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Zuoan Qin,1,2 Nuohan Liao,3 Xuelin Lu,4 Xiangjie Duan,5 Quan Zhou,6 Liangqing Ge1,2 1Jinan University, Guangzhou, 510632, People’s Republic of China; 2Department of Cardiology, The First People’s Hospital of Changde City, Changde, 415003, People’s Republic of China; 3University of South China, Hengyang, Hunan, 421002, People’s Republic of China; 4Department of Pathology, The First People’s Hospital of Changde City, Changde, 415003, People’s Republic of China; 5Department of Infectious Diseases, The First People’s Hospital of Changde City, Changde, 415003, People’s Republic of China; 6Department of Science and Education, The First People’s Hospital of Changde City, Changde, 415003, People’s Republic of ChinaCorrespondence: Liangqing Ge, Email geliangqing@163.comAim: To investigate the association between the hemoglobin-to-red cell distribution width (RDW) ratio (HRR) and all-cause mortality in ischemic stroke patients with atrial fibrillation (AF).Design: This study was a retrospective cohort analysis. In total, 1018 ischemic stroke patients with AF were enrolled using the Medical Information Mart for Intensive Care database, (MIMIC)-IV. The patients were divided into four groups according to the HRR values. The primary outcome was 180-day all-cause mortality.Methods: Multivariate Cox proportional risk regression models were used to examine the association between HRR and all-cause mortality. The non-linear relationship between HRR and all-cause mortality was confirmed using a Cox proportional risk regression model fitted by cubic spline function and smooth curve fitting.Results: A total of 246/1018 patients (24.17%) died. The serum HRR values were negatively associated with 180-day all-cause mortality (hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.68– 0.94). A two-piecewise regression model was used to obtain a threshold inflection point value of 9.74. The HR and the 95% CI on the left inflection point were 0.73 and 0.61– 0.87 (p = 0.0005); on the right inflection point they were 1.06 and 0.82– 1.38 (p = 0.6383).Conclusion: The relationship between all-cause mortality and the HRR values was non-linear in ischemic stroke patients with AF. All-cause mortality and HRR values were negatively correlated when the HRR value was ≤ 9.74.Keywords: ischemic stroke, atrial fibrillation, all-cause mortality, MIMIC-IV

Lingzhu Wen,1,* Guochun Zhang,1,* Chongyang Ren,1,* Xuerui Li,1 Hsiaopei Mok,1 Minghan Jia,1 Yulei Wang,1 Bo Chen,1 Kai Li,1 Li Cao,1 Cheukfai Li,1 Weikai Xiao,1 Jianguo Lai,1 Jiali Lin,1 Guangnan Wei,1 Yingzi Li,1 Yuchen Zhang,1 Xiaoqing Chen,2 Ning Liao1 1Department of Breast Cancer, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Guangzhou, Guangdong, People’s Republic of China; 2Department of Breast Surgical Oncology, Foshan Maternity and Children’s Healthcare Hospital Affiliated to Southern Medical University, Foshan, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning LiaoDepartment of Breast Cancer, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), No. 106, Zhongshan 2nd Road, Yuexiu District, Guangzhou, Guangdong, People’s Republic of ChinaTel/Fax +86 20-83827812Email syliaoning@scut.edu.cnPurpose: This study aimed to investigate AKT gene mutation status in Chinese breast cancer patients.Methods: The study included 411 breast cancer patients hospitalized in Guangdong Provincial People’s Hospital (GDPH) from June 1, 2017 to September 27, 2018. Mastectomy or breast conserving surgery was performed, and tissue samples were subjected to next-generation sequencing (NGS) to determine AKT gene mutation status. Meanwhile, the expression of human epidermal growth factor receptor 2 (Her2), progesterone receptor (PR), and estrogen receptor (ER) was analyzed by immunohistochemistry staining. The Cancer Genome Atlas (TCGA) database was used for comparative studies.Results: Patients in the GDPH cohort had an older age (P < 0.001), higher postmenopausal rate (P < 0.001), larger tumor size (P < 0.001), higher histologic type of infiltrating duct cancer (P < 0.001), higher metastatic rate (P < 0.001), higher expression of ER (P = 0.015) and HER2 (P < 0.001), and higher percentage of the HR/HER2 subtype (P < 0.001) than those in the TCGA cohort. The GDPH cohort displayed lower rates of overall AKT and AKT3 mutation (P < 0.001), but a higher AKT1 mutation rate (P < 0.0001) compared with the TCGA cohort. Notably, the NGS studies identified missense mutation and copy number amplification as the most common AKT variation type in the GDPH and TCGA cohorts, respectively. Specifically, E17K mutation in AKT1 was predominantly detected in GDPH cohort, while being absent in TCGA cohort. Moreover, in the GDPH cohort, AKT variation was correlated with a number of clinicopathological variables, including age over 50, HER2-, HR+/HER2-, and PR+.Conclusion: Patients in the GDPH cohort had lower rates of AKT and AKT3 mutation and higher AKT1 mutation rate than those in the TCGA cohort, while harboring missense mutations detected predominantly as E17K mutation in AKT1. In GDPH cohort, there were correlations between AKT mutation and the clinicopathological characteristics of patients.Keywords: AKT, next-generation sequencing, breast cancer, somatic mutations, population study

Wenzhen Zhu,* Chongyang Ren,* Yulei Wang, Lingzhu Wen, Guochun Zhang, Ning Liao Department of Breast Cancer, Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning LiaoDepartment of Breast Cancer, Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou 510080, People’s Republic of ChinaEmail syliaoning@scut.edu.cnBackground: ESR1 mutation and its possible relation to endocrine therapy resistance in ER-positive breast cancers have been studied with respect to genetic sequencing data from Western patients but rarely from Chinese patients. This study aimed to investigate the prevalence of ESR1 mutation in Chinese primary and metastatic ER-positive breast cancer.Methods: Tumor samples from 297 primary breast cancer (PBC) patients and blood samples from 43 metastatic breast cancer (MBC) patients were obtained to perform whole exon sequencing of the ESR1 gene through next-generation sequencing (NGS). Clinicopathological features of MBC patients were listed and grouped to explore potential factors in ESR1 mutations.Results: A total of 15 ESR1 variations, including 11 point mutations, 1 in-frame deletion mutation, 1 synonymous mutation, and 2 amplifications were identified in 13 patients. The ESR1 mutation rate was 1% (3/297) in PBC patients and 18.6% (8/43) in MBC patients. All ESR1 point mutations occurred in the estrogen receptor ligand-binding domain. Six (54.5%) of the 11 point mutations were hotspot mutations. Among all MBC patients, the ESR1 mutation rate in those who had a treatment history using aromatase inhibitors (AI) was significantly higher than those who did not (25.8% versus 0%, P=0.015). Moreover, the ESR1 mutation rate in those who received AI treatment over a period of 12 months was significantly higher than in those whose treatment lasted less than 12 months [36.3% versus 0%, P< 0.001].Conclusion: ESR1 mutations were more frequently observed in the circulating cell-free DNA of MBC patients than in PBC patients among the Chinese cohort, and higher among those pretreated with AI, suggesting that such mutations may undergo selection during AI treatment.Keywords: breast cancer, ESR1 mutation, endocrine therapy resistance, NGS, aromatase inhibitors

Guo Xia He,1,2,* Ning Li,1,3,* Lei Ren,2,4,* Hong Hua Shen,2 Ning Liao,5 Jian Jun Wen,6 Yi Min Xu,2 Jing Wang,4 Qing Yun Li1,3 1Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People’s Republic of China; 2Department of Respiratory Rehabilitation, The Fourth Rehabilitation Hospital of Shanghai (Shanghai Jingan Geriatric Hospital), Shanghai 200042, People’s Republic of China; 3Institute of Respiratory Disease, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People’s Republic of China; 4Department of Respiratory Medicine, The Second Affiliated Hospital of Suzhou University, Jiangsu 215004, People’s Republic of China; 5West-Nanjing Road Community Health-care Center of Shanghai, Shanghai 200040, People’s Republic of China; 6Caojiadu Community Health Service of Shanghai, Shanghai 200042, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing Yun LiDepartment of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin 2nd Road, Shanghai 200025, People’s Republic of ChinaTel +86 1 350 173 8686Fax +86 215 764 3271Email liqingyun68@hotmail.comPurpose: Pulmonary rehabilitation (PR) is essential to manage patients with COPD. The aim of this study was to investigate the appropriate intensity of PR exercise training for patients with moderate-to-severe COPD.Patients and methods: A prospective multicenter randomized controlled trial was conducted from January 2014 to October 2018. The subjects were randomly assigned to three groups with different intensities of PR, according to their maximum oxygen uptake percentage determined by cardiopulmonary exercise testing. After 20 weeks of exercise training, the effects of low-, moderate-, and high-intensity exercise interventions on patients were compared to determine the most appropriate PR prescription.Results: For patients with moderate COPD, all the measured parameters were significantly improved in the moderate- and high-intensity PR groups (P0.05).Conclusion: High-intensity PR exercise is helpful for patients with moderate to severe COPD. Moderate COPD patients need to receive intensive PR training; the improvement degrees from PR intervention were higher than those of the severe COPD patients. For patients with severe COPD, high-intensity PR exercise may be more beneficial if patients can tolerate it.Keywords: chronic obstructive pulmonary disease, cardiopulmonary exercise testing, exercise therapy, pulmonary rehabilitation

Xiang Zhang,1–3 Fei Wang,2,3 Yanbing Huang,1–3 Kun Ke,1–3 Bixing Zhao,2,3 Lihong Chen,4 Naishun Liao,2,3 Lei Wang,2,3 Qin Li,5 Xiaolong Liu,2,3 Yingchao Wang,2,3 Jingfeng Liu1–3,6 1The First Affiliated Hospital of Fujian Medical University, Fuzhou, China; 2The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; 3The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, China; 4Department of Pathology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; 5Department of Infectious Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; 6Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China Purpose: The aim of this work was to investigate the clinicopathological significance of fibrinogen gamma chain (FGG) and its biological roles during hepatocellular carcinoma (HCC) development and progression.Methods: The expression of FGG was examined by Western blot and reverse transcription quantitative PCR in two different sample sets, including 24 or 35 pairs of HCC tumor tissues and their corresponding adjacent non-tumorous tissues. Afterward, association analysis between the expression of FGG and clinicopathological characteristics was systematically analyzed in 79 HCC patients. Subsequently, the mobility and invasiveness of SK-HEP-1 cells with FGG overexpression or knockdown were evaluated by transwell assay and wound healing assay. Additionally, the expressions of epithelial to mesenchymal transition (EMT)-associated markers were also detected in FGG overexpressed or silenced SK-HEP-1 cells.Results: The expression of FGG was significantly increased in primary HCC tissues comparing with its corresponding adjacent non-tumorous tissues. Clinical pathological analysis demonstrated that upregulation of intracellular FGG was significantly associated with increased vascular invasion, more satellite nodules, and more advanced TNM stage, and HCC patients with stronger expression of FGG had a higher recurrence rate and correspondingly a shorter overall survival time. Meanwhile, the high expression of FGG was also proved to be an independent risk factor for disease-free survival after surgical resection. In vitro phenotype studies showed that overexpression of FGG could promote the migration and invasion in SK-HEP-1 cells; conversely, these phenotypes could be significantly inhibited by knocking down the expression of FGG. Mechanism studies indicated that FGG could promote the migration and invasion through EMT signaling pathway by regulating the expressions of Slug and ZEB1.Conclusion: FGG played important roles in enhancing cancer cell motility and invasiveness through EMT signaling, and might serve as a potential prognostic biomarker for HCC patients. Keywords: hepatocellular carcinoma, fibrinogen gamma chain, epithelial to mesenchymal transition, recurrence, metastasis

Bo Chen,1,* Hailin Tang,2,* Xi Chen,3,* Guochun Zhang,1 Yulei Wang,1 Xiaoming Xie,2 Ning Liao1 1Department of Breast Cancer, Cancer Center, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China; 2Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; 3Department of Anatomy, Hengyang Medical College, University of South China, Hengyang, China *These authors contributed equally to this work Purpose: There are significant differences in the biological behavior between triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (non-TNBC). In the present study, we identify key differential genes and clinical outcomes between TNBC and non-TNBC. Materials and methods: Transcriptomic analyses used GEO datasets (GSE76275), gene ontology, KEGG pathway analysis and cBioPortal. Quantitative RT-PCR analysis (qRT-PCR) was used to validate the differentially expressed genes. We used the KM Plotter Online Tool and 240 patients with TNBC tissue microarray to assay the prognostic value of HORMAD1. Results: The upregulated differentially expressed genes were enriched in transcription factor activity, sequence-specific DNA binding and nucleic acid binding transcription factor activity. Only 16 genes were upregulated when further screened for fold change >4-fold change. HORMAD1 and SOX8 exhibited high frequencies of change of greater than 10% (HORMAD1 was close to 20%). qRT-PCR results indicated that HORMAD1 and SOX8 mRNA levels were significantly upregulated in TNBC samples. In KM Plotter Online Tool, high HORMAD1 was associated with worse outcome. In our tissue microarray (including 240 TNBC tissues), IHC analysis revealed that 29.7% (55/240) of the tumor samples exhibited high HORMAD1 expression and 70.3% (185/240) of the tumor samples exhibited low HORMAD1 expression levels. Meanwhile, high HORMAD1 group has a bad prognosis. Conclusion: The status of transcriptional activation is an important difference between TNBC and non-TNBC. HORMAD1 is a key differential gene associated with poor outcome in TNBC. Epigenetic therapy and agents targeting cancer/testis antigens might potentially help to customize therapies of TNBC. Keywords: HORMAD1, triple-negative breast cancer, non-triple-negative breast cancer, prognostic factor, transcriptome

Kun Ke,1–3,* Geng Chen,2–4,* Zhixiong Cai,2–4 Yanbing Huang,1–3 Bixing Zhao,2,3 Yingchao Wang,2,3 Naishun Liao,2,3 Xiaolong Liu,2,3 Zhenli Li,2,3 Jingfeng Liu1–3,5 1The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China; 2The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China; 3The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, China; 4School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; 5Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China *These authors contributed equally to this work Purpose: Prediction of hepatocellular carcinoma (HCC) prognosis faced great difficulty due to tumor heterogeneity. We aimed to identify the prognosis-associated molecular subtypes existing in HCC patients and construct an evaluation model based on identified molecular classification. Materials and methods: Non-negative matrix factorization consensus clustering was performed using 371 HCC patients from The Cancer Genome Atlas (TCGA) to identify molecular subtypes, based on the expression profile of the survival-associated genes. Signature genes for different subtypes were identified by Significance Analysis of Microarray and Prediction Analysis for Microarrays . Model for subtype discrimination and prognosis evaluation was established using binary logistic regression. The model and its clinical implications were further validated in GSE5436 cohort and Fujian cohort. Results: Based on TCGA data, we observed two molecular subtypes with distinct clinical outcomes including significantly different overall survival, tumor differentiation, TNM stage, and vascular invasion (all P

This paper describes a publicly available, open source software framework designed to support research efforts on algorithms and control for digital microfluidic biochips (DMFBs), an emerging laboratory-on-a-chip (LoC) technology. The framework consists of two parts: a compiler, which converts an assay, specified using the BioCoder language, into a sequence of electrode activations that execute out the assay on the DMFB; and a printed circuit board (PCB) layout tool, which includes algorithms to reduce the number of control pins and PCB layers required to drive the chip from an external source. The framework also includes a suite of visualization tools for debugging, and a collection of front-end algorithms that generate mixing/dilution trees for sample preparation.

Synthesis of digital microfluidic biochips (DMFBs) is a crucial to the advancement and realization of miniaturized, automated, programmable biochemistry solutions; synthesis is performed in three steps: scheduling, placement and routing. In principle, algorithms for specific steps should be interchangeable with one another; however, different research groups typically develop algorithms for each step in isolation from one another. Thus, it is difficult to compare algorithms against one another, or to determine which algorithms for different steps share synergies. We introduce an open source DMFB synthesis framework to encourage collaboration between researchers working in the area. We introduce a common interface and describe the internal data structures that must be updated to ensure that the interfaces are adhered to. We also present and describe a number of high-quality 2D and 3D debugging tools that provide graphical output for each stage of synthesis. © 2012 IEEE.

The nonlinear response affects the effect of imaging system response non-uniformity correction (NUC) methods. Most of the methods are effective in a certain range of responses. In this paper, a new NUC method is proposed based on the mechanism of imaging system response non-uniformities production. Optical system-related non-uniformity is described as radiation transmission non-uniformity (RTNU) and detector-related non-uniformity is described as radiation conversion non-uniformity (RCNU). The RTNU is removed by inverse operation and RCNU is removed by regularization optimization. We verify the proposed method with respect to visual effect evaluation of actual scene images and three performance metrics evaluation of statistical F ratio, F-norm roughness and chromatic aberration ellipse. The experimental results verify the effect of our method. The proposed method is effective for NUC in a larger range of responses. [ABSTRACT FROM AUTHOR]

Landfill, one of the major approaches for waste treatment in China, is a significant source of carbon emissions; compiling landfill carbon emission accounting standards in China will support the construction of a statistical accounting system for carbon emissions and promote the achievement of the carbon peaking and carbon neutrality goals. This study reviews the research progress of landfill carbon emission accounting standards and guidelines in China and abroad, analyzes the challenges faced by the development of these standards in China, and proposes relevant development suggestions based on an in-depth discussion of the baseline methodology for the standards and the priority tasks for compilation. The international standards and guidelines currently available for reference are not fully applicable to China’s landfill carbon emission accounting, and there is a lack of standardized and unified landfill carbon emission accounting methodology as well as reliable accounting inventory data in China. Therefore, based on the waste characteristics and technical status of landfills in China, recommendations for carbon emission accounting methodology, scope, and inventory are proposed, priorities for the standards compilation are clarified, and approaches for obtaining inventory data applicable to China’s landfill scenarios are provided. Subsequently, regional factors can be fully considered and characteristic data of China can be adopted in order to obtain landfill carbon emission accounting results that are more in line with the actual situation, and the compilation of landfill carbon emission accounting standards in China can be carried out accordingly.

Treatment of breast cancer with low expression of human epidermal growth factor receptor 2 (HER2; HER2-low) has drawn much attention in recent years. With the proven therapeutic effect of trastuzumab deruxtecan (T-DXd) in patients with HER2-low (immunohistochemistry [IHC] 1+, or IHC2+/in situ hybridization [ISH]-) breast cancer, HER2-low may become a new subtype of targeted therapy for breast cancer. The expert committee formulated this consensus based on the current clinical studies and clinical medication experience. The current consensus is the collaborative work of an interdisciplinary working group, including experts in the fields of pathology and oncology. The purpose of this consensus was to guide the clinical diagnosis and treatment of HER2-low breast cancer, thereby prolonging the overall survival of patients.

Objective To investigate the achieved intrusion amount of the maxillary incisors and the influencing factors in clear aligner cases treated with extraction of premolars. Methods This study has been reviewed and approved by the Ethics Committee, and informed consent has been obtained from patients. Thirty adult female patients who underwent extraction of the bilateral maxillary first premolars followed by clear aligner therapy were included. CBCT data before and after treatment were obtained, and three-dimensional reconstruction with registration alignment was performed. A spatial coordinate system was established, and the achieved intrusion amount was measured, followed by calculation of the intrusion efficacy. The factors related to the achieved intrusion amount were investigated through multiple linear regression analysis. Results The overall efficacy of maxillary incisor intrusion was 54%, with the maxillary central incisors (48%) lower than the lateral incisors (59%), which was statistically significant (P