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The Facility for Rare Isotope Beams (FRIB) began operation with 1 kW beam power for scientific users in May 2022 upon completion of 8 years of project construction. The ramp-up to the ultimate beam power of 400 kW, planned over a 6-year period, will enable the facility to reach its full potential for scientific discovery in isotope science and applications. In December 2023, a record-high beam power of 10.4 kW uranium was delivered to the target. Technological developments and accelerator improvements are being made over the entire facility and are key to completion of the power ramp-up. Major technological developments entail the phased deployment of high-power beam-intercepting systems, including the charge strippers, the charge selection systems, the production target, and the beam dump, along with support systems, including non-conventional utilities (NCU) and remote handling facilities. Major accelerator improvements include renovations to aging legacy systems associated with experimental beam lines and system automation for improved operational efficiency and better machine availability. Experience must be gained to safely handle the increased radiological impacts associated with high beam power; extensive machine studies and advanced beam tuning procedures are needed to minimize uncontrolled beam losses for the desired operating conditions. This paper discusses the technological developments and accelerator improvements with emphasis on major R&D efforts.

Jiaqin Yu,1,* Ting Shen,2,* Zongshan Li,3 Tian Lv,4 Lisan Zhang3 1School of Medicine, Shaoxing University, Shaoxing, Zhejiang, People’s Republic of China; 2Department of Neurology, Zhuji People’s Hospital of Zhejiang Province, Zhuji, People’s Republic of China; 3Department of Neurology and Center for Sleep Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4Department of Neurology, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lisan Zhang, Department of Neurology and Center for Sleep Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Email zls09@zju.edu.cnAbstract: Narcolepsy type 1 (NT1) is a unique central sleepiness disorder that affects individuals with excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, and hypnagogic hallucinations. The etiology and pathogenesis of NT1 remains unclear, although some viral infections are thought to be related to NT1. This paper reports an unusual case of late-onset NT1 with human immunodeficiency virus (HIV) infection and antiretroviral therapy for five years. The relationship between HIV infection, immune, Immune reconstitution inflammatory syndrome (IRIS) and NT1 should be further investigated, as excessive daytime sleepiness is more common in HIV-infected patients than in the general population.Keywords: narcolepsy, excessive daytime sleepiness, HIV, immune, Immune reconstitution inflammatory syndrome

Siyi Zhang,1,2,* Yue Zhou,1,* Jinghui Wang,2 Qingan Fu,1 Tianzhou Shen,2 Guanrui Pan,2 Renfei Luo,1 Xinlei Yang,3 Long Jiang,1 Hui Hu4 1Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 2Department of Clinical Medicine, Queen Mary School of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 3Department of Biobank Center, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 4Department of Medical Big Data Center, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Long Jiang, Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China, Tel +86-13767026990, Email skyiadx@hotmail.com Hui Hu, Department of Medical Big Data Center, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China, Tel +86-13576978125, Email huhuillz@sina.comBackground: Lipoprotein(a) [Lp(a)] is a well-established risk factor for ischaemic stroke (IS). It is unclear whether Lp(a) is associated with IS in patients with atrial fibrillation (AF). The aim of this study is to explore the association between the concentration of Lp(a) and the risk of IS in AF patients, hope to find the potential risk factor for the IS in AF patients.Methods: This study is a retrospective cohort study. The screened AF patients between January 2017 and July 2021 were matched at 1:1 by the propensity score matching (PSM) method in the Second Affiliated Hospital of Nanchang University. Associations between Lp(a) and ischaemic stroke were analysed using logistic regression models, stratified analysis and sensitivity analysis. Statistical analyses were conducted using IBM SPSS software.Results: The number of enrolled participates is 2258, which contains 1129 non-AF patients and 1129 AF patients. Among IS patients, the median Lp(a) concentration was higher than that of controls (17.03 vs. 15.36 mg/dL, P = 0.032). The Spearman rank-order correlation coefficients revealed significant positive relationships between IS and Lp(a) (P = 0.032). In addition, a significant increase in IS risk was associated with Lp(a) levels > 30.00 mg/dL in unadjusted model [OR:1.263, 95% CI(1.046– 1.523), P = 0.015], model 1 [OR:1.284, 95% CI(1.062,1.552), P = 0.010], model 2 [OR: 1.297, 95% CI(1.07,1.573). P = 0.008], and model 3 [OR: 1.290, 95% CI (1.064, 1.562). P = 0.009]. The stratified analysis indicated that this correlation was not affected by female sex [1.484 (1.117, 1.972), P = 0.006], age ≤ 60 [1.864 (1.067-3.254), P=0.029], hypertension [1.359 (1.074, 1.721), P = 0.011], or non-coronary heart disease (CHD) [1.388 (1.108, 1.738), P = 0.004].Conclusion: High levels of Lp(a) were significantly related to IS in AF patients and may be a potential risk factor in the onset of an IS in AF patients. Keywords: ischaemic stroke, Lipoprotein(a), atrial fibrillation, risk factor, retrospective cohort study

High-temperature superconducting REBa{2} Cu{3}O{7-x} (rebco) conductors have the potential to generate a high magnetic field over a broad temperature range. The corresponding accelerator magnet technology, still in its infancy, can be attractive for future energy-frontier particle colliders such as a multi-TeV muon collider. To help develop the technology, we explore the requirements and potential characteristics of a rebco magnet, operating at 4.2 or 20 K, with a dipole field of 8-10 T in a clear aperture of 150 mm. We use the canted \cos \theta magnet configuration to reduce the electromagnetic stresses on the conductors. We present the resulting dipole fields, field gradients for combined-function cases, conductor stresses, magnet dimensions and conductor lengths. We also discuss the conductor performance that is required to achieve the target dipole field at 4.2 and 20 K. The information can provide useful input to the development of rebco magnet and conductor technology for collider-ring magnets in a muon collider.

Ying Zhu,1 Liyuan Jiang,2 Tiantian Ye,3 Yan Liu,4 Li Sun,2 Lijuan Xiao,5 Jiayu Chen,6 Ting Wang,7 Yinghua Ren,8 Hongjun Xu,8 Huihui Zhao,8 Xiaozhen Mao,8 Tiantian Shen9 1School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2Department of Acupuncture and Rehabilitation, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, 310005, People’s Republic of China; 3The 1st Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 4The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 5Department of Rehabilitation, Chun’an County Hospital of Traditional Chinese Medicine, Chun’an, 311799, People’s Republic of China; 6Department of Rehabilitation, Huzhou Central Hospital, Huzhou, 313099, People’s Republic of China; 7The 3rd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 8Department of Acupuncture and Tuina, Community Health Service Center of Zhuantang Street, Hangzhou, 310024, People’s Republic of China; 9Department of Acupuncture and Rehabilitation, Shengzhou Municipal Hospital of Traditional Chinese Medicine, Hangzhou, 312499, People’s Republic of ChinaCorrespondence: Liyuan Jiang, Department of Acupuncture and Rehabilitation, Hangzhou Hospital of Traditional Chinese Medicine, No. 453, Stadium Road, Xihu District, Hangzhou, 310005, People’s Republic of China, Tel +86-13018976755, Email Jiangliyuan520j@163.comPurpose: Diastasis recti abdominis (DRA) is a condition in which the linea alba is stretched and widened, and the abdominal muscles are separated from each other. DRA typically occurs in pregnant and postpartum women. We aimed to determine the risk factors and patient-reported outcomes (PROs) of DRA in Chinese postpartum women.Methods: This observational study was conducted in Hangzhou Hospital of Traditional Chinese Medicine, and involved 534 women who filled out the following risk-factor and PRO questionnaires: SF-MPQ-2, SF-ICIQ, LDQ, EPDS, MBIS, HerQles, and SF-36 (all Chinese versions). The inter-recti distance was measured by palpation. Statistical analyses were performed using SPSS v25.0 software and the Mann–Whitney U-test, chi-square test, binary logistic regression analysis (for risk factors of DRA), and the Kendall and Spearman tests (for correlation analysis).Results: After childbirth, 78.1% (417/534) of the enrolled women had DRA. Abdominal surgery (P = 0.002), number of pregnancies (P = 0.035), parity (P = 0.012), number of births (P = 0.02), fetal birth weight (P = 0.014), and waist-to-hip ratio in the supine position (P = 0.045) significantly differed between the DRA and non-DRA groups. Caesarean delivery was an independent risk factor for DRA. The PROs were significantly worse in the DRA group than in the non-DRA group.Conclusion: Caesarean delivery was an independent risk factor for DRA. Women with DRA are more likely to have limited physical activity or function after childbirth, lower self-confidence, and a decreased quality of life.Keywords: risk factors, patient-reported outcome measures, diastasis recti abdominis, postpartum period

Weinan Hu,* Wenting Cai,* Yan Wu, Chengda Ren, Donghui Yu, Tingting Li, Tianyi Shen, Ding Xu, Jing Yu Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ding Xu; Jing Yu, Email 15821885240@163.com; dryujing@aliyun.comBackground: Age-related macular degeneration (AMD) stands as the foremost cause of irreversible central vision impairment, marked by choroidal neovascularization (CNV). The prevailing clinical approach to AMD treatment relies on intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs. However, this method is encumbered by diverse complications, prompting exploration of non-invasive alternatives such as ocular administration via eye drops for anti-VEGF therapy.Methods: Two complexes, 5-FITC-CPP-Ranibizumab (5-FCR) and 5-FITC-CPP-Conbercept (5-FCC), were synthesized by incorporating the anti-VEGF drugs Ranibizumab (RBZ) or Conbercept (CBC) with cell-penetrating peptide (CPP). Circular dichroism spectrum (CD) facilitated complexes characterization. Eye drops was utilized to address laser-induced CNV in mice. Fluorescein fundus angiography (FFA) observe the CNV lesion, while FITC-dextran and IB4 dual fluorescent staining, along with hematoxylin-eosin (HE) staining, assessed in lesion size. Tissue immunofluorescence examined CD31 and VEGF expression in choroidal/retinal pigment epithelial (RPE) tissues. Biocompatibility and biosafety of 5-FCR and 5-FCC was evaluated through histological examination of various organs or cell experiments.Results: Both 5-FCR and 5-FCC exhibited favorable biocompatibility and safety profiles. VEGF-induced migration of Human umbilical vein endothelial cells (HUVECs) significantly decreased post-5-FCR/5-FCC treatment. Additionally, both complexes suppressed VEGF-induced tube formation in HUVECs. FFA results revealed a significant improvement in retinal exudation in mice. Histological examination unveiled the lesion areas in the 5-FCR and 5-FCC groups showed a significant reduction compared to the control group. Similar outcomes were observed in histological sections of the RPE-choroid-sclera flat mounts.Conclusion: In this study, utilizing the properties of CPP and two anti-VEGF drugs, we successfully synthesized two complexes, 5-FCR and 5-FCC, through a straightforward approach. Effectively delivering the anti-VEGF drugs to the target area in a non-invasive manner, suppressing the progression of laser-induced CNV. This offers a novel approach for the treatment of wet AMD. Keywords: age-related macular degeneration, choroidal neovascularization, cell-penetrating peptide, ranibizumab, conbercept, drug delivery

Hong-Ping Wang,1,&ast; Yuan-Ying Xu,1,&ast; Bi-Lin Xu,1 Jun Lu,1 Juan Xia,1 Tian Shen,1 Ji Fang,1,2 Tao Lei1 1Department of Endocrinology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, Shanghai, 200333, People’s Republic of China; 2Department of Nephrology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, Shanghai, 200333, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Lei, Department of Endocrinology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, No. 164 of Lanxi Road, Putuo District, Shanghai, 200333, People’s Republic of China, Tel +86 021-22233222-58142, Email leitao5899@126.com Ji Fang, Department of Nephrology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, No. 164 of Lanxi Road, Putuo District, Shanghai, 200333, People’s Republic of China, Tel +86 021-22233222-58082, Email 13601833102@163.comObjective: To investigated the link between the distribution of abdominal fat and the concentration of serum uric acid (SUA) in individuals recently diagnosed with type 2 diabetes.Methods: Studied 364 individuals had been diagnosed with type 2 diabetes within one month, and evaluated factors such as the distribution of fat in the abdomen, indicators related to glucose and lipid metabolism. The participants’ SUA concentrations were divided into a normal control group (CG) and a hyperuricemia group (HG).Results: The HG group had elevated abdominal subcutaneous fat area (SFA), visceral fat content (VFA), body mass index (BMI), fasting blood glucose (FBG), 2-hour postprandial blood glucose (PBG), glycosylated albumin (GA), serum creatinine (SCr), triacylglycerol (TG), and lower values in glomerular filtration rate (eGFR), high-density lipoprotein cholesterol (HDL-C) when compared to the CG group (P < 0.05). Among the obese individuals, the hyperuricemia subgroup exhibited higher measurements in waistline, hipline, VFA, SFA, BMI, PBG, SCr, TG, and lower HDL-C (P < 0.05) compared to the subgroup with normal uric acid levels. In the non-obese group, the hyperuricemia subgroup showed higher VFA, SCr, and FBG levels, and lower HDL-C (P < 0.05). There was a positive correlation between VFA and serum uric acid (SUA) levels (r = 0.329, P < 0.0001). Logistic regression analysis indicated a 24% increased risk of hyperuricemia with every 10cm2 increase in abdominal VFA. Generate the Receiver Operating Characteristic (ROC) curve analysis revealed that VFA was the most effective predictor of hyperuricemia and insulin resistance (P < 0.05).Conclusion: Newly diagnosed type 2 diabetes patients exhibit a strong correlation between abdominal visceral fat and SUA concentration, the former is identified as an autonomous risk factor for hyperuricemia and an effective indicator for assessing the presence of hyperuricemia and predicting insulin resistance.Keywords: abdominal fat distribution, newly diagnosed type 2 diabetes, serum uric acid, visceral fat area

Wei Sun,1,2,&ast; Songyi Xu,3,&ast; Tianlun Shen,1,3,&ast; Guangyao Li,1 Jingfeng Zhang,2 Chunshu Pan,1,2 Wei Lu,1,2 Xiangrui Liu,1 Jianjun Zheng,2 Jun Ling,1,3 Jihong Sun1 1Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Radiology, Ningbo No. 2 Hospital, Ningbo, People’s Republic of China; 3MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jihong Sun, Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Tel +86 13857176538, Email sunjihong@zju.edu.cn Jianjun Zheng, President of Ningbo No. 2 Hospital, Ningbo, People’s Republic of China, Tel +86 574 83870280, Email zhjjnb2@163.comPurpose: Chemotherapy treatments for cancer are always accompanied by a low concentration of drug delivered in the tumor area and severe side effects including systemic toxicity. Improving the concentration, biocompatibility, and biodegradability of regional chemotherapy drugs is a pressing challenge in the field of materials.Methods: N-Phenyloxycarbonyl-amino acids (NPCs) which exhibit significant tolerance to nucleophiles, such as water and hydroxyl-containing compounds, are promising monomers for the synthesis of polypeptides and polypeptoids. Cell line and mouse models were used to comprehensively explore how to enhance the tumor MRI signal and evaluate the therapeutic effect of Fe@POS-DOX nanoparticles.Results: In this study, poly(3,4-dihydroxy-L-phenylalanine)-b-polysarcosine (PDOPA-b-PSar, simplified as POS) was synthesized by the block copolymerization of DOPA-NPC with Sar-NPC. Fe@POS-DOX nanoparticles were prepared in order to utilize the strong chelation of catechol ligands to iron (III) cations and the hydrophobic interaction between DOX and DOPA block to deliver chemotherapeutics to tumor tissue. The Fe@POS-DOX nanoparticles exhibit high longitudinal relaxivity (r1 = 7.06 mM− 1·s− 1) and act as T1-weighted magnetic resonance (MR) imaging contrast agents. Further, the main focus was improving tumor site-specific bioavailability and achieving therapeutic effects through the biocompatibility and biodegradability of Fe@POS-DOX NPs. The Fe@POS-DOX treatment exhibited excellent antitumor effects.Conclusion: Upon intravenous injection, Fe@POS-DOX delivers DOX specifically to the tumor tissues, as revealed by MR, and leads to the inhibition of tumor growth without overt toxicity to normal tissues, thus displaying considerable potential for use in clinical applications.Graphical Abstract: Keywords: poly (α-amino acid)s, polypeptides, polypeptoids, MRI, chemotherapy, nanoparticles

Although the high-temperature superconducting (HTS) REBa2Cu3O x (REBCO, RE-rare earth elements) material has a strong potential to enable dipole magnetic fields above 20 T in future circular particle colliders, the magnet and conductor technology needs to be developed. As part of an ongoing development to address this need, here we report on our CORC® canted cosθ magnet called C2 with a target dipole field of 3 T in a 65 mm aperture. The magnet was wound with 70 m of 3.8 mm diameter CORC® wire on machined metal mandrels. The wire had 30 commercial REBCO tapes from SuperPower Inc. each 2 mm wide with a 30 µm thick substrate. The magnet generated a peak dipole field of 2.91 T at 6.290 kA, 4.2 K. The magnet could be consistently driven into the flux-flow regime with reproducible voltage rise at an engineering current density between 400-550 A mm-2, allowing reliable quench detection and magnet protection. The C2 magnet represents another successful step towards the development of high-field accelerator magnet and CORC® conductor technologies. The test results highlighted two development needs: continue improving the performance and flexibility of CORC® wires and develop the capability to identify locations of first onset of flux-flow voltage.

Yingying Pan,1,&ast; Xianrong Feng,2,&ast; Wei Song,1,&ast; Xin Zhou,1 Zhen Zhou,3 Gaoyang Chen,1 Tao Shen,1 Xiaobo Zhang1 1School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia&ast;These authors contributed equally to this workCorrespondence: Xiaobo Zhang; Tao Shen, School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China, Email zhangxiaobo@stu.cdutcm.edu.cn; shentaotcm@aliyun.comBackground: Atherosclerosis (AS) is an immunoinflammatory disease associated with dyslipidemia. Zhuyu Pill (ZYP) is a classic Chinese herbal compound that has been shown to exhibit anti-inflammatory and lipid-lowering effects on AS in our previous studies. However, the underlying mechanisms by which ZYP ameliorates atherosclerosis have not yet been fully investigated. In this study, network pharmacology and in vivo experiments were conducted to explore the underlying pharmacological mechanisms of ZYP on ameliorating AS.Methods: The active ingredients of ZYP were acquired from our previous study. The putative targets of ZYP relevant to AS were obtained from TCMSP, SwissTargetPrediction, STITCH, DisGeNET, and GeneCards databases. Protein-protein interactions (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted using the Cytoscape software. Furthermore, in vivo experiments were carried out for target validation in apolipoprotein E (ApoE) -/- mice.Results: Animal experiments revealed that ZYP ameliorated AS mainly through lowering blood lipids, alleviating vascular inflammation, and decreasing the levels of vascular cell adhesion molecule-1 (VCAM1), intercellular adhesion molecule-1 (ICAM1), monocyte chemotactic protein-1 (MCP-1), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α). Additionally, the results of Real-Time quantitative PCR revealed that ZYP inhibited the gene expressions of mitogen-activated protein kinase (MAPK) p38, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-B (NF-κB) p65. The Immunohistochemistry and Western blot assays showed the inhibitory effect of ZYP on the proteins level of p38, p-p38, p65, and p-p65.Conclusion: This study has provided valuable evidence on the pharmacological mechanisms of action of ZYP in ameliorating AS that will be useful for forming the rationale of future research studying the cardio-protection and anti-inflammation effects of ZYP.Keywords: atherosclerosis, Zhuyu Pill, network pharmacology, MAPK, NF-κB

Nb3Sn accelerator magnets are poised to enable the luminosity upgrade of the Large Hadron Collider (LHC) at CERN, improving its potential for exploring physics beyond the standard model of particle physics. The prototype Nb3Sn magnets consistently need 10-25 quenches to achieve their best performance. A hypothesis is that the long training of these magnets may at least be partially induced by epoxy cracking and bonding failures. In 2018, we showed that several existing epoxies have a higher toughness and less tendency to crack at low temperatures than CTD-101K, the epoxy resin with which almost all Nb3Sn accelerator magnets have been impregnated. Here we explore a new high toughness formulation for reducing quench training of Nb3Sn accelerator magnets, through combining two amine curing agents to achieve a good glass transition temperature $(T_{g})$, adding a viscosity reducer to achieve low viscosity, and experimenting a coupling agent for improved bonding strengths. We report results of comprehensive materials tests, including thermal shock, tensile, compressive, shear tests, viscosity and $T_{g}$ tests.

Fast quench detection is a key requirement for the successful implementation of superconducting magnet technology. In high temperature superconductor magnets, this issue is especially challenging due to the low quench propagation velocity, and presently represents one of the main factors limiting their application. A new detection technique based on stray-capacitance monitoring is proposed. The capacitance between electrically-insulated magnet elements, such as magnet structure and end parts, is utilized as an indication of local heat deposition in the conductor. In fact, the relative permittivity of helium drops when it changes from the liquid to the gaseous phase. Thus, when heating occurs, part of the helium impregnating the insulation layers boils off, and the monitored stray-capacitance decreases. The proposed technique is successfully demonstrated on three small-scale Bi-2212 magnets manufactured at the Lawrence Berkeley National Laboratory. Results from the detection of thermal runaways and spot-heater induced quenches are reported and discussed. Advantages and limitations of the stray-capacitance method with respect to conventional quench detection methods are assessed.

Yu Wang,1,&ast; Hanning Zha,1,&ast; Xiang Fang,2 Tianjiao Shen,1 Kunyun Pan,1 Jianping Zhang,1 Keqiang He,1 Sheng Wang,1 Liguo Hu1 1Department of Anesthesiology, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2Department of Anesthesiology, Hefei BOE Hospital, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sheng Wang; Liguo Hu, Email iamsheng2020@ustc.edu.cn; hulg@163.comObjective: The dose selection of ropivacaine for spinal anesthesia in clinical work mainly depends on the experience of the anesthesiologist. In this study, a prospective and modified up-down sequential allocation design was used to provide the optimal dose selection of ropivacaine for spinal anesthesia.Patients and methods: This study was divided into two stages, and a total of 164 elderly patients with elective hip fractures were included. In stage I, the dose of ropivacaine was selected using the up-down sequential method of height correction, and the 50% effective dose (ED50) and 95% effective dose (ED95) were obtained. A nomogram for predicting satisfactory anesthesia and a formula for predicting the optimal dose was also given in this stage. In stage II, the dose of ropivacaine was calculated by using the optimal dose prediction formula, so as to evaluate the efficacy and safety of the model.Results: The ED50 and ED95 of the stage I were 7.036 mg (95%CI 6.549– 7.585 mg) and 8.709 mg (95%CI 7.902– 14.275 mg), respectively. And provided a nomogram predicting satisfactory anesthesia with a C-index of 0.847 (95%CI 0.774– 0.92). The optimal dose prediction formula of ropivacaine was calculated, including variables for age, gender, height, and weight. This formula was found to be 90% efficient. It is worth mentioning that the incidence of direct transfer to the ward in the two stages was as high as 86.84% and 93.33%, respectively, and no patients were transferred to the ICU in stage II.Conclusion: The ED50 and ED95 of ropivacaine were 7.036 mg and 8.709 mg, respectively, and the nomograms are sufficiently accurate to predict satisfactory anesthesia. Beyond that, the dose prediction equation provided in this study has high efficacy and safety, and can guide the dose selection of spinal anesthesia in elderly patients with hip fracture in clinical practice.Clinical trials registration: ChiCTR2100046982Keywords: ropivacaine, dose selection, elder, spinal anesthesia, Hip fracture, sequential design

The U.S. Magnet Development Program (MDP) is exploring the possibility of combining low-and higherature superconductor technologies, using cosine-theta and canted-cosine-theta (CCT) Nb3Sn dipole magnets together with Bi-2212 CCT inserts, with the ultimate goal of constructing a 20-T dipole. The MDP short-term goal is a Bi-2212 CCT insert capable of reaching 5 T in the bore when operating as a stand-alone and 3 T when operating under a background field of 15 T. This paper reports on the fabrication of our BIN4 dipole magnet and our BIN5a and BIN5b coils, designed and built at the Lawrence Berkeley National Laboratory to address potential fabrication issues of Bi-2212 coils and verify the design of our 18-20-T dipole magnet. BIN4 is a two-layer 50-cm-long CCT magnet that uses a nine-strand Rutherford cable made with 0.8-mm-diameter Bi-2212 strands. Its goal is to investigate critical current, insulation integrity, manufacturing challenges, and quench protection issues after heat treating both layers together under oxygen at standard atmosphere (1 bar). BIN5a and BIN5b are two identical coils, similar to the outer layer of BIN4, with the difference that the length is 39 cm, and they will undergo 50-bar overpressure processing heat treatment. BIN5 coils are made from the state-of-the-art strand with an engineering critical current density of 1150 A/mm2 at 4.2 K and 5 T.

We fabricated three racetrack coils (RC1, RC2, and RC3) from Bi-2212 Rutherford cables (17-strand, thickness × width = 1.44 mm × 7.8 mm, strand diameter = 0.8 mm) and applied overpressure processing heat treatment (OPHT). The quench currents of RC1 and RC2 reached 5268 A and 5781 A, respectively, despite them still, surprisingly, exhibiting some Bi-2212 leakage to the surface. After removing most of the leakages using a simple-to-implement insulation scheme, the quench current of RC3 improved to 6485 A, which is about three times the average quench current of a dozen racetrack coils that had been fabricated and reacted using the conventional 1 bar heat treatment. The results confirm the effectiveness of the OPHT technology and the new leakage control scheme for coils made from Bi-2212 Rutherford cables. Coils exhibited an increased quench current with increasing the current ramp rate from 5 to 200 A s-1; they were quite stable against point and transient disturbances, and were capable of adsorbing persistent Joule heating at ∼80 mW for >15 s before quenching. These behaviors are different from Nb-Ti and Nb3Sn accelerator magnets. Overall, our results provide a critical evaluation and verification of Bi-2212 wire and magnet technologies (wire, insulation, heat treatment, coil fabrication, and coil operation), reveal crucial new stability features of Bi-2212 magnets, and demonstrate technological options for it to become a practical high-field magnet technology.

Huiyang Wang,1,&ast; Siqi Wang,2,&ast; Xisong Zhu,3 Wenxiu Ding,4 Tianlun Shen,2 Hongjie Fan,1 Yanhua Zhang,5 Lijun Peng,6 Hong Yuan,6 Xiangrui Liu,7 Jun Ling,2 Jihong Sun1 1Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China; 2MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, People’s Republic of China; 3Department of Radiology, Quzhou Central Hospital Affiliated to Zhejiang Chinese Medical University, Quzhou, 324002, People’s Republic of China; 4Department of Ultrasound Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, People’s Republic of China; 5Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China; 6College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310030, People’s Republic of China; 7Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jihong Sun, Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China, Tel +13857176538, Fax +571-86006762, Email sunjihong@zju.edu.cn Jun Ling, MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, People’s Republic of China, Tel +13645717301, Fax +571-87953739, Email lingjun@zju.edu.cnPurpose: To develop an iron-based solid lipid nanoparticle (SLN) absorbable by the intestinal wall and assess the differential diagnostic value of intestinal lesions in magnetic resonance imaging (MRI).Methods: SLNs were prepared with the simultaneous loading of trivalent Fe ions (Fe3+), levodopa methyl ester (DM), and fluorescein isothiocyanate (FITC). We evaluated the particle size, loading rate, encapsulation efficiency, and cytotoxicity of SLNs. The T1 contrast effects of the FeDM-FITC-SLNs and gadolinium-based contrast agent (GBCA) were compared in different mouse models: acute ulcerative colitis (AUC), chronic ulcerative colitis (CUC), colon adenocarcinoma (COAD), and normal control. MRI was performed in the same mouse with intravenous injection of GBCA on day 1 and enema of FeDM-FITC-SLNs on day 2. The signal-to-noise ratios (SNRs) were compared using one-way analysis of variance. Tissues were then collected for histology.Results: The average particle size of FeDM-FITC-SLN was 220 nm. The mean FeDM loading rate was 94.3%, and the encapsulation efficiency was 60.3%. The relaxivity was 4.02 mM− 1·s− 1. After enema with FeDM-FITC-SLNs, MRI showed the following contrast enhancement duration: AUC = COAD > normal > CUC. Confocal fluorescence microscopy confirmed that FeDM-FITC-SLNs were mainly distributed in the intestinal mucosa and tumor capsule.Conclusion: Iron-based SLNs are promising alternatives for contrast enhancement at T1-weighted MRI and will help in the differential diagnosis of intestinal bowel diseases (IBDs).Keywords: solid lipid nanoparticles, magnetic resonance imaging, contrast agent, ferric iron, intestinal bowel diseases

The critical current density of Bi-2212 round wires has seen significant improvement over the past two years. We present the magnetic design and stress analysis of two Bi-2212 dipoles based on Canted-Cosine-Theta (CCT) technology using the state-of-the-art wires. The first design, based on a 19-strand Rutherford cable of θ0.8mm strands, is a two-layer dipole with a bore diameter of 40 mm and an outer diameter of 98.4 mm; it generates 5.4Twhen operating in stand-alone configuration and 18.9T in 15 T background field. The second design, based on a 13-strand Rutherford cable of θ0.8mm strands, is also a two-layer dipole with a bore diameter of 40 mm and an outer diameter of 81 mm; it generates 4.0 T when operating in stand-alone configuration and 17.8 T in 15 T background field. Normal stresses on the conductor in these magnets do not exceed 35 MPa when working under background field.Moreover, we propose a novel approach for increasing the efficiency of CCT magnets using keystoned Rutherford cable while removing the midplane ribs. with this method, it is possible to increase the efficiency of small radius CCT coils by 20%. We conclude that Bi-2212 can be used to increase the limit of accelerator magnet dipole fields beyond 15 T while managing stresses in the coils to acceptable levels.

In article I of this series, we described a spiral coil quench technique for probing the influence of the superconductor stress and strain state during normal operation on its margin to degradation during a quench and applied to a Bi-2212 round wire. Here we extend this technique to study the failure mechanisms and limits of high-strength Bi-2223 tapes experiencing a quench while carrying a large current in a high magnetic field. In contrast to Bi-2212 magnets made via a wind-and-react technique for which bending strains can be ignored, Bi-2223 magnets are made with a react-and-wind technique for which bending strain is significant. The critical tensile stress of Bi-2223 tapes (type HT-NX) decreases from >440 MPa for straight samples to 185 MPa after being bent to a diameter D of 50 mm. For HT-NX tapes with D = 50 mm, the quench degradation limit, measured using maximum allowable temperature during a quench T allowable, is greater than 300 K for axial tensile stress < 94 MPa; it decreases with increasing tensile axial stress nonlinearly, dropping to 230 K for = 125 MPa. T allow able experimental data at D = 50 mm is consistently predicted by a general strain model that assumes that quench degradation in NX/Bi-2223 is driven by axial tensile strain in Bi-2223 filaments exceeding the irreversible strain limit. The T allowable is then predicted for various D including D = 80 mm important for NMR magnets. The given T allowable is easy to use and important for finding the balance between operation stress, and therefore magnetic field generation efficiency, and operation margin when designing a superconducting magnet using Bi-2223 tapes.

Zhen Wang,&ast; Huilin Yan,&ast; Dingcai Cheng, Lei Xu, Tianming Shen, Yi Chen, Rongbo Han, Yanshi Xue Department of Urology, Taixing People’s Hospital, Taixing City, 225400, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanshi Xue; Rongbo HanDepartment of Urology, Taixing People’s Hospital, No. 1 Changzheng Road, Taixing City, 225400, Jiangsu Province, People’s Republic of ChinaTel +86 523-87656001Email yanshi_xue@163.com; hanrongbo1020@163.comBackground: LncRNA plays a vital role in tumorigenesis and development. This study aimed to explore the novel lncRNA affecting bladder cancer progression.Methods: The open-access data of bladder cancer patients, including transcriptome profiles and corresponding clinical information were all obtained from The Cancer Genome Atlas database. All the statistical analysis were performed using R software, SPSS and GraphPad Prism 8. CCK8, colony formation, apoptosis detection and tumorigenicity assay were used to assess cell proliferation ability. Transwell assay and wound-healing assay were used to evaluate cell metastasis potential.Results: Our result showed that the lncRNA LINC01614 was highly expressed in bladder cancer tissue and cell lines. Meanwhile, patients with high LINC01614 expression level tend to have poor clinical features and shorter survival time. Further experiments demonstrated that the inhibition of LINC01614 could significantly hamper the proliferation and invasion of bladder cancer cells. Then, we found that the LINC01614 could regulate RUNX2 expression through miR-137. GSEA analysis indicated that the Wnt/β-catenin signaling pathway might be the downstream pathway of LINC01614. Further experiments showed that the LINC01614 act as an oncogene in bladder cancer partly depending on the RUNX2/Wnt/β-catenin axis, making it an underlying therapeutic target.Conclusion: In all, LINC01614 facilitates bladder cancer cells proliferation, migration and invasion through the miR-217/RUNX2/Wnt/β-catenin axis.Keywords: LINC01614, bladder cancer, lncRNA, Wnt/β-catenin

Rui-Wen Huang,1 Tao Shen,2 Lei-Ming Ge,3 Lu Cao,4 Jian-Feng Luo,5– 7 Shi-Yu Wu1 1Department of Science and Education, RuiJin Hospital LuWan Branch, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 2Department of Psychiatry, Shanghai Huangpu District Mental Health Center, Shanghai, People’s Republic of China; 3Department of General practice, Changfeng Community Health Service Center of Putuo, Shanghai, People’s Republic of China; 4Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Department of Biostatistics, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 6NHC Key Laboratory of Health Technology Assessment, Fudan University, Shanghai, People’s Republic of China; 7Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Shi-Yu Wu; Jian-Feng Luo Email wushiyu317@163.com; jfluo@shmu.edu.cnPurpose: The COVID-19 pandemic may increase the development of psychiatric disorders, such as posttraumatic stress disorder (PTSD) among medical staff. A brief validated screening tool is essential for the early diagnosis of PTSD. The purpose of the present study was to evaluate the validation of a Chinese version of the Primary Care-PTSD-5 (C-PC-PTSD-5) and determine an appropriate cutoff score with optimal sensitivity and specificity for medical staff in China during the COVID-19 pandemic.Participants and Methods: An online cross-sectional survey was conducted on medical staff (n = 1104) from 17 medical institutions in Shanghai. Questionnaires comprising general information, medical-related traumatic event experiences, the PTSD Checklist (PCL-5), and C-PC-PTSD-5 were distributed to participants using the online Questionnaire Star electronic system. Internal consistency, convergent validity, and test–retest reliability were calculated. Receiver operating characteristic (ROC) analysis was performed to determine diagnostic accuracy and the optimal cutoff score of the C-PC-PTSD-5 for medical staff.Results: We included 1062 valid questionnaires for the analysis. Data of 838 traumatic experiences were analyzed. Internal consistency of the C-PC-PTSD-5 was satisfied (Cronbach’s α = 0.756). The total score of the C-PC-PTSD-5 showed good test–retest reliability (r = 0.746). We found a strong correlation between the C-PC-PTSD-5 score and PCL-5 total score (r = 0.669, p < 0.001), which indicated good convergent validity. The ROC analysis showed an area under the curve of 0.81 ± 0.016. A cutoff score of 2 provided optimal sensitivity and specificity for the C-PC-PTSD-5 (sensitivity = 0.632, specificity = 0.871, Youden index = 0.503, and overall efficiency = 0.768).Conclusion: Our results indicated that the C-PC-PTSD-5 can be employed as a brief and efficient screening instrument for medical staff exposed to the COVID-19 pandemic. A score of 2 was identified as the optimal threshold for probable clinical PTSD symptoms.Keywords: PTSD, COVID-19, self-reported screens, medical staff, PCL-5, PC-PTSD-5

Cable and magnet applications require bending REBa2 Cu3O 7-δ (REBCO, RE = rare earth) tapes around a former to carry high current or generate specific magnetic fields. With a high aspect ratio, REBCO tapes favor the bending along their broad surfaces (easy way) than their thin edges (hard way). The easy-way bending forms can be effectively determined by the constant-perimeter method that was developed in the 1970s to fabricate accelerator magnets with flat thin conductors. The method, however, does not consider the strain distribution in the REBCO layer that can result from bending. Therefore, the REBCO layer can be overstrained and damaged even if it is bent in an easy way as determined by the constant-perimeter method. To address this issue, we developed a numerical approach to determine the strain in the REBCO layer using the local curvatures of the tape neutral plane. Two orthogonal strain components are determined: the axial component along the tape length and the transverse component along the tape width. These two components can be used to determine the conductor critical current after bending. The approach is demonstrated with four examples relevant for applications: a helical form for cables, forms for canted cos θ dipole and quadrupole magnets, and a form for the coil end design. The approach allows us to optimize the design of REBCO cables and magnets based on the constant-perimeter geometry and to reduce the strain-induced critical current degradation.

Jialing Wu,&ast; Kaiyun You,&ast; Xingsheng Qiu,&ast; Ting Shen, Juanjuan Song, Changlong Chen, Yanhui Jiang, Yimin Liu Department of Radiation Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yimin Liu; Yanhui JiangDepartment of Radiation Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Yuexiu District, Guangzhou City, Guangdong Province, People’s Republic of ChinaTel +86 18922182513Email liuyimin@mail.sysu.edu.cn; jiangyh26@mail.sysu.edu.cnPurpose: Local failure after endoscopic laryngeal surgery (ELS) for early glottic cancer mounts a challenge to researchers to investigate risk factors of recurrence. The present study was therefore designed to explore the prognostic factors in patients who underwent ELS for early glottic cancer.Patients and Methods: We reviewed 328 patients with T1-2N0 glottic cancer who were treated with either ELS or open surgery between 2007 and 2018 at our institution. Survival, univariate and multivariate analyses were performed in different groups (ELS vs open surgery; < 65 vs ≥ 65 years).Results: Age was discovered to be the independent prognostic factor of DFS for patients treated with ELS (HR = 3.673, p = 0.003), but not for patients who underwent open surgery. Survival analysis performed on young patients (< 65 years) showed that survival outcomes between different surgery modalities were significantly different (ELS vs open surgery: five-year DFS: 72.5 vs 84.7%, p = 0.034). Univariate and multivariate analyses further confirmed the finding, whereas these results did not appear in old patients (≥ 65 years).Conclusion: Young patients (< 65 years) treated with ELS had less favorable oncologic outcomes than those treated with open surgery. Young patients (< 65 years) are advised to consider open surgery over ELS.Keywords: early glottic cancer, age, recurrence, prognostic factor, surgery

Ting Shen, Zijian Yang Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, Shanghai, People’s Republic of ChinaCorrespondence: Zijian YangDepartment of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, No. 197 Second Ruijin Road, Shanghai, People’s Republic of ChinaEmail doctoryzj2020@163.comBackground: To establish a novel delivery system of pemirolast potassium-loaded gellan gum in situ gel in allergic conjunctivitis therapy.Methods: The prepared in situ gels were studied in the following aspects: in vitro gelation, in vitro release, stability, viscosity measurement, in vivo tear kinetics and pharmacodynamics.Results: In this study, the results showed that the viscosity of the in situ gels significantly increased when the preparation was in contact with simulated tear fluid and it also exhibited good stability in a period of three months. In vitro release showed that the release of pemirolast potassium from in situ gels had a good sustained release ability. No ocular damage or abnormal clinical signs to the cornea, iris, or conjunctivae were visible. Consistent with the in vitro studies, pemirolast potassium in situ gels were highly efficient in suppressing the inflammatory symptoms and improving the ocular bioavailability.Conclusion: Pemirolast potassium ocular in situ gels are safe and promising therapeutic alternatives to the existing medications for allergic conjunctivitis therapy.Keywords: pemirolast potassium, gellan gum, in situ gel, allergic conjunctivitis, pharmacodynamic

Tian Shen,1,* Jing Wang,1,* Wen Yang,1 Linke Li,1 Yixin Qiao,1 Xiaohong Yan,1 Min Chen,2 Xiangdong Tang,3 Jian Zou,1 Yu Zhao1 1Department of Otorhinolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Otorhinolaryngology Head and Neck Surgery, Chengdu Shangjin Nanfu Hospital, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Sleep Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu Zhao; Jian ZouDepartment of Otolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaTel +86-18980601410; +86-18980605883Email yutzhao@163.com; zoujian926@163.comObjective: To investigate the possible correlation between obesity and hematological parameters in children with obstructive sleep apnea (OSA).Methods: A total of 460 children was initially included in our study, which were divided into children with OSA and children without OSA. Multiple analysis was performed for obesity by adjusting confounding factors such as age and gender in 460 children. Further, to minimize the influence of confounding factors and selective bias, propensity score matching (PSM) was performed in children with OSA. Hematological parameters such as inflammatory and coagulable parameters were compared between the normal weight children with OSA and the obese children with OSA following PSM.Results: OSA (OR = 3.061; P< 0.001; 95% CI, 1.772– 5.288) represented an independent risk factor for obesity. Besides, the obese children with OSA had higher levels of white blood cell (WBC) (P< 0.001), neutrophil (NEUT) (P< 0.001), neutrophil-lymphocyte ratio (NLR) (P=0.006), fibrinogen (FIB) (P=0.033), while had a lower level of activated partial thromboplastin time (APTT) (P=0.048). No significant differences were observed in other hematological parameters. In linear regression, the results indicated that the levels of WBC (R2 = 0.123, Beta = 0.289, P< 0.001), NEUT (R2 = 0.124, Beta = 0.282, P< 0.001), NLR (R2 = 0.105, Beta = 0.184, P=0.026) and FIB (R2 = 0.086, Beta = 0.246, P=0.003) were positively correlated with BMI, while the level of APTT (R2 = 0.057, Beta = − 0.171, P=0.044) was significantly negatively correlated with BMI.Conclusion: OSA was an independent risk factor contributing to obesity. WBC, NEUT, NLR, FIB and APTT are correlated with obesity in children with OSA (aged from 2 to 14 years). These indicators could be used to estimate the status of inflammation and hypercoagulation in the obese children with OSA.Keywords: obstructive sleep apnea, obesity, propensity score matching, hematological parameter, inflammation, hypercoagulation

The critical current of many practical superconductors is sensitive to strain, and this sensitivity is exacerbated during a quench that induces a peak local strain which can be fatal to superconducting magnets. Here, a new method is introduced to quantify the influence of the conductor stress and strain state during normal operation on the margin to degradation during a quench, as measured by the maximum allowable hot spot temperature T allowable, for composite wires within superconducting magnets. The first conductor examined is Ag-sheathed Bi2Sr2CaCu2Ox round wire carrying high engineering critical current density, J E, of 550 A mm-2 at 4.2 K and 15 T. The critical axial tensile stress of this conductor is determined to be 150 MPa and, in the absence of Lorentz forces, T allowable is greater than 450 K. With increasing axial tensile stress, σ a, however, T allowable decreases nonlinearly, dropping to 280 K for σ a = 120 MPa and to 160 K for σ a = 145 MPa. T allowable(σ a) is shown to be nonlinear and independent of magnetic field from 15 to 30 T. T allowable(σ a) dictates the balance between magnetic field generation, which increases with the magnet operating current and stress, and the safety margin, which decreases with decreasing T allowable, and therefore has important engineering value. It is also shown that T allowable(σ a) can be predicted accurately by a general strain model, showing that strain control is the key to preventing degradation of superconductors during a quench.