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Pei-Pei Huang,1,&ast; Samantha Yun-Kai Poon,2,&ast; Shao-Hsuan Chang,3 Chien-Wen Kuo,4 Ming-Wen Chien,1 Chien-Chih Chen,5 Shao-Chin Chiang2,6 1Division of Outpatient Pharmacy, Department of Pharmacy, Cheng Hsin General Hospital, Taipei, Taiwan; 2Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University (Yang Ming Campus), Taipei, Taiwan; 3Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA; 4Department of Pharmacy, Cheng Hsin General Hospital, Taipei, Taiwan; 5Division of Colorectal Surgery, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan; 6Department of Pharmacy, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan&ast;These authors contributed equally to this workCorrespondence: Shao-Chin Chiang, Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University (Yang Ming Campus), Taipei, Taiwan, Tel +886-983641216, Email scchiang316@nycu.edu.tw; scchiang@kfsyscc.orgPurpose: Medication reconciliation (MedRec) is a process to ensure complete and accurate communication of patient medication information throughout care transitions to prevent medication errors. Hospitals in Taiwan have stride to implement a universal protocol for MedRec. To establish a feasible protocol indigenously, the World Health Organization (WHO) protocol was incorporated with the Taiwan National Health Insurance (NHI) PharmaCloud patient medication profile. The efficiency and error detection capability of this modified protocol was evaluated in two hospitals.Methods: A prospective, non-randomized, unblinded, multicenter cohort study was conducted. Subjects were recruited among patients admitted for colorectal or orthopedic surgery with at least 4 or more chronic drugs. To obtain the best possible medication history (BPMH), the control group was conducted according to the WHO protocol, and the experimental group used the modified WHO protocol with the medication data from the PharmaCloud system. The time spent on the two protocols was recorded. Admission and discharge orders were reconciled against the BPMH to identify any discrepancies. Discrepancies were evaluated by appropriateness, prescribing intentions, and types of inappropriateness. The levels of potential harm were classified for inappropriate discrepancies.Results: The mean time to obtain BPMH in the control group was 34.3± 10.8 minutes and in the experimental group 27.5± 11.5 minutes (P = 0.01). The experimental group had more subjects with discrepancies (87.9%) than the control (58.3%) (p < 0.001). The discrepancies in both admission and discharge orders for the experimental group (84.5 and 67.2%) were higher than those of the control (47.9 and 37.5%). Many inappropriate discrepancies were classified as the potential harm of level 2 (77.8%).Conclusion: Through the establishment of BPMH with the medication data from the Taiwan NHI PharmaCloud, MedRec could be achieved with greater efficiency and error detection capability in both the admission and discharge order validation processes.Keywords: medication reconciliation, prescription discrepancy, PharmaCloud, best possible medication history, BPMH

Wen-Tung Hsu,1 Deng-Ho Yang,1– 4 Chun-Cheng Liao,3,5 Jia -Wen Chen,6 Wen-Hsiu Hsu,3,7 Chia-Wen Kuo,3,8 Hung-Chang Hsu,9 Sheng-Huang Chang,10 Li-Mien Chen2,3 1Division of Laboratory, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China; 2Department of Internal Medicine, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China; 3School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China; 4Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan, Republic of China; 5Department of Family Medicine, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China; 6Medicine Laboratory, Ministry of Health and Welfare Feng Yuan Hospital, Taichung, Taiwan, Republic of China; 7Division of Gastroenterology, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China; 8Division of Nephrology, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China; 9Division of Laboratory, Ching Chyuan Hospital, Taichung, Taiwan, Republic of China; 10Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nantou, Taiwan, Republic of ChinaCorrespondence: Li-Mien ChenDepartment of Internal Medicine, Taichung Armed Force General Hospital, No. 348, Sec. 2, Chung-Shan Road, Taiping, Taichung, Taiwan, Republic of ChinaEmail c332860@ms65.hinet.netPurpose: To evaluate the blood glucose and renal function, determine the prevalence of hyperglycemia/diabetes mellitus (DM) and renal disease (nephropathy), and investigate the association between hyperglycemia/DM and renal disease in patients with viral hepatitis (VH).Patients and Methods: A total of 491 subjects were included in the study. Patients with VH were further divided into the hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and HBV-HCV co-infection subgroups. Fasting blood glucose, glycated hemoglobin (HbA1c), glycated albumin (GA), glutamic oxaloacetic transaminase (GOT), creatinine (Cr), and cystatin C (Cys C) levels were measured. Urine microalbumin levels were also assessed. Formulas for estimated average glucose calculated using glycated albumin(eAG(GA)), estimated average glucose calculated using HbA1c (eAG(HbA1c)), and estimated glomerular filtration rate calculated using cystatin C (eGFRcys) were used to evaluate the average glucose and renal function.Results: The prevalence of hyperglycemia/DM and renal disease was significantly higher in the VH group, especially in the HCV subgroup. The prevalence of renal disease was significantly higher in patients with VH with eAG(GA) ≥ 200 mg/dL.Conclusion: Our study used multiple parameters to evaluate blood glucose and renal function in patients with VH and found that hyperglycemia/DM and renal disease are closely associated with VH, especially in subjects with HCV infection. Patients with VH, especially those with HCV infection and hyperglycemia/DM, were particularly vulnerable to renal disease.Keywords: viral hepatitis, hyperglycemia, diabetes mellitus, renal disease, nephropathy

Shu-Han Chang,1 Ting-Chang Chang,1,2 Min-Yu Chen,1 Wei-Chun Chen,1,3 Hung-Hsueh Chou1,2 1Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan, Taiwan; 2Chang Gung University, College of Medicine, Taoyuan, Taiwan; 3Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Keelung Branch, Keelung, TaiwanCorrespondence: Hung-Hsueh ChouDepartment of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, #5 Fushing Street, Kwei-Shan, Taoyuan, 333, TaiwanTel +886-33281200Email ma2012@cgmh.org.twObjective: We aimed to investigate the effects of dinalbuphine sebacate (DNS), fentanyl-based patient-controlled analgesia (PCA), and conventional analgesia (CA) for pain management after laparotomy for gynecologic cancers.Methods: A total of 137 eligible patients who underwent laparotomy through a midline incision wound for gynecologic cancer between July 2019 and June 2020 were retrospectively evaluated. The patients were divided into three groups as follows: the intramuscular DNS, intravenous PCA, and CA groups. Postoperative pain (POP) intensity as measured with a numerical rating scale (NRS), total consumption of analgesics, and incidence of treatment-emergent adverse events were compared between the three groups.Results: The DNS group showed significant reduction in NRS pain intensity than the PCA and CA groups on day 1 (4.8 vs 6.2, p < 0.01 and 6.2, p < 0.05, respectively), day 2 (3.0 vs 4.7, p < 0.01 and 4.8, p < 0.001, respectively), day 3 (2.0 vs 3.9, p < 0.001 and 3.5, p < 0.001, respectively), day 4 (1.1 vs 3.1, p < 0.001 and 2.9, p < 0.001, respectively), and day 5 (0.7 vs 2.3, p < 0.001 and 2.4, p < 0.001, respectively). The total consumption of morphine equivalents per day was similar between the DNS and PCA groups (142.8 ± 7.3 mg vs 137.7 ± 70.0 mg, p = 0.8032) and lowest in the CA group (11.7 ± 30.7 mg, p < 0.0001). The overall safety profile was comparable between the DNS, PCA, and CA groups. The patients in the DNS group complained less of dizziness postoperatively than those in the PCA group (27% vs 47%) and had less nausea than those in the CA group (13% vs 33%).Conclusion: A single DNS injection was more effective for relieving POP than PCA and CA in the patients who had a longitudinal incision for gynecologic cancer surgery. DNS was well tolerated and had less adverse effects than PCA and CA.Keywords: dinalbuphine sebacate, postoperative pain, nalbuphine, PCA, laparotomy

Chen-Na Huang,* Xiao-Bing Tian,* Shu-Min Jiang, Sheng-Hui Chang, Nan Wang, Ming-Qi Liu, Qiu-Xia Zhang, Ting Li, Lin-Jie Zhang, Li Yang Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Yang Tel +86-22-60814536Fax +86-22-60817471Email yangli2001@tmu.edu.cnObjective: Infectious encephalitis (IE) and autoimmune encephalitis (AE) are symptomatically similar in clinic, however essentially different in pathogenesis. Therefore, the objective of this study was to identify specific features to distinguish the two types of encephalitis for early effective diagnosis and treatments through a comparative analysis.Methods: Fifty-nine IE patients and 36 AE patients were enrolled. The patients with IE were divided into viral encephalitis (VE) and bacterial encephalitis (BE) according to the pathogens in cerebrospinal fluid (CSF). Patients with AE were categorized by with or without neural autoantibodies (NAAb). We further divided patients with NAAb into those with neural cell-surface antibodies (NSAbs) or intracellular antibodies (Abs). Clinical features, laboratory data, and imaging findings were compared between AE, IE, and subgroups.Results: Memory deficits, involuntary movement, and seizures were relatively more commonly presenting symptoms in AE patients (p < 0.05). The positive rate of Pandy test was higher in IE patients (p = 0.007). Decreased leukocyte, erythrocyte, and platelet counts in blood were found in IE patients (p < 0.05). Lower serum calcium level was found in VE compared to BE (p = 0.027). Meanwhile, higher serum calcium level was found in patients with NSAbs compared with intracellular Abs (p = 0.034). However, higher levels of LDH in CSF were found in patients with intracellular Abs (p = 0.009). In magnetic resonance imaging, hippocampus lesions were more commonly present in patients with AE (p = 0.042). Compared with AE patients, more IE patients displayed the background electroencephalogram rhythm of slow-frequency delta (p = 0.013).Conclusion: Involuntary movement and memory deficits were more specifically present in AE patients. CSF Pandy, blood routine test and hippocampus lesions detections were potential markers for distinguishing AE and IE. Further, CSF LDH, and serum calcium levels were potentially useful to distinguish subgroups of encephalitis.Keywords: infectious encephalitis, autoimmune encephalitis, cell-surface antibodies, intracellular antibodies, imaging findings

Chen-Hung Lee,1 Ming-Jer Hsieh,1 Shang-Hung Chang,1 Kuo-Chun Hung,1 Chao-Jan Wang,2 Ming-Yi Hsu,2 Jyuhn-Huarng Juang,3 I-Chang Hsieh,1 Ming-Shien Wen,1 Shih-Jung Liu4,5 1Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Chang Gung University College of Medicine, Linkou, Taiwan; 2Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, Tao-Yuan, Taiwan; 4Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 5Department of Orthopedic Surgery, Chang Gung Memorial Hospital-Linkou, Tao-Yuan 33305, TaiwanCorrespondence: Shih-Jung LiuBiomaterials Lab, Department of Mechanical Engineering, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, TaiwanTel +886 3 211 8166Fax +886 3 211 8558Email profsjliu5347@gmail.comBackground: The high lifetime risk of vascular disease is one of the important issues that plague patients with diabetes mellitus. Systemic oral vildagliptin administration favors endothelial recovery and inhibits smooth muscle cell (SMC) proliferation. However, the localized release of vildagliptin in the diabetic vessel damage has seldom been investigated.Research design and methods: In this work, nanofiber-eluting stents that loaded with vildagliptin, a dipeptidyl peptidase-4 enzyme (DPP-4) inhibitor, was fabricated to treat diabetic vascular disease. To prepare nanofibers, the poly (D,L)-lactide-co-glycolide (PLGA) and vildagliptin were mixed using hexafluoroisopropanol and electrospinning process. In vitro and in vivo release rates of the vildagliptin were characterized using high-performance liquid chromatography.Results: Effective vildagliptin concentrations were delivered for more than 28 days from the nanofibrous membranes coating on the surface of the stents in vitro and in vivo. The vildagliptin-eluting PLGA membranes greatly accelerated the recovery of diabetic endothelia and reduced SMC hyperplasia. The type I collagen content of the diabetic vascular intimal area that was treated by vildagliptin-eluting stents was lower than that of the non-vildagliptin-eluting group.Conclusion: The experimental results revealed that stenting with vildagliptin-eluting PLGA membranes could potentially promote healing for diabetic arterial diseases.Keywords: re-endothelialization, neointimal hyperplasia, vildagliptin, biodegradable drug-eluting nanofibers

Chun-Yu Chen,1,2 Ying-Hsuan Lee,1 Shih-Hsin Chang,1,3–5 Yung-Fong Tsai,1,2 Jia-You Fang,1–3,5 Tsong-Long Hwang1–3,5,61Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; 2Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; 3Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan; 4Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; 5Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; 6Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City 243, TaiwanAim: This paper reports on the incorporation of oleic acid (OA) within nanostructured lipid carriers (OA-NLC) to improve the anti-inflammatory effects in the presence of albumin.Materials and methods: NLCs produced via hot high-shear homogenization/ultrasonication were characterized in terms of particle size, zeta potential, and toxicity. We examined the effects of OA-NLC on neutrophil activities. Dermatologic therapeutic potential was also elucidated by using a murine model of leukotriene B4-induced skin inflammation.Results: In the presence of albumin, OA-NLC but not free OA inhibited superoxide generation and elastase release. Topical administration of OA-NLC alleviated neutrophil infiltration and severity of skin inflammation.Conclusion: OA incorporated within NLC can overcome the interference of albumin, which would undermine the anti-inflammatory effects of OA. OA-NLC has potential therapeutic effects in topical ointments.Keywords: oleic acid, nanostructured lipid carrier, neutrophil, reactive oxygen species, superoxide, elastase

Mei-Hing Ng,1,2 Vincent Chin-Hung Chen,3,4 Hua Ting,1,5 Tsang-Yaw Lin,2 Sheng-Huang Chang,2 Michael Gossop61Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 2Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nan-Tou County, Taiwan; 3Department of Psychiatry, Chang Gung Medical Foundation, Chiayi Chang Gung Memorial Hospital, Chiayi County, Taiwan; 4Department of Psychiatry, School of Medicine, Chang Gung University, Taoyuan City, Taiwan; 5Department of Physical Medicine and Rehabilitation, Chung-Shan Medical, University Hospital, Chung-Shan Medical University, Taichung, Taiwan; 6National Addiction Center, Institute of Psychiatry, King’s College London, London, UKPurpose: Few empirical studies have investigated hematological parameters among people with a heroin use disorder. This study explores the prevalence of macrocytosis and associated factors among patients with heroin use disorder who were entering methadone maintenance treatment (MMT) in Taiwan.Patients and methods: In this cross-sectional study, hematological parameters were measured and the prevalence of macrocytosis was assessed in a sample of 958 patients with a heroin use disorder entering the MMT program at Tsaotun Psychiatric Center in Taiwan. The demographic characteristics, heroin-related issues, other substance use history, and other clinical variables were analyzed. Univariate analysis was used to assess the association of all variables. Multivariable logistic regression was used to identify the relationship between the significant factors and macrocytosis.Results: The study found that nearly one-fifth (19.5%) of the participants had macrocytosis. Older age, longer duration of heroin use, and more days of alcohol use within the previous month were associated with macrocytosis.Conclusion: We found that concurrent use of alcohol was an important factor related to macrocytosis among people with a heroin use disorder. The prevalence of macrocytosis indicated that alcohol use is common among this population. It is suggested that policies and practices regarding alcohol use should be addressed within methadone maintenance programs.Keywords: addiction, opioid dependence, substitution treatment, megalocytes

Cheng-Hung Lee,1 Ming-Jer Hsieh,1 Kuo-Sheng Liu,2,3 Che-Wei Cheng,3 Shang-Hung Chang,1 Shih-Jung Liu,3,4 Chao-Jan Wang,5 Ming-Yi Hsu,5 Kuo-Chun Hung,1 Yung-Hsin Yeh,1 Wei-Jan Chen,1 I-Chang Hsieh,1 Jyuhn-Huarng Juang,6 Ming-Shien Wen1 1Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Tao-Yuan, Taiwan; 2Department of Cardiovascular Surgery, Chang Gung Memorial Hospital-Linkou, Tao-Yuan, Taiwan; 3Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 4Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan; 5Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan; 6Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, Tao-Yuan, Taiwan Objective: The current treatment of atherosclerotic coronary heart disease with limus-eluting stents can lead to incomplete endothelialization and substantial impairment of arterial healing relative to treatment with bare-metal stents. The sustained and local delivery of ticagrelor, a reversibly binding P2Y12 receptor inhibitor, using hybrid biodegradable nanofibers/stents, was developed to reduce neointimal formation and endothelial dysfunction.Methods: In this investigation, a solution of ticagrelor, poly(D,L)-lactide-co-glycolide, and hexafluoro isopropanol was electrospun to fabricate ticagrelor-eluting nanofibrous drug-eluting stents. The in vitro and in vivo ticagrelor concentrations were measured using a high-performance liquid chromatography assay. The effectiveness of ticagrelor-eluting stents was examined relative to that of sirolimus-eluting stents. Results: Adequate ticagrelor levels were detected for four weeks in vitro. Less HES5-positive labeling was found near the ticagrelor-eluting stented vessels (0.33±0.12) than close to the sirolimus-eluting stented vessels (0.57±0.15) (p

Shang-Hung Chang,1 Cheng-Hung Lee,1 Yung-Hsin Yeh,1 Shih-Jung Liu,2 Chao-Jan Wang,3 Ming-Yi Hsu,3 Wei-Jan Chen1 1Cardiovascular Department, Chang Gung Memorial Hospital, Chang-Gung University College of Medicine, Tao-Yuan, Taiwan; 2Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 3Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan Background: The drug-eluting stent is a standard approach for the treatment of coronary artery disease. Propylthiouracil (PTU), an antithyroid drug, has been proven to suppress neointimal formation after balloon injury. Materials and methods: This study used a biodegradable polymer coating with PTU to test its effects on platelet function, re-endothelialization, and neointimal formation after vascular injury. Electrospinning was used to fabricate hybrid stents and generate PTU-loaded nanofibers.Results: PTU-eluting stents maintained a stable release of PTU for 3 weeks. The PTU-coated stent markedly decreased the neointimal formation induced by vascular injury in the descending aorta of rabbits. Moreover, the PTU coating reduced platelet adhesion on the surface of the biodegradable membrane, which was reflected by the decreased expression of adhesion molecule in PTU-treated endothelial cells. The PTU coating enhanced re-endothelialization in injured aortas. In vitro, PTU exerted less suppressive effect on the proliferation and migration of endothelial cells than on those of vascular smooth muscle cells. Furthermore, treatment of endothelial cells with PTU induced phosphorylation (Ser1177) of endothelial nitric oxide synthase as well as its association with heat shock protein 90, supporting the protective role of PTU in endothelial function. The level of thyroid-stimulating hormone remained unchanged during the experimental period. Conclusion: This study indicates that PTU can be released locally and steadily in injured aortas, with some local effects but without systemic effects. Furthermore, PTU-coated stents may have beneficial effects on neointimal formation, endothelial cell, and platelet functions. Keywords: drug-eluting stent, propylthiouracil, neointimal formation, endothelial cell, platelet

Cheng-Hung Lee,1,2 Chia-Ying Yu,2 Shang-Hung Chang,1 Kuo-Chun Hung,1 Shih-Jung Liu,2 Chao-Jan Wang,3 Ming-Yi Hsu,3 I-Chang Hsieh,1 Wei-Jan Chen,1 Yu-Shien Ko,1 Ming-Shien Wen1 1Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Tao-Yuan, Taiwan; 2Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 3Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan Introduction: This work reports on the development of a biodegradable dual-drug-eluting stent with sequential-like and sustainable drug-release of anti-platelet acetylsalicylic acid and anti-smooth muscle cell (SMC) proliferative paclitaxel.Methods: To fabricate the biodegradable stents, poly-L-lactide strips are first cut from a solvent-casted film. They are rolled onto the surface of a metal pin to form spiral stents. The stents are then consecutively covered by acetylsalicylic acid and paclitaxel-loaded polylactide-polyglycolide nanofibers via electrospinning.Results: Biodegradable stents exhibit mechanical properties that are superior to those of metallic stents. Biodegradable stents sequentially release high concentrations of acetylsalicylic acid and paclitaxel for more than 30 and 60 days, respectively. In vitro, the eluted drugs promote endothelial cell numbers on days 3 and 7, and reduce the proliferation of SMCs in weeks 2, 4, and 8. The stents markedly inhibit the adhesion of platelets on days 3, 7, and 14 relative to a non-drug-eluting stent. In vivo, the implanted stent is intact, and no stent thrombosis is observed in the stent-implanted vessels without the administration of daily oral acetylsalicylic acid. Promotion of endothelial recovery and inhibition of neointimal hyperplasia are also observed on the stented vessels.Conclusion: The work demonstrates the efficiency and safety of the biodegradable dual-drug-eluting stents with sequential and sustainable drug release to diseased arteries. Keywords: sequential-like and sustainable release, biodegradable drug-eluting stents, poly-L-lactide, polylactide-polyglycolide, mechanical properties

Cheng-Hung Lee,1,2 Yu-Huang Lin,3 Shang-Hung Chang,1 Chun-Der Tai,3 Shih-Jung Liu,2 Yen Chu,4 Chao-Jan Wang,5 Ming-Yi Hsu,5 Hung Chang,6 Gwo-Jyh Chang,7 Kuo-Chun Hung,1 Ming-Jer Hsieh,1 Fen-Chiung Lin,1 I-Chang Hsieh,1 Ming-Shien Wen,1 Yenlin Huang81Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, 2Department of Mechanical Engineering, 3Graduate Institute of Medical Mechatronics, Chang Gung University, 4Laboratory of Cardiovascular Physiology, Division of Thoracic and Cardiovascular Surgery, 5Department of Medical Imaging and Intervention, 6Hematology-Oncology Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, 7Graduate Institute of Clinical Medicinal Sciences, Chang Gung University College of Medicine, Linkou, 8Department of Anatomical Pathology, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, TaiwanAbstract: Incomplete endothelialization, blood cell adhesion to vascular stents, and inflammation of arteries can result in acute stent thromboses. The systemic administration of acetylsalicylic acid decreases endothelial dysfunction, potentially reducing thrombus, enhancing vasodilatation, and inhibiting the progression of atherosclerosis; but, this is weakened by upper gastrointestinal bleeding. This study proposes a hybrid stent with biodegradable nanofibers, for the local, sustained delivery of acetylsalicylic acid to injured artery walls. Biodegradable nanofibers are prepared by first dissolving poly(D,L)-lactide-co-glycolide and acetylsalicylic acid in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution is then electrospun into nanofibrous tubes, which are then mounted onto commercially available bare-metal stents. In vitro release rates of pharmaceuticals from nanofibers are characterized using an elution method, and a high-performance liquid chromatography assay. The experimental results suggest that biodegradable nanofibers release high concentrations of acetylsalicylic acid for three weeks. The in vivo efficacy of local delivery of acetylsalicylic acid in reducing platelet and monocyte adhesion, and the minimum tissue inflammatory reaction caused by the hybrid stents in treating denuded rabbit arteries, are documented. The proposed hybrid stent, with biodegradable acetylsalicylic acid-loaded nanofibers, substantially contributed to local, sustained delivery of drugs to promote re-endothelialization and reduce thrombogenicity in the injured artery. The stents may have potential applications in the local delivery of cardiovascular drugs. Furthermore, the use of hybrid stents with acetylsalicylic acid-loaded nanofibers that have high drug loadings may provide insight into the treatment of patients with high risk of acute stent thromboses.Keywords: biodegradable drug-eluting nanofibers, acetylsalicylic acid, release characteristics, cell adhesion to vascular stents

We report a search for narrow resonances, produced in p p̄ collisions at √ s=1.96 TeV, that decay into muon pairs with invariant mass between 6.3 and 9.0 GeV/c 2. The data, collected with the CDF II detector at the Fermilab Tevatron collider, correspond to an integrated luminosity of 630 pb -1. We use the dimuon invariant mass distribution to set 90% upper credible limits of about 1% to the ratio of the production cross section times muonic branching fraction of possible narrow resonances to that of the Υ(1S) meson. © 2009 Springer-Verlag.

We report a search for narrow resonances, produced in p p̄ collisions at √ s=1.96 TeV, that decay into muon pairs with invariant mass between 6.3 and 9.0 GeV/c 2. The data, collected with the CDF II detector at the Fermilab Tevatron collider, correspond to an integrated luminosity of 630 pb -1. We use the dimuon invariant mass distribution to set 90% upper credible limits of about 1% to the ratio of the production cross section times muonic branching fraction of possible narrow resonances to that of the Υ(1S) meson. © 2009 Springer-Verlag.

PURPOSE: When performing thoracic aortic endovascular repair (TEVAR) on lesions of the aortic arch, physician-modified fenestration or in situ fenestration is often used to maintain patent branches. We designed a new adjustable prefenestration aortic stent graft that can both isolate pathologies in the aortic arch and obtain patent branches simultaneously. In this study, we use this new type of stent to perform fenestrated TEVAR in a canine’s aorta. This study aims to evaluate the safety and feasibility of the new device, which may provide preliminary data for potential human application. METHODS: Eight Labrador Retriever canines underwent fenestrated TEVAR using the new stent device. Digital subtract angiography (DSA) was performed before and after fenestrated TEVAR to evaluate the safety and feasibility of the procedure. For the device deployment, at the “large curvature” side in the endograft, there is a rectangular prefenestration area (2 × 5 cm) without the polytetrafluoroethylene membrane, and at both longer side edges of the fenestration, there are two slide rails. A moveable membrane that covers the same area as the prefenestration area is initially set at the prefenestration position. A stay line is connected from the distal site of the moveable membrane that controls it to the distal position along the slide rail, which releases the fenestration. After the positioning of the prefenestration is determined, the outer sheath of the delivery system is released, and the stay line at the end of the delivery system is pulled outside the body. The animals were divided into a 1-month group (n = 4) and a 3-month group (n = 4) after the fenestrated TEVAR. Computed tomography (CT) was performed before euthanasia, and video of the DSA during the procedures and CT angiography (CTA) images were then studied. RESULTS: The procedure success rate was 100%, but the total survival rate was only 87.5%. There were no aortic-related deaths during follow-up, and during the operation, there were no stent-graft-related accidents. In addition, no stent-graft migrations were observed in the CTA, and all branch arteries were kept patent by the adjustable fenestration. Finally, histological examination and electron microscope results showed no obvious vascular injury or inflammation. CONCLUSION: Based on the results of this study, we judge the safety and feasibility of the use of the newly designed adjustable prefenestration aortic stent graft in a fenestrated-TEVAR canine model to be acceptable. Our preliminary data may serve as an initial reference for evaluating the potential application of the new stent in humans.

Abstract The levels of fasting-state serum bile acids (BAs) in individuals with polycystic ovary syndrome (PCOS) differ from those of control subjects. However, there is a lack of research on the BAs profile in lean women with PCOS and whether these changes are linked to the host metabolism. Therefore, our objective was to investigate the synthesis and metabolism of serum BAs in lean women with PCOS and assess the correlation between BAs and clinical characteristics. This study employed a cross-sectional design of lean women with PCOS (n = 240) in comparison to a control group (n = 80) consisting of healthy lean women. The findings revealed significant increases in the levels of non-12-OH BAs and chenodeoxycholic acid (CDCA)% (both P

Abstract As the Internet of Vehicles advances, the demand for timely data acquisition by vehicle users continues to escalate, albeit confronted with the challenge of excessive data retrieval latency. The emergence of edge computing provides technical support for the development of vehicular networks by caching data in advance to reduce data acquisition latency. Therefore, how to effectively cache and query data becomes a key issue in addressing the timeliness of data acquisition in vehicular networks. In this paper, we investigate an efficient query optimization model to minimize data acquisition latency. Firstly, based on the distribution of data query frequencies across different servers, we propose an edge collaborative caching strategy using a tabu search algorithm. This strategy prioritizes high-traffic data by finding two optimal storage nodes for each high-traffic data in descending order of data popularity, ensuring a backup within the collaborative domain for each data segment. This not only reduces data transmission latency between nodes during task execution but also prevents single-point failures. Secondly, we deploy cuckoo filters on edge nodes to enable rapid localization of cached data nodes when users query data, thus reducing data processing latency. Finally, simulation results demonstrate that the proposed query optimization model outperforms other schemes in terms of average data query latency.

Abstract Three-dimensional Spatial Transcriptomics has revolutionized our understanding of tissue regionalization, organogenesis, and development. However, existing approaches overlook either spatial information or experiment-induced distortions, leading to significant discrepancies between reconstruction results and in vivo cell locations, causing unreliable downstream analysis. To address these challenges, we propose ST-GEARS (Spatial Transcriptomics GEospatial profile recovery system through AnchoRS). By employing innovative Distributive Constraints into the Optimization scheme, ST-GEARS retrieves anchors with exceeding precision that connect closest spots across sections in vivo. Guided by the anchors, it first rigidly aligns sections, next solves and denoises Elastic Fields to counteract distortions. Through mathematically proved Bi-sectional Fields Application, it eventually recovers the original spatial profile. Studying ST-GEARS across number of sections, sectional distances and sequencing platforms, we observed its outstanding performance on tissue, cell, and gene levels. ST-GEARS provides precise and well-explainable ‘gears’ between in vivo situations and in vitro analysis, powerfully fueling potential of biological discoveries.

Multi-resonant metasurfaces are of great significance in the applications of multi-band nanophotonics. Here, we propose a novel metasurface design scheme for simultaneously supporting quasi-bound states in continuum (QBIC) and other resonant modes, in which QBIC resonance is generated by mirror or rotational symmetry breaking in oligomers while other resonant modes can be simultaneously excited by rationally designing the shapes of meta-atoms within oligomers. As an example, the simultaneous excitation of QBIC and anapole modes are demonstrated in a dimer metasurface composed of asymmetric dumbbell-shaped apertures. Based on the far-field multipole decomposition and near-field electromagnetic field distributions, the origin mechanisms of QBIC and anapole mode are elucidated. The symmetry breaking of dumbbell-shaped dimer results in QBIC. Within a certain asymmetric variation range, the contributions of toroidal dipole moment and electric dipole moment with approximately equal magnitudes remain dominant, which allows the anapole mode to always present. The effectiveness of the proposed design scheme is further confirmed by the experimental results identical with the evolutions of numerical simulation. In terahertz biosensing experiments, the anapole mode exhibits a higher sensitivity of 271.3 GHz (nmol/μl)−1, whereas the QBIC can achieve a lower detection limit of 0.015 nmol/μl and expands the detection range by almost an order of magnitude. Our findings are beneficial to designing multi-resonant metasurfaces with different resonance modes and promote the corresponding applications in the fields of biosensing, lasers, filtering, and nonlinearity.

Microglia mediated neuronal inflammation has been reported to be responsible for neurodegenerative disease. Isoquercitrin (IQC), widely found in fruits, vegetables and foods, has high bioavailability and offers many benefits of humans. Although IQC has been shown to possess pleiotropic biological activities, but its anti-inflammatory mechanism in microglia at molecular level remains largely unclear. Therefore, this study aimed to investigate IQC’s inhibition on inflammation within BV2 microglia cells induced by lipopolysaccharide (LPS) and the underlying mechanism.

Abstract Background A stent with characteristics of a hybrid design may have advantages in improving the patency of symptomatic iliofemoral vein obstruction. This study assessed the safety and effectiveness of the V-Mixtent Venous Stent in treating symptomatic iliofemoral outflow obstruction. Methods Eligible patients had a Clinical-Etiologic-Anatomic-Physiologic (CEAP) C classification of ≥ 3 or a Venous Clinical Severity Score (VCSS) pain score of ≥ 2. The primary safety endpoint was the rate of major adverse events within 30 days. The primary effectiveness endpoint was the 12-month primary patency rate. Secondary endpoints included changes in VCSS from baseline to 6 and 12 months, alterations in CEAP C classification, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) scores at 12 months, and stent durability measures. Results Between December 2020 and November 2021, 171 patients were enrolled across 15 institutions. A total of 185 endovenous stents were placed, with 91.81% of subjects receiving one stent and 8.19% receiving 2 stents. Within 30 days, only two major adverse events occurred (1.17%; 95% confidence interval [CI], 0.14–4.16%), below the literature-defined performance goal of 11% (P

In this study, three representative pears ('Yali' Pear, 'Huangguan' Pear, and 'Xuehua' Pear) peel/flesh polyphenol extracts were characterized by their antioxidant activity, polyphenol composition, and in vitro cholesterol/cholates binding capacity. 'Yali' Pear polyphenol extracts were selected to further investigate the mechanism of in vitro cholesterol/cholates lowering capacity. Lagergren adsorption kinetic and Freundlich isotherm models confirmed the occurrence of this combination. Turbidity, average particle size, transmission electron microscopy, and zeta potential combined confirmed the existence of some interaction between polyphenols and cholesterol/cholates. Cholesterol/cholates quenched the exogenous fluorescence of polyphenols by static mechanism. The thermodynamic interaction results revealed that the interaction between polyphenols and cholesterol is a spontaneous process, primarily driven by hydrogen bonding and hydrophobic interactions. Overall, this study aimed to investigate the confirmation of the binding removal properties of pear polyphenols on cholesterol/cholates to mitigate the adverse health effects of a high-fat diet.

Abstract The emerging pseudohalide metal-free perovskite (pseudohalide–MFPs) X-ray detector caters to the demands of timely mobile diagnosis owing to its lightweight, flexibility, and cost-effectiveness. However, the performance of these devices is severely limited by poor X-ray absorption, ultra-wide band gap, relative instability, and their unknown biotoxicity. Herein, we construct heavy atom covalent bonds (C–Br/Cl) on the A-site organic cation to reinforce component coordination to modulate X-ray absorption and band gap in pseudohalide–MFPs and further enhance its stability. Molecular dynamics simulations demonstrate that the introduction of halogen atoms can strengthen hydrogen bonding interactions, thereby improving the coordination between different components. The resultant (MDABCOBr)–NH4(BF4)3 (MDABCO = N-methyl-N’-diazabicyclo[2.2.2]octonium) single crystal significantly increases X-ray absorption cross-section and crystalline density (from 1.728 to 1.950 g cm−3), and synergistically realizes the band nature modulation (from 7.4 to 5.5 eV) and enhanced ionic migration inhibition (628 meV) with optimized stability. As such, our X-ray detectors realized a sensitivity of 2377 μC Gyair −1 cm−2, an ultralow detection limit of 50.1 nGyair s−1, and impressive operation stability. Moreover, cytotoxicity assay confirmed the compatibility of pseudohalide metal-free perovskite. Finally, within this framework, we successfully fabricate the (MDABCOBr)–NH4(BF4)3-based flexible device to create an ideal in vitro wearable X-ray detection.

Abstract Purpose Bietti crystalline dystrophy (BCD) is an inherited retinal degeneration disease caused by mutations in the CYP4V2 gene. Currently, there is no clinical therapy approach available for BCD patients. Previous research has suggested that polyunsaturated fatty acids (PUFAs) may play a significant role in the development of BCD, implicating the involvement of ferroptosis in disease pathogenesis. In this work, we aimed to investigate the interplay between ferroptosis and BCD and to detect potential therapeutic strategies for the disease. Methods Genetic-edited RPE cell line was first established in this study by CRISPR-Cas9 technology. Cyp4v3 (the homologous gene of human CYP4V2) knock out (KO) mice have also been used. Lipid profiling and transcriptome analysis of retinal pigment epithelium (RPE) cells from Cyp4v3 KO mice have been conducted. Ferroptosis phenotypes have been first investigated in BCD models in vitro and in vivo, including lipid peroxidation, mitochondrial changes, elevated levels of reactive oxygen species (ROS), and altered gene expression. Additionally, an iron chelator, deferiprone (DFP), has been tested in vitro and in vivo to determine its efficacy in suppressing ferroptosis and restoring the BCD phenotype. Results Cyp4v3 KO mice exhibited progressive retinal degeneration and lipid accumulation, similar to the BCD phenotype, which was exacerbated by a high-fat diet (HFD). Increased levels of PUFAs, such as EPA (C22:5) and AA (C20:4), were observed in the RPE of Cyp4v3 KO mice. Transcriptome analysis of RPE in Cyp4v3 KO mice revealed changes in genes involved in iron homeostasis, particularly an upregulation of NCOA4, which was confirmed by immunofluorescence. Ferroptosis-related characteristics, including mitochondrial defects, lipid peroxidation, ROS accumulation, and upregulation of related genes, were detected in the RPE both in vitro and in vivo. Abnormal accumulation of ferrous iron was also detected. DFP, an iron chelator administration suppressed ferroptosis phenotype in CYP4V2 mutated RPE. Oral administration of DFP also restored the retinal function and morphology in Cyp4v3 KO mice. Conclusion This study represented the first evidence of the substantial role of ferroptosis in the development of BCD. PUFAs resulting from CYP4V2 mutation may serve as substrates for ferroptosis, potentially working in conjunction with NCOA4-regulated iron accumulation, ultimately leading to RPE degeneration. DFP administration, which chelates iron, has demonstrated its ability to reverse BCD phenotype both in vitro and in vivo, suggesting a promising therapeutic approach in the future.

Objective To investigate the factors influencing interbody cage subsidence after stand-alone oblique lumbar interbody fusion (OLIF). Methods A total of 65 patients (72 lumbar vertebrae) who underwent OLIF in our hospital from Ja-nuary 2019 to January 2023 were selected and divided into subsidence group (n=19) and non-subsidence group (n=53) according to the loss of disc height. The clinical data of the two groups were collected and compared, including gender, age, body mass index, number of lumbar vertebrae requiring surgery, responsible vertebral endplate sclerosis, cage height and length, preoperative CT values of the responsible vertebral body and its upper and lower endplates, preoperative multifidus muscle cross-sectional area at responsible vertebral body, degree of multifidus muscle atrophy, and degree of preoperative articular process degeneration. Logistic regression analysis was used to explore the factors influencing cage subsidence. Results There were significant differences between the two groups in the preoperative CT values of responsible vertebral body and its upper endplate, the proportion of patients with preoperative responsible vertebral body endplate sclerosis, the preoperative multifidus muscle cross-sectional area at responsible vertebral body, the proportion of patients with preoperative severe atrophy of the multifidus muscle, the proportion of patients with cage height 14 mm, the proportion of patients with cage length 55 mm, and the proportion of patients with articular process degeneration of degree 3 (t=2.332-3.097,χ2=4.545-6.246,P

Abstract Background Human parasitic infections caused by Adenophorean nematodes encompass a range of diseases, including dioctophymiasis, trichuriasis, capillariasis, trichinellosis, and myositis. These infection can result in adverse impacts on human health and cause societal and economic concerns in tropical and subtropical regions. Methods This review conducted searches in PubMed, Embase and Google Scholar for relevant studies that published in established databases up to April 26, 2024. Studies that focused on the common morphology, life cycle, disease distribution, clinical manifestations, and prevention and control strategies for Adenophorean parasitic diseases in humans were included. Results Adenophorean nematodes exhibit shared morphological characteristics with a four-layered cuticle; uninucleate epidermal cells; pseudocoelom with six or more coelomocytes; generally three caudal glands; five esophageal glands; two testes in males with median-ventral supplementary glands in a single row; tail in males rarely possessing caudal alae; amphids always postlabial; presence of cephalic sensory organs; absence of phasmids; and a secretory-excretory system consisting of a single ventral gland cell, usually with a non-cuticularized terminal duct. Humans play two important roles in the life cycle of the nematode class, Adenophorea: 1) as a definitive host infected by ingesting undercooked paratenic hosts, embryonated eggs, infective larvae in fish tissue and meat contaminated with encysted or non-encysted larvae, and 2) as an accidental host infected by ingesting parasitic eggs in undercooked meat. Many organs are targeted by the Adenophorean nematode in humans such as the intestines, lungs, liver, kidneys, lymphatic circulation and blood vessels, resulting in gastrointestinal problems, excessive immunological responses, cell disruption, and even death. Most of these infections have significant incidence rates in the developing countries of Africa, Asia and Latin America; however, some parasitic diseases have restricted dissemination in outbreaks. To prevent these diseases, interventions together with education, sanitation, hygiene and animal control measures have been introduced in order to reduce and control parasite populations. Conclusions The common morphology, life cycle, global epidemiology and pathology of human Adenophorean nematode-borne parasitic diseases were highlighted, as well as their prevention and control. The findings of this review will contribute to improvement of monitoring and predicting human-parasitic infections, understanding the relationship between animals, humans and parasites, and preventing and controlling parasitic diseases. Graphical Abstract

Abstract Background Pedicle screw instrument surgeries can result in the development of aortic pseudoaneurysm, which is a rare yet potentially severe complication; therefore, the purpose of this work is to describe the case of pseudoaneurysm of the thoracic aorta caused by the severe migration of a pedicle screw after surgery. Case presentation We herein report a patient who underwent endovascular repair for the pseudoaneurysm of the descending thoracic aorta following thoracic vertebral fixation surgery. A 28–80 mm covered stent was initially inserted through the right femoral artery, and intraoperative aortography revealed a minor extravasation of contrast material. Subsequently, an additional 28–140 mm covered stent was implanted. The patient recovered well during the 8-year follow-up period. Conclusions Vascular complications resulting from spinal surgery are severe and rare, necessitating early diagnosis and intervention.

ObjectivesBalloon dilation followed by balloon-expandable stent implantation is an effective treatment for improving hemodynamic status in patients with coarctation of the aorta (CoA). However, limited evidence exists regarding the safety and efficacy of covered balloon-expandable stents (CBSs) in a large cohort. In this meta-analysis, we aimed to evaluate the overall success rates, hemodynamic and anatomical benefits, complications, and mid-term results of CBSs in treating CoA.MethodsThe PubMed, Embase, and Cochrane Library databases were systemically searched for studies reporting outcomes of CBSs in treating CoA. Single-group rate meta-analyses were performed to calculate estimated pooled procedural success rates, the incidence of complications, and re-coarctation rates. A meta-analysis using standardized mean differences was conducted to compare pre- and postoperative trans-coarctation pressure gradients (PGs), coarctation diameter, and overall changes in systolic blood pressure (SBP). Subgroup analyses were performed to identify potential sources of heterogeneity.ResultsThe final analysis included 12 studies with a total of 411 patients. The estimated pooled procedural success rate was 100% [95% confidence interval (CI): 98%–100%, I2 = 0, P = 0.78]. Significant decreases in trans-coarctation PGs and SBP were observed. The pooled incidences of stent-related, aortic, and access site complications were 2% (95% CI: 0%–5%, I2 = 30.4%, P = 0.15), 2% (95% CI: 0%–4%, I2 = 0%, P = 0.76), and 3% (95% CI: 1%–7%, I2 = 52.9%, P = 0.02), respectively. Subgroup analyses showed that implantation of BeGraft stents was related to a significantly higher incidence of access site complications.ConclusionCovered balloon-expandable stent implantation in treating CoA is safe and effective with high procedural success rates, an acceptable incidence of complications, and a low incidence of re-coarctation.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, PROSPERO (CRD42023430356).

BackgroundMicrobial communities significantly influence the vector capacity of ticks, which, along with tick-borne diseases, pose an increasing global threat. Due to the substantial individual variability caused by various factors, it is essential to assess tick microbial communities and vectorial capacities under different environmental conditions. However, there is a relative scarcity of research on the microbial communities and pathogen transmission of ticks in different physiological states and environmental conditions, especially in Hainan Island, southern China.MethodsFrom 2021 to 2022, we collected 4,167 tick samples, grouping them by blood meal status, developmental stage, sex, time, geographical location, and tick species. We selected 128 samples for full-length 16S rRNA sequencing to describe microbial community characteristics and identify potential biomarkers. Seven hundred seventy-two samples were tested for seven tick-borne pathogens (Rickettsia, Borrelia burgdorferi, Ehrlichia, Anaplasma, Theileria, Babesia, and Hepatozoon), and sera from 208 residents of Hainan Island were tested for IgG antibodies against Rickettsia and B. burgdorferi.ResultsBlood meal status, developmental stage, sex, time, geographical location, and tick species significantly influenced the microbial communities of ticks. We observed distinct microbial community characteristics across different states. We noted the non-random replacement of stable and transient species, with functional differences between parasitic and engorged ticks mainly driven by transient species. Functionally, we observed three distinct response patterns: driven by stable species, transient species, and both together in response to the six factors. We identified 273 potential biomarkers (200 robust core species and 73 robust differential species). Six genera and eight species of pathogens were detected in ticks, with an overall positivity rate of 12.44% (96/772). Among humans, 18.27% (38/208) of serum samples were positive for at least one tick-borne pathogen IgG.ConclusionOur findings indicate that these six factors significantly influence both tick microbial communities and vectorial capacity, with varying effects on vector competence for different pathogens and inconsistent impacts on microbial communities under different conditions. This study supplemented the understanding of tick microbial communities on Hainan Island, assessed the relatively high risk of tick-borne pathogens in the region, and evaluated the impact of these factors on both microbial communities and vectorial capacity.

IntroductionMultiple myeloma (MM) is a leading cause of hematopoietic cancer-related mortality, accounting for 20% of deaths. MM-targeted therapies have demonstrated efficacy, and since 2015, the United States Food and Drug Administration (FDA) has approved five targeted drugs. However, their cardiovascular safety has not been comprehensively evaluated.ObjectiveThis study aimed to investigate the association between MM-targeted therapy and cardiovascular adverse events (AEs).MethodsDisproportionality analysis was conducted on reports from the FDA AE Reporting System database from 2014 to the second quarter of 2023. Cardiovascular AEs were grouped into nine narrow categories using the Standardized Medical Dictionary for Regulatory Activities Queries (SMQs).ResultsA total of 3,228 cardiovascular AE cases involving MM-targeted therapy were extracted and analyzed. Significant disproportionality was identified for daratumumab, elotuzumab, and isatuximab. Among the nine narrow SMQ categories, the three most reported cardiovascular AEs were cardiomyopathy, cardiac arrhythmias, and embolic and thrombotic events. Noninfectious myocarditis/pericarditis, cardiac arrhythmias, and embolic and thrombotic events exhibited the strongest signal strengths. The cardiovascular AE risk was higher within the first month and gradually decreased thereafter; however, it increased rapidly again after 1 year. This trend was observed for all cardiovascular AEs. The Kaplan–Meier curve and the log-rank test revealed that isatuximab and elotuzumab exhibited a significantly lower probability of cardiovascular AEs than daratumumab (p < 0.001).ConclusionsMM-targeted therapy is significantly associated with an increased risk of previously unknown cardiovascular AE profiles, with the range and onset differing among various drugs, thereby warranting specific monitoring and appropriate management.

BackgroundOsteoporosis is a multifactorial bone disease in which lipid metabolism plays an important role. Bone Mineral Density (BMD) measured by Dual-energy X-ray Absorptiometry (DXA) is a critical indicator for diagnosing osteoporosis. The cardiometabolic index (CMI) is a novel metric that combines two quantitative indicators of blood lipids—triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). This study explores the association between CMI and BMD and seeks to elucidate the role of lipid metabolism in the context of bone health.MethodsBased on the data of the National Health and Nutrition Examination Survey (NHANES) 2017–March 2020-pre-pandemic, weighted multiple linear regression and smooth curve fitting were used to study the relationship between CMI and femoral BMD. Stratified analyses were also conducted for age, gender, BMI, ethnicity, diabetes and hypertension status. And, the saturation threshold effect of CMI was further analyzed using a two-stage linear regression model.ResultThis study enrolled a total of 1,650 participants (48.7% males), with an average age of 63.0 ± 8.6 years. After adjusting for multiple confounding factors, CMI was positively correlated with total femur BMD, trochanter BMD, and intertrochanter BMD, while the correlation with femur neck BMD was not statistically significant. In the fully adjusted model, each unit increase in CMI was associated with a 0.026 (g/cm2) increase in total femur BMD, a 0.022 (g/cm2) increase in trochanter BMD, and a 0.034 (g/cm2) increase in intertrochanter BMD. Subjects in the highest quartile of CMI had a 0.034 (g/cm2) increase in total femur BMD, a 0.035 (g/cm2) increase in trochanter BMD, and a 0.039 (g/cm2) increase in intertrochanter BMD in the fully-adjusted model compared to those in the lowest quartile. In addition, saturation was observed between CMI and total femur BMD, trochanter BMD and intertrochanter BMD, with saturation thresholds of 1.073, 1.431 and 1.073, respectively.ConclusionCMI is strongly associated with BMD, indicating its potential relevance in bone metabolism. However, the role of CMI in the context of bone health, especially regarding osteoporosis risk, requires further investigation in large-scale prospective studies.

Background:Colorectal cancer (CRC) and its treatments cause significant acute, chronic, or latent adverse effects, leading to decreased physical function and quality of life. Robust evidence supports the positive effects of physical activity (PA) on various health outcomes in CRC patients. However, there is limited understanding regarding the factors that influence PA engagement, including facilitators, preferences, and barriers in this population.Purpose:This scoping review aims to document the breadth and depth of literature concerning the various aspects of PA participation among patients with CRC. We conducted a scoping review of PA among CRC patients.Methods:We searched several databases, including PubMed, Web of Science, Embase, and Cochrane, from their inception to 25 July 2023. Multiple reviewers were involved in all screening and data abstractions. The search yielded 834 individual citations after removing duplicates. After screening the titles and abstracts, 20 articles underwent full-text review, and 11 were included.Results:Our research findings indicate that among CRC patients, the most prevalent facilitators/preferences for PA are understanding its importance and perceiving its benefits, whereas treatment-related effects and lack of time are the most common barriers.Conclusion:CRC patients have unique facilitators and barriers concerning PA. Further research and clinical interventions are required to support and encourage this population to participate in and maintain regular PA.

Triclosan (TCS) is an environmental pollutant. In recent years, there has been increasing level of concern regarding the potential toxicity of TCS in animals and humans, especially its effects on the nervous system. However, whether TCS induces ADHD-like behaviour and the mechanism by which it affects neural function are unclear. The impact of 60 days of continuous exposure to TCS on the behaviour of offspring rats was assessed in this research. According to the results of this study, TCS exposure led to ADHD-like behaviour in offspring rats and activated microglia in the prefrontal cortex (PFC), inducing inflammatory factor release. In vitro studies showed that TCS increased the levels of inflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α, in HMC3 cells. More importantly, we found that TCS regulated the STAT3 pathway by upregulating PKM2 via hnRNPA1. In summary, this study suggested that TCS can induce ADHD-like behaviour in offspring rats and continuously activate HMC3 microglia through the hnRNPA1-PKM2-STAT3 feedback loop, promoting inflammatory cytokine secretion.

In recent years, exposure to triclosan (TCS) has been linked to an increase in psychiatric disorders. Nonetheless, the precise mechanisms of this occurrence remain elusive. Therefore, this study developed a long-life TCS-exposed rat model, an SH-SY5Y cell model, and an atomoxetine hydrochloride (ATX) treatment model to explore and validate the neurobehavioral mechanisms of TCS from multiple perspectives. In the long-life TCS-exposed model, pregnant rats received either 0 mg/kg (control) or 50 mg/kg TCS by oral gavage throughout pregnancy, lactation, and weaning of their offspring (up to 8 weeks old). In the ATX treatment model, weanling rats received daily injections of either 0 mg/kg (control) or 3 mg/kg ATX via intraperitoneal injection until they reached 8 weeks old. Unlike the TCS model, ATX exposure only occurred after the pups were weaned. The results indicated that long-life TCS exposure led to attention-deficit hyperactivity disorder (ADHD)-like behaviors in male offspring rats accompanied by dopamine-related mRNA and protein expression imbalances in the prefrontal cortex (PFC). Moreover, in vitro experiments also confirmed these findings. Mechanistically, TCS reduced dopamine (DA) synthesis, release, and transmission, and increased reuptake in PFC, thereby reducing synaptic gap DA levels and causing dopaminergic deficits. Additional experiments revealed that increased DA concentration in PFC by ATX effectively alleviated TCS-induced ADHD-like behavior in male offspring rats. These findings suggest that long-life TCS exposure causes ADHD-like behavior in male offspring rats through dopaminergic deficits. Furthermore, ATX treatment not only reduce symptoms in the rats, but also reveals valuable insights into the neurotoxic mechanisms induced by TCS.

The metasurfaces have shown great potential for miniaturizing conventional optics while offering extended flexibility. Recently, there has been considerable interest in using algorithms to generate meta-atom shapes for these metasurfaces, as they offer vast design freedom and not biased by the human intuition. However, these complex designs significantly increase the difficulty of fabrication. To address this, we introduce a design process that rigorously enforces the fabricability of both the material-filled (fill) and empty (void) regions in a metasurface design. This process takes into account specific constraints regarding the minimum feature size for each region. Additionally, it corrects any violations of these constraints across the entire device, ensuring only minimal impact on performance. Our method provides a practical way to create metasurface designs that are easy to fabricate, even with complex shapes, hence improving the overall production yield of these advanced meta-optical components.

Epigenetic modifications play an important role in cellular senescence, and enhancer of zeste homolog 2 (EZH2) is a key methyltransferase involved in epigenetic remodeling in multiple myeloma (MM) cells. We have previously demonstrated that GSK126, a specific EZH2 inhibitor, exhibits anti-MM therapeutic efficacy and safety in vivo and in vitro; however, its specific mechanism remains unclear. This study shows that GSK126 induces cellular senescence in MM, which is characterized by the accumulation of senescence-associated heterochromatin foci (SAHF) and p21, and increased senescence-associated β galactosidase activity. Furthermore, EZH2 is inhibited in ribonucleotide reductase regulatory subunit M2 (RRM2)-overexpressing OCI-MY5 and RPMI-8226 cells. RRM2 overexpression inhibits the methyltransferase function of EZH2 and promotes its degradation through the ubiquitin-proteasome pathway, thereby inducing cellular senescence. In this senescence model, Lamin B1, a key component of the nuclear envelope and a marker of senescence, does not decrease but instead undergoes aberrant accumulation. Meanwhile, phosphorylation of extracellular signal-regulated protein kinase (ERK1/2) is significantly increased. The inhibition of ERK1/2 phosphorylation in turn partially restores Lamin B1 level and alleviates senescence. These findings suggest that EZH2 inhibition increases Lamin B1 level and induces senescence by promoting ERK1/2 phosphorylation. These data indicate that EZH2 plays an important role in MM cellular senescence and provide insights into the relationships among Lamin B1, p-ERK1/2, and cellular senescence.

Abstract Background Ticks are blood-feeding significant arthropods that can harbour various microorganisms, including pathogens that pose health risks to humans and animals. Tick-symbiont microorganisms are believed to influence tick development, but the intricate interactions between these microbes and the relationships between different tick-borne microorganisms remain largely unexplored. Results Based on 111 tick pool samples presenting questing and engorged statuses including 752 questing tick and 1083 engorged tick from cattle and goats, which were collected in two types of geographic landscape (semi-desert and alpine meadow). We observed significant variations in the composition of tick-borne microorganisms across different environments and blood-engorgement statuses, with a pronounced divergence in symbionts compared to environmental bacteria. Metabolic predictions revealed over 90 differential pathways for tick-borne microorganisms in distinct environments and more than 80 metabolic variations in response to varying blood engorgement statuses. Interestingly, nine pathways were identified, particularly related to chorismate synthesis and carbohydrate metabolism. Moreover, microbial network relationships within tick-borne microorganism groups were highly distinct across different environments and blood-engorgement statuses. The microbial network relationships of symbionts involve some pathogenic and environmental microorganisms. Regression modelling highlighted positive correlations between the Coxiella symbiont and related pathogens, while some environmental bacteria showed strong negative correlations with Coxiella abundance. We also identified commensal bacteria/pathogens in bacterial cooccurrence patterns. Furthermore, we tested pathogenic microorganisms of each tick sample analysis revealed that 86.36% (1601/1855) of the tick samples carried one or more pathogenic microorganisms, The total carrier rate of bacterial pathogens was 43.77% ((812/1855). Most blood samples carried at least one pathogenic microorganism. The pathogens carried by the ticks have both genus and species diversity, and Rickettsia species are the most abundant pathogens among all pathogens. Conclusion Our findings underscore that the bacterial pattern of ticks is dynamic and unstable, which is influenced by the environment factors and tick developmental characteristics.

Abstract Growing evidence suggests an association between osteocalcin (OCN), a peptide derived from bone and involved in regulating glucose and lipid metabolism, and the risk of Alzheimer’s disease (AD). However, the causality of these associations and the underlying mechanisms remain uncertain. We utilized a Mendelian randomization (MR) approach to investigate the causal effects of blood OCN levels on AD and to assess the potential involvement of glucose and lipid metabolism. Independent instrumental variables strongly associated (P

The peel of pitaya fruit is a promising source of pectin, and non- or low-methylesterified pectin has multiple bioactivities and application scenarios. In this study, non-methylated pectin was prepared from pitaya peel and the structure was characterized. Single factor experiment and response surface methodology were conducted to optimize the procedure of ultrasonic-assisted extraction for pectin. Under the optimal conditions (solid-liquid ratio of 1:40 g·mL−1, extraction temperature at 56 °C, extraction time of 25 min and ultrasonic power of 200 W), the pectin yield was up to 9.93% ± 0.97%. Degree of methylesterification and FTIR analysis confirmed that the extracted pectin was almost non-methylesterified. The pectin possessed less linear homogalacturonan (HG) but more rhamnogalacturonan (RG) regions according to the molar ratios of monosaccharides. Meanwhile, the molecular weight of the pectin was 33.52 kDa and the crystalline index was only 0.60%. Furthermore, the nanoscale structure observed by atomic force microscopy showed that the pectin was rich in highly branched polymers. Generally, pitaya peel pectin extracted by ultrasonic-assisted extraction showed a wide range of potential use as a non-or low- methylesterified pectic substance to reach the efficient utilization of fruit waste.

Complicated terrains, specific regions, and high wind turbulence intensity frequently trigger shutdown protection of wind turbines due to vibration beyond the designated limit, resulting in serious loss of power generation. This paper aims at reducing the frequency of shutdowns and improving operational stability of wind turbines. Operational characteristics of wind turbines under complicated conditions such as specific regions and strong turbulent wind were analyzed. A fuzzy control approach was proposed based on pertinent theory, to deal with complicated operating conditions at specific sites. This strategy incorporates a vibration recognition algorithm to classify vibration conditions and a fuzzy control algorithm for vibration suppression based on the categorized conditions. Compared with the conventional shutdown or sector-based control methods, the proposed fuzzy control strategy of vibration suppression eliminates the frequent starting and stopping of wind turbines, thus ensuring power generation and improving operational stability. Furthermore, a simulation analysis was performed using Bladed software, taking 3.x MW wind turbines as the research object. Subsequent experimental verification was carried out at a wind farm. In the experiment, the application of the fuzzy vibration suppression control method effectively led to the quick ride-through of the wind turbine amid the complicated operating conditions including the specific region and strong turbulent wind. A 23.87% reduction in the maximum RMS of the front and rear accelerations of the nacelle demonstrated a substantial enhancement in the wind turbine reliability.

For the low parameter tuning efficiency, accuracy and adaptability of the traditional PID parameter tuning method currently adopted in the wind turbine variable-pitch system, this paper presents a method for self-optimization of wind turbine variable-pitch control parameters based on adaptive genetic algorithm, including variable-gain variable-pitch PID parameter self-optimization and tower damping parameter self-optimization. The author first described the basic principle of variable-pitch control system; then based on the genetic algorithm, planned and designed constraint conditions for different wind turbine models, covering initial population selection, self-optimization algorithm constraints and adaptability function design; and finally compared and analyzed the response curve, simulation and field operation results of the traditional parameter tuning method and self-optimization parameter tuning method. The results show that, compared with the traditional parameter tuning method, the self-optimization parameter tuning method reduces the motor speed fluctuation by about 10%, and the fatigue My load of the tower bottom by about 2%. This shows the self-optimization parameter tuning method can improve the tuning efficiency, accuracy and adaptability.

Abstract Background Dyslipidemia, a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic variations, particularly those in the low-density lipoprotein receptor (LDLR) gene. This study aimed to elucidate the effects of LDLR polymorphisms on baseline serum lipid levels and the therapeutic efficacy of atorvastatin in an adult Han population in northern China with dyslipidemia. Methods In this study, 255 Han Chinese adults receiving atorvastatin therapy were examined and followed up. The 3’ untranslated region (UTR) of the LDLR gene was sequenced to identify polymorphisms. The associations between gene polymorphisms and serum lipid levels, as well as changes in lipid levels after intervention, were evaluated using the Wilcoxon rank sum test, with a P

Abstract Purpose To identify MRI-detected anatomical risk factors for non-contact anterior cruciate ligament (ACL) injuries across genders. Methods A retrospective analysis was performed on 141 ACL-reconstructed patients (35 females, 106 males) and 142 controls (37 females, 105 males) from January 2020 to April 2022. Inclusion criteria were primary non-contact ACL injuries. The tibial plateau slope, lateral femoral condyle index, Insall-Salvati index, and patellar tendon angle were measured, using binary logistic regression for gender-specific risk evaluation. Results Increased lateral tibial plateau slope, reduced intercondylar notch width index, lateral femoral condyle index, and patellar tendon angle correlated with ACL injuries in both genders. The Insall-Salvati index was a significant risk factor in females but not in males. Conclusion This study identifies the lateral tibial plateau slope, notch width index, lateral femoral condyle index, and patellar tendon angle at near-extension as risk factors for ACL injuries in both genders, with the Insall-Salvati index also implicated in females.

Abstract Background Interstitial brachytherapy is a form of intensive local irradiation that facilitates the effective protection of surrounding structures and the preservation of organ functions, resulting in a favourable therapeutic response. As surgical robots can perform needle placement with a high level of accuracy, our team developed a fully automatic radioactive seed placement robot, and this study aimed to evaluate the accuracy and feasibility of fully automatic radioactive seed placement for the treatment of tumours in the skull base. Methods A fully automatic radioactive seed placement robot was established, and 4 phantoms of skull base tumours were built for experimental validation. All the phantoms were subjected to computed tomography (CT) scans. Then, the CT data were imported into the Remebot software to design the preoperative seed placement plan. After the phantoms were fixed in place, navigation registration of the Remebot was carried out, and the automatic seed placement device was controlled to complete the needle insertion and particle placement operations. After all of the seeds were implanted in the 4 phantoms, postoperative image scanning was performed, and the results were verified via image fusion. Results A total of 120 seeds were implanted in 4 phantoms. The average error of seed placement was (2.51 ± 1.44) mm. Conclusion This study presents an innovative, fully automated radioactive particle implantation system utilizing the Remebot device, which can successfully complete automated localization, needle insertion, and radioactive particle implantation procedures for skull base tumours. The phantom experiments showed the robotic system to be reliable, stable, efficient and safe. However, further research on the needle-soft tissue interaction and deformation mechanism of needle puncture is still needed.

Background: Idiopathic pulmonary fibrosis (IPF) is an irreversible lung disease with unclear pathological mechanisms. In this study, we utilized bidirectional Mendelian randomization (MR) to analyze the relationship between serum metabolites and IPF, and conducted metabolic pathway analysis. Aim: To determine the causal relationship between serum metabolites and IPF using MR analysis. Methods: A two-sample MR analysis was conducted to evaluate the causal relationship between 824 serum metabolites and IPF. The inverse variance weighted (IVW) method was used to estimate the causal relationship between exposure and results. Sensitivity analysis was conducted using MR Egger, weighted median, and maximum likelihood to eliminate pleiotropy. Additionally, metabolic pathway analysis was conducted to identify potential metabolic pathways. Results: We identified 12 serum metabolites (6 risks and 6 protective) associated with IPF from 824 metabolites. Among them, 11 were known and 1 was unknown. 1-Eicosatrienoylglycophorophospholine and 1-myristoylglycophorophospholine were bidirectional MR positive factors, with 1-myristoylglycophorophospholine being a risk factor (1.0013, 1.0097) and 1-eicosatrienoylglycophorine being a protective factor (0.9914, 0.9990). The four lipids (1-linoleoylglycerophoethanolamine*, total cholesterol in large high-density lipoprotein [HDL], cholesterol esters in very large HDL, and phospholipids in very large HDL) and one NA metabolite (degree of unsaturation) were included in the known hazardous metabolites. The known protective metabolites included three types of lipids (carnitine, 1-linoleoylglycerophoethanolamine*, and 1-eicosatrienoylglycerophophophorine), one amino acid (hypoxanthine), and two unknown metabolites (the ratio of omega-6 fatty acids to omega-3 fatty acids, and the ratio of photoshopids to total lipids ratio in chylomicrons and extremely large very low-density lipoprotein [VLDL]). Moreover, sn-Glycerol 3-phosphate and 1-Acyl-sn-glycero-3-phosphocline were found to be involved in the pathogenesis of IPF through metabolic pathways such as Glycerolide metabolism and Glycerophospholipid metabolism. Conclusion: Our study identified 6 causal risks and 6 protective serum metabolites associated with IPF. Additionally, 2 metabolites were found to be involved in the pathogenesis of IPF through metabolic pathways, providing a new perspective for further understanding the metabolic pathway and the pathogenesis of IPF.

Abstract The aim of this study is to research the expression of the transient receptor potential canonical channel 3 (TRPC3) in a neonatal hyperoxic lung injury model of bronchopulmonary dysplasia (BPD), and to further investigate the role of the TRPC3/nuclear factor‐κB (NF‐κB) signaling pathway in hyperoxia‐induced BPD by a TRPC3 agonist (GSK1702934A). The hyperoxic lung injury model of BPD was established in Sprague–Dawley neonatal rats. Hematoxylin and eosin (HE) staining and radial alveolar count (RAC) values showed that the hyperoxic lung injury model of BPD was successfully established in the neonatal rats, and pulmonary edema was found in the neonatal rats with BPD. The results of reference transcriptome sequencing, Quantitative real‐time PCR (qPCR), and western blot showed lower pulmonary expression of TRPC3 in the BPD group than in the control group. Immunofluorescence showed predominant expression of TRPC3 in airways and pulmonary vessels, and the fluorescence intensity of the BPD group was lower than that of the control group. Lung dry‐to‐wet weight ratio, HE staining, and RAC value showed that the lung histomorphology significantly improved in the BPD + TRPC3 agonist group compared with the BPD group on day 14 but did not revert to the level of the control group. According to qPCR results, compared with the control group, the expression of NF‐κB1 decreased and the expression of NF‐κBiz increased in the BPD group, whereas the expression of NF‐κBiz decreased in the BPD + TRPC3 agonist group. Therefore, we draw the conclusion that TRPC3 may activate NF‐κB by inhibiting NF‐κBiz to promote cell proliferation and lung growth and development.

Abstract Aortic root aneurysm is a potentially life‐threatening condition that may lead to aortic rupture and is often associated with genetic syndromes, such as Marfan syndrome (MFS). Although studies with MFS animal models have provided valuable insights into the pathogenesis of aortic root aneurysms, this understanding of the transcriptomic and epigenomic landscape in human aortic root tissue remains incomplete. This knowledge gap has impeded the development of effective targeted therapies. Here, this study performs the first integrative analysis of single‐nucleus multiomic (gene expression and chromatin accessibility) and spatial transcriptomic sequencing data of human aortic root tissue under healthy and MFS conditions. Cell‐type‐specific transcriptomic and cis‐regulatory profiles in the human aortic root are identified. Regulatory and spatial dynamics during phenotypic modulation of vascular smooth muscle cells (VSMCs), the cardinal cell type, are delineated. Moreover, candidate key regulators driving the phenotypic modulation of VSMC, such as FOXN3, TEAD1, BACH2, and BACH1, are identified. In vitro experiments demonstrate that FOXN3 functions as a novel key regulator for maintaining the contractile phenotype of human aortic VSMCs through targeting ACTA2. These findings provide novel insights into the regulatory and spatial dynamics during phenotypic modulation in the aneurysmal aortic root of humans.