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Wubin Zheng,1,* Fan Wu,1,* Kai Fu,1,* Guangshun Sun,1 Guoqiang Sun,1 Xiao Li,1 Wei Jiang,1 Hongyong Cao,1 Hanjin Wang,1 Weiwei Tang2 1Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Hepatobiliary/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Transplantation, Chinese Academy of Medical Sciences, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongyong Cao; Hanjin Wang Email caohongy6167@163.com; wanghanjin1971@163.comAbstract: Colorectal cancer is currently the third largest malignant tumor in the world, with high new cases and high mortality. Metastasis is one of the most common causes of death of colorectal cancer, of which liver metastasis is the most fatal. Since the beginning of the Human Genome Project in 2001, people have gradually recognized the 3 billion base pairs that make up the human genome, of which only about 1.5% of the nucleic acid sequences are used for protein coding, including proto-oncogenes and tumor suppressor genes. A large number of differences in the expression of proto-oncogenes and tumor suppressor genes have also been found in the study of colorectal cancer, which proves that they are also actively involved in the progression of colorectal cancer and promote the occurrence of liver metastasis. Except for 1.5% of the coding sequence, the rest of the nucleic acid sequence does not encode any protein, which is called non-coding RNA. With the deepening of research, genome sequences without protein coding potential that were originally considered “junk sequences” may have important biological functions. Many years of studies have found that a large number of abnormal expression of ncRNA in colorectal cancer liver metastasis, indicating that ncRNA plays an important role in it. To explore the role and mechanism of these coding sequences and non-coding RNA in liver metastasis of colorectal cancer is very important for the early diagnosis and treatment of liver metastasis of colorectal cancer. This article reviews the coding genes and ncRNA that have been found in the study of liver metastasis of colorectal cancer in recent years, as well as the mechanisms that have been identified or are still under study, as well as the clinical treatment of liver metastasis of colorectal cancer.Keywords: colorectal cancer, liver metastasis, mechanisms, treatment

Xiaoying Xu,1 Qiongli Zhai,1 Hao Jin,2 Yong Yu,3 Dongmei Han,2 Huilai Zhang,4 Kai Fu,5 Bin Meng1 1Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2International Personalized Cancer Center, Tianjin Cancer Hospital Airport Hospital, Tianjin, People’s Republic of China; 3Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China; 4Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China; 5Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USACorrespondence: Bin MengDepartment of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of ChinaTel +86-18622221609Fax +86-22-23340123-6202Email mbincn@163.comKai FuDepartment of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USATel +1-716-8451300-4219Email Kai.fu@roswellpark.orgAbstract: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is rare and associated with poor clinical outcome especially in adults. ETP tumor cells that express cross-lineage antigens or lack pan T markers usually pose big challenges to diagnosis, and their prognostic implications are therefore more uncertain. This study reports the unique case of a 44-year-old woman with breast mass as the initial presentation of acute leukemia possessing both T- and B-cell features (cytoplasmic CD3+CD7+CD19+CD79a+). Despite the presence of gene rearrangements of IGH and IGK probably in a small amount of B cells, the patient was diagnosed with T-ALL mainly according to WHO criteria, and further ETP-ALL rather than mixed phenotype ALL based on additional positive expression of stem/myeloid lineage antigens (CD34+CD13+CD33+HLA-DR+). Moreover, in spite of normal karyotype, SET-NUP214 gene fusion is identified, which has not been described in ETP-ALL with bi-phenotype. After intensive chemotherapy, the patient achieved short-term morphologic complete remission but relapsed within one month. This report may expand immunophenotype and clinical behavior of ETP-ALL in adults. Comprehensive evaluations are emphasized in making a differential diagnosis and distinguishing subtypes of acute leukemia.Keywords: adult acute lymphoblastic leukemia, early T-cell precursor, mixed phenotype acute leukemia, breast infiltration, SET-NUP214 fusion gene

Liang Zhao,1,* Xiyi Liao,1,* Ganji Hong,1 Yanzhen Zhuang,2 Kaili Fu,1 Peiqiong Chen,2 Yuhuan Wang,2 Haojun Chen,3 Qin Lin1 1Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China; 2Department of Pathology, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China; 3Department of Nuclear Medicine & Minnan PET Center, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China *These authors contributed equally to this work Purpose: To analyze the mismatch repair (MMR) status and PD-L1 expression in nasopharyngeal carcinoma (NPC), and investigate whether PD-L1 and MMR status could be used as a biomarker for predicting response of immune checkpoint blockades (ICBs) treatment.Patients and methods: A total of 108 patients were initially histopathologically diagnosed with NPC between December 2017 and September 2018. All tissue specimens were collected before any treatment. Tumor tissue MMR status was determined by both immunohistochemistry and PCR. The expression of PD-L1 in NPC tissue was analyzed immunohistochemically. High PD-L1 expression in tumor cells (TC) or tumor-infiltrating immune cells (TIIC) was defined as ≥50% of corresponding cells with membranous staining.Results: Tissue samples were obtained from 102 patients after written informed consent was obtained. Seventy-one (69.6%) patients were treated in our hospital after diagnosis. Disease in stages I–III accounted for 35 (49.3%) cases, while stage IVa–IVb was identified in 36 (50.7%) cases. Only two of 102 patients were identified as MMR-deficient (dMMR) by IHC and PCR. High PD-L1 expression in TC was confirmed in 77 of the 102 (75.5%) NPC cases, while only 13 of the 102 (12.7%) NPC cases were considered to exhibit high PD-L1 expression in TIIC. PD-L1 expression in TC was positively correlated with T stage (P=0.033), while PD-L1 expression in TIIC was negatively associated with plasma Epstein–Barr virus DNA load (P=0.021), N stage (P=0.009), M stage (P=0.014), and clinical stage (P=0.001).Conclusion: dMMR is a rare event in NPC and may not be a prospective biomarker to predict the effectiveness of treatment with ICBs in clinical practice. It was also determined that high PD-L1 expression in NPC is quite common and the importance of distinguishing PD-L1 expression in TC and TIIC was highlighted. Keywords: immunotherapy, biomarker, microsatellite instability, PD-L1, tumor-infiltrating immune cells

Dawei Rong, Chaoxi Dong, Kai Fu, Hanjin Wang, Weiwei Tang, Hongyong Cao Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China Background: Circular RNAs (circRNAs), which have closed-loop structure, are involved in the pathogenesis of human diseases including various types of carcinomas. The present study aimed to investigate the relationship between a new circular RNA named circ_0066444 and gastric cancer (GC) carcinogenesis.Materials and methods: The circ_0066444 levels in 106 paired gastric carcinoma tissues and related adjacent normal tissues were detected by real-time quantitative reverse-transcription polymerase chain reaction. The correlation between the expression of circ_0066444 and clinicopathological features was analyzed. The impact of circ_0066444 expression on cell proliferation, invasion, as well as migration was evaluated in vitro using knockdown expression strategies. Finally, a network of circ_0066444-targeted miRNA interactions and their corresponding mRNAs was constructed.Results: circ_0066444 was found to be significantly upregulated in 106 GC tissues as compared with paired adjacent nontumorous tissues (P=0.025), showing a high positive correlation with lymphatic metastasis (P=0.023). Furthermore, in vitro assays of the GC cell lines BGC-823 and AGS demonstrated that knockdown of circ_0066444 reduced cell proliferation, invasion, and migration significantly. Prediction and annotation revealed circ_0066444 was able to sponge to 5 miRNAs and 15 corresponding target mRNAs.Conclusion: Our study indicated upregulation of circ_0066444 promotes gastric cell proliferation, invasion, and migration ability and might serve as a novel biomarker for GC. Keywords: migration, invasion, proliferation, diagnoses, miRNA

Shibo Zhu, Guochang Liu, Wen Fu, Jinhua Hu, Kai Fu, Wei Jia Department of Pediatric Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China Purpose: Overexpression of Axl has been reported in many tumors, where it promotes tumorigenesis and progression, as well as correlates with the prognosis of different malignancies. However, Axl expression and its function have rarely been reported in Wilms’ tumor (WT). This study aimed to reveal the clinical significance of Axl expression in patients with WT and determine its mechanisms.Materials and methods: We analyzed the expression of Axl and its correlations with various clinicopathological features in 72 WT tissues and 72 adjacent non-cancerous tissues by immunohistochemistry. Cox proportional hazards regression models were used to investigate the correlations between Axl expression and the prognosis of WT patients. Fresh frozen samples from 20 WT patients were examined using Western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). In WT cell line, after Axl knockdown by sh-Axl and growth arrest-specific 6 (Gas6) stimulation, the cell proliferation, migration and invasion abilities were detected by methyl-thiazolyl-tetrazolium (MTT), clone-forming, wound-healing and trans­well assays. Meanwhile, the tumor-forming ability was tested on nude mice xenograft models. Finally, the expression of several proteins in signal pathways was quantified by WB assays.Results: Compared with the adjacent non-cancerous tissues, the expression of Axl was significantly higher in WT tissues (P

TerraSwarm applications, or swarmlets, are characterized by their ability to dynamically recruit resources such as sensors, communication networks, computation, and information from the cloud; to aggregate and use that information to make or aid decisions; and then to dynamically recruit actuation resources. The TerraSwarm vision cannot be achieved by a single vendor providing the components as an integrated system. What is needed instead is the swarm equivalent of the common, general framework that has recently enabled smartphones and similar devices to rapidly deploy and serve a vast range of often unanticipated applications by recruiting resources and composing services. The SwarmOS must support continual reconfiguration of applications and of its own service definitions without ever having the luxury of a clean restart. It must also support richly heterogeneous computing. TerraSwarm protocols will need to detect compromises, distinguish trusted from untrusted data and resources, and be robust to the presence of a certain number of malicious nodes.

The worldwide obesity epidemic.sup.1 makes it important to understand how lipid turnover (the capacity to store and remove lipids) regulates adipose tissue mass. Cross-sectional studies have shown that excess body fat is associated with decreased adipose lipid removal rates.sup.2,3. Whether lipid turnover is constant over the life span or changes during long-term weight increase or loss is unknown. We determined the turnover of fat cell lipids in adults followed for up to 16 years, by measuring the incorporation of nuclear bomb test-derived .sup.14C in adipose tissue triglycerides. Lipid removal rate decreases during aging, with a failure to reciprocally adjust the rate of lipid uptake resulting in weight gain. Substantial weight loss is not driven by changes in lipid removal but by the rate of lipid uptake in adipose tissue. Furthermore, individuals with a low baseline lipid removal rate are more likely to remain weight-stable after weight loss. Therefore, lipid turnover adaptation might be important for maintaining pronounced weight loss. Together these findings identify adipose lipid turnover as an important factor for the long-term development of overweight/obesity and weight loss maintenance in humans. Long-term changes in body weight are determined by rates of adipose lipid turnover., Author(s): P. Arner [sup.1] , S. Bernard [sup.2] , L. Appelsved [sup.3] , K.-Y. Fu [sup.3] , D. P. Andersson [sup.1] , M. Salehpour [sup.4] , A. Thorell [sup.5] [sup.6] [...]