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Yanbo Luo,1 Fenglin Sun,1 Xiaowen Peng,2 Dong Dong,3 Wentao Ou,3 Yongke Xie,3 Yuqi Luo1 1Department of Gastrointestinal and Hepatobiliary Surgery, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, Guangdong, People’s Republic of China; 2Department of Laboratory Medicine, Nansha Hospital, Guangzhou First People’s Hospital, School of Medicine, Southern China University of Technology, Guangzhou, Guangdong, 511457, People’s Republic of China; 3Department of General Surgery, Nansha Hospital, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 511457, Guangdong, People’s Republic of ChinaCorrespondence: Yuqi LuoDepartment of Gastrointestinal and Hepatobiliary Surgery, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, Guangdong, People’s Republic of ChinaTel/Fax +86755-28015466Email eyluoyuqi@scut.edu.cnObjective: To identify the value of key differentially expressed genes (DEGs) regulated by differentially methylated regions (DMRs) in predicting the prognosis of human colon cancer.Materials and Methods: RNA sequencing data and DNA methylation data of 455 colon adenocarcinoma (COAD) cases and 41 normal controls were downloaded from The Cancer Genome Atlas (TCGA). Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by the DAVID database. To identify the hub genes regulated by methylation, univariate Cox and multivariate Cox regression analyses were carried out. A nomogram based on the risk score was built to identify the power of the hub genes to predict prognosis in patients with colon cancer.Results: A total of 133 DEGs regulated by DMRs were identified through analyzing RNA sequencing data and DNA methylation data from TCGA. GO functional enrichment and KEGG pathway enrichment analysis showed the genes involved in the initiation and progression of colon cancer. Univariate Cox regression analysis and multivariate Cox regression analysis focused on the seven hub genes (CDH4, CR2, KRT85, LGI4, NPAS4, RUVBL1 and SP140) associated with overall survival, the expression of which negatively correlated with their methylation level. The risk score and nomogram model showed that the hub genes served as potential biomarkers for the prognosis prediction of patients with colon cancer.Conclusion: Our findings suggest that the DEGs regulated by DMRs are involved in the carcinogenesis and development of colon cancer, and the aberrantly methylated DEGs associated with overall survival of patients may be potential diagnostic and therapeutic targets for colon cancer.Keywords: colon cancer, DNA methylation, gene expression regulation, prognosis prediction

Fa Jin, Weiyang Ou, Boyang Wei, Haiyan Fan, Chengcong Wei, Dazhao Fang, Guangxu Li, Wenchao Liu, Jiahui Liu, Lei Jin, Xuying He, Chuanzhi Duan Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, People’s Republic of ChinaCorrespondence: Chuanzhi Duan; Xuying He Tel +86 135 399 622 33; +86 136 888 771 33Fax +86 206 164 3010Email doctor_duanzj@163.com; 2517079319@qq.comBackground: Ischemic stroke is one of the leading causes of mortality and disability worldwide. Following stroke, there is secondary neuroinflammation that promotes further injury. Identifying the long non-coding RNA (lncRNA) involved in neuroinflammation after cerebral ischemic stroke will promote the discovery of potential therapeutic targets.Methods: We identified differentially expressed genes from genome-wide RNA-seq profiles of mice with focal ischemia using Gene Ontology Term Enrichment, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment analyses. Immune cell infiltration deconvolution, protein-protein interaction network construction, and co-expression network analyses were also used to screen lncRNAs. In further experiments, lncRNA Neat1 knockdown animal models were developed by intraventricular injection of the antisense oligonucleotide before performing middle cerebral artery occlusion (MCAO). An enzyme-linked immunosorbent assay was performed to measure the level of cytokines. Hematoxylin-eosin staining and immunohistochemical staining were used to observe the changes in morphology.Results: Enrichment analysis revealed that differential mRNAs induced neuroinflammation after MCAO. Immune deconvolution showed that the proportion of microglia gradually increased while monocytes decreased within 24 h. We identified six hub lncRNAs (Neat1, Gm10827, Trp53cor1, Mir670hg, C730002L08Rik, and Mir181a-hg) that were highly correlated with activated-microglia mRNAs (cor > 0.8). We found that Neat1 had the highest correlation coefficient with pro-inflammatory factor mRNA levels. In vivo experiments demonstrated that Neat1 had abnormally high expression after MCAO. Knockdown of Neat1 could significantly alleviate brain damage by reducing the number of activated microglia and reducing their release of proinflammatory cytokines.Conclusion: We identified inflammation-associated lncRNA Neat1 as crucial, which means it is a potential target for ischemic stroke treatment.Keywords: bioinformatics, lncRNA Neat1, ischemic stroke, MCAO, microglia, neuroinflammation

Jiaofeng Huang,1 Weijie Ou,1 Mingfang Wang,1 Medha Singh,2 Yuxiu Liu,1 Shiying Liu,1 Yinlian Wu,1 Yueyong Zhu,1,3 Rahul Kumar,4,* Su Lin1,* 1Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of General Medicine, Tan Tock Seng Hospital, Singapore; 3Fujian Key Laboratory of Precison Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4Department of Gastroenterology and Hepatology, Duke-NUS Academic Medical Centre, Changi General Hospital, Singapore*These authors contributed equally to this workCorrespondence: Su LinDepartment of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, Fujian, 350005, People’s Republic of ChinaEmail sumer5129@fjmu.edu.cnBackground and Aims: Metabolic associated fatty liver disease (MAFLD) is diagnosed in patients with hepatic steatosis when they have the following three metabolic conditions: obesity/overweight, diabetes and metabolic dysregulation, either alone or in combination. There is no clarity whether subtypes of MAFLD diagnosed by different metabolic conditions carry different levels of risk for intra- and extra-hepatic organs. This study aims to depict the characteristics of these subtypes in a large population.Methods: The data were retrieved from the third National Health and Nutrition Examination Surveys of the United States. The clinical and biochemical features in different MAFLD subtypes were compared. The outcome of interest was significant and advanced fibrosis.Results: Out of 4,087 (31.24%) participants with MAFLD, 1,165 (28.51%) were diagnosed by single metabolic condition, 2,053 (50.23%) by two conditions, and 869 (21.26%) by all three metabolic conditions. With increasing numbers of metabolic conditions, participants tended to be older, were more likely to be female, and had more severe renal impairment and liver fibrosis (P< 0.05). MAFLD patients with a lower number of metabolic conditions were more likely to have excessive alcohol consumption. Among MAFLD with single metabolic condition, those diagnosed by diabetes alone had the highest proportion of advanced fibrosis identified by non-invasive fibrosis models (P< 0.05).Conclusion: More metabolic conditions upon the diagnosis of MALFD indicate higher risk of fibrosis. Patients with MAFLD diagnosed by diabetes alone are more likely to have advanced hepatic fibrosis than those with other metabolic conditions alone. Individualized management is required for MAFLD with different subtypes.Keywords: metabolic associated fatty liver disease, nonalcoholic fatty liver disease, metabolic syndromes, NHANES, fibrosis

Zhiyuan Weng,1 Weijie Ou,2 Jiaofeng Huang,2 Medha Singh,3 Mingfang Wang,2 Yueyong Zhu,2 Rahul Kumar,4,* Su Lin2,* 1Cardiology Department, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350001, People’s Republic of China; 2Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350001, People’s Republic of China; 3Department of General Medicine, Tan Tock Seng Hospital 308433, Singapore; 4Department of Gastroenterology and Hepatology, Duke-NUS Academic Medical Centre, Changi General Hospital 529889, Singapore*These authors contributed equally to this workCorrespondence: Su LinDepartment of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, Fujian 350001, People’s Republic of ChinaEmail sumer5129@fjmu.edu.cnBackground and Aims: Circadian misalignment (CM) leads to metabolic disorder. Metabolic (dysfunction) associated fatty liver disease (MAFLD) is a novel definition for fatty liver disease that requires the presence of metabolic dysfunction. As the association between CM and MAFLD remains unclear, this study is designed to explore whether there is an association between CM and MAFLD.Methods: NHANES 2017– 2018 database was used in this study. Liver steatosis and fibrosis were diagnosed by Fibroscan®. CM was defined by the presence of mistimed sleep, late sleep or irregular chronotype. Propensity score matching (PSM) was used to match subjects for their age and gender.Results: A total of 4552 participants were included in the study, with 2089 (45.89%) identified as MAFLD and 894 (19.64%) as CM. Participants with CM were significantly younger than those without (46.06 ± 18.06 vs 50.93 ± 17.78, p< 0.001). PSM for age and gender resulted in 894 participants with CM and 892 with non-CM. CM group had higher body mass index, liver enzymes, glucose and lipid levels. The prevalence of MAFLD was higher in the CM group than the non-CM group (45.41% vs 28.48%, p< 0.001). The presence of CM increased the risk of MAFLD by more than twofold. Short sleep duration (< 6 hours) was not independently associated with MAFLD or fibrosis if additionally adjusting for CM.Conclusion: CM is independently associated with MAFLD, while short sleep duration (< 6 hours) is not an independent risk factor for MAFLD or liver fibrosis after adjusting for CM.Keywords: fatty liver disease, MAFLD, circadian, sleep, fibrosis

Jie Lv, Wei Ou, Xiao-Hua Zou, Yin Yao, Jin-Li Wu Department of Anesthesia, Guizhou Medical University Affiliated Hospital, Guiyang, People’s Republic of China Abstract: The study aimed to explore the effect of dexmedetomidine (DEX) on hippocampal neuron development process and on molecular expression of brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling pathway in neonatal rats. The hippocampal neuron cells were isolated from newborn neonatal rats and cultured in vitro. One control group and three treated groups with 1, 10, and 100 µmol/L DEX were used for the study. Cell activity and apoptosis were detected by the MTT and terminal deoxynucleotidyl transferase-mediated biotinylated uridine triphosphate (UTP) nick end labeling assays. The synaptophysin (SYN) and postsynaptic density 95 (PSD95) were detected by quantitative polymerase chain reaction. There was no difference in the viability of neuron cells among the different dose groups of DEX and the control group during days 2-10 (P>0.05). Compared to the control group, there was no significant difference (P>0.05) in the expressions of SYN and PSD95 in the groups treated with 1 and 10 µmol/L DEX, whereas significant difference in the expression was observed in the group treated with 100 µmol/L DEX (P

Abstract Background Growth hormone (GH) positive pituitary neuroendocrine tumors do not always cause acromegaly. Approximately one-third of GH-positive pituitary tumors are classified as non-functioning pituitary tumors in clinical practice. They typically have GH and serum insulin-like growth factor 1 (IGF-1) levels in the reference range and no acromegaly-like symptoms. However, normal hormone levels might not exclude the underlying hypersecretion of GH. This is a rare and paradoxical case of pituitary tumor causing acromegaly-associated symptoms despite normal GH and IGF-1 levels. Case presentation We report a case of a 35-year-old woman with suspicious acromegaly-associated presentations, including facial changes, headache, oligomenorrhea, and new-onset diabetes mellitus and dyslipidemia. Imaging found a 19 × 12 × 8 mm pituitary tumor, but her serum IGF-1 was within the reference, and nadir GH was 0.7ng/ml after glucose load at diagnosis. A thickened skull base, increased uptake in cranial bones in bone scan, and elevated bone turnover markers indicated abnormal bone metabolism. We considered the pituitary tumor, possibly a rare subtype in subtle or clinically silent GH pituitary tumor, likely contributed to her discomforts. After the transsphenoidal surgery, the IGF-1 and nadir GH decreased immediately. A GH and prolactin-positive pituitary neuroendocrine tumor was confirmed in the histopathologic study. No tumor remnant was observed three months after the operation, and her discomforts, glucose, and bone metabolism were partially relieved. Conclusions GH-positive pituitary neuroendocrine tumors with hormonal tests that do not meet the diagnostic criteria for acromegaly may also cause GH hypersecretion presentations. Patients with pituitary tumors and suspicious acromegaly symptoms may require more proactive treatment than non-functioning tumors of similar size and invasiveness.

C44H34Cl2N6O2Zn, triclinic, P 1‾ $\overline{1}$ (no. 2), a = 10.875(9) Å, b = 11.755(9) Å, c = 16.471(13) Å, α = 105.924(14)°, β = 97.552(13)°, γ = 104.507(13)°, V = 1,914(3) Å3, Z = 2, R gt(F) = 0.0455, wR ref(F 2) = 0.1154, T = 296 K.

Abstract Background Obesity and hypertension are major risk factors for cardiovascular diseases that affect millions of people worldwide. Both conditions are associated with chronic low-grade inflammation, which is mediated by adipokines such as adiponectin. Adiponectin is the most abundant adipokine that has a beneficial impact on metabolic and vascular biology, while high serum concentrations are associated with some syndromes. This “adiponectin paradox” still needs to be clarified in obesity-associated hypertension. The aim of this study was to investigate how adiponectin affects blood pressure, inflammation, and metabolic function in obesity hypertension using a Chinese adult case-control study. Methods A case-control study that had finished recruiting 153 subjects divided as four characteristic groups. Adiponectin serum levels were tested by ELISA in these subjects among these four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Analyzation of correlations between the research index and differences between groups was done by SPSS. Results Serum adiponectin levels in the| normal healthy group (NH group) were significantly higher than those in the newly diagnosed untreated just-obesity group (JO group), and negatively correlated with the visceral adiposity index. With multiple linear egression analysis, it was found that, for serum adiponectin, gender, serum albumin (ALB), alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDLC) were the significant independent correlates, and for SB, age and HDLC were the significant independent correlates, and for DB, alkaline phosphatase (ALP) was the significant independent correlate. The other variables did not reach significance in the model. Conclusions Our study reveals that adiponectin’s role in obesity-hypertension is multifaceted and is influenced by the systemic metabolic homeostasis signaling axis. In obesity-related hypertension, compensatory effects, adiponectin resistance, and reduced adiponectin clearance from impaired kidneys and liver all contribute to the “adiponectin paradox”.

Accurate haplotyping facilitates distinguishing allele-specific expression, identifying cis-regulatory elements, and characterizing genomic variations, which enables more precise investigations into the relationship between genotype and phenotype. Recent advances in third-generation single-molecule long read and synthetic co-barcoded read sequencing techniques have harnessed long-range information to simplify the assembly graph and improve assembly genomic sequence. However, it remains methodologically challenging to reconstruct the complete haplotypes due to high sequencing error rates of long reads and limited capturing efficiency of co-barcoded reads. We here present a pipeline, AsmMix, for generating both contiguous and accurate diploid genomes. It first assembles co-barcoded reads to generate accurate haplotype-resolved assemblies that may contain many gaps, while the long-read assembly is contiguous but susceptible to errors. Then two assembly sets are integrated into haplotype-resolved assemblies with reduced misassembles. Through extensive evaluation on multiple synthetic datasets, AsmMix consistently demonstrates high precision and recall rates for haplotyping across diverse sequencing platforms, coverage depths, read lengths, and read accuracies, significantly outperforming other existing tools in the field. Furthermore, we validate the effectiveness of our pipeline using a human whole genome dataset (HG002), and produce highly contiguous, accurate, and haplotype-resolved assemblies. These assemblies are evaluated using the GIAB benchmarks, confirming the accuracy of variant calling. Our results demonstrate that AsmMix offers a straightforward yet highly efficient approach that effectively leverages both long reads and co-barcoded reads for haplotype-resolved assembly.

Plant proteins, as sustainable resources with various health benefits, have gradually been widely researched as substitutes for animal proteins. Walnut protein, as a plant-based protein source, is rich in essential amino acids and has a reasonable proportion of eight essential amino acids, making it a potential high-quality protein that has attracted widespread attention. The potential application of walnut protein as a sustainable protein source is summerized in this review. Firstly, the amino acid composition, protein classification, and functional properties of walnut protein were discussed. Secondly, the main limitations of walnut protein utilization were discussed, such as anti-nutritional factors, poor functional properties, and allergenicity were discussed. Finally, commonly used modification methods, including physical methods, chemical methods, biological methods, and backbone hybridization technology to improve the functional characteristics of walnut protein, as well as its potential application for use in the food industry were summarized. This review provides new ideas for its development and utilization.

Polarized light has promising applications in biological inspections, displays, and precise measurements. Direct emission of polarized light from a semiconductor device is highly desired in order to reduce the size and energy-consumption of the whole system. In this study, we demonstrate a semipolar GaN-based microcavity light-emitting diode (MCLED) that could simultaneously produce green light with perpendicular and parallel polarizations to the c*-axis. Orthogonally polarized emission with a narrow linewidth (∼0.2 nm) arises from the valence band splitting and birefringent nature of the semipolar GaN material, as well as the mode selection of the resonant cavity. By modulating the cavity length, the device is capable of switching between single- and multi-mode emission spectra. We believe that the approach of employing a cavity structure and semipolar GaN can be extended to produce orthogonally and linearly polarized blue, red, and violet light by adjusting the material compositions.

Seeking food-derived antioxidants and inhibitors of α-glucosidase and α-amylase has been recognized as an effective way for managing diabetes. Coffee silver skin (CSS) is rich in phenolic compounds, which may be potential agents as antioxidants and for α-glucosidase and α-amylase inhibition. But whether phenolics in different forms show similar bioactivity remains unknown. In this study, phenolic compounds in CSS were extracted as free phenolics (FPs), esterified phenolics (EPs), and bound phenolics (BPs). The phenolic profiles and antioxidant activities of them were investigated. Their inhibitory effects on α-glucosidase and α-amylase were analyzed, and the inhibitory mechanisms were elucidated by molecular docking and molecular dynamic simulation. Results showed that FPs exhibited the best antioxidant ability and inhibitory effects on α-glucosidase and α-amylase. A total of 17 compounds were identified in FPs with 3-caffeoylquinic acid, 4-feruloylquinic acid, and dicaffeoylquinic acids as the dominant ones. Typical phenolics in FPs could bind to α-glucosidase and α-amylase through hydrogen bonds and form hydrophobic interaction with several key amino acid residues. In addition, 3,4-dicaffeoylquinic acid and 3-caffeoylquinic acid might be the principal components that account for the inhibitory effect of FPs on α-glucosidase. The results of this study may provide some scientific support for CSS utilization as a health-beneficial component in functional food development for type 2 diabetes mellitus management.

Nutritional supplementation enriched with protein and antioxidants has been demonstrated to effectively strengthen skeletal muscle function and mitigate the risk of sarcopenia. Dietary protein has also been a common carrier to establish bioactive delivery system. Therefore, in this study, a Pickering emulsion delivery system for rutin was constructed with whey protein, and its structural characteristics, bioaccessibility, and molecular interactions were investigated. In the in vivo study, zebrafish (n = 10 in each group), which have a high genetic homology to humans, were treated with dexamethasone to induce sarcopenia symptoms and were administered with rutin, whey protein and the Pickering emulsion, respectively, for muscle movement ability evaluation, and zebrafish treated with or without dexamethasone was used as the model and the control groups, respectively. Results showed that the Pickering emulsion was homogeneous in particle size with a rutin encapsulation rate of 71.16 ± 0.15% and loading efficiency of 44.48 ± 0.11%. Rutin in the Pickering emulsion exhibited a significantly higher bioaccessibility than the free form. The interaction forces between rutin and the two components of whey proteins (α-LA and β-LG) were mainly van der Waals forces and hydrogen bonds. After treatment for 96 h, the zebrafish in Picking emulsion groups showed a significantly increased high-speed movement time and frequency, an increased level of ATP, prolonged peripheral motor nerve length, and normalized muscular histological structure compared with those of the model group (p < 0.05). The results of this study developed a new strategy for rutin utilization and provide scientific evidence for sarcopenia prevention with a food-derived resource.

Abstract Background Pseudohypoparathyroidism type 1 (PHP1) is a rare disease featuring hypocalcemia and elevated PTH level. Though disturbed calcium and phosphorus metabolism under PTH resistant have been widely studied, glucolipid metabolism abnormalities observed in PHP1 patients have received little attention. The aim of this research is to explore the glucolipid metabolism features in a rather large cohort of PHP1 patient. In the current study, PHP1 patients and primary hyperparathyroidism patients as well as normal control were recruited for the investigation. Glucolipid metabolic indices as well as the level of four adipokines were examined. Results A total of 49 PHP1 patients, 64 PHPT patients and 30 healthy volunteers were enrolled. A trend of higher HOMA-β index was found in PHP1 patients than normal controls (median 97.08% vs 68.19%, p = 0.060). Both the PHP1 and PHPT group presented with significantly lower TNFα level compared to normal controls (average 10.74 pg/ml and 12.53 pg/ml vs 15.47 pg/ml, p = 0.002 and 0.041, respectively). FGF21 level was significantly higher in PHPT group than in PHP1 group (median 255.74 pg/ml vs 167.46 pg/ml, p = 0.019). No significant difference in glucolipid metabolic indices and adipokines was found between PHP1A or PHP1B patients and normal controls, while overweight/obese PHP1 patients tended to have higher leptin than normal-BMI cases (p = 0.055). Multiple linear regression analysis showed BMI rather than PTH or HOMA-IR to be an independent variable of leptin in PHP1. Conclusion Metabolic stress given upon especially overweight PHP1 patients may resulted in possible β-cell compensation. Elevated TNFα may be related with hyper-PTH level regardless of calcium level.

Wei-Fan Ou,1 Pei-Ya Liao,1 Yu-Wei Hsu,2,3 Yen-Hsiang Huang,1,4– 6 Kuo-Hsuan Hsu,6,7 Jeng-Sen Tseng,1,4– 6,8 Gee-Chen Chang,4,9– 11 Tsung-Ying Yang1,6,12 1Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Cancer Prevention and Control Center, Taichung Veterans General Hospital, Taichung, Taiwan; 3Computer and Communications Center, Taichung Veterans General Hospital, Taichung, Taiwan; 4Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; 5College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 6Lung Cancer Comprehensive Care and Research Center, Taichung Veterans General Hospital, Taichung, Taiwan; 7Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 8Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 9Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; 10School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 11Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 12Department of Life Sciences, National Chung Hsing University, Taichung, TaiwanCorrespondence: Jeng-Sen Tseng, Lung Cancer Comprehensive Care and Research Center, Taichung Veterans General Hospital, No. 1650, Sect. 4, Taiwan Boulevard, Taichung, 407, Taiwan, Tel +886-4-23592525 ext. 3232, Fax +886-4-23741320, Email tzeng64@gmail.comBackground: Antiangiogenetic therapy and lung cancer, per se, are associated with an increased risk of thromboembolic events (TE). We aim to evaluate the pattern and outcome of TE as well as its influence on survival time of advanced non-small cell lung cancer (NSCLC) patients receiving antiangiogenic therapy.Methods: This was a retrospective cohort study, which included advanced NSCLC patients receiving antiangiogenic therapy. All TE were confirmed by objective image studies. We disclosed the presentation and risk factors of TE and evaluated its influence on outcome.Results: A total of 427 patients were included. TE occurred in 43 patients (10.1%). Deep vein thrombosis (DVT) was the most common TE (n = 20). Up to 46.2% of DVT did not occur in the typical lower extremities. Two patients died of TE. Among patients with continuous use or reuse of antiangiogenetic therapy, 18.2% had recurrent TE events. At the occurrence of TE, 28 patients experienced progressive disease (TE with PD), while tumor status remained stable in another 15 patients (TE without PD). The post-TE survival of patients without and with PD were 8.9 months (95% CI 3.9– 13.9) vs 2.2 months (95% CI 0.1– 4.3), P = 0.012. As compared with patients without TE (31.4 months [95% CI 27.1– 35.7]), TE with PD patients experienced a significantly shorter overall survival (20.1 months [95% CI 15.5– 24.6]), but TE without PD patients had comparable survival time (32.7 months [95% CI 7.4– 28.1]) (P = 0006). The use of hormone analogue and proteinuria predicted the events among TE with PD group (aOR 2.79 [95% CI 1.13=6.92]; P = 0.027) and TE without PD group (aOR 4.30 [95% CI 1.13– 16.42]; P = 0.033), respectively.Conclusion: Owing to the different risk factors and influences on the survival time, TE with and without PD may be two different disease entities.Keywords: non-small cell lung cancer, NSCLC, antiangiogenesis, bevacizumab, ramucirumab, thromboembolism