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It is widely accepted that the next lepton collider beyond a Higgs factory would require center-of-mass energy of the order of up to 15 TeV. Since, given reasonable space and cost restrictions, conventional accelerator technology reaches its limits near this energy, high-gradient advanced acceleration concepts are attractive. Advanced and novel accelerators (ANAs) are leading candidates due to their ability to produce acceleration gradients on the order of 1-100 GV/m, leading to compact acceleration facilities. However, intermediate energy facilities (IEF) are required to test the critical technology elements on the way towards multi-TeV-class collliders. Here a science case for a 20-100 GeV center-of-mass energy ANA-based lepton collider that can be a candidate for an intermediate energy facility is presented. The IEF can provide numerous opportunities for high energy physics studies including precision Quantum Chromodynamics and Beyond the Standard Model physics measurements, investigation of charged particle interactions with extreme electromagnetic fields, and exploring muon and proton beam acceleration. Possible applications of this collider include the studies of γγ and electron beam-fixed target/beamdump collider designs. Thus, the goal of the proposed IEF is to both carry out particle physics measurements in the 20-100 GeV ranges as well as to serve as an ANA demonstrator facility.

Zesi Liu,1 Chunli Jing2 1Department of Gynecology and Obstetrics, The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Department of Ultrasound of Gynecology and Obstetrics, The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of ChinaCorrespondence: Chunli Jing, Department of Ultrasound of Gynecology and Obstetrics, The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China, Tel +86-133-522-31070, Fax +86-82866055, Email tg980927@126.comBackground: Retroperitoneal ectopic pregnancy (REP) is an extremely rare type of ectopic pregnancy that can be life threatening. The pathogenesis of REP remains inconclusive and the diagnosis and treatment modalities are unclear.Case Presentation and Review of the Literature: A 27-year-old woman (gravida: 3; parturition: 0) underwent transvaginal ultrasound (TVS) 40 days after in vitro fertilization-embryo transfer (IVF-ET); no intrauterine gestational sac was detected. The patient was asymptomatic and had no abnormalities on physical examination. β-HCG and progesterone were 18.210 mIU/mL and 10.891 ng/mL, respectively. Transabdominal ultrasound (TAS) showed that the gestational sac had implanted adjacent to the abdominal aorta and near a branch of the iliac artery. Laparoscopic exploration was performed under general anesthesia; intraoperative findings showed that the gestational sac was approximately 2.5 cm in diameter and in the same location as suggested by preoperative ultrasound. Histopathological examination confirmed the diagnosis of EP. On day three post-surgery, the levels of β-HCG had fallen to 911 mIU/mL. We further systematically reviewed the REP cases reported in the English literature and performed a review on the diagnosis and treatment of REP.Conclusion: Clinicians should be alert to the occurrence of REP. Combined radiological examinations including ultrasonography (TAS and TVS), CT, and MRI are essential for the early diagnosis of REP. Once a definitive diagnosis is made, appropriate treatment should be administered immediately. Although there are cases of successful drug treatment described in the literature, surgery remains as the primary treatment option for REP.Keywords: retroperitoneal ectopic pregnancy, ultrasound, surgery, diagnosis, review

The genetic factors involved in disease progression and drug resistance in multiple myeloma (MM) are varied and complex. Here, genomic and transcriptomic profiling of 511 relapsed and refractory MM patients reveals genetic alterations in several oncogenic pathways contributing to progression and resistance to MM therapies.

Lei Yang,1,2,* Xiafei Li,3,* Yiting Wu,4 Pengchong Du,1,5 Lulu Sun,1 Zhenyang Yu,2 Shuang Song,1 Jianshen Yin,1 Xianfen Ma,1 Changqin Jing,1 Junqiang Zhao,3 Hongli Chen,1 Yuzhen Dong,2 Qiqing Zhang,1 Liang Zhao1,6,7 1College of Life Science and Technology, Xinxiang Medical University, Xinxiang, People’s Republic of China; 2Department of Orthopedics, First Affiliated Hospital, Xinxiang Medical University, Xinxiang, People’s Republic of China; 3College of Medical Engineering, Xinxiang Medical University, Xinxiang, People’s Republic of China; 4Xiacun Community Health Service Center, Shenzhen Hospital, University of Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 5Department of Cardio-Thoracic Surgery, Third Affiliated Hospital, Xinxiang Medical University, Xinxiang, People’s Republic of China; 6Key Laboratory of Cardiac Structure Research, Zhengzhou Seventh People’s Hospital, Zhengzhou, People’s Republic of China; 7The Central Lab, The Third People’s Hospital of Datong, Datong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang Zhao; Yuzhen Dong Email zhaoliang4321@163.com; dongyuzhen1998@163.comPurpose: The development of tissue-engineered blood vessels provides a new source of donors for coronary artery bypass grafting and peripheral blood vessel transplantation. Fibrin fiber has good biocompatibility and is an ideal tissue engineering vascular scaffold, but its mechanical property needs improvement.Methods: We mixed polyurethane (PU) and fibrin to prepare the PU/fibrin vascular scaffolds by using electrospinning technology in order to enhance the mechanical properties of fibrin scaffold. We investigated the morphological, mechanical strength, hydrophilicity, degradation, blood and cell compatibility of PU/fibrin (0:100), PU/fibrin (5:95), PU/fibrin (15:85) and PU/fibrin (25:75) vascular scaffolds. Based on the results in vitro, PU/fibrin (15:85) was selected for transplantation in vivo to repair vascular defects, and the extracellular matrix formation, vascular remodeling, and immune response were evaluated.Results: The results indicated that the fiber diameter of the PU/fibrin (15:85) scaffold was about 712nm. With the increase of PU content, the mechanical strength of the composite scaffolds increased, however, the degradation rate decreased gradually. The PU/fibrin scaffold showed good hydrophilicity and hemocompatibility. PU/fibrin (15:85) vascular scaffold could promote the adhesion and proliferation of mesenchymal stromal cells (MSCs). Quantitative RT-PCR experimental results showed that the expression of collagen, survivin and vimentin genes in PU/fibrin (15:85) was higher than that in PU/fibrin (25:75). The results in vivo indicated the mechanical properties and compliance of PU/fibrin grafts could meet clinical requirements and the proportion of thrombosis or occlusion was significantly lower. The graft showed strong vasomotor response, and the smooth muscle cells, endothelial cells, and ECM deposition of the neoartery were comparable to that of native artery after 3 months. At 3 months, the amount of macrophages in PU/fibrin grafts was significantly lower, and the secretion of pro-inflammatory and anti-inflammatory cytokines decreased.Conclusion: PU/fibrin (15:85) vascular scaffolds had great potential to be used as small-diameter tissue engineering blood vessels.Keywords: PU/fibrin scaffold, small diameter, in vitro biocompatibility, biomechanical properties, vascular remodeling

Context Patients treated with maintenance hemodialysis experience significant symptom burden resulting in impaired quality of life. However, the association of patient reported symptom burden and the risk of healthcare use for patients with end stage kidney disease on hemodialysis has not been fully explored. Objectives To investigate if higher symptom burden, assessed by the Edmonton Symptom Assessment System-revised (ESASr), is associated with increased healthcare use in patients with end stage kidney disease on hemodialysis. Methods Prospective, single-center, study of adult patients on HD. Participants completed the ESASr questionnaire at enrollment. Baseline demographic, clinical information as well as healthcare use events during the 12-month following enrollment were extracted from medical records. The association between symptom burden and healthcare use was examined with a multivariable adjusted negative binomial model. Results Mean (SD) age of the 80 participants was 71 (13) years, 56% diabetic, and 70% male. The median (IQR) dialysis vintage was 2 (1–4) years. In multivariable adjusted models, higher global [incident rate ratio (IRR) 1.02, 95% confidence interval (CI) 1.00–1.04, p = .025] and physical symptom burden score [IRR 1.03, CI 1.00–1.05, p = .034], but not emotional symptom burden score [IRR 1.05, CI 1.00–1.10, p = .052] predicted higher subsequent healthcare use. Conclusions Our preliminary evidence suggests that higher symptom burden, assessed by ESASr may predict higher risk of healthcare use amongst patients with end stage kidney disease on hemodialysis. Future studies need to confirm the findings of this preliminary study and to assess the utility of ESASr for systematic symptom screening.

Jiajia Lin,1,* Tingting Fang,1,* Mengxuan Zhu,1,* Xin Xu,1 Juan Zhang,1 Susu Zheng,1 Chuyu Jing,1 Meixia Zhang,1 Binbin Liu,1 Boheng Zhang1,2 1The Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China; 2Center for Evidence-Based Medicine, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Boheng Zhang; Binbin LiuThe Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai 200032, People’s Republic of ChinaTel +86 216 403 8038Fax +86 216 403 8038Email zhang.boheng@zs-hospital.sh.cn; liu.binbin@zs-hospital.sh.cnObjective: Prognostic performance of inflammation-based prognostic scores, including the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI) has been explored in patients with varied types of cancer, though little data is available in intrahepatic cholangiocarcinoma (ICC). This study sought to evaluate the impact of systemic inflammation on the overall survival (OS) of ICC patients, and to identify more optimal prognostic indices.Patients and methods: The prognostic power of all the scores mentioned above was compared in 123 patients underwent curative surgery for ICC using Kaplan–Meier curves, COX regression models and the receiver operating characteristics (ROC) curves. The results were validated in a cohort of 95 ICC patients.Results: Multivariate analysis identified LMR as the only independent inflammation-based predictor for OS in the training cohort (P=0.007, HR 2.082, 95% CI 1.218–3.558). More importantly, the combined score of LMR and pTNM designated the inflammation-based pathological stage (IPS) outperformed other established scores in terms of discriminatory ability, monotonicity and homogeneity in the training and validation cohorts.Conclusion: This study reveals that preoperative LMR is an independent predictor of OS in ICC patients after hepatectomy, and the IPS can be applied as a novel prognostic indicator in these patients.Keywords: inflammation-based prognostic score, the lymphocyte to monocyte ratio, intrahepatic cholangiocarcinoma, prognostic marker, staging system

Zeqiang Zhan,1 Xuebin Xu,2 Zhen Gu,3 Jianghong Meng,4 Xiayidan Wufuer,5 Mingliu Wang,6 Meilian Huang,7 Jianhui Chen,8 Chunmei Jing,9 Zhiying Xiong,1 Mei Zeng,10 Ming Liao,1 Jianmin Zhang1 1National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Key Laboratory of Zoonoses, Ministry of Agriculture, Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Animal Infectious Diseases Laboratory, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China; 2Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; 3Emerging Infections Program China Office, Beijing, 102206, China; 4Department of Food Science and Nutrition, University of Maryland, College Park, Maryland 20742, USA; 5Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention, Urumchi 830001, China; 6Guangxi Zhuang Autonomous Region Disease Prevention and Control Center, Nanning 530028, China; 7Xiamen City Children’s Hospital, Xiamen 361006, China; 8Fujian Provincial Center for Disease Control and Prevention, Fuzhou 350001, China; 9Chongqing City Children’s Hospital, Chongqing 400014, China; 10Department of Infectious Diseases, Children’s Hospital of Fudan University, Shanghai 200336, ChinaCorrespondence: Mei ZengDepartment of Infectious Diseases, Children’s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102, ChinaEmail zengmeigao@aliyun.comJianmin ZhangCollege of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, ChinaTel +86 20 8528 0240Fax +86 20 8528 5282Email junfeng-v@163.comPurpose: Human infections caused by invasive non-typhoidal Salmonella (iNTS) are highly prevalent worldwide. However, data for such infections in China are scarce. This study reports the epidemiology of iNTS in China.Methods: INTS isolates were recovered from blood and other clinical specimens collected during 2007–2016 across five provinces (Shanghai, Xinjiang, Fujian, Guangxi, and Chongqing) in China. Antimicrobial susceptibility was performed using the agar dilution method and molecular epidemiology was performed using standard microbiological techniques.Results: A total of 178 iNTS isolates were recovered from approximately 9700 patient specimens during 2007–2016. The predominant serovars were Salmonella Enteritidis (57/178, 32%), Salmonella Choleraesuis (47/178, 26.4%), and Salmonella Typhimurium (24/178, 13.5%). Up to 50 isolates (28.1%) were from patients who were ≤1 year of age, while 28 (15.7%) were from patients who were ≥60 years. Among these isolates, high rates of resistance to nalidixic acid (114/178, 64%), sulfisoxazole (59%), ciprofloxacin (15.2%), and cefotaxime (8.4%) were found. Moreover, 53.4% (95/178) exhibited multidrug resistance, and 3.9% (7/178) showed co-resistance to third-generation cephalosporins and ciprofloxacin. Steadily increasing numbers of nalidixic acid, cefotaxime, and ciprofloxacin-resistant isolates, but decreasing numbers of multidrug resistance isolates were detected during the study period. Detection of quinolone genes in 114 nalidixic acid-resistant isolates showed that 58.3% (67/114) harbored plasmid-mediated quinolone resistance (PMQR) genes [aac(6´)-Ib-cr, qnrA, qnrB, oqxAB, qepA, qnrS, and qnrD] and 98.2% (112/114) exhibited mutations in quinolone resistance determining regions [gyrA, parC, and parE]. Furthermore, we detected beta-lactamases genes in the ceftriaxone-resistant isolates. The most common were blaTEM-1 (93.3%), followed by blaCTX-M-55 (40%), blaCMY-2 (33.3%), and blaOXA-1 (33.3%). Finally, a range of pulsed-field gel electrophoresis patterns were detected among the Salmonella Enteritidis and Salmonella Typhimurium isolates.Conclusion: High rates of multidrug resistance and steadily increasing cefotaxime and ciprofloxacin-resistant iNTS could pose a significant challenge for the effective treatment of salmonellosis in China.Keywords: invasive non-typhoidal Salmonella, fluoroquinolones, multidrug resistant, beta-lactamases, pulsed field gel electrophoresis, China

Our earth is immersed in the near-earth space plasma environment, which plays a vital role in protecting our planet against the solar-wind impact and influencing space activities. It is significant to investigate the physical processes dominating the environment, for deepening our scientific understanding of it and improving the ability to forecast the space weather. As a crucial part of the National Major Scientific and Technological Infrastructure–Space Environment Simulation Research Infrastructure (SESRI) in Harbin, the Space Plasma Environment Research Facility (SPERF) builds a system to replicate the near-earth space plasma environment in the laboratory. The system aims to simulate the three-dimensional (3-D) structure and processes of the terrestrial magnetosphere for the first time in the world, providing a unique platform to reveal the physics of the 3-D asymmetric magnetic reconnection relevant to the earth's magnetopause, wave–particle interaction in the earth's radiation belt, particles' dynamics during the geomagnetic storm, etc. The paper will present the engineering design and construction of the near-earth space plasma simulation system of the SPERF, with a focus on the critical technologies that have been resolved to achieve the scientific goals. Meanwhile, the possible physical issues that can be studied based on the apparatus are sketched briefly. The earth-based system is of great value in understanding the space plasma environment and supporting space exploration. [ABSTRACT FROM AUTHOR]

Jianzhong Wu,1,* Junwei Qu,1,* Haixia Cao,1 Changwen Jing,1 Zhuo Wang,1 Heng Xu,2 Rong Ma11Research Center for Clinical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu 210000, People’s Republic of China; 2Laboratory of Pharmaceutical Chemistry, Jiangsu Province Institute of Materia Medica, Nanjing Tech University, Nanjing, Jiangsu 211816, People’s Republic of China*These authors contributed equally to this work Background: This study was designed to investigate the antitumor activity of the mAb (AC10364) in vitro and elucidate the related mechanisms of inhibition to cell growth using bel/fu cells treated with AC10364. Methods: The inhibitory effects of AC10364 on the proliferation of Bel/fu cells were examined using a cytotoxicity assay. Apoptosis of Bel/fu cells was detected using FITC annexin V and PI staining following treatment with AC10364 for 24 h. The factors regulating apoptosis were identified by Western blot using lysates of Bel/fu cells treated with AC10364 for 0, 12, 24, or 36 h. Genes associated with tumorigenesis or growth were analyzed by reverse transcription–quantitative polymerase chain reaction using Bel/fu cells treated for 12, 24, or 36 h with AC10364. Results: The early apoptotic ratios of Bel/fu cells treated with AC10364 increased in a dose-dependent manner. The levels of caspases, including cleaved caspase-3, caspase-3 and caspase-9, were significantly high in Bel/fu cells treated with AC10364 (P

We report an index case of histiocytic sarcoma arising in a 70-year-old patient with long-standing chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The patient presented in 2017 with painful, enlarging swelling of the left neck. He had remote history of cutaneous squamous cell carcinoma with no sign of recurrence, and his CLL/SLL was thought to be in remission. Computed tomography showed mild splenomegaly and multifocal lymphadenopathy including a 3-cm left neck mass. Biopsy of the left neck mass showed CLL/SLL with associated histiocytic sarcoma. Flow cytometry demonstrated a B cell neoplasm with CLL/SLL phenotype. Despite radiation therapy, he expired 3 months after presentation. Two similar cases (CLL/SLL and histiocytic sarcoma, follicular lymphoma and Langerhans cell sarcoma) from another institution are also illustrated. The pathological features of combined tumors in lymphoid neoplasms, a general framework to the work-up to determine interrelatedness of tumor components, and the clinical relevance are discussed.

Sol–gel encapsulation has been used as the basis for detecting cortisol by an immunoassay approach. Previous research showed that antibodies immobilized in the pores of a sol–gel derived silica were able to bind cortisol and be used as an immunosensor. However, this approach was not effective when measuring cortisol levels in human serum because of interference from other fluorescence sources. The present paper describes a protocol which overcomes these limitations and enables sol–gel immunoassays to effectively measure cortisol in human serum over the physiological range of cortisol blood concentrations in an adult (2–28 μg/dL). The method involves a standard additions approach in which various amounts of cortisol are added to the serum. The cortisol concentration values obtained with our sol–gel immunoassay were typically within 10% of the values obtained by traditional analytical methods. The protocol presented here represents a significant contribution to sol–gel sensing and immunoassays in particular, because of the ability to detect an analyte in human serum. In addition, this work reports the first comparison between results from a sol–gel immunosensor and an alternative immuno-binding method for analyte detection.