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Xin Chen,1– 3,&ast; Xing Zhong,1,4,&ast; Dan Luo,1– 3,&ast; Yuhua Lei,1– 3 Rui Huang1– 3 1Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, People’s Republic of China; 2Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshii, Hubei Province, People’s Republic of China; 3Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshii, Hubei Province, People’s Republic of China; 4Department of Medicine, Hubei Minzu University, Enshi, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhua Lei; Rui Huang, Email yuhualei0319@163.com; henry0923@whu.edu.cnBackground: Heart failure (HF) is a chronic disease with a poor prognosis, making it extremely important to assess the prognosis of patients with HF for accurate treatment. Secreted modular calcium-binding protein 2 (SMOC2) is a cysteine-rich acidic secreted protein that plays a pathophysiological role in many diseases, including regulation of vascular growth factor activity. It has previously been found that SMOC2 plays an essential role in cardiac fibrosis in our previous preclinical study, but whether it can be used as a clinical marker in heart failure patients remains unclear. The purpose of this research was to evaluate the correlation between plasma levels of SMOC2 and the prognosis for individuals with HF.Methods: HF patients diagnosed with ischemic cardiomyopathy were enrolled from January to December 2021. Baseline plasma levels of SMOC2 were measured after demographic and clinical features were collected. Linear and nonlinear multivariate Cox regression models were used to determine the association between plasma SMOC2 and patient outcomes during follow-up. All analysis was performed using SPSS, EmpowerStats, and R software.Results: The study included 188 patients, and the average follow-up time was 489.5± 88.3 days. The plasma SMOC2 concentrations were positively correlated with N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), left ventricular end-diastolic diameter (LVEDd), and length of hospital stay and were negatively correlated with left ventricular ejection fraction (LVEF) at baseline. A total of 53 patients (28.2%) were rehospitalized due to cardiac deterioration, 14 (7.4%) died, and 37 (19.7%) developed malignant arrhythmias. A fully adjusted multivariate COX regression model showed that SMOC2 is associated with readmission (HR = 1.02, 95% CI:1.012– 1.655). A significant increase in rehospitalization risk was observed in group Q2 (HR =1.064, 95% CI: 1.037, 3.662, p=0.005) and group Q3 (HR =1.085, 95% CI:1.086, 3.792, p=0.009) in comparison with group Q1. The p for trend also shows a linear correlation across the three models (P < 0.001). SMOC2 was associated with the severity of HF in patients, but not with all-cause deaths and arrhythmias during follow-up.Conclusion: Plasma SMOC2 is associated with the severity of HF and readmission rate, and is a good predictor of the risk of readmission in patients.Keywords: SMOC2, heart failure, ischemic cardiomyopathy, readmission rate, myocardial fibrosis

Chunxia Jiang,1– 4,&ast; Xiumei Ma,1– 4,&ast; Jiao Chen,2– 5,&ast; Yan Zeng,1– 4 Man Guo,2– 4 Xiaozhen Tan,2– 4 Yuping Wang,1,6 Peng Wang,1 Pijun Yan,2– 4 Yi Lei,1– 4 Yang Long,2– 4 Betty Yuen Kwan Law,1 Yong Xu1– 4 1Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Endocrinology, The Third’s Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, People’s Republic of China; 6Department of Breast, Thyroid and Vascular Surgery, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Betty Yuen Kwan Law, Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, 999078, People’s Republic of China, Email yklaw@must.edu.mo Yong Xu, Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Email xywyll@swmu.edu.cnPurpose: To establish nomograms integrating serum lactate levels and traditional risk factors for predicting diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients.Patients and methods: A total of 570 T2DM patients and 100 healthy subjects were enrolled. T2DM patients were categorized into normal and high lactate groups. Univariate and multivariate logistic regression analyses were employed to identify independent predictors for DKD. Then, nomograms for predicting DKD were established, and the model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis (DCA).Results: T2DM patients exhibited higher lactate levels compared to those in healthy subjects. Glucose, platelet, uric acid, creatinine, and hypertension were independent factors for DKD in T2DM patients with normal lactate levels, while diabetes duration, creatinine, total cholesterol, and hypertension were indicators in high lactate levels group (P< 0.05). The AUC values were 0.834 (95% CI, 0.776 to 0.891) and 0.741 (95% CI, 0.688 to 0.795) for nomograms in both normal lactate and high lactate groups, respectively. The calibration curve demonstrated excellent agreement of fit. Furthermore, the DCA revealed that the threshold probability and highest Net Yield were 17– 99% and 0.36, and 24– 99% and 0.24 for the models in normal lactate and high lactate groups, respectively.Conclusion: The serum lactate level-based nomogram models, combined with traditional risk factors, offer an effective tool for predicting DKD probability in T2DM patients. This approach holds promise for early risk assessment and tailored intervention strategies.Keywords: serum lactate, diabetic kidney disease, nomograms, prediction model, risk factors

Jinhui Bu,1,2,&ast; Zhenfei Wang,2,&ast; Chao Ma,1,2 Juan Gao,2 Guangpu Liu,2 Libo Pang,2 Bo He,1 Minghui Dong,1 Quan Zhang,1 Yan Lei,1 Long Xu,2 Sen Huang,1 Yuming Li,3 Guangwang Liu1,2 1Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou, People’s Republic of China; 3Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA&ast;These authors contributed equally to this workCorrespondence: Yuming Li, Tel +1-8573524988, Fax +1-8572188459, Email yuming.li@childrens.harvard.edu; Guangwang Liu, Tel +86-18012018238, Fax +86-51683956400, Email guangwangliu@163.comObjective: To validate whether a residual mass demonstrated on early postoperative MR after percutaneous endoscopic lumbar discectomy (PELD) is indeed an intraoperatively retained annulus fibrosus, and explore the correlation between imaging changes in the residual mass and clinical prognosis of patients.Methods: A prospective study of 118 patients were included. During surgery, a contrast medium, Gadopentetate Dimeglumine, was injected around the ruptured annulus fibrosus. The intensity of the T2 signal, the size of the remaining mass (SR), and the cross-sectional area of the spinal canal (SCSA), VAS, and ODI were assessed at preoperative, 1-h (7-day), 6-month, and 12-month postoperative intervals. Based on VAS at 7 days post-surgery, patients were classified into either a non-remission group (Group A, VAS > 3) or a remission group (Group B, VAS ≤ 3).Results: Six patients who developed recurrent LDH were excluded. A residual mass was detected on MRI 1 h after surgery in 94.6% (106/112). During one year of follow-up, 90.1% (101/112) of the patients displayed fibrous annulus remodeling, although 68.7% (77/112) still exhibited herniation. Significant differences were found in the ODI between Groups A and B one week after surgery (p < 0.001). However, no significant differences were observed in T2 signal intensity, SR, and SCSA at 1-h, 6-month and 12-month post-surgery (p > 0.05) between the two groups. In a multiple linear regression analysis, early postoperative ODI changes were associated with T2 signal (B = − 10.22, sig < 0.05), long-term changes were associated with alterations in SR (B = 5.63, sig < 0.05) and SCSA (B = − 0.13, sig < 0.05).Conclusion: The residual mass observed in early postoperative MR images after PELD was the retained annulus fibrosus intraoperatively. Short-term changes in clinical symptoms after PELD were linked to T2 signal intensity, while long-term changes were associated with changes in SR and SCSA.Keywords: spinal endoscopy, residual mass, remodeling of fibrous annulus, contrast medium

He L, Lei Y, Hou J, Wu J, Lv G. Onco Targets Ther. 2020;13:5901–5911. We, the Editor and Publisher of the journal OncoTargets and Therapy have retracted the published article. Following publication, concerns were raised regarding the use of non-verifiable cell lines described in the article. The concerns related specifically to the use of cell lines which were found to be either contaminated, wrongly identified, improperly indexed, unavailable through external cell line repositories, and/or lacking publications describing their establishment. Overall, these concerns raised doubts about the validity of the findings described in the article. The corresponding author did not respond to our queries and was unable to provide information relating to the use of these cell lines or provide original data relating to the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Cheng-Yi Hu,1 Wen-Shuai Cui,1 Yi Lei,1 Yu-Wen Tang,1 Yan-Yan Zhang,1 Qi-Min Su,1 Fang Peng,2 Yun-Fei Zeng,1 Jia-Lin Song,1 Cheng-Na Luo,1 Yan Zhou,1 Xin-Yan Li,1 Zhu-Xiang Zhao1 1Department of Infectious Diseases, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 2Department of Critical Care Medicine, the Third Affiliated Hospital of Guang Zhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Zhu-Xiang Zhao, Department of Infectious Diseases, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510515, People’s Republic of China, Email zhaozhuxiang@126.comPurpose: To compare the effectiveness of azvudine and nirmatrelvir/ritonavir for the treatment of coronavirus disease (COVID-19).Patients and Methods: We conducted a retrospective analysis of data from 576 patients with COVID-19, comprising 195 patients without antiviral therapy, 226 patients treated with azvudine, 114 patients treated with nirmatrelvir/ritonavir, and 41 patients were treated with azvudine and nirmatrelvir/ritonavir concurrently. We compared their symptoms, mortality rates, and the length and cost of hospitalization.Results: The incidence of symptoms was similar in patients treated with azvudine and in those treated with nirmatrelvir/ritonavir. However, among patients experiencing weakness, the duration of weakness was significantly shorter in the azvudine group than in the nirmatrelvir/ritonavir group (P=0.029). Mortality did not differ significantly between the azvudine group and the nirmatrelvir/ritonavir group (18.14% vs.10.53%, P=0.068). Among “severe patients”, the mortality rate was markedly lower in patients treated with nirmatrelvir/ritonavir than in patients treated with azvudine (16.92% vs.32.17%, P=0.026). In patients with hepatic insufficiency, those treated with nirmatrelvir/ritonavir had substantially lower mortality than those treated with azvudine (15.09% vs.34.25%, P=0.016). In addition, patients treated with nirmatrelvir/ritonavir had longer hospital stays (P=0.002) and higher hospital costs (P< 0.001) than those receiving azvudine. Compared with patients treated with nirmatrelvir/ritonavir or azvudine alone, patients taking nirmatrelvir/ritonavir and azvudine concurrently had no significant improvement in survival (P> 0.05), length of stay (P> 0.05), or hospital costs (P> 0.05).Conclusion: Azvudine is recommended for patients with non-severe COVID-19 with weakness. Nirmatrelvir/ritonavir is recommended for patients with severe COVID-19, to reduce mortality, and it could be the best choice for patients with hepatic insufficiency. The concurrent use of nirmatrelvir/ritonavir and azvudine in patients with COVID-19 could be not recommended.Keywords: azvudine, nirmatrelvir/ritonavir, COVID-19, SARS-CoV-2

Xing Zhong,1,&ast; Rui Huang,2,&ast; Xin Chen,2 Yuhua Lei2 1Cardiovascular Disease Center, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Minzu University, Enshi, People’s Republic of China; 2Cardiovascular Disease Center, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhua Lei, Email yuhualei0319@163.comBackground: Engeletin (ENG) is a natural flavonoid compound known for its diverse physiological and pharmacological effects, such as anti-inflammatory, antioxidant, and immunomodulatory properties. It has garnered significant attention as a promising candidate for drug development.Objective: This article aims to comprehensively review the clinical application, pharmacological action, and potential mechanisms of ENG, while exploring its prospects in clinical pharmacology.Methods: We conducted a systematic search of PubMed, Science Direct, Google Scholar, Web of Science, Scopus, and MEDLINE for a thorough review of high-quality articles on the source, extraction, and application of ENG, or the primary active ingredient for improving bodily injuries.Results: ENG exhibits significant potential in treating a variety of diseases across different systems, attributed to its anti-inflammatory, antioxidant, anti-tumor, and metabolic regulatory activities. These effects are linked to direct or indirect interactions with multiple pathways involving key molecules upstream and downstream.Conclusion: While ENG shows promise, its development requires further exploration. Future studies should focus on elucidating its mechanisms of action, identifying targets through clinical studies, and optimizing compounds for drug development. These research directions are crucial for advancing the development and application of flavonoids. This review underscores the significant research potential of ENG, paving the way for its application in diverse clinical settings.Keywords: engeletin, pharmacological, agent, liliaceous plants

Yu Liu,1,&ast; Enyi Zhu,1,&ast; Yan Lei,1,&ast; Ailing Luo,2 Yaping Yan,2 Mansi Cai,2 Shanshan Liu,2 Yan Huang,3 Hui Guan,1 Ming Zhong,1 Weinian Li,4 Lian Lin,1 Michael Hultstöm,5,6 Enyin Lai,7 Zhihua Zheng,1 Xiaoping Liu,2 Chun Tang1 1Department of Nephrology, Center of Kidney and Urology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, People’s Republic of China; 2Department of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, People’s Republic of China; 3The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China; 4Department of Rheumatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, 510623, People’s Republic of China; 5Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden; 6Department of Medical Cell Biology, Unit for Integrative Physiology, Uppsala University, Uppsala, Sweden; 7Department of Physiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun Tang; Xiaoping Liu, Email tangch28@mail.sysu.edu.cn; liu_xiaoping@gwcmc.orgPurpose: Methyltransferase like 1 (METTL1) regulates epitranscriptomes via the m7G modification in mammalian mRNA and microRNA. Systemic lupus erythematosus (SLE) is caused by abnormal immune reactivity and has diverse clinical manifestations. RNA methylation as a mechanism to regulate gene expression is widely implicated in immune regulation. However, the role of m7G in immune response of SLE has not been extensively studied.Patients and Methods: Expression of METTL1 was identified in the public dataset GSE122459 and validated in an independent cohort of SLE patients. We investigated the association between METTL1-expression and clinical manifestations of SLE. Subsequently, differentially expressed genes (DEG) that were correlated with METTL1-expression in GSE122459 were used for functional enrichment analysis. The correlation between infiltrating immune cells and METTL1, as well as candidate biomarkers identified to be correlated with either METTL1 or immune cell infiltration were assessed by single-sample GSEA. Potential mechanisms were explored with Gene ontology and KEGG pathway enrichment. Diagnostic performances of candidate biomarkers in SLE were analyzed.Results: The mRNA and protein expression of METTL1 in SLE patients were significantly decreased in both datasets. METTL1-coexpressed DEGs were enriched in several key immune-related pathways. Activated CD8 T cells, activated CD4 T cells, memory B cells and type 2 helper T cells were different between patients with high and low METTL1 expression. Further, activated CD8 T-cells, activated CD4 T-cells, memory B-cells were correlated with METTL1. The genes of LAMP3, CD83, PDCD1LG2, IGKVD3D-20, IGKV5-2, IGKV2D-30, IGLV3-19 and IGLV4-60 were identified as candidate targets that were correlated with immune cell proportion. Moreover, LAMP3, CD83, and PDCD1LG2 expression were of diagnostic value in SLE as indicated by ROC analysis.Conclusion: Our findings suggested that METTL1 and its candidate targets LAMP3, CD83, PDCD1LG2 may be used for diagnosing SLE and could be explored for developing targeted molecular therapy for SLE.Keywords: methyltransferase like 1, systemic lupus erythematosus, immunity, single sample gene set enrichment analysis, biomarker

Ziting Qu,1,&ast; Yanxun Han,2,&ast; Qingbo Zhu,1,&ast; Wenxi Ding,1 Yuyan Wang,1 Yan Zhang,1 Wei Wei,1 Yu Lei,1 Min Li,1 Yang Jiao,1 Kangsheng Gu,1,&ast; Yiyin Zhang1,&ast; 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kangsheng Gu; Yiyin Zhang, Department of Oncology, The First Affiliated Hospital of Anhui Medical University, 218th Jixi Road, Hefei, Anhui, 230022, People’s Republic of China, Email gukangsheng@ahmu.edu.cn; zhangyiyin@ahmu.edu.cnBackground: Neutrophil extracellular traps (NETs) released by neutrophils are crucial for cancer development, metastasis, and can indicate gastric cancer (GC) patients’ prognosis. This study reveals the relevance of NETs-related genes to GC through transcriptome analysis.Methods: We obtained transcriptome sequencing data of GC from UCSC Xena and screened prognostic NETs-related genes by GEPIA2 database. The signature for NETs was subsequently created using the LASSO–Cox regression. The clinical value of model was further explored using the nomogram and was externally validated by the GEO database. After that, we employed GO, KEGG, and GSEA enrichment analyses to evaluate the bio-functional enrichment and related pathways. Additionally, ESTIMATE, MCP counter, and ssGSEA scores were used to investigate the immunological microenvironment of GC patients. Finally, in the external cohort, neutrophil elastase (NE)-DNA complexes were measured by ELISA, and the prognostic value of NE-DNA in GC was investigated using Cox analysis.Results: Seven NETs-associated genes (PDE4B, CD93, CTSG, IL6, ELANE, KCNJ15, and CRISPLD2) were filtered to establish the signature and participated in building the nomogram. In comparison to the high-risk group, the overall survival (OS) was much longer in the low-risk group (P=0.005). The validation cohort demonstrated the acceptable predictive ability of the nomogram. The signature was enriched in biological features such as extracellular matrix organization, epithelial-mesenchymal transition and inflammatory response. Moreover, there were substantial differences in immune cell infiltration across the different risk groups (p< 0.001), especially the high-risk group having more immune cells that are engaged in the antigen presentation process and associated functions. Finally, in the external cohort, NE-DNA levels were shown to be an independent factor affecting OS prognosis (p=0.006).Conclusion: Overall, this research identified a novel signature based on seven NETs-associated genes to predict prognosis and identify tumor microenvironment of GC. And high NE-DNA level may be a critical factor in the poor OS associated with NETs.Keywords: NETs, gastric cancer, gene signature, tumor microenvironment, prognosis

Shiying Li,1 Jin Tong,2 Hu Li,1 Chenxue Mao,3 Wei Shen,1 Yu Lei,1 Peng Hu1 1Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Respiratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Laboratory Diagnosis, ChongQing KingMed Center for Clinical Laboratory Co., Ltd, Chongqing, 400050, People’s Republic of ChinaCorrespondence: Peng Hu, Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, 74&num; Linjiang Road, Chongqing, 400010, People’s Republic of China, Email hp_cq@163.com; hupengcq@hospital.cqmu.edu.cnAbstract: We report a case of a 34-year-old lady with multiple joint pain. Autoimmune diseases were considered first with a positive result of anti-Ro antibody and her right knee joint cavity effusion. Later, bilateral interstitial changes in her lungs and mediastinal lymphadenopathy were found after chest CT scanning. Empirical quinolone therapy was given although pathological examinations of blood, sputum and bronchoalveolar lavage fluid (BALF) did not find anything. Finally, Legionella pneumophila was identified by target next-generation sequencing (tNGS) detection. This case highlighted the timely use of tNGS, a new tool with fast speed, high accuracy and effective cost, could help to identify atypical infection and start an early therapy.Keywords: case report, Legionella pneumophila, targeted next-generation sequencing, tNGS, precision treatment, levofloxacin

Yinhua Luo,1,&ast; Jinbo Zhao,2,&ast; Xueru Chen,3,&ast; Rui Huang,2 Ling Hou,2 Ke Su,2 Yuhua Lei,2 Yuanhong Li1,2 1Department of Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, Hubei Province, 442000, People’s Republic of China; 2Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi Prefecture, Hubei Province, 445000, People’s Republic of China; 3Department of General Practice, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Li, Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi Prefecture, People’s Republic of China, Email shaoyiju75482@163.comBackground: Ischemic cardiomyopathy (ICM) with high mobility and mortality is closely linked to immunology, oxidative stress, inflammatory response and so on. Early diagnosis counts for the effective treatment of ICM. However, there are still no distinctive diagnostic signatures. This research aims to investigate effective signatures and build the diagnostic model for ICM.Methods: The Gene Expression Omnibus was used to retrieve the microarray data of GSE9800 and GSE580, which were obtained from tissue biopsy samples. Differentially expressed genes (DEGs), GO, and KEGG analyses were then carried out on the microarray data. The PPI network was constructed via STRING database.Following that, CIBERSORT techniques in conjunction with the LM22 feature matrix were used to assess the immune infiltration of the samples.The expression of a few chosen genes served as the predictor variable, and the occurrence of ICM served as the responder variable, in the construction of the best subset stepwise regression model.Results: A total of 28 DEGs were found. And according to the GO and KEGG studies, numerous biological processes were enriched. Patients with ICM and their normal counterparts had considerably distinct immune cell types infiltrating. For the construction of the PPI network, the top 20 most significant DEGs were selected and were used to build the original regression model. The optimal subset screened using stepwise regression analysis contained three pivotal genes (SCD, SNX25, WNT7B) and the area under the curve (AUC) values in this model was 0.891.Conclusion: We identified several possible hub genes, including SCD, SNX25, and WNT7B, which may be strongly related to the development of ICM. Based on the three genes, the logistic regression model could be used to accurately diagnose ICM patients.Keywords: ischemic cardiomyopathy, ICM, immunology, inflammatory responses, diagnosis, differently expressed genes, bioinformatic analysis, the optimal subset stepwise regression

Wusheng Deng,1,&ast; Yun Jiang,2,&ast; Jiaoxia Qin,1,&ast; Gang Chen,3,&ast; Yongjie Lv,1 Yanmei Lei,1 Jing Luo,1 Kangkang Hong,1 Bing Huang,1 Luhai Qin,4 Xiujia Tang,1 Liumei Ye,1 Yuhai Dang,1 Chao Wang,1 Feiyang Long,1 Ke Wang,1 Jinliang Kong1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Shaoyang University, Shaoyang, Hunan, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Department of Pulmonology, Hechi Traditional Chinese Medicine Hospital, Hechi, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinliang Kong; Ke Wang, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, People’s Republic of China, Email kjl071@163.com; keewang@hotmail.comBackground: Aspergillus fumigatus is an opportunistic fungal pathogen, which is commonly found in lungs and rarely causes infections in mediastinum. Mediastinal Aspergillus abscess is a serious infectious condition, and is characterized by difficult diagnosis due to its clinical manifestations being nonspecific.Case Presentation: Here, we report a case of a mediastinal Aspergillus fumigatus abscess in an immunocompetent patient. The patient was a 45-year-old woman who presented with a 20-day history of sore throat without any underlying diseases. Chest computed tomography (CT) showed a mass in the anterior superior mediastinum. Metagenomic next-generation sequencing (mNGS) identified Aspergillus fumigatus sequences in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) tissue, indicating the mediastinal Aspergillus fumigatus infection of this patient. The following mediastinal biopsy histological analysis and tissue fungi culture also suggested Aspergillus fumigatus infection, confirming the mNGS detection. The patient was diagnosed with mediastinal aspergillosis caused by Aspergillus fumigatus. After timely voriconazole treatment, the patient was discharged with good condition.Conclusion: Our study presented a rare case with mediastinal Aspergillus fumigatus abscess in an immunocompetent patient. As a new clinical diagnostic method, mNGS could assist timely diagnosis and precise treatment of Aspergillus infection.Keywords: mediastinal abscess, Aspergillus fumigatus, metagenomic next-generation sequencing, diagnosis, case report

Ya’nan Sun,1,&ast; Yi An,2,&ast; Xiran Fan,2 Changxin Liu,3 Duoduo Li,3 Yuan Lei,3 Zhiwen Weng,3 Yuanyuan Gong,3 Xiyou Wang,3 Changhe Yu3 1Traditional Chinese Medicine Department, Xuanwu Hospital Capital Medical University, Beijing, People’s Republic of China; 2First Clinical College, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, People’s Republic of China; 3Tuina and Pain Management Department, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiyou Wang; Changhe Yu, Email dwxy658@163.com; yakno2@163.comAim: Lumbar spinal stenosis (LSS) is a long-term degenerative disease. Considering the risks and advantages of the patient’s age range and the characteristics of the condition, non-surgical treatment is recommended. To determine the best first-line non-surgical therapy for LSS, few studies have examined different non-surgical therapies. Therefore, the main objective of this study is to determine whether the selection of comprehensive Chinese medicine (CM) treatment for LSS is more successful than non-surgical conservative treatment.Patients and Methods: In this two-armed, parallel, single-centered, pragmatic randomized controlled study, 94 LSS participants will be randomized to receive 24 sessions of comprehensive CM therapy or conservative treatment for 3 months, with follow-up assessments at 6, 9, 12, and 15 months. The primary outcome will be based on the success rate of the Zurich Claudication Questionnaire (ZCQ) for the most clinical important difference (MCID) at 3 and 15 months. Secondary outcomes include Numerical Rating Scale (NRS) scores for back and leg pain, ZCQ scores, Oswestry Disability Index scores for lumbar dysfunction, and Short-Form 12 scores for health-related quality of life at 3, 6, 9, 12, and 15 months. Adverse events and incidences of surgery will be reported anytime during the trial and follow-up.Conclusion: This protocol examines the comparative efficacy of comprehensive CM therapy compared with conventional care through a pragmatic randomized controlled trial to present data to facilitate clinical or policy decision-making. The outcomes will make it easier to decide which patient-centered treatments to prioritize for LSS.Keywords: lumbar spinal stenosis, Chinese medicine, comprehensive treatment, conservative treatment, pragmatic randomized controlled trial, patient centered

Yinqiang Liu,&ast; Jin Duan,&ast; Fujun Zhang,&ast; Fanghao Liu, Xiaoyu Luo, Yunfei Shi, Youming Lei Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youming Lei; Yunfei Shi, Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, No. 295, Xichang Road, Kunming, 650031, People’s Republic of China, Email 2399041054@qq.com; Km-syf@163.comBackground: The prognosis of non-small cell lung cancer (NSCLC) patients has been comprehensively studied. However, the prognosis of resectable (stage I–IIIA) lung squamous cell carcinoma (LUSC) has not been thoroughly investigated at genomic and transcriptional levels.Methods: Data of genomic alterations and transcriptional-level changes of 355 stage I–IIIA LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) database, together with the clinicopathological information (training cohort). A validation cohort of 91 patients was retrospectively recruited. Data were analyzed and figures were plotted using the R software.Results: Training cohort was established with 355 patients. TP53 (78%), TTN (68%), CSMD3 (39%), MUT16 (36%) and RYR2 (36%) were genes with the highest mutational frequency. BRINP3, COL11A1, GRIN2B, MUC5B, NLRP3 and TENM3 exhibited significant higher mutational frequency in stage III (P < 0.05). Patients with stage III also exhibited significantly higher tumor mutational burden (TMB) than those with stage I (P < 0.01). The mutational status of 10 genes were found to have significant stratification on patient prognosis. TMB at threshold of 25 percentile (TMB = 2.39 muts/Mb) also significantly stratified the patient prognosis (P = 0.0003). Univariate and multivariate analyses revealed TTN, ADGRB3, MYH7 and MYH15 mutational status and TMB as independent risk factors. Further analysis of transcriptional profile revealed many significantly up- and down-regulated genes, and multivariate analysis found the transcriptional levels of seven genes as independent risk factors. Significant factors from the multivariate analyses were used to establish a Nomogram model to quantify the risk in prognosis of individual LUSC patients. The model was validated with a cohort containing 91 patients, which showed good predicting efficacy and consistency.Conclusion: The influencing factors of prognosis of stage I–III LUSC patients have been revealed. Risk factors including gender, T stage, cancer location, and the mutational and transcriptional status of several genes were used to establish a Nomogram model to assess the patient prognosis. Subsequent validation proved its effectiveness.Keywords: lung cancer, squamous cell carcinoma, prognosis, mutation, transcription, resectable

An Jia,1,&ast; Yi Lei,2,&ast; Dan-Ping Liu,2 Lu Pan,2 Hui-Zhen Guan,2 Bicheng Yang1,2 1Medical School, Huanghe Science and Technology College, Zhengzhou, People’s Republic of China; 2Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bicheng Yang, Jiangxi Provincial Key Laboratory of Birth Defect for Prevention and Control, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, 330006, People’s Republic of China, Tel +86 15350402147, Email yangbc1985@126.comObjective: The context was designed to optimize the diagnostic utility of clinically focused exome sequencing (CFES) and shorten the diagnostic odyssey among pediatric patients suspected of monogenic disorders (MDs).Methods: Here, we retrospectively analyzed the clinical notes of 372 patients from different areas in the Jiangxi province that were referred for a diagnostic CFES and analysis from June 2018 to March 2022 with symptoms suggestive of MDs. In our study, preliminary tests using the proband-only clinical exome sequencing as a cost-effective first-tier diagnostic test for pediatric patients with unidentified MDs, supplemented by family segregation studies for targeted variants when indicated.Results: Probands with confirmed diagnostic (CD) or likely diagnostic (LD) genetic influences accounted for 12% of all cases, whereas those with an uncertain diagnosis accounted for 48%. We also found that systemic primary carnitine deficiency (CDSP) (SLC22A5 gene) and phenylketonuria (PAH gene) were relatively more prevalent, and these patients with CDSP had the most frequent c.1400C > G variant (p.S467C) and c.51C > G variant (p. F17L) in this study. In addition, statistical analysis revealed that the estimates of diagnostic yields varied across certain phenotypic features of patients, and patients with specific phenotypic traits tended to benefit more from CFES.Conclusion: The CFES may be a first-line genetic test for diagnosing young children with suspected genetic conditions, as it validates the identification of molecular genetics alterations and facilitates comprehensive medical management. Moreover, we found that infants exhibiting metabolism/homeostasis abnormalities, craniofacial /otolaryngology/ ophthalmologic abnormalities, and/or the integument were significantly more likely to receive a genetic diagnosis via CFES than infants without such features. However, due to the current study’s low diagnostic yield and inherent limitations, high-quality clinical studies with larger sample sizes are still needed to provide more likely results and confirm our findings.Keywords: clinical exome sequencing, monogenic diseases, diagnostic rate, phenotypic features, clinical management

Jinbo Zhao,1,&ast; Ling Hou,2,&ast; Ni Zhu,3,&ast; Rui Huang,1 Ke Su,1 Yuhua Lei,1 Yuanhong Li1 1Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi Prefecture, Hubei Province, 445000, People’s Republic of China; 2Department of Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, Hubei Province, 442000, People’s Republic of China; 3Department of Pathology, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi Prefecture, Hubei Province, 445000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Li, Email lyh0101@vip.comObjective: The CHA2DS2-VASc score, a system which has been initially recommended for the assessment of thromboembolic risk in patients with atrial fibrillation (AF), arouses attention in the field of adverse coronary events. The purpose of this study was to explore the predictive value of preprocedural CHA2DS2-VASc score on ISR in patients after drug-eluting stent (DES) implantation.Methods: To further investigate the relationship between CHA2DS2-VASc scores and ISR after DES, a retrospective study of DES was carried on. Additionally, the preoperative variables for the ISR and control groups were contrasted. Predictive factors were chosen using the optimal subset regression. We validate the model using internal validation. The prediction model was evaluated using the receiver operator characteristic (ROC) analysis.Results: We used a 3:7 ratio to create an experimental group and a validation group, and then ran a stepwise regression with the data from each of the two groups. The results showed that CHA2DS2-VASc score was an independent risk factor for ISR in both the experimental (p = 0.0139) and validation groups (p = 0.0014), and both had significant predictive value for ISR. The area of the ROC curve was greater than 0.5 in both groups (AUC = 0.78, 0.719, respectively) indicating that the model fit was good in both groups.Conclusion: The CHA2DS2-VASc score is a reliable predictor of in-stent restenosis (ISR) after DES implantation.Keywords: CHA2DS2-VASc score, drug-eluting stents, DES, percutaneous coronary intervention, PCI, in-stent restenosis, ISR

Yunyue Liu,1,* Mengyu Su,1,* Yang Lei,1 Jinping Tian,1,2 Leng Xue,1 Lin Zhang1 1School of Nursing, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Cardiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang Lei, School of Nursing, Nanjing Medical University, No. 101, Longmian Avenue, Jiangning District, Nanjing, Jiangsu Province, People’s Republic of China, Tel +86 19955062997, Fax +86 258 6869 555, Email nursleiyang@njmu.edu.cn Jinping Tian, The First Affiliated Hospital with Nanjing Medical University, No. 300, Guangzhou Road, Gulou District, Nanjing, Jiangsu Province, People’s Republic of China, Tel +86 13851550156, Fax +86 519 6809 1881, Email tianjp6@163.comBackground: Although a large number of studies have demonstrated the effectiveness of cardiac rehabilitation(CR), patient preferences for CR remain unclear. Knowing patient preferences may contribute to increasing patient participation and adherence, thus improving patient prognosis.Methods: A systematic search was carried out using electronic databases and manual reference checks from inception until 15th June 2022. Quantitative studies, qualitative studies and mixed methods studies assessing patient preferences for CR were included. Two researchers independently conducted study selectionand data extraction. CR preferences were divided into three categories: CR settings, CR components, and CR contents. A narrative synthesis was applied to integrate the results of the included studies. The Mixed Methods Appraisal Tool (MMAT) was used to assess the quality of included studies.Results: Ultimately, 17 publications were included in this study. Regarding CR settings, most patients preferred the hospital to home, some considered both, and a few were willing to accept the local CR club as an alternative setting to the hospital. For CR components, regardless of age and gender, patients considered exercise training and nutrition counseling to be the most important and smoking cessation to be the least important. In exercise intervention of CR contents, progress discussion and encouragement were rated as most critical, and non-conflicting with other activities was rated as least critical. In psychological intervention of CR contents, most patients were willing to accept psychological intervention, and a few patients wanted to heal the trauma with the passage of time.Conclusion: This systematic review provides important insights into patient preferences for CR, clarifying patient preferences for CR settings, components, and contents, along with possible influencing factors. Patient preferences may change due to the COVID-19 epidemic, and there is still a need to focus on patient preferences for CR and conduct more relevant primary research to validate the findings of this paper in the future.Keywords: cardiac rehabilitation, patient preference, systematic review, COVID-19

Chen Y, Lei Y, Lin J, et al. Onco Targets Ther. 2020;13:10707-10719. At the author’s request, we, the Editors and Publisher of OncoTargets and Therapy have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 2, 4 and 7 with images from other unrelated articles. Specifically, Images for Figure 2D have been duplicated with images for Figure 2F from Luo J, Jin Y, Li M, Dong L. Tumor suppressor miR‑613 induces cisplatin sensitivity in non‑small cell lung cancer cells by targeting GJA1. Molecular Medicine Reports. 2021;23:385. https://doi.org/10.3892/mmr.2021.12024. The images for Figure 4A, sh-LINC01260 and sh-Control have been duplicated with the images for Figure 3A, NC and miR-613 mimics, respectively, from Luo et al, 2021. Images for Figure 4F have been duplicated with images for Figure 1D from Xu L, Zhang B, Li W. Downregulated expression levels of USP46 promote the resistance of ovarian cancer to cisplatin and are regulated by PUM2. Molecular Medicine Reports. 2021;23:263. https://doi.org/10.3892/mmr.2021.11902; Figure 3F from Zhang X, Lian T, Fan W, et al. Long-Noncoding RNA CASC9 Promotes Progression of Non-Small Cell Lung Cancer by Promoting the Expression of CDC6 Through Binding to HuR. Cancer Manag Res. 2020;12:9033-9043. https://doi.org/10.2147/CMAR.S268375; Figure 7d from Qu Z, Li S. Long noncoding RNA LINC01278 favors the progression of osteosarcoma via modulating miR-133a-3p/PTHR1 signaling. J Cell Physiol. 2020;1–13. https://doi.org/10.1002/jcp.29582 and Figure 7F from Zhang RL, Aimudula A, Dai JH, Bao YX. RASA1 inhibits the progression of renal cell carcinoma by decreasing the expression of miR-223-3p and promoting the expression of FBXW7. Biosci Rep. 2020;40(7):BSR20194143. doi: https://doi.org/10.1042/BSR20194143. The image for Figure 4G, PCNA, sh-LINC01260 has been duplicated with the image 3E, Ki-67, NC from Luo et al, 2021. Images for Figure 7F have been duplicated with images for Figure 1e from Liu S, Liu LH, Hu WW, Wang M. Long noncoding RNA TUG1 regulates the development of oral squamous cell carcinoma through sponging miR-524-5p to mediate DLX1 expression as a competitive endogenous RNA. J Cell Physiol. 2019;234:20206–20216. https://doi.org/10.1002/jcp.28620 and Figure 2D and 2H from Xing T, Chen P, Wu J, et al. UPF1 Participates in the Progression of Endometrial Cancer by Inhibiting the Expression of lncRNA PVT1. Onco Targets Ther. 2020;13:2103-2114. https://doi.org/10.2147/OTT.S233149. The authors explained that a third party had carried out the experiments and there had been an equipment malfunction. However, it was not made clear how this subsequently led to the duplication of several images across multiple, unrelated articles. In addition, the authors were unable to provide original data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the authors requested to retract the article and the Editor and Publisher agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Yinhua Luo,1,&ast; Xiaohong He,2,&ast; Linbo Hu,3 Jinbo Zhao,1 Ke Su,1 Yuhua Lei,1 Yuanhong Li1 1Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, People’s Republic of China; 2Centre for Disease Control and Prevention, Enshi Center for Disease Control and Prevention, Enshi Prefecture, People’s Republic of China; 3Health Management Centre, Central Hospital of Tujia and Miao Autonomous Prefecture, Enshi Prefecture, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Li, Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, People’s Republic of China, Email lyh0101@vip.163.comBackground: Ischemic cardiomyopathy (ICM) with high morbidity and mortality is closely associated with an abnormal equilibrium of circulation selenium levels. The oxidative stress theory is the most accepted theory of selenium causing ischemic cardiomyopathy. However, the role of inflammatory responses in ICM has received limited attention.Methods: This study included 119 subjects, 43 of whom were patients with ICM, and 76 were healthy controls. Blood specimens were collected from subjects and serum levels of inflammatory and oxidative stress indicators and plasma levels of selenium were measured.Results: When plasma selenium and indicators of inflammation and oxidative stress were compared between groups, plasma selenium levels were significantly lower in the ICM group than in the control group (68.83874 vs 104.39775, p=0.02032), while indicators of inflammation such as tumour necrosis factor-alpha (TNF-α) (79.09773 vs 46.15634, p< 0.001), interleukin-6 (IL-6) (49.41484 vs 38.46923, p< 0.01) and neutrophil/lymphocyte ratio (3.696574 vs 2.383658, p< 0.001) were significantly higher in the ICM group than in the control group (all of these results were statistically different). Additionally, malondialdehyde (MDA), a marker of oxidative stress, was considerably higher in the ICM group than in the control group (61.63078 vs 39.0609, p< 0.01). In contrast, there were no significant differences in superoxide dismutase (SOD) levels between groups (p> 0.05). The Poisson regression analysis revealed a significant association between selenium and high levels of MDA, IL-6 and TNF-α (p< 0.05). Additionally, selenium was negatively connected with SOD levels and the neutrophil/lymphocyte ratio, but this relationship was not statistically significant (p=0.96, 0.15, respectively).Conclusion: Selenium deficiency is strongly associated with the development of ICM, and with levels of inflammation and oxidative stress in patients with ICM. Selenium can prevent the development and delay the progression of ICM by alleviating inflammatory responses.Keywords: inflammatory responses, ischemic cardiomyopathy, oxidative stress, selenium

Xuchao Gu,1,2,&ast; Wenhao Wang,1,2,&ast; Yijing Yang,1,2,&ast; Yiming Lei,1,2 Dehua Liu,1,2 Xiaojun Wang,1,2 Tao Wu1,2 1Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 2Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Wu; Xiaojun Wang, Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, No. 221 West Yan-An Road, Shanghai, 200040, People’s Republic of China, Tel +86 13641673915 ; +86 13062796919, Email taowuh@hotmail.com; 13681803275@163.comAbstract: Sarcopenia is an age-related systemic disease characterized by skeletal muscle aging that generally severely affects the quality of life of elderly patients. Metabolomics analysis is a powerful tool for qualitatively and quantitatively characterizing the small molecule metabolomics of various biological matrices in order to clarify all key scientific problems concerning cell metabolism. The discovery of optimal therapy requires a thorough understanding of the cellular metabolic mechanism of skeletal muscle aging. In this review, the relationship between skeletal muscle mitochondria, amino acid, vitamin, lipid, adipokines, intestinal microbiota and vascular microenvironment has been separately reviewed from the perspective of metabolomics, and a new therapeutic direction has been suggested.Keywords: sarcopenia, metabolomics, mitochondria, intestinal microbiota, vascular endothelium

YunYu Lin,1,&ast; Yan Lei,2,&ast; LinWei Li,2 Xiaoxing Su,2 Qiqi Tian,1 Wendy Wu2 1Respiratory Medicine, NingHai First Hospital, NingBo, 315600, People’s Republic of China; 2Berry Oncology Institutes, Berry Oncology Corporation, Fuzhou, 350200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiqi Tian; Wendy Wu, Email 252446462@qq.com; wujy3261@berryoncology.comObjective: Previous studies have shown that fusion partners have a potential role in influencing different tumorigenic abilities of ROS1 fusion variants, as well as potential differential responses to crizotinib. Therefore, it is important to accurately identify the type of ROS1 rearrangement in NSCLC for clinical treatment selection.Materials and Methods: Deep-coverage targeting solid tumor 31 cancer-related genes panel was used to capture DNA-based NGS information to detect gene fusion. RNA fusion panel based on hybrid capture sequencing was performed to verify gene fusions from total RNA which isolated from formalin fixed paraffin-embedded (FFPE) tissue blocks.Results: Using DNA-targeted NGS method, we identified a novel BAIAP2-ROS1 fusion in a 71-year-old non-smoking female patient with stage IVB lung adenocarcinoma. Rearrangement consisted of BAIAP2 in exon1-exon13 of chr17: q23 and ROS1 in exon35-exon43 of chr6: q22, which were further confirmed by RNA-based NGS methodology. A complete kinase domain in ROS1 fusion was preserved. The patient subsequently received crizotinib and showed significant tumor reduction until 17 months, who got benefit from targeted therapy.Conclusion: This study discovered a novel BAIAP2-ROS1 rearrangement; it provides more knowledge of ROS1 fusion in clinical personalized treatment. The good response to crizotinib therapy emphasizes the importance of DNA-based and RNA-based NGS in rare fusion identification in clinical practice.Keywords: BAIAP2-ROS1 fusion, advanced lung adenocarcinoma, sensitive to crizotinib, next-generation sequencing

Rui Huang,1,&ast; Yinhua Luo,2,&ast; Yuhua Lei,1 Yuanhong Li1 1Cardiovascular Disease Center, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, Hubei Province, People’s Republic of China; 2Department of Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, 442000, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong LiCardiovascular Disease Center, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, Hubei Province, People’s Republic of ChinaEmail lyh0101@163.vip.comAbstract: It is reported that the incidence of congenital long QT syndrome (cLQTS) is very low, with the incidence of LQTS caused by transient receptor potential melastatin 4 (TRPM4) being even lower, leading to less research on the gene TRPM4. We reported a case of an elderly male patient presenting with frequent syncopal episodes since the age of 20. Electrocardiography showed sinus bradycardia (mean heart rate 59 beats), prolonged QT interval (540ms), and torsade de pointes. His sister also had experienced an episode of syncope, but his other families had not. A novel mutation in the TRPM4 gene was discovered in this patient and his sister, according to genetic analysis. All in all, we provided a new heterozygous shift mutation (NM_017636: exon4: c.434delC, p. Ala145ValfsTer133) on TRPM4, which has never been reported in the past and thus may hopefully serve as useful feedback information for genetic pathogenesis of cLQTS caused by TRPM4 variants.Keywords: long QT syndrome, LQTS, TRPM4, mutation

Mengxin Tang,1,2,&ast; Jie Huang,3,&ast; Wen Zeng,1,2 Yanmei Huang,4 Yaoqiang Lei,5 Ye Qiu,6 Jianquan Zhang1,2,4 1Department of Respiratory and Critical Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Tuberculosis Ward, Nanning Fourth People’s Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 4Department of Respiratory and Critical Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518000, People’s Republic of China; 5Department of Infectious Diseases, Yongning District People’s Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 6Department of Comprehensive Internal Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye QiuDepartment of Comprehensive Internal Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaTel +8615676192180Fax +86771– 5719573Email yeqiu2013graduated@163.comJianquan ZhangDepartment of Respiratory and Critical Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaTel +8613978123845Fax +86755-23482484Email jqzhang2002@126.comPurpose: Disseminated nontuberculous mycobacterial (DNTM) infection can involve multiple organs, including the lungs, skin and soft tissues and lymph nodes. However, NTM infection leading to osteolysis has been rarely reported. Here, we analyzed the clinical features, osteolytic mechanisms, treatment and prognosis of patients with DNTM disease with osteolytic lesions.Patients and Methods: This retrospective study was conducted between January 1, 2011, and December 31, 2020, at the First Affiliated Hospital of Guangxi Medical University and the Fourth People’s Hospital of Nanning City. Patients who had culture and/or histopathological proof of DNTM disease with osteolytic lesions were included.Results: Ten HIV-negative patients with DNTM disease with osteolytic lesions were enrolled. Five of these patients had underlying diseases. Seven and three of the patients were positive and negative for anti-interferon-γ autoantibodies (AIGAs), respectively. The AIGA positivity rate was 70% (7/10). Ostealgia and anemia were the most common symptoms, followed by fever, emaciation, cough, expectoration, anorexia, subcutaneous abscesses and lymphadenopathy. Leukocyte and neutrophil counts were increased. The most common sites were the vertebrae, sternum, clavicle and ribs, although the femur, ilium, humerus, and scapula were also involved. Radiography and computed tomography (CT) showed moth-eaten or irregular destruction of bone, bone defects, pathological fracture, periosteal proliferation and surrounding abscesses. Emission CT (ECT) bone scans showed significantly increased uptake in many skeletal regions. Positron emission tomography(PET)/CT showed metabolic activity in multiple bones. All patients received anti-nontuberculous therapy, and five underwent surgery. Two died during treatment.Conclusion: DNTM infection of bone and leading to osteolysis usually occurs in patients with AIGA-positive antibodies. DNTM disease with osteolysis is characterized by increased leukocytes and neutrophil counts, focal suppurative granulomas, and multiple areas with moth-eaten or irregular destruction of bone with increased radioactive concentrations. Early diagnosis and timely, effective combination anti-NTM therapy can improve the prognosis.Keywords: HIV-negative, nontuberculous mycobacteria, osteolytic lesion, anti-IFN-γ autoantibodies

Rui Huang,1,&ast; Li Yan,2,&ast; Yuhua Lei1 1Cardiovascular Disease Center, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi Prefecture, 445000, Hubei Province, People’s Republic of China; 2Pediatrics Department, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi Prefecture, 445000, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhua Lei No. 158 Wuyang Avenue, Enshi Prefecture, Hubei Province, People’s Republic of ChinaEmail yuhualei0319@163.comAbstract: Accumulating evidence has demonstrated that gut microbial-derived metabolite trimethylamine N-oxide (TMAO) plays a crucial role in the pathogenesis of many diseases and can be served as a prognostic biomarker for several cardiovascular disorders, including arrhythmia. Recently, some studies have documented that TMAO was associated with the occurrence, progression, recurrence, and embolism risk of atrial fibrillation (AF). The activation of related inflammatory signal pathways and the cardiac sympathetic nervous system (CSNS) caused by elevated TAMO may be the underlying mechanism. It is worth noting that intervention in the metabolic pathway of TMAO may be an underlying therapeutic target of AF. In addition, standardized and individualized treatment strategies in clinical practice may be of great significance for AF patients, particularly those with high serum TMAO concentrations. However, there are also contradictions in the current research on TMAO and AF. Moreover, notwithstanding the positive preclinical and clinical findings, data supporting a direct association between TMAO and AF is a paucity. Thus, conclusive evidence from preclinical studies and multi-center randomized controlled trials to reveal the essential relationship between TMAO and AF is needy. In this review, we have attempted to summarize recent studies on TMAO and AF, highlighted the potential therapeutic strategies for AF patients, followed by a discussion on directions for future research in this field.Keywords: trimethylamine N-oxide, TMAO, atrial fibrillation

Xingyu Zhu,1,&ast; Yuqi He,2,&ast; Yin Wang,3,&ast; Yan Lei,3 Xiaoxing Su,3 Yifan Liu,1 Shuangxiu Wu,3 Zhengfu He1 1Department of Thoracic Surgery, Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China; 2Monash School of Medicine, Monash University, Clayton, VIC, 3800, Australia; 3Berry Oncology Corporation, Beijing, 102206, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuangxiu WuBerry Oncology Corporation, Beijing, 102206, People’s Republic of ChinaEmail wushx3173@berryoncology.comZhengfu HeDepartment of Thoracic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qing Chun Road, Hangzhou, 310006, Zhejiang, People’s Republic of ChinaTel/Fax +86 571-86006156Email hezhengfu@zju.edu.cnBackground: Approximately 2– 7% of patients with non-small cell lung cancer harbor anaplastic lymphoma kinase (ALK) rearrangement events. Of note, typical ALK actionable rearrangements are sensitive to treatment with tyrosine kinase inhibitors (TKIs). However, different types of ALK fusion influence the clinical outcomes of this therapeutic approach. Approximately 10– 40% of patients with ALK-fusion positive non-small cell lung cancer do not response to ALK-TKI therapy. Therefore, it is important to accurately identify the types of ALK rearrangement for appropriate selection of clinical treatment.Case Report: Using a DNA-targeted next-generation sequencing technique, we found a novel solute carrier family 8 member A1 (SLC8A1)-ALK fusion type in a patient with lung adenocarcinoma. Further reverse transcriptase-polymerase chain reaction and Sanger sequencing demonstrated the rearrangement as a B-cell CLL/lymphoma 11A (BCL11A)-ALK fusion at the transcriptional level. The patient showed a rapid and strong response to treatment with crizotinib, which lasted for 9 months. The patient also responded well to treatment with alectinib after developed resistance to crizotinib.Conclusion: A strategy combining DNA-targeted next-generation sequencing with RNA reverse transcriptase-polymerase chain reaction and sequencing, besides fluorescence in situ hybridization and immunohistochemistry, may provide an effective and practical solution for correct identification of partner genes and fusion structures in the diagnosis of ALK rearrangements, particularly for non-canonical expression patterns of ALK fusion events. The combined approach may lead to more benefits for patients.Keywords: lung adenocarcinoma, anaplastic lymphoma kinase rearrangement, tyrosine kinase inhibitor, treatment, case

Xin Zhang,&ast; Dingyi Yang,&ast; Yong Jiang, Luo Huang, Can Wang, Dan Tao, Xianfeng Liu, Yongyang Lei, Yongzhong Wu, Wei Zhou Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongzhong Wu; Wei ZhouChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, 181 Han Yu Road, Chongqing, 400030, People’s Republic of ChinaTel +86 18323064006Email cqmdwyz@163.com; 1052308491@qq.comPurpose: We sought to compare the symptomatic radiation pneumonitis (RP) in lung cancer patients treated with helical tomotherapy (HT) versus intensity-modulated radiotherapy (IMRT), and examine the predictive value of circulating lymphocyte subsets affecting the occurrence of RP.Patients and Methods: Circulating lymphocyte subsets, clinical characteristics, dosimetric parameters and pulmonary function were collected from 130 lung cancer patients treated with HT (n = 53) or IMRT (n = 77) from 2016 through 2020. Symptomatic RP was compared between groups. Binary logistic regression was used to identify predictors of RP.Results: The IMRT group had larger planning target volume (319.9 vs 240.8 cc, P = 0.041); more ECOG performance status 0– 1 (96.1% vs 79.2%, P = 0.002); more stage III–IV disease (94.8% vs 37.6%, P = 0.028); and more combined systemic therapy (85.7% vs 69.8%, P = 0.022). Grade ≥ 2 RP were comparable between IMRT and HT groups (16.9% vs 15.1%, P = 0.785). For stage III–IV disease, IMRT was associated with lower lung V10 (31.9% vs 35.8%, P = 0.047) and lower incidence of grade 5 RP (0% vs 9.1%, P = 0.018). All lymphocyte subsets reduced after radiotherapy. The decrease degree of total T cell count and CD4+ T cell count were larger after IMRT than HT (P = 0.043, P = 0.021). In univariate analysis, the smoking status, lower baseline FEV1, and higher total T cell count, higher CD8+ T cell count, lower total B cell count, lower CD4+/CD8+ ratio after radiotherapy were associated with the development of grade ≥ 2 RP. The higher CD8+T cell count after radiotherapy was the only risk factor associated with grade ≥ 2 RP in multivariable analysis (OR 1.003; 95% CI: 1.000– 1.005; P = 0.044).Conclusion: IMRT was associated with lower lung V10 and less grade 5 RP than HT for stage III–IV lung cancer. Higher CD8+ T cell count after radiotherapy was associated with an increased risk of RP. HT may better preserve total T cell and CD4+ T cell than IMRT.Keywords: radiation pneumonitis, lung cancer, helical tomotherapy, intensity-modulated radiotherapy, circulating lymphocyte

Zhenzhu Zheng, Ying Lei, Yinna Wang, Chunli Lin, Jiansheng Lin Department of Laboratory Medicine, Quanzhou Women’s and Children’s Hospital, Quanzhou, People’s Republic of ChinaCorrespondence: Jiansheng LinDepartment of Laboratory Medicine, Quanzhou Women’s and Children’s Hospital, 700 Fengze Street, Fengze District, Quanzhou, Fujian Province, 350122, People’s Republic of ChinaTel +86 0595 22196131Email 63678462@qq.comBackground: The purpose of this study was to evaluate the prevalence of mobile colistin resistance genes (mcr) in Gram-negative bacteria and to analyze the molecular characteristics of mcr-1 positive Salmonella typhimurium strain 75 and Escherichia coli strain 107 from the Quanzhou Women’s and Children’s Hospital in China.Methods: The genes mcr-1 through mcr-9 were screened via multiplex PCR. Antibiotic susceptibility was detected using a GN11 card with the VITEK-2 compact automated system. Whole genomes were sequenced using PacBio’s single molecule real-time (SMRT) technology.Results: In this study, mcr-1 was detected in only four strains, with a positivity rate of 0.65% (4/616). All the four strains were resistant to more than three different kinds of antibiotics. The mcr-1 positive S. typhimurium strain 75 harbored IncHI2 plasmid, which carried mcr-1 gene, while the mcr-1 positive E. coli strain 107 contained four plasmids including one mcr-1 harboring IncHI2 plasmid, one IncFII plasmid and two IncI1-I (Alpha) plasmids. Mobile elements carrying mcr-1 in the 75_plasmid and 107_plasmid-1 were located in the IS1086(ISApl1)-IS30A(ISApl1)-mcr-1-hp and IS1086(ISApl1)-mcr-1-hp regions, respectively. Tn6010 carrying drug efflux pump genes was found in 75_plasmid, while cn_31611_IS26 carrying multi-drug resistance (MDR) genes were found in 107_plasmid-1.Conclusion: This study found that mcr-1 was prevalent at a low frequency in the Quanzhou Women’s and Children’s Hospital. A similar genetic pattern of mcr-1 transmission was found in both E. coli and S. typhimurium.Keywords: mcr-1, Salmonella typhimurium, Escherichia coli, molecular characteristics

Yu Lei,&ast; Xiaoyu Liu,&ast; Jingmei Liu, Min Zhang, Yan Zhou, Wei Yan, Dean Tian, Ping Zhang, Ping Han Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Zhang; Ping HanDepartment of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, People’s Republic of ChinaEmail 845917536@qq.com; hanzhouping@163.comBackground: Isolated terminal ileitis (ITI) is a phenomenon often observed during colonoscopy, but in most cases, the specific etiology of ITI is unclear. Helicobacter pylori (H. pylori) infection has been reported to be associated with a wide variety of diseases, especially gastrointestinal diseases. Here, we conducted a retrospective study to explore a potential correlation between H. pylori infection and unexplained ITI (UITI).Materials and Methods: The retrospective study was conducted at Sino-French New City Branch of Tongji Hospital, Wuhan, China, from April 2017 to October 2020. All subjects underwent total colonoscopy, with the endoscope being inserted more than 10cm into the terminal ileum. Subjects also received a 13C-urea breath test (13C-UBT). Data on the age, gender, endoscopic manifestations, and main clinical symptoms of subjects were collected. The presence of H. pylori infection was defined as a positive 13C-UBT result. Logistic regression models were used to analyze the potential correlation between H. pylori infection and UITI.Results: There were 247 subjects (25.1%) in the H. pylori (+) group and 739 subjects (74.9%) in the H. pylori (-) group. The prevalence of UITI in the H. pylori (+) group was significantly lower than that in the H. pylori (-) group (OR = 0.518; 95% CI 0.281– 0.956; P = 0.035), and there was no difference in other clinical features between groups. Stratification analysis results showed that there was an inverse association between H. pylori infection and UITI in subjects with age < 60 (P = 0.046).Conclusion: These data showed that H. pylori infection was negatively correlated with UITI. Additional studies are needed to validate these findings in a larger cohort as well as to explore the underlying mechanisms.Keywords: Helicobacter pylori infection, unexplained isolated terminal ileitis, colonoscopy, 13C-urea breath test

Rui Huang,1,* YinHua Luo,2,* Jingbo Zhao,1 Ke Su,1 YuHua Lei,1 Yuanhong Li1 1Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi Prefecture, 445000, Hubei Province, People’s Republic of China; 2Department of Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, 442000, Hubei Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanhong LiCardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi Prefecture, No. 158 Wuyang Avenue, Enshi City, Hubei Province, People’s Republic of ChinaEmail lyh0101@vip.163.comBackground: ARVC is a rare genetic-related disease characterized by fibrous fat replacement in the ventricular myocardium, caused by mutations in genes encoding for the desmosomal proteins, such as the desmoglein-2 gene (DSG2). It is reported in the literature that other genetic factors may play a role in disease penetrance. Herein, we report a Chinese proband with ARVC, which was probably caused by DSG2 p.Val149Ile mutation as genetic background when carrying heterozygous PRRT2 p.Arg217ProfsTer8 mutation.Case Presentation: A 17-year-old male with a history of paroxysmal kinesigenic dyskinesia (PKD) presented to the hospital for syncope induced by ventricular tachycardia. According to relevant clinical data and the diagnostic criteria of ARVC, a precise positive diagnosis of ARVC was finally made. Gene testing revealed that the patient carried a DSG2 heterozygous missense mutation (NM_001943: exon5: c.445G>A, p.Val149Ile) as well as frameshift mutation of PRRT2 (NM_001256442: exon2: p. Arg217Profs Ter8).Conclusion: This is the first time to report a Chinese proband with ARVC and a history of PKD carrying both DSG2 p. val149ile mutation and PRRT2 p. Arg217ProfsTer8 mutation, which can provide a new direction for gene screening of patients with ARVC and further supplements for its diagnostic criteria.Keywords: arrhythmogenic right ventricular cardiomyopathy, ARVC, desmosomal proteins, desmoglein-2 gene, DSG2

Zi-Yang Zhang,1 Lin-Xiao Huang,1 Zhi-Wei Xu,1 Peng Wang,1 Yun Lei,1,2 Ai-Lin Liu1,2 1Department of Pharmaceutical Analysis, The School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 2Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, The School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of ChinaCorrespondence: Yun Lei; Ai-Lin LiuDepartment of Pharmaceutical Analysis, The School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of ChinaTel +86 591 22862016Email lypiglet@163.com; ailinliu@fjmu.edu.cnPurpose: The PML/RARα fusion gene as a leukemogenesis plays a significant role in clinical diagnosis of the early stage of acute promyelocytic leukemia (APL). Here, we present an electrochemical biosensor for PML/RARα fusion gene detection using carbon dots functionalized graphene oxide (CDs/GO) nanocomposites modified glassy carbon electrode (CDs/GO/GCE).Materials and Methods: In this work, the CDs/GO nanocomposites are produced through π-π stacking interaction and could be prepared in large quantities by a facile and economical way. The CDs/GO nanocomposites were decorated onto electrode surface to improve the electrochemical activity and as a bio-platform attracted the target deoxyribonucleic acid (DNA) probe simultaneously.Results: The CDs/GO/GCE was fabricated successfully and exhibits high electrochemical activity, good biocompatibility, and strong bioaffinity toward the target DNA sequences, compared with only the pristine CDs on GCE or GO on GCE. The DNA biosensor displays excellent sensing performance for detecting the relevant pathogenic DNA of APL with a detection limit of 83 pM (S/N = 3).Conclusion: According to the several experimental results, we believe that the simple and economical DNA biosensor has the potential to be an effective and powerful tool for detection of pathogenic genes in the clinical diagnosis.Keywords: acute promyelocytic leukemia, pathogenic genes, electrochemical biosensor, ex-situ method, carbon nanomaterials

Rui Huang,1,* Li Yan,2,* Yuhua Lei,1 Yuanhong Li1 1Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi Prefecture, 445000, Hubei Province, People’s Republic of China; 2Pediatrics Department, Central Hospital of Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi Prefecture, 445000, Hubei Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanhong Li No. 158 Wuyang Avenue, Enshi City, Hubei Province, People’s Republic of ChinaEmail lyh0101@vip.163.comBackground: Thyroxine is closely related to cardiovascular diseases, such as coronary heart disease, ventricular arrhythmia, atrioventricular block, myocardial systolic weakness, pericardial effusion, low cardiac output and hypertension. Previous studies have also found that hypothyroidism can also lead to mental disorders. Here, we present a rare case of severe hypothyroidism patient accompanied by sick sinus syndrome (SSS) as a cardiovascular manifestation needing cardiac pacing and severe mental disorders.Case Presentation: A 42-year-old female patient, previously healthy, was referred to our hospital because of bradycardia complicated with sick sinus syndrome which requiring cardiac pacing and severe mental disorders. Her clinical features along with laboratory findings strongly suggested that the patient had severe hypothyroidism with sick sinus syndrome and mental disorders, both of which were reversible and successfully treated with levothyroxine.Conclusion: This is the first reported case of hypothyroidism with sick sinus syndrome requiring pacemakers and psychiatric disorders, and the symptoms can be improved and reversed after thyroxine supplementation. This case highlights the importance of hypothyroidism screening when faced with unexplained psychosis or sick sinus syndrome, especially if combined.Keywords: hypothyroidism, sick sinus syndrome, psychiatric disorder, case report

The study on the surface morphology and crystal orientation of the Zn-0.5Sn coating could offer some guidance to improve the surface performance of the hot-dip galvanizing coating. In this paper, a scanning electron microscope (SEM) and an energy dispersive spectrometer (EDS) were used to analyze the typical morphology and the element distribution of spangles. The surface texture of the coating was analyzed by X-ray diffraction (XRD). Electron backscatter diffraction (EBSD) was used to analyze the crystal orientation of spangles. The results show that Sn segregates among the spangle dendrites while a metastable divorced eutectic structure can be maintained in the tin-rich phase, where the composition tends to be very similar. The crystal orientation of spangles affects their morphology, leading to the formation of feathery, ridged, and orthogonal dendrite arm spangles. When the angle among the orientation of the spangle crystal and the normal of the steel base surface changes from 0° to 90°, feathery spangles change to orthogonal dendrite arms spangles. The misorientation within a spangle is small while that among spangles is quite large. The orientation changes in the direction of the dendrite arm are relatively smooth and low, while the orientation changes which are perpendicular to the dendrite arm have a saltatory and irregular fluctuation.

Xuhui Zhang,1,* Jiemei Feng,2,* Xiaoxing Su,3 Yan Lei,3 Wendy Wu,3 Xiangyang Cheng4 1Department of Oncology, Guangdong Second Provincial General Hospital, Guangzhou, People’s Republic of China; 2Department of Respiratory and ICU, Guigang People’s Hospital, Guigang, 537100, People’s Republic of China; 3Clinical Research Division, Berry Oncology Corporation, Fuzhou, 350200, People’s Republic of China; 4Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wendy Wu; Xiangyang Cheng Email wujy3261@berryoncology.com xuewu1901@sina.comObjective: Synchronous multiple primary lung cancer (SMPLC) has a reported occurrence from 0.5% to 2% in lung cancer, and the surgical treatment and prognosis were quite diverse. With the discovery of driver mutations in lung adenocarcinoma (ADC), next-generation sequencing (NGS) would provide an explicit answer to the key question, whether individual tumors represent intrapulmonary metastases or independent tumors. Here, we reported a 64-year-old female diagnosed with a synchronous trilateral early-stage ADC with distinct driver alterations.Materials and Methods: NGS test targeting 31 cancer-relevant genes and amplification RNA sequencing (if gene fusion was found on DNA level) were performed on the surgical tumor tissue.Results: A 64-year-old Chinese female never smoker was found with one nodule in the right upper lobe and two nodules in the right middle lobe through chest computed tomography. The lesions were resected through video-assisted thoracic surgery and diagnosed with stage IA ADC, T1N0M0, in the postoperative pathology. NGS detected three independent driver mutations in three primary sites, respectively, EGFR 19del, EGFR 20ins and ROS1 fusion.Conclusion: This is the first report of a synchronous trilateral early-stage ADC with distinct driver alterations. All individual tumors were independent identified by NGS methodology, which had provided a clear answer to the key question of SMPLC in this case and should be used as a routine genetic test to explore fully pathological diagnosis and more comprehensive oncogenesis information in the early-stage ADC clinical prevention.Keywords: synchronous multiple primary lung cancer, lung adenocarcinoma, NGS, EGFR mutation, ROS1 fusion

Yun Shu,1,* Hui Li,2,* Hongjuan Shang,1 Jun Chen,1 Xiaoxing Su,2 Wei Le,1 Yan Lei,2 Liming Tao,1 Cailiang Zou,1 Wendy Wu2 1Department of Medical Oncology, Third People’s Hospital of Jiujiang City, Jiujiang 332000, People’s Republic of China; 2Berry Oncology Corporation, Fuzhou 350200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wendy Wu Email wujy3261@berryoncology.comYun Shu Email shuyun1972@163.comObjective: ROS1 fusions have been identified in 1– 2% of non-small-cell lung cancer (NSCLC) patients; they are validated as a driver of carcinogenesis and could be subjected to inhibition by crizotinib. However, previous studies suggested a variable progression-free survival (PFS) ranging from 9.1 to 20.0 months for crizotinib treatment in ROS1-rearranged NSCLC. Here, we reported a 45-year-old female diagnosed with stage IVB lung adenocarcinoma with multiple lymph nodes and bone metastasis carrying a novel MPRIP-ROS1 fusion, which was identified by RNA-based NGS (next-generation sequencing) and was sensitive to crizotinib treatment.Materials and Methods: A targeted NGS panel was used to analyze genomic DNA and total RNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue block of the patient. An RNA fusion panel based on amplicon sequencing was designed for detection fusion variation. Fusion results were validated using reverse transcriptase polymerase chain reaction and Sanger sequencing.Results: We reported a novel MPRIP-ROS1 fusion identified in this advanced lung adenocarcinoma case. The rearrangement was generated by exons 1– 21 of MPRIP at chr17: p11.2 joined to exons 35– 43 of ROS1 at chr6: q22.1, which retained an intact kinase domain of ROS1. The primary tumor and metastatic lymph nodes were eliminated on computed tomographic (CT) scan imaging after 2 months’ crizotinib treatment, and the multiple bone metastatic lesions were significantly relieved according to bone scintigraphy images. To date, the treatment has lasted 16 months, and the patient is still in follow-up showing sustained response to crizotinib.Conclusion: The study identified a novel MPRIP-ROS1 fusion that was sensitive to crizotinib, which provided a new driver of lung adenocarcinoma and potential therapeutic target for crizotinib. It also expanded NSCLC treatment of ROS1 rearrangement and highlighted the importance of genetic testing for precise treatment decision-making.Keywords: MPRIP-ROS1 fusion, advanced lung adenocarcinoma, sensitive to crizotinib, next-generation sequencing

Yangming Chen,1,* Yujie Lei,2,* Jianbin Lin,1 Yunchao Huang,2 Jiguang Zhang,1 Kai Chen,1 Shihui Sun,1 Xing Lin1 1Department of Thoracic Surgery, Shengli Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian 350001, People’s Republic of China; 2Department of Thoracic Surgery I, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, The International Cooperation Key Laboratory of Regional Tumor in High Altitude Area, Kunming, Yunnan 650106, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing LinDepartment of Thoracic Surgery, Shengli Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian 350001, People’s Republic of ChinaEmail fzlinxing@163.comPurpose: Recently, long noncoding RNAs (lncRNAs) have been identified as novel and potential therapeutic targets in various cancer types. Nonetheless, the levels and biological effects of lncRNAs in non-small cell lung cancer (NSCLC) remain largely unknown. In this study, we aimed to identify the effects of lncRNA-LINC01260 throughout the progression of NSCLC and explore the underlying mechanism.Methods: Quantitative real-time PCR (qRT-PCR) and Western blot were performed to measure LINC01260, miR-562, and CYLD expression and protein levels. Luciferase reporter assay was employed to investigate the relationship between LINC01260 and miR-562, and miR-562 and CYLD, respectively. The viability and migration of cells were evaluated using CCK-8, colony formation, and transwell assays. The effects of LINC01260 were identified through tumorigenesis in vivo. ELISA was performed to detect the activity of NF-κB and p65 expression.Results: In NSCLC tissues and cell lines, LINC01260 expression was downregulated, which corresponded to a lower survival rate of patients with NSCLC. Knockdown of LINC01260 accelerated the proliferation, colony formation, and migration of NSCLC cells. Moreover, downregulation of LINC01260 inhibited apoptosis of NSCLC cells by regulating the expression of Bcl-2 and Bax proteins in vitro. In vivo, the downregulation of LINC01260 promoted tumor growth. miR-562 was identified as the target gene of LINC01260, which was upregulated in NSCLC tumors. Furthermore, CYLD was identified as the target gene of miR-562. The effects of LINC01260 were exerted by regulating CYLD via sponging miR-562. ELISA confirmed that the upregulation of CYLD inhibited NF-κB activity; however, the co-transfection of sh-LINC01260 partly reversed the inhibition. Additionally, CYLD reduced p65 expression; however, downregulation of LINC01260 slightly increased the expression level.Conclusion: This study revealed a novel LINC01260/miR-562/CYLD/NF-κB pathway in the pathogenesis of NSCLC and suggested a potential therapeutic target for NSCLC.Keywords: non-small cell lung cancer, long noncoding RNA, miR-562, CYLD

Lirui He, Yunpeng Lei, Jianing Hou, Jianlong Wu, Guoqing Lv Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518000, People’s Republic of ChinaCorrespondence: Guoqing LvPeking University Shenzhen Hospital, No. 1120 Lianhua Road, Futian District, Shenzhen, Guangdong 518000, People’s Republic of ChinaEmail GuoqingLv123@126.comBackground: Gastric cancer (GC) is an aggressive malignancy with high lethality. Systematic chemotherapy is the main therapeutic strategy for advanced GC patients. The overexpression of Axl is associated with poor prognosis and regulates tumor growth and metastasis in many types of cancer. However, the role of Axl in GC progression remains elusive.Materials and Methods: Western blot and quantitative real-time PCR assay (RT-PCR) assays were used to detect the expression of Gas6, Axl, ZEB1 and epithelial-mesenchymal transition (EMT)-related markers in GC cells. Cell proliferation was determined by EdU cell proliferation assay and CCK-8 assay. Transwell invasion assay was performed to explore the effect of Axl and ZEB1 on cell invasion. Tumor xenografts and lung metastasis models were conducted to examine the effect of Axl on the growth and lung metastasis of GC cells.Results: In our study, we found that high levels of Gas6 and Axl expression were associated with reduced overall survival (OS) in GC patients and the expression of Gas6 and Axl was upregulated in GC cell lines. Ectopic expression of Axl induced EMT and promoted GC cell invasion and proliferation. The knockdown of Axl inhibited EMT and suppressed the proliferation and invasion of GC cell. In vivo study showed that inhibition of Axl impaired tumor growth and lung metastasis of GC cells. Mechanistic investigations revealed that Axl promoted EMT, invasion, and proliferation via upregulating ZEB1 expression in GC cells.Conclusion: Our results demonstrated that the Gas6/Axl/ZEB1 signaling pathway regulated EMT, invasion, and proliferation in GC cells and might represent a potential therapeutic target for GC treatment.Keywords: gastric cancer, Gas6/Axl signaling pathway, ZEB1, EMT, invasion, proliferation

The thermodynamic properties of impurity components in silicon solutions play an important role in the chemical removal process to the metallurgical route. In this paper, the component activity coefficients and interaction parameters of dilute silicon solutions were estimated by the molecular interaction volume model (MIVM). The activity coefficients (γi) of component i in dilute binary Si-i and ternary Si-i-j solutions at 1687-1873 K were firstly calculated. The concentration dependences of the interaction parameter and activity coefficient were also obtained. The self-interaction parameters (εi,i) for Si-i system were obtained as εB,B= -2.728-362.031/T, εAl,Al = 2.157-1876.776/T, εFe,Fe= -4.842+14445.926/T and εP,P = -2.543+13767.036/T. At the same time, the interaction parameters among components B, Al, and Fe in dilute ternary Sii- j solutions were also derived as εFe,B=-1.2758-2946.306/T, εAl,B = 0.7467-9765.9298/T and εFe,Al= -1.39677+3319.6803/T. Most important of all, the temperature dependences of the interaction parameters and activity coefficients in dilute Si-i and Si-i-j solutions with a certain i or j concentration were deduced. The results show that the predicted self-interaction parameters of B, Al, Fe, and P in binary silicon solutions reasonably agree with the experimental data. This further shows that MIVM is of reliability and can be expanded to a multi-component dilute silicon solution.

The interactions among impurity components in Si-based solution are the important thermodynamic parameters for the purification of silicon materials. A “same concentration” method was used to determine the activity interaction coefficients of Fe to B and Al to B in the silicon solution. Fe and Al were respectively dissolved into the binary Si-B solution at 1723 K with the holding time of 5 h, 7 h, 9 h, and 11 h. The equilibrium concentrations of Fe, B in the Si-B-Fe system and Al, B in the Si-B-Al system were determined. The interaction coefficients of Fe to B and Al to B were obtained by fitting the solubility data of B, Fe, and Al. The solubility relationships between B and [%Fe], and between B and [%Al] were obtained, respectively. It was found by the SEM and EPMA pictures of the samples that the third component Fe or Al added to the binary Si-B solution was alloyed, which verifies the accuracy of the experimental determination results. The significance of the activity interaction coefficient of B on boron removal from industrial silicon was analyzed.

Linlin Song,1 Jianyong Lei,1 Ke Jiang,1 Yali Lei,2 Yuting Tang,2 Jingqiang Zhu,1 Zhihui Li,1 Huairong Tang2 1Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of China; 2Health and Management Center, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaCorrespondence: Huairong TangHealth and Management Center, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaTel/Fax +86-28-85422933Email thrhuaxi11@163.comBackground and Aim: The relationship between subclinical hypothyroidism (SHYPO) and sleep quality is still unclear. Our objective was to compare the sleep quality between SHYPO patients and a control group with normal thyroid function.Methods: A total of 2224 patients with SHYPO and 12,622 euthyroid (EUTH) control group patients were included in the present study. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The sleep outcomes were compared to explore the association between SHYPO and sleep quality. Furthermore, we tried to identify the risk factors of poor sleep in SHYPO patients.Results: Compared to the EUTH control patients, SHYPO patients had a higher PSQI score (6.83 ± 2.67 vs 6.64 ± 2.63, p =0.004) and a higher proportion of poor sleepers (67.09% vs 64.75%, p =0.033). Moreover, subjects with SHYPO were associated with poorer sleep (Odd Ratio (OR) 1.120, 95% Confidence Intervals (CI) 1.016 to 1.235, p =0.023), longer sleep latency (OR 1.162, 95% CI 1.053 to 1.282, p =0.003), and shorter sleep duration (OR 1.148, 95% CI 1.019 to 1.293, p =0.023) after adjusting for potential confounders. Furthermore, we found that lower age, lower body mass index, and women were risk factors for poor sleep quality in SHYPO patients.Conclusion: Our findings suggest a relationship between SHYPO and poor sleep quality in a large Chinese population.Keywords: subclinical hypothyroidism, sleep quality, PSQI

Fang Yuan,1,* Jinliang Wang,1,* Ruixin Li,1,* Xiao Zhao,1 Yuxuan Zhang,2 Biao Liu,3 Yonghong Lei,4 Yi Hu1 1Department of Oncology, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China; 2Princeton International School of Mathematics and Science, Princeton, NJ 08540, USA; 3Department of Biological Analysis, Explore (Beijing) Biotech Co, Ltd, Beijing 100091, People’s Republic of China; 4Department of Plastic Surgery, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonghong LeiDepartment of Plastic Surgery, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, People’s Republic of ChinaTel +86 10 13161281016Email lyhhlx@126.comYi HuDepartment of Oncology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, People’s Republic of ChinaTel +86 10 13911031186Email huyi0401@aliyun.comBackground: Yes-associated protein (YAP) is downstream of the Hippo signaling pathway, which regulates several cellular processes. P53 is a key transcriptional regulator that responds to a variety of cellular stresses and regulates key cellular processes such as DNA repair, cell-cycle progression, angiogenesis, and apoptosis. Overexpression of YAP antagonizes P53 activity and targets its expression. However, the mechanism that underlies the post-transcriptional crosstalk between P53 and YAP has not been well dissected.Methods: We performed an integrated analysis and found that SIRT1 is a key candidate that connects YAP and P53 by modulating their acetylation.Results: We found that YAP promotes P53 deacetylation, promotes cell survival by inhibiting P53-induced G0/G1 arrest and apoptosis in A549 cells. Conversely, P53 enhances YAP acetylation, and decreases A549 cell survival by strengthening YAP acetylation-induced G0/G1 arrest and apoptosis both in vitro and in vivo.Conclusion: Our results demonstrate that SIRT1 is responsible for YAP and P53 deacetylation of specific residues, and reveal for the first time, a new regulatory mechanism of P53 and YAP crosstalk by SIRT1-mediated deacetylation, which may be involved in lung tumorigenesis.Keywords: P53, YAP, SIRT1, crosstalk

Yuanming Cai,1,* Ruxue Jia,2,3,* Haozhe Xiong,4 Qun Ren,2,3 Weimin Zuo,2,3 Tingting Lin,2,3 Rong Lin,2 Yan Lei,2 Ping Wang,2 Huiyue Dong,2 Hu Zhao,2,3 Ling Zhu,3 Yunfeng Fu,3 Zhiyong Zeng,5 Wei Zhang,6 Shuiliang Wang2,31Undergraduate Grade 2015, The 5th Clinical Medical School of Xinjiang Medical University, Urumchi, People’s Republic of China; 2Department of Urology, The 900th Hospital of the Joint Logistics Team, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Fujian Key Laboratory of Transplant Biology, Affiliated Dongfang Hospital, Xiamen University School of Medicine, Fuzhou, Fujian, People’s Republic of China; 4Undergraduate Grade 2017, Department of Bioengineering, College of Life Science, Fujian Normal University, Fuzhou, Fujian, People’s Republic of China; 5Department of Thoracic Surgery, The 900th Hospital of the Joint Logistics Team, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 6Department of Emergency, The 900th Hospital of the Joint Logistics Team, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China*These authors contributed equally to this workBackground: Paclitaxel has shown significant anti-tumor activity against non-small cell lung cancer (NSCLC); however, resistance to paclitaxel frequently occurs and represents a significant clinical problem and its underlying molecular mechanism remains elusive.Methods: Long-term treatment of culture cell with paclitaxel was carried out to mimic the development of acquired drug resistance in NSCLC. Cell proliferation and clonogenic assay and apoptosis evaluation were carried out to determine the efficacy of paclitaxel on NSCLC cells. Western blot analyses were performed to determine the expression and activation of proteins. Apoptosis enzyme-linked immunosorbent assay was used to quantify cytoplasmic histone-associated DNA fragments. Microarray analyses were applied to explore both mRNA and miRNA expression profiles in NSCLC cells followed by integrative analysis. qRT-PCR was carried out to verify the differentially expressed mRNAs and miRNAs.Results: The expression of 652 genes was shown to be changed at least 2-fold in paclitaxel-resistant NSCLC (H460_TaxR) cells with 511 upregulated and 141 downregulated as compared with that in parental H460 cells. The differentially expressed genes were functionally enriched in regulating the cell proliferation, cell death, and response to endogenous stimulus, and clustered in pathways such as cancer and signaling by the G protein-coupled receptor (GPCR). Moreover, 43 miRNAs were shown to be differentially expressed in H460_TaxR cells with 15 upregulated and 28 downregulated as compared with parental H460 cells. A total of 289 pairs of miRNA-potential target gene were revealed in H460_TaxR cells by bioinformatics analysis. Furthermore, integrative analysis of miRNAs and gene expression profiles revealed that dysregulated miR-362-3p, miR-766-3p, and miR-6507-3p might confer paclitaxel resistance in NSCLC via targeting MAPT simultaneously.Conclusion: Our findings suggested that specific manipulation of MAPT-targeting miRNAs may be a novel strategy to overcome paclitaxel resistance in patients with NSCLC especially large-cell lung carcinoma.Keywords: integrative analysis, non-small cell lung cancer, paclitaxel-resistance, gene expression profile, miRNAs

Ming Jiang1,*, Jinhua Bo1,*, Yishan Lei,1 Fan Hu,2 Zhengrong Xia,2 Yue Liu,1 Cui’e Lu,1 Yu’e Sun,1 Bailing Hou,1 Kun Ni,1 Zhengliang Ma,1 Xiaoping Gu1 1Department of Anesthesiology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, People’s Republic of China; 2Department of Basic Medicine, Analytical & Testing Center, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workBackground: Preoperative anxiety is associated with postoperative hyperalgesia; however, few studies have investigated the mechanism underlying this association in female surgical patients. Research has suggested that ON cells in the rostral ventromedial medulla (RVM) receive nerve impulses via cholecystokinin 2 (CCK2) receptors, facilitating hyperalgesia. Additionally, the downstream serotonergic projection system from the RVM to the spinal cord has a dual regulating effect on pain responses, and the 5-hydoxytryptophan 2B (5-HT2B) receptor in spinal dorsal horn neurons is critically involved in mechanical allodynia.Methods: Ovariectomized rats were treated with estrogen replacement, single prolonged stress (SPS), and plantar incision. Various receptor agonists and antagonists were then administered into the RVM and spinal cord to study the mechanism underlying postoperative hyperalgesia caused by preoperative anxiety in female rats.Results: Behavioral testing revealed that preoperative SPS induced postoperative hyperalgesia, as well as the expression of the CCK2 receptor in the RVM and the expression of the 5-HT2B receptor, protein kinase Cγ (PKCγ), and phosphorylation of the N-methyl-d-aspartate receptor1 (p-NR1) in the spinal cord increased confirmed by Western blot. RVM microinjection of the CCK2 receptor agonist CCK-8 and intrathecal injection of the 5-HT2B receptor agonist BW723C86 both produced hyperalgesia in female rats after plantar incision, whereas the CCK2 receptor antagonist YM022, the 5-HT2B receptor antagonist RS127445, and the PKCγ inhibitor C37H65N9O13 decreased the rats’ sensitivity to the same stimulus. Additionally, electrophysiological analysis suggested that activation of the 5-HT2B receptor increased the whole-cell current (IBa) in superficial dorsal horn neurons through the PKCγ pathway.Conclusion: Our study demonstrated that preoperative anxiety-induced postoperative hyperalgesia in female rats is associated with descending pain pathways. The CCK2 receptor in the RVM and spinal 5-HT2B receptor may play a role in this hyperalgesic effect.Keywords: cholecystokinin 2 receptor, 5-hydoxytryptophan 2B receptor, preoperative anxiety, postoperative hyperalgesia, rostral ventromedial medulla, spinal cord

Xin-Yu Liao,1,* Yang Lei,2,* Song-Feng Chen,2 Jing Cheng,3 Dan Zhao,4 Zhi-Feng Zhang,2 Xin Han,5 Ya Zhang,2 Hua-Bao Liao,2 Yang Zhuang,2 Juan Chen,6 Hai-Bing Zhou,5 Qi Wan,7 Ying-Ying Zou,11Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming 650500, People’s Republic of China; 2Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, Wuhan 430071, People’s Republic of China; 3Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, People’s Republic of China; 4Department of Physiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, People’s Republic of China; 5School of Pharmacy, Wuhan University, Wuhan 430071, People’s Republic of China; 6Department of Neurology, The Central Hospital of Wuhan, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430013, People’s Republic of China; 7Institute of Neuroregeneration & Neurorehabilitation, Collaborative Innovation Center for Brain Science, Department of Neurosurgery of the Affiliated Hospital, Qingdao University, Qingdao 266071, People’s Republic of China*These authors contributed equally to this work Background: The authors have recently designed a new compound bisperoxovandium (pyridin-2-squaramide) [bpV(pis)] and verified that bpV(pis) confers neuroprotection through suppressing PTEN and activating ERK1/2, respectively. Intracerebral hemorrhage (ICH) is the second most common cause of stroke and has severe clinical outcome. In this study, we investigate the effect of bpV(pis) in ICH model both in vivo and in vitro.Materials and methods: The novel drug bpV(pis) was synthesized in the Faculty of Pharmacy, Wuhan University School of Medicine. An ICH model was generated on both SD rats and cells. bpV(pis) was injected into intracerebroventricular or culture media. Western blotting was applied to test the signal pathway. To determine the effect of bpV(pis) on PTEN inhibition and ERK1/2 activation, we measured the phosphorylation level of AKT (a direct downstream target of PTEN that negatively regulates AKT) and ERK1/2. FJC, MTT, and LDH were applied to measure the cell viability. Neurobehavioral tests were performed to measure the effect of bpV(pis).Results: The in vivo results showed that intracerebroventricular administration of bpV(pis) significantly alleviates hematoma, the damage of brain–blood barrier and brain edema. The in vitro results demonstrated that bpV(pis) treatment reduces ICH-induced neuronal injury. Western blotting results identified that bpV(pis) exerts a neuroprotective effect by significantly increasing the phosphorylation level of AKT and ERK1/2 after experimental ICH. Neurobehavioral tests indicate that bpV(pis) promotes functional recovery in ICH animals.Conclusion: This study provides first and direct evidence for a potential role of bpV(pis) in ICH therapy.Keywords: bpV(pis), intracerebral hemorrhage, PTEN, AKT, ERK1/2, neuroprotection

Ping Han, Yu Lei, Dongxiao Li, Jingmei Liu, Wei Yan, Dean Tian Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China Abstract: Since the blood vessel epicardial substance or Popeye domain-containing protein 1 (BVES/POPDC1) was first identified in the developing heart by two independent laboratories in 1999, an increasing number of studies have investigated the structure, function, and related diseases of BVES/POPDC1. During the first 10 years following the discovery of BVES/POPDC1, studies focused mainly on its structure, expression patterns, and functions. Based on these studies, further investigations conducted over the previous decade examined the role of BVES/POPDC1 in human diseases, such as colitis, heart diseases, and human cancers. This review provides an overview of the structure and expression of BVES/POPDC1, mainly focusing on its potential role and mechanism through which it is involved in human cancers. Keywords: blood vessel epicardial substance, Popeye domain-containing protein 1, cancer, Rho

Yuan-Yuan Lei,1 Suzanne C Ho,2 Ashley Cheng,3 Carol Kwok,3 Ka Li Cheung,1 Yi-Qian He,1 Chi-Kiu Iris Lee,1 Roselle Lee,1 Winnie Yeo1,4 1Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; 2Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; 3Department of Clinical Oncology, Princess Margaret Hospital, Kwai Chung, Hong Kong Special Administrative Region, China; 4Hong Kong Cancer Institute, State Key Laboratory in Oncology in South China, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China Background: The diagnosis of cancer can motivate patients to change their dietary habits. Evidence on changes in dietary intake before and after breast cancer diagnosis in Chinese women has been limited. Patients and methods: In an ongoing prospective cohort study which involved 1,462 Chinese women with early-stage breast cancer, validated food frequency questionnaire was used to assess prediagnostic dietary intake (using questionnaire to recall dietary intake before diagnosis, which completed at baseline, ie, 0–12 months after diagnosis) and postdiagnostic dietary intake at 18-month and 36-month follow-ups after diagnosis. This study quantitatively compared dietary intake across three time points before and after breast cancer diagnosis. Results: Breast cancer patients significantly and continuously increased vegetables and fruits consumption, from 4.54 servings/day at prediagnosis to 5.19 and 5.59 servings/day at 18-month and 36-month follow-ups postdiagnosis, respectively (each compared to baseline, P

Yiyan Lei, Zhaoguo Liu, Weilin Yang Department of General Thoracic Surgery, The First Affiliated Hospital, Sun-Yat Sen University, Guangzhou, Guandong, People’s Republic of China Background: The aim of this study was to observe the expression of microRNA-222 (miR-222) and matrix metalloproteinase inhibitor 3 (TIMP3) in non-small cell lung cancer (NSCLC) and discuss their significance.Methods: A total of 230 patients with NSCLC were enrolled in the observation group during the operation. Ninety-eight normal adjacent tissues were used as the control group. Two groups of miR-222 and TIMP3 were detected by in situ hybridization and immunohistochemistry. The distribution of miR-222 and TIMP3 in A549/H358/PC9 cells was observed by immunofluorescence. Chi-squared and Spearman correlation tests were used to analyze the relationship among miR-222, TIMP3 expression, and clinicopathological parameters of NSCLC. Kaplan–Meier and Cox proportional hazards regression were used to analyze the prognostic impact of miR-222 and TIMP3.Results: Immunohistochemistry showed that the expression of miR-222 in lung cancer tissue was significantly higher, but TIMP3 was lower than that in normal lung tissue (P = 0.0001 for the former and P = 0.0002 for the latter). Meanwhile, miR-222 and TIMP3 were mainly distributed in the cytoplasm. Among them, cTIMP3 accounted for 70.29% (72/101), cmiR-222 for 59.35% (92/155), 14.85% for nTIMP3 (15/101), and 18.06% for nmiR-222 (28/155). There was a significant difference in distribution (both P < 0.0001). The expression of miR-222 and TIMP3 were negatively correlated in lung cancer tissues (r = -0.43, P = 0.0219). With the progression of clinical stage, the positive intensity of cTIMP3 showed a decreasing trend, while the cmiR-222 showed a reverse trend (the former P = 0.0024 and the latter P < 0.0001). In the Kaplan–Meier prognostic analysis, we found that the high expression of cTIMP3 could predict a better prognosis (P = 0.0040), whereas cmiR-222 was the opposite (P = 0.0016). Multivariate analysis shows that both can be used as independent factors.Conclusion: TIMP3 expression in lung cancer is relatively low and has a negative correlation with lung cancer staging and prognosis, suggesting that it may play a defensive function in the development of lung cancer, while miR-222 has the opposite effect, and the expression of both proteins is negatively correlated, suggesting that in lung cancer progresses, both proteins may play some role together. Keywords: lung cancer,tumor markers, A549/h358/pc9, biological mechanism, immuno­fluorescence

Wenjing Huang,1 Yan Lang,1 Abdul Hakeem,1 Yan Lei,2 Lu Gan,1 Xiangliang Yang1 1Department of Nanomedicine and Biopharmaceuticals, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; 2Pharmacy of School Hospital, Huazhong University of Science and Technology, Wuhan 430074, China Background: Multidrug resistance (MDR) is one of the major obstacles to successful cancer chemotherapy. Developing efficient strategies to reverse MDR remains a major challenge. Surfactin (SUR), a cyclic lipopeptide biosurfactant, has been found to display anticancer activity. Methods: In this paper, SUR was assembled by solvent-emulsion method to load the anticancer drug doxorubicin (DOX). The cytotoxicity of DOX-loaded SUR nanoparticles (DOX@SUR) against DOX-resistant human breast cancer MCF-7/ADR is measured by MTT assay. The cellular uptake and intracellular retention of DOX@SUR are determined by flow cytometry. The tumor accumulation and anticancer activity of DOX@SUR are evaluated in MCF-7/ADR-bearing nude mice. Results: DOX@SUR induce stronger cytotoxicity against DOX-resistant human breast cancer MCF-7/ADR cells compared to free DOX. DOX@SUR nanoparticles exhibit enhanced cellular uptake and decreased cellular efflux, which might be associated with reduced P-glycoprotein expression. After internalization into MCF-7/ADR cells by macropinocytosis- and caveolin-mediated endocytosis, DOX@SUR nanoparticles are colocalized with the lysosomes and translocated to the nucleus to exert cytotoxicity. Furthermore, in vivo animal experiment shows that the DOX@ SUR nanoparticles are accumulated more efficiently in tumors than free DOX. Meanwhile, DOX@SUR nanoparticles display stronger tumor inhibition activity and fewer side effects in MCF-7/ADR-bearing nude mice. Conclusion: This study indicates that SUR-based nanocarrier might present a promising platform to reverse MDR in cancer chemotherapy. Keywords: multidrug resistance, cellular uptake, cellular efflux, biodistribution

Cai Y, Jia R, Xiong H, et al. Cancer Manag Res. 2019;11:7391—7404. The authors have advised due to an error at the time of figure assembly, Figure 1D on page 7393 is incorrect. The correct Figure 1 is shown below. The authors apologize for this error and advise it does not affect the results of the paper. Read the original article

Wenjie Chen,1 Jianyong Lei,1 Jiaying You,2 Yali Lei,3 Zhihui Li,1 Rixiang Gong,1 Huairong Tang,3 Jingqiang Zhu1 1Thyroid and Parathyroid Surgery Center, 2West China School of Clinical Medicine, 3Health and Management Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of China Background: Recurrent laryngeal nerve (RLN) invasion in papillary thyroid carcinoma (PTC) is one of the main predictors of poor prognosis. The present study investigated the risk factors for RLN invasion in PTC patients.Methods: A total of 3,236 patients who received thyroidectomy due to PTC in Thyroid and Parathyroid Surgery Center of West China Hospital of Sichuan University were reviewed. Demographics and clinical factors, imaging examination (ultrasonography) characteristics, surgical details, postoperative pathological details, recurrence, and postoperative complications were recorded. Univariate and multivariate analyses were used to study the risk factors of RLN invasion, Kaplan–Meier method was performed to compare the outcomes of tumor recurrence.Results: Patients with RLN invasion had a higher recurrence rate than those in the control group (p

Yu Sun,1,* Yangshan Chen,1,* Shuhua Li,1,* Yiyan Lei,2 Di Xu,3 Neng Jiang,1 Yang Zhang,4 Jessica Cao,5 Zunfu Ke1,* 1Department of Pathology, 2Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Thoracic Surgery, The Central Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China; 4Biomedical Engineering, The University of Texas at El Paso, El Paso, TX, USA; 5Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada *These authors contributed equally to this work Abstract: Lung adenocarcinoma (LADC) is among the most malignant cancers that frequently develops micrometastases even in early stages of the disease. Circulating tumor cell (CTC) number, matrix metalloproteinase (MMP) 7, and MMP9 show great prospects as predictive biomarkers in many tumors. However, the interactions between these biomarkers and the molecular basis of their roles in the metastasis and prognosis of LADC remain unclear. The present study revealed that an elevated CTC count and overexpression of MMP7 and MMP9 correlate with metastasis and clinical progression in LADC patients (n=143). Furthermore, MMP7 and MMP9 upregulation facilitates LADC cell migration in vitro and enhances serum CTC levels in a xenograft mouse model. More importantly, receiver operating characteristic (ROC) curves and Kaplan–Meier analysis confirmed more accurate prediction of metastasis and overall survival (OS) with a combination panel of CTC, MMP7, and MMP9. Taken together, our data show, for the first time, the involvement of MMP7 and MMP9 in the release of CTCs into the peripheral blood, and our data reveal that CTC count and expression of MMP7 and MMP9 can be used together as an effective clinical prediction panel for LADC metastasis and prognosis. Keywords: lung adenocarcinoma, circulating tumor cell, MMP7/MMP9, metastasis, prognosis