body mass index

Zheng S, Zhang M, Bai H, et al. Int J Nanomedicine. 2019;14:9513–9524. The authors have advised due to an error at the time of figure assembly, the image of Spleen at 1 day in Figure 8B on page 9522 is incorrect. The correct Figure 8 is shown below. Figure 8 In vivo toxicity test of Mn-MoS2 QDs: (A(a–l)) Mouse serum biochemistry analysis and blood routine analysis before (0d, control) and after injection of Mn-MoS2 QDs for 1, 7, 21d. (B) Histological images of the heart, lungs, liver, spleen and kidneys of mice 1, 7 and 21 days post-intravenous injection of Mn-MoS2 QDs and in control mice. The organs were sectioned and stained with hematoxylin and eosin (H&E) and observed under a light microscope, scale bar = 100 μm. The authors apologize for this error and advise it does not affect the results of the paper.

Yanwan Shangguan,&ast; Zhongkang Ji,&ast; Wanru Guo, Wenjuan Hu, Xiaomeng Li, Kaijin Xu State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaijin Xu, State Key Laboratory for 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, People’s Republic of China, Tel/Fax +86-0571-87236440, Email zdyxyxkj@zju.edu.cnAbstract: Linezolid-induced black hairy tongue is a self-limiting benign disease that is rare. Here, we report three patients who developed black hairy tongue after linezolid treatment. The severe dysbiosis of oral bacterial communities was observed in all these patients. Proteobacteria was the most prevalent phylum (over 90%) at the black tongue stage. Furthermore, the dramatic oral bacterial alteration took a long time to reverse after the BHT resolved.Keywords: tuberculosis infection, linezolid, treatment, side-effect, black-hairy tongue, microorganism metabolism

Zihao Qin, Ke Xu, Wen Mo, Jie Ye, Jinhai Xu Orthopedics Department, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Jinhai Xu; Jie Ye, Longhua Hospital Shanghai University of Traditional Chinese Medicine, 725, South Wanping Road, Xuhui District, Shanghai, 200030, People’s Republic of China, Tel +86 18016006692 ; +86 3301880301, Email jinhaixu@126.com; yejie1977@126.comPurpose: This randomized controlled trial aimed to evaluate the clinical efficacy of Jianyao Migu granules (JYMGG) in the treatment of primary osteopenic low back pain (LBP).Patients and Methods: A total of 108 patients with primary osteopenic LBP were randomly divided into the JYMGG group and placebo group. Both groups took 600 mg of oral Caltrate D daily; in addition, the JYMGG group was given oral JYMGG, while the placebo group was given placebo granules. The treatment period was 6 months for both groups. The pre- to post-treatment changes in the bone mineral density (BMD), visual analogue scale (VAS) score, Oswestry disability index (ODI), and bone turnover markers were compared between the two groups.Results: The post-treatment VAS score and ODI were significantly lower than baseline in both groups (P< 0.05). In the JYMGG group, the lumbar BMD increased from 0.88± 0.07 g/cm2 to 0.90± 0.13 g/cm2 and the hip BMD increased from 0.77± 0.08 g/cm2 to 0.78± 0.10 g/cm2, giving increases of 2.70% and 1.96% respectively, but the differences were not statistically significant. The post-treatment levels of ALP, osteocalcin, P1NP, and β-CTX were increased compared with baseline in both groups, but the differences were not statistically significant. The thyrotropin level was significantly increased after treatment in the placebo group (P< 0.05). There were no abnormalities detected in routine blood and kidney function tests performed during the observation period. Some patients showed elevated liver enzymes and gastrointestinal reactions.Conclusion: JYMGG effectively relieved the bone pain, and improved the quality of life of patients with primary osteopenic LBP.Keywords: chinese herb, clinical trial, Jianyao Migu granules, osteoporosis

Jia Wang,1 Huizhong Wang,2 Juan Jiang,2 Xiaotong Cheng,3 Ke Xu,4 Fan Xia,2 Le Chang,2 Yede Ji,5 Zhengzhi Feng1 1Department of Developmental Psychology of Armyman, School of Psychology, Army Medical University, Chongqing, People’s Republic of China; 2School of Psychology, Army Medical University, Chongqing, People’s Republic of China; 3Unit 32298 of the Chinese People’s Liberation Army, Weifang, People’s Republic of China; 4Shigatse Branch, Xinqiao Hospital, Army 953 Hospital, Army Medical University, Shigatse, People’s Republic of China; 5Army Engineering University, Xuzhou, People’s Republic of ChinaCorrespondence: Zhengzhi Feng, Developmental Psychology for Armyman, Department of Medical Psychology, Army Medical University, No. 30, Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Email fzz@tmmu.edu.cnBackground: Employees in high-risk occupations are exposed to tremendous work stress that hinders organizational effectiveness and personal mental health. Based on positive psychology, courage can be considered a protective factor that buffers the adverse effect of high-risk surroundings on employees. However, little is known about the way courage is simulated or evaluated in response to safety concerns. Virtual reality (VR) is an accessible tool for courage simulation due to its immersive qualities, presence and interactive features and may provide a promising pathway to achieve a scientific, accurate and ecologically valid evaluation of high-risk employees.Methods: The sample consisted of 51 high-risk employees who were recruited voluntarily. Before and after experiencing the VR courage scenarios, the participants completed the VR features questionnaire, the Physical Courage at Work Scale (PCWS), the Courage Measure (CM), and the Positive and Negative Affect Scale (PANAS). During the process of watching the VR courage scenarios, the participants’ heart rate and skin conductance at resting-state baseline and during virtual courage scenarios were recorded through HTC VIVE Pro Eye and BioGraph Infiniti 8.Results: The results support the hypothesis and reveal that the interaction, immersion and presence scores of the scenarios were all significantly higher than the median 4 points. The score for the CM in the posttest was significantly higher than that in the pretest. The scared and afraid scores for the posttest were significantly higher than those for the pretest. The heart rate and skin conductance of each scenario showed an increase compared with the baseline. The Pearson’s correlation between physiological indicators and the score of the PCWS was 0.28∼ 0.54.Conclusion: This study developed virtual courage for high-risk occupations based on well-established theory and VR technology. Experimental data revealed that the paradigm conformed to the requirements of VR features and was able to activate fear and evoke the quality of courage. Thus, the virtual courage paradigms have good validity in simulating scenarios for high-risk employees, which might accelerate organizational effectiveness while buffering working stress.Keywords: high-risk occupations, employees, courage, virtual reality

Yunzhen Shi,1,&ast; Wanru Guo,2,&ast; Wenjuan Hu,2 Xiaomeng Li,2 Yanwan Shangguan,2 Xuewen Feng,2 Ming Hu,2 Jiafeng Xia,2 Shuting Wang,2 Jingnan Li,1 Li Hong,1 Bin Lu,1 Kaijin Xu2 1Department of Infectious Diseases, Dongyang People’s Hospital, Dongyang, People’s Republic of China; 2State Key Laboratory for 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, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaijin Xu, Email zdyxyxkj@zju.edu.cnAbstract: Tuberculous aortitis (TA) is a rare disease with a high mortality rate. Aortic pseudoaneurysm is the most common vascular pattern of TA, and isolated arterial wall thickening and arterial stenosis can also be seen in TA. We report two cases of disseminated tuberculosis involving the aorta with clinical improvement after treatment. One patient who had an aortic ulcer and intermural hematoma received anti-tuberculosis along with steroids therapy. The other patient, who developed a tubercular abdominal aortic pseudoaneurysm during anti-tuberculosis therapy, successfully received endovascular stent implantation. Clinicians should be aware that TA should be considered in patients with aortitis and active tuberculosis.Keywords: tuberculosis aortitis, aortic pseudoaneurysm, anti-tuberculosis therapy, steroids, endovascular stent implantation

Lijuan Yang, Huihui Deng, Wei Pan, Xiaoyan Huang, Ke Xu, Xingxing Zhang, Xiang Hu, Xuejiang Gu Department of Endocrine and Metabolic Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Xiang Hu; Xuejiang Gu, Department of Endocrine and Metabolic Diseases, the First Affiliated Hospital of Wenzhou Medical University, Ouhai District, Wenzhou, 325000, People’s Republic of China, Tel/Fax +86-577-55579381, Email huxiang@wmu.edu.cn; guxuejiang@wmu.edu.cnPurpose: Recent studies revealed that high levels of thigh fat were independently associated with better glucose and lipid metabolism, as well as lower risk of hypertension and cardiometabolic disease. Therefore, the purpose of this study was to evaluate the association between leg fat mass (FM) and osteoporosis (OP) in individuals with type 2 diabetes (T2DM).Patients and Methods: In this cross-sectional study, a total of 1,259 individuals aged 50 years or older with T2DM (female 536, male 723) were included. A bioelectrical impedance analyser was used to assess the segment body composition containing FM and lean mass (LM) of arms, legs, and trunk. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry.Results: Leg FM was positively correlated with BMD of all sites in females and BMD of femoral neck and total hip in males after adjusting age, diabetes duration, glucose and lipid metabolism indexes, and lifestyle (all P< 0.05). LM was positively associated with BMD at almost sites (P< 0.001), while leg FM/LM ratio had no relationship with BMD at any skeleton sites (P> 0.05). Compared with the bottom tertile group of leg FM, the risk of OP was significantly lower in the top tertile group both in females (T3 vs T1: OR=0.206, 95% CI=0.098– 0.433, P< 0.001) and males (T3 vs T1: OR=0.385, 95% CI=0.182– 0.815, P< 0.05), even after adjusting for LM.Conclusion: In the present study, higher leg FM was correlated with the lower risk of OP in both men and postmenopausal women with T2DM independently of total LM.Keywords: leg fat mass, bone mineral density, osteoporosis, type 2 diabetes mellitus

Guocan Yu,1,&ast; Linhua Wang,2 Yanqin Shen,1 Likui Fang,1 Jun Yang,1 Bo Ye,1 Kan Xu,1 Fangming Zhong1,&ast; 1Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Hospital Infection, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guocan Yu; Fangming Zhong, Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China, Email dabaitwo@163.com; zhongfangm@126.comPurpose: We evaluated CapitalBio Mycobacterium RT-PCR assay diagnosing tuberculous pericarditis (TBP), performed a head-to-head comparison with Xpert MTB/RIF, and assessed the impact of a parallel test (positive result for either of these two tests).Methods: We reviewed suspected TBP patients with Xpert MTB/RIF, CapitalBio Mycobacterium RT-PCR assay, and Mycobacterium tuberculosis (MTB) culture. We analyzed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC).Results: Seventy-four patients were included. Overall sensitivity, specificity, PPV, NPV, and AUC of CapitalBio Mycobacterium RT-PCR assay compared with culture were 50%, 91.1%, 64.3%, 85%, and 0.71, respectively. Overall sensitivity, specificity, PPV, NPV, and AUC of Xpert MTB/RIF for TBP were 61.1%, 91.1%, 68.8%, 87.9%, and 0.76. Parallel test values were 72.2%, 91.1%, 72.2%, 91.1%, and 0.82. The diagnostic accuracy of Xpert MTB/RIF was higher than CapitalBio Mycobacterium RT-PCR assay but was not significant (P > 0.05). The parallel test could improve diagnostic accuracy, but it was not significant compared to single tests (P > 0.05).Conclusion: CapitalBio Mycobacterium RT-PCR assay had a moderate diagnostic accuracy, similar to Xpert MTB/RIF. The parallel test maximized diagnostic efficacy, but differences were not significant. CapitalBio Mycobacterium RT-PCR assay and Xpert MTB/RIF for TBP could be an initial option for early diagnosis.Keywords: tuberculosis pericarditis, polymerase chain reaction, Xpert MTB/RIF, CapitalBio, accuracy

Hong Zhao,&ast; Huilan Tu,&ast; Xia Yu,&ast; Junwei Su, Xuan Zhang, Kaijin Xu, Yu Shi, Yunqing Qiu, Jifang Sheng State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jifang Sheng; Yunqing Qiu, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of China, Tel +86 571 8723 6491, Fax +86 571 8723 6491, Email jifang_sheng@zju.edu.cn; qiuyq@zju.edu.cnAim: To analyze the possible risk factors of delayed virus clearance in hospitalized patients with coronavirus disease 2019 (COVID-19).Methods: Retrospective analysis of patients with COVID-19 admitted to the isolation wards from our hospital from 19th Jan 2020 to 18th March 2020. We were collected patient’s data including demographic, epidemiologic, and clinical information, as well as laboratory and radiologic findings. The possible confounding risk factors for prolonged viral RNA shedding of COVID-19 during hospitalization were explored by univariate analysis and any variables with a p value less than 0.05 after univariate analysis were included in a subsequent multivariate logistic regression model analysis.Results: The 104 patients included 30 mild patients and 74 severe or critically ill patients. The median duration of viral RNA positivity in sputum was 11 days, and the longest duration of viral RNA positivity was 49 days after admission. Multivariate analysis shown that the used with darunavir/cobicistat treatment (odds ratio [OR]: 4.25, 95% confidence interval [CI]: 1.25– 14.42, p = 0.020), duration of fever (OR: 1.15, 95% CI: 1.03– 1.30, p = 0.015) and time to radiological improvement (OR: 1.14, 95% CI: 1.01– 1.30, p = 0.033) were associated with delayed clearance of SARS-CoV-2 in sputum from COVID-19 patients. Then adjusted in the multivariate binary logistic regression analysis model in severe COVID-19 and found that critical COVID-19 patients (OR: 13.25, 95% CI: 1.45– 12.07, p = 0.022), lower virus cycle threshold (CT) values of RT-PCR (OR: 0.96, 95% CI: 0.93– 0.99, p = 0.004) and used with darunavir/cobicistat treatment (OR: 8.44, 95% CI: 2.21– 32.28, p = 0.022) were associated with delayed clearance of SARS-CoV-2 in sputum from COVID-19 patients.Conclude: Clearance of viral RNA in sputum was delayed in severe COVID-19 patients, especially with lower virus CT value. And antivirals with darunavir/cobicistat has little advantage in eliminating SARS-CoV-2.Keywords: COVID-19, SARS-CoV-2, clearance, critical disease, viral load

Rongxiu Huo,1,&ast; Qianyu Guo,1,&ast; Junping Hu,2 Na Li,1 Rui Gao,1 Liangyu Mi,1 Zhaoliang Zhang,1 Hechao Liu,1 Zhiying Guo,1 Hanxi Zhao,3 Liyun Zhang,1 Ke Xu1 1Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences; Tongji Shanxi Hospital, Department of Rheumatology and Immunology, Taiyuan, 030032, People’s Republic of China; 2Department of Immunology, Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 3SILC Business School, Shanghai University, Shanghai, 200444, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Xu, Email zhaoxuke@hotmail.comAbstract: Interstitial lung disease (ILD) refers to a heterogeneous group of diseases characterized by lung fibroblast proliferation, interstitial inflammation, and fibrosis-induced lung damage. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is known to be activated by pro-fibrotic/pro-inflammatory cytokines such as IL-6 and IL-13, whose levels are elevated in ILD. The overexpression of growth factors such as transforming growth factor β 1 in ILD activates the JAK/STAT pathway through classical or non-classical pathways, promotes macrophage activation, increases the release of pro-inflammatory and pro-fibrosis factors, and facilitates fibroblast differentiation into myofibroblasts. These findings implicate that the JAK/STAT pathway plays an important role in the course of ILD. Recent evidence also suggests that JAK inhibition alleviates excessive inflammation and pulmonary fibrosis. Accordingly, the JAK inhibitors may serve as promising drugs for the treatment of JAK/STAT-induced ILD.Keywords: interstitial lung disease, Janus kinase, signal transducers and activators of transcription, JAK inhibitor, animal model

Simin Liu,1,&ast; Ming Feng,2,&ast; Tingting Qiao,1,&ast; Haidong Cai,1 Kele Xu,3 Xiaqing Yu,1 Wen Jiang,1 Zhongwei Lv,1 Yin Wang,2 Dan Li1 1Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2School of Electronic and Information Engineering, Tongji University, Shanghai, People’s Republic of China; 3National Key Laboratory of Parallel and Distributed Processing, National University of Defense Technology, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongwei Lv; Dan LiDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University, Yanchangzhong Road 301, Shanghai, 200072, People’s Republic of ChinaTel +86 21-66302075Email Lvzwjs2020@163.com; plumredlinda@163.comObjective: To develop an approach for automatically analyzing bone metastases (BMs) on bone scintigrams based on deep learning technology.Methods: This research included a bone scan classification model, a regional segmentation model, an assessment model for tumor burden and a diagnostic report generation model. Two hundred eighty patients with BMs and 341 patients with non-BMs were involved. Eighty percent of cases were randomly extracted from two groups as training set. Remaining cases were as testing set. A deep residual convolutional neural network with different structures was used to determine whether metastatic bone lesions existed, regions of lesions were automatically segmented. Bone scan tumor burden index (BSTBI) was calculated; finally, diagnostic report could be automatically generated. The sensitivity, specificity and accuracy of classification model were compared with three physicians with different clinical experience. The Dice coefficient evaluated the effect of segmentation model and compared to the result of nnU-Net model. The correlation between BSTBI and blood alkaline phosphatase (ALP) level was analyzed to verify the efficiency of BSTBI. The performance of report generation model was evaluated by the accuracy of interpretation of report.Results: In testing set, the sensitivity, specificity and accuracy of classification model were 92.59%, 85.51% and 88.62%, respectively. The accuracy showed no statistical difference with moderately and experienced physicians and obviously outperformed the inexperienced. The Dice coefficient of BMs area was 0.7387 in segmentation stage. Based on the whole model frame, our segmentation model outperformed the nnU-Net. BSTBI value changed as the BMs changed. There was a positive correlation between BSTBI and ALP level. The accuracy of report generation model was 78.05%.Conclusion: Deep learning based on automatic analysis frameworks for BMs can accurately identify BMs, preliminarily realize a fully automatic analysis process from raw data to report generation. BSTBI can be used as a quantitative evaluation indicator to assess the effect of therapy on BMs in different patients or in the same patient before and after treatment.Keywords: bone metastases, bone scintigraphy, deep learning, tumor burden, automatic report generation

Cao J, Li L, Han X, et al. Onco Targets Ther. 2019;12:433–441. At the authors request, the Editor and Publisher of OncoTargets and Therapy are retracting the published article. The authors were made aware of data concerns relating to their paper and an investigation found images in Figure 5 had been duplicated with those from Yang C, Zheng J, Xue Y, Yu H, Liu X, Ma J, Liu L, Wang P, Li Z, Cai H, Liu Y. The Effect of MCM3AP-AS1/miR-211/KLF5/AGGF1 Axis Regulating Glioblastoma Angiogenesis. Frontiers in Molecular Neuroscience. 2018; 10:437 (https://doi.org/10.3389/fnmol.2017.00437). Specifically, From the published article, Figure 5E, pcDNA 3.1, pcDNA 3.1-VEGFA; pcDNA 3.1-VEGF+miRNA NC; pcDNA 3.1-VEGFA+miR-302a mimics; pcDNA 3.1-VEGFA+miR-302b mimics; pcDNA 3.1-VEGFA+miR-302c mimics and pcDNA 3.1-VEGFA+miR-302d mimics have been duplicated with images in Figure 2F, Control and anti-miR-211; Figure 6E, Control; Figure 2F, pre-NC and anti-NC; Figure 4E, KLF5 (-)-NC and Figure 6E, AGGF1 (-)-NC, respectively from Yang et al, 2018. The authors advised that data relating to the original study was no longer available and they were unable to explain how the images came to be duplicated. As the validity of the published work cannot not be verified the Editor and Publisher have agreed to retract the article. 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”.

Xiaojiao Zheng,1,2 Xiuyi Lv,1 Linyan Zhu,1 Kejun Xu,1 Cong Shi,1 Lining Cui,1 Huiqing Ding1 1Department of Obstetrics and Gynecology, Ningbo First Hospital, Ningbo, Zhejiang, 315035, People’s Republic of China; 2Department of Biochemistry & Genetics, The National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang Province, People’s Republic of ChinaCorrespondence: Lining Cui; Huiqing Ding Email 1935148739@qq.com; 1209256240@qq.comBackground: Mounting evidence indicates altered circadian rhythm represents a critical factor affecting carcinogenesis and tumor progression. The circadian gene neuronal PAS domain protein 2 (NPAS2) constitutes a newly discovered prognostic biomarker. NPAS2 dysregulation is found in multiple malignancies, although its functions in uterine corpus endometrial carcinoma (UCEC) remain largely unknown.Objective: To evaluate NPAS2’s roles in UCEC and to explore the underlying mechanisms.Methods: NPAS2 transcription levels, patient prognosis, different clinical stages and target microRNAs in UCEC cases were comparatively assessed based on public databases, including UALCAN, GEPIA, TIMER, Kaplan–Meier plotter, starBase database, LinkedOmics and String. Then, qRT-PCR and immunohistochemical analysis were applied to analyze the expression of NPAS2 in UCEC tissue samples. CCK-8, clonogenic assay and flow cytometry were carried out for detecting cell viability, colony formation ability and cell apoptosis, respectively.Results: NPAS2 was upregulated in tissue samples from UCEC cases compared with the corresponding control specimens. NPAS2 overexpression was associated with decreased overall (OS), disease free (DFS) and relapse free (RFS) survival in UCEC. In addition, NPAS2 overexpression was associated with clinical stage, tumor grade, estrogen receptor status, myometrial invasion in UCEC. Furthermore, NPAS2 knockdown or overexpression altered cell proliferation and apoptosis in UCEC. Moreover, NPAS2 showed significant negative correlations with miR-17-5p and miR-93-5p, and positive correlations with miR-106a-5p and miR-381-3p in UCEC.Conclusion: NPAS2 overexpression is associated with poor prognosis and clinicopathological characteristics in UCEC and promotes proliferation and colony formation while inhibiting apoptosis. Finally, NPAS2 is associated with several miRNAs in UCEC.Keywords: NPAS2, circadian rhythm, cell cycle, apoptosis, uterine corpus endometrial carcinoma

Jinbao Chen,1,&ast; Wentao Wu,1,&ast; Xue He,1 Linlin Jia,1 Jiahua Yang,1 Xianke Si,1 Kun Yu,1 Sen Li,1 Yanyan Qiu,1 Ke Xu,2 Peihao Yin,1,3 Yijun Cao,1 Qiong Li,4 Wei Li1 1Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Institute of Translational Medicine, Shanghai University, Shanghai, People’s Republic of China; 3Interventional Cancer Institute of Chinese Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei LiDepartment of General Surgery, Putuo Hospital, Shanghai University of Traditional, Chinese Medicine, Shanghai, 200062, People’s Republic of ChinaEmail liwei1511972@163.comQiong LiDepartment of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201100, People’s Republic of ChinaEmail 1030190686@qq.comPurpose: As rapidly dividing cells are usually the target of anticancer chemotherapy, it is inevitable that rapidly dividing normal cells become damaged, with myelosuppressive effects being a serious side effect of this therapy. Many recent studies have found that exosomal microRNAs (miRNAs) are related to the occurrence of some diseases.Patients and Methods: Small RNA sequencing was used to investigate differential exosomal miRNAs with the same expression trend between groups after chemotherapy: MildA (before chemotherapy in patients with mild myelosuppression) and MildB (after chemotherapy in patients with mild myelosuppression); SevereA (before chemotherapy in patients with severe myelosuppression) and SevereB (after chemotherapy in patients with severe myelosuppression). A Venn diagram was generated to screen exosomal miRNAs related to chemotherapy. Small RNA sequencing was also used to investigate differentially expressed exosomal miRNAs among these groups, and exosomal miRNAs related to myelosuppression after chemotherapy was explored using a Venn diagram. RT-qPCR was applied to further verify the sequencing results. We performed target gene prediction and functional analysis for candidate exosomal miRNAs.Results: Compared with that in the MildA or SevereA group, an increase in exosomal miR-122-5p was found in the MildB or SevereB group, and the expression level was lower in the SevereB group than in the MildB group. However, we found no notable difference in its expression level between the MildA and SevereA groups. Similar results were not obtained for the remaining miRNAs. RT-qPCR confirmed the screening results. Further analyses indicated that exosomal miR-122-5p targets CDK4 to inhibit the cell cycle.Conclusion: The expression level of exosomal miR-122-5p in the serum of patients with colorectal cancer correlates with the severity of myelosuppression caused by chemotherapy, and miR-122-5p targets CDK4 to inhibit cell cycle progression.Keywords: colorectal cancer, chemotherapy, myelosuppression, miR-122-5p

Li J, You J, Wu C, et al. Int J Nanomedicine. 2018;13:4607-4625. An error during the preparation of Figure S1 for publishing led to the inadvertent creation of a duplicate region in figure part S1B on page 4622. The journal wishes to apologise for this error. The correct version of Figure S1 is as follows. Figure S1 Transmission electron microscopy characterizations of Fe3O4 nanoparticles (NPs) (A) and Fe3O4@mSiO2 NPs (B). The insert in (A) is the distribution of Fe3O4 NP size.

Smith AO, Ju W, Adzraku SY, et al. J Inflamm Res. 2021;14:3277–3288 Following a review of the paper post-publication, the authors realized they had mistakenly duplicated the immunofluorescence on Figure 6 during the figure preparation. On page 3286, the corrected Figure 6 is shown in Download Article: Figure 6 Gamma radiation directly activates Caspase-1 dependent pathway in microvascular endothelial cells. Abbreviation: NS, not significant. Notes: (A) Immunofluorescence images of cleaved caspase −1 in microvascular endothelial cells. (B) The mean fluorescence intensity of cleaved caspase −1 in microvascular endothelial cells in the graph was relatively quantified by image J, which shows a dose-dependent increase in the expression of cleaved caspase-1. The results were representative of 6 independent experiments of four repeats (N=4) (mean ± SD) *P